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DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
21 CFR Part 1160
[Docket No. FDA–2024–N–5471]
RIN 0910–AI76

Tobacco Product Standard for Nicotine
Yield of Cigarettes and Certain Other
Combusted Tobacco Products
Food and Drug Administration,
Department of Health and Human
Services (HHS).
ACTION: Proposed rule.
AGENCY:

The Food and Drug
Administration (FDA, the Agency, or
we) is proposing a tobacco product
standard that would regulate nicotine
yield by establishing a maximum
nicotine level in cigarettes and certain
other combusted tobacco products. FDA
is proposing this action to reduce the
addictiveness of these products, thus
giving people who are addicted and
wish to quit the ability to do so more
easily. The proposed product standard
is anticipated to benefit the population
as a whole. For example, it would help
to prevent people who experiment with
cigarettes and cigars from developing
addiction and using combusted tobacco
products regularly.
DATES: Either electronic or written
comments on the proposed rule must be
submitted by September 15, 2025.
Submit comments (including
recommendations) on the collection of
information under the Paperwork
Reduction Act of 1995 (PRA) by
September 15, 2025.
ADDRESSES: You may submit comments
as follows. Please note that late,
untimely filed comments will not be
considered. The https://
www.regulations.gov electronic filing
system will accept comments until
11:59 p.m. Eastern Time at the end of
September 15, 2025. Comments received
by mail/hand delivery/courier (for
written/paper submissions) will be
considered timely if they are received
on or before that date.
SUMMARY:

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Electronic Submissions
Submit electronic comments in the
following way:
• Federal eRulemaking Portal:
https://www.regulations.gov. Follow the
instructions for submitting comments.
Comments submitted electronically,
including attachments, to https://
www.regulations.gov will be posted to
the docket unchanged. Because your
comment will be made public, you are

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solely responsible for ensuring that your
comment does not include any
confidential information that you or a
third party may not wish to be posted,
such as medical information, your or
anyone else’s Social Security number, or
confidential business information, such
as a manufacturing process. Please note
that if you include your name, contact
information, or other information that
identifies you in the body of your
comments, that information will be
posted on https://www.regulations.gov.
• If you want to submit a comment
with confidential information that you
do not wish to be made available to the
public, submit the comment as a
written/paper submission and in the
manner detailed (see ‘‘Written/Paper
Submissions’’ and ‘‘Instructions’’).
Written/Paper Submissions
Submit written/paper submissions as
follows:
• Mail/Hand Delivery/Courier (for
written/paper submissions): Dockets
Management Staff (HFA–305), Food and
Drug Administration, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments
submitted to the Dockets Management
Staff, FDA will post your comment, as
well as any attachments, except for
information submitted, marked, and
identified, as confidential, if submitted
as detailed in ‘‘Instructions.’’
Instructions: All submissions received
must include the Docket No. FDA–
2024–N–5471 for ‘‘Tobacco Product
Standard for Nicotine Yield of Cigarettes
and Certain Other Combusted Tobacco
Products.’’ Received comments, those
filed in a timely manner (see
ADDRESSES), will be placed in the docket
and, except for those submitted as
‘‘Confidential Submissions,’’ publicly
viewable at https://www.regulations.gov
or at the Dockets Management Staff
between 9 a.m. and 4 p.m., Monday
through Friday, 240–402–7500.
• Confidential Submissions—To
submit a comment with confidential
information that you do not wish to be
made publicly available, submit your
comments only as a written/paper
submission. You should submit two
copies total. One copy will include the
information you claim to be confidential
with a heading or cover note that states
‘‘THIS DOCUMENT CONTAINS
CONFIDENTIAL INFORMATION.’’ The
Agency will review this copy, including
the claimed confidential information, in
its consideration of comments. The
second copy, which will have the
claimed confidential information
redacted/blacked out, will be available
for public viewing and posted on
https://www.regulations.gov. Submit

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both copies to the Dockets Management
Staff. If you do not wish your name and
contact information to be made publicly
available, you can provide this
information on the cover sheet and not
in the body of your comments and you
must identify this information as
‘‘confidential.’’ Any information marked
as ‘‘confidential’’ will not be disclosed
except in accordance with 21 CFR 10.20
and other applicable disclosure law. For
more information about FDA’s posting
of comments to public dockets, see 80
FR 56469, September 18, 2015, or access
the information at: https://
www.govinfo.gov/content/pkg/FR-201509-18/pdf/2015-23389.pdf.
Docket: For access to the docket to
read background documents or the
electronic and written/paper comments
received, go to https://
www.regulations.gov and insert the
docket number, found in brackets in the
heading of this document, into the
‘‘Search’’ box and follow the prompts
and/or go to the Dockets Management
Staff, 5630 Fishers Lane, Rm. 1061,
Rockville, MD 20852, 240–402–7500.
Go to the Federal eRulemaking Portal
at https://www.regulations.gov for
access to the rulemaking docket,
including any background documents
and the plain-language summary of the
proposed rule of not more than 100
words in length required by the
Providing Accountability Through
Transparency Act of 2023.
Submit comments on the information
collection under the Paperwork
Reduction Act of 1995 to the Office of
Management and Budget (OMB) at
https://www.reginfo.gov/public/do/
PRAMain. Find this particular
information collection by selecting
‘‘Currently under Review—Open for
Public Comments’’ or by using the
search function. The title of this
proposed collection is ‘‘Tobacco
Product Standard for Nicotine Yield of
Cigarettes and Certain Other Combusted
Tobacco Products.’’
FOR FURTHER INFORMATION CONTACT:
With regard to the proposed rule: Nate
Mease or Dhanya John, Center for
Tobacco Products, Food and Drug
Administration, 10903 New Hampshire
Ave., Silver Spring, MD 20993–0002,
877–287–1373, CTPRegulations@
fda.hhs.gov.
With regard to the information
collection: JonnaLynn Capezzuto, Office
of Operations, Food and Drug
Administration, Three White Flint
North, 10A–12M, 11601 Landsdown St.,
North Bethesda, MD 20852, 301–796–
3794, [email protected].
SUPPLEMENTARY INFORMATION:

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Table of Contents
I. Executive Summary
A. Purpose of the Proposed Rule
B. Summary of the Major Provisions of the
Proposed Rule
C. Legal Authority
D. Costs and Benefits
II. Table of Abbreviations/Commonly Used
Acronyms in This Document
III. Background
A. Need for the Regulation
B. Relevant Regulatory History
C. Legal Authority
IV. Nicotine in Cigarettes and Other
Combusted Tobacco Products:
Addiction, Initiation, Dependence,
Cessation, Relapse, Health Effects, and
Consumer Perceptions
A. Nicotine Is Addictive
B. The Developing Brain’s Vulnerability to
the Effects of Nicotine Leads to
Progression to Regular Cigarette Use
Among Youth and Young Adults Who
Experiment
C. Youth and Adult Cigarette Smoking
Cessation and Relapse
D. Smoking Cigarettes and Other
Combusted Tobacco Products Causes
Serious Negative Health Effects
E. Tobacco Product Marketing Has
Contributed to Disparities in Use and
Health Outcomes
F. Consumer Knowledge, Attitudes,
Beliefs, and Perceptions About Nicotine
V. History and Perceptions of VLNC
Cigarettes
A. History of LNC and VLNC Cigarettes
B. Consumer Knowledge, Attitudes,
Beliefs, and Perceptions Regarding VLNC
Cigarettes and Regulation of Levels of
Nicotine in Tobacco
VI. Rationale for Products Covered by the
Proposed Product Standard
A. Prevalence and Abuse Potential of
Cigarettes and Other Combusted Tobacco
Products
B. Potential for Tobacco Product Switching
VII. Discussion of Nicotine-Related Topics
A. Approach To Limiting User Exposure to
Nicotine
B. Scientific Evidence Supports the Target
Level of Nicotine
C. An Immediate Nicotine Reduction
Approach Is Strongly Supported by
Scientific Evidence
D. Scientific Evidence Supports the Use of
an Analytical Test Method To Determine
Nicotine Level
E. Scientific Evidence Supports the
Technical Achievability of the Proposed
Maximum Nicotine Level Target
F. Proposal Does Not Seek To Limit
Nicotine to Zero
VIII. Determination That the Standard Is
Appropriate for the Protection of the
Public Health
A. Approach To Estimating Impacts to the
Population as a Whole
B. The Likelihood That Nonusers Would
Start Using Cigarettes or Other
Combusted Tobacco Products
C. The Likelihood That Existing Users
Would Reduce Cigarette and Other
Combusted Tobacco Product
Consumption or Stop Smoking

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D. Benefits and Risks to the Population as
a Whole
E. Approach Concerning Adjustments to
Inputs to the Model Accounting for
Other Tobacco Product Standards
F. Benefits and Risks to the Population as
a Whole Accounting for Other Tobacco
Product Standards
G. Conclusion
IX. Additional Considerations and Requests
for Comment
A. Section 907 of the FD&C Act
B. Pathways to Market
C. Considerations and Request for
Comments on Scope of Products
D. Considerations and Request for
Comments on the Potential for Illicit
Trade
X. Description of Proposed Regulation
A. General Provisions (Proposed Subpart
A)
B. Product Requirements (Proposed
Subpart B)
C. Manufacturing Code and Recordkeeping
Requirements (Proposed Subpart C)
XI. Proposed Effective Date
XII. Preliminary Economic Analysis of
Impacts
A. Introduction
B. Summary of Costs and Benefits
XIII. Analysis of Environmental Impact
XIV. Paperwork Reduction Act of 1995
XV. Federalism
XVI. Severability
XVII. Consultation and Coordination With
Indian Tribal Governments
XVIII. References

I. Executive Summary
A. Purpose of the Proposed Rule
Each year, 480,000 people die
prematurely from a smoking-attributable
disease, making tobacco use the leading
cause of preventable disease and death
in the United States (Ref. 1). Nearly all
these adverse health effects are
ultimately the result of addiction to the
nicotine in combusted tobacco products,
leading to repeated exposure to
toxicants from those products. Nicotine,
the primary addictive constituent in
tobacco products, can be delivered
through a variety of products along a
continuum of risk. To protect youth and
reduce tobacco-related disease and
death, the Agency utilizes a
comprehensive approach to tobacco and
nicotine regulation (https://
www.fda.gov/media/174911/download).
As part of this comprehensive approach,
FDA is proposing a tobacco product
standard that would regulate nicotine
yield by establishing a maximum
nicotine level in cigarettes 1 and certain
1 Throughout this document, FDA generally uses
the term ‘‘cigarettes’’ to refer to combusted
cigarettes, unless specifically stated or context
indicates that noncombusted cigarettes are
referenced. In general, the term is not meant to
include any noncombusted tobacco products that
meet the definition of cigarette in section 900(3) of
the Federal Food, Drug, and Cosmetic Act (21
U.S.C. 387(3)).

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other combusted tobacco products
(proposed product standard).
As the U.S. District Court for the
District of Columbia recognized in
United States v. Philip Morris USA, Inc.
et al., 449 F.Supp.2d 1 (D.D.C. 2006),
aff’d in relevant part, 566 F.3d 1095
(D.C. Cir. 2009), the tobacco industry
has long known that nicotine creates
and sustains addiction, and the industry
is dependent on maintaining this
addiction. Id. at 307. The court noted
how cigarette companies have engaged
in extensive research to understand how
nicotine operates within the human
body and then designed their cigarettes
to precisely control nicotine delivery
and provide nicotine doses to create and
sustain addiction. Id. at 307–309.
Moreover, the court confirmed that
industry documents supported the
conclusion that these companies ‘‘knew
early on in their research that if a
cigarette did not deliver a certain
amount of nicotine, new smokers would
not become addicted, and ‘confirmed’
smokers would be able to quit.’’ Id. at
219. In fact, the tobacco industry has
had programs in place since the 1960s
to obtain ‘‘any level of nicotine desired’’
(Ref. 2). These companies sought to
identify the ‘‘optimum’’ dose needed to
‘‘satisfy’’ people who smoke cigarettes
and, thereby, assure their continued
smoking. Philip Morris, 449 F.Supp.2d
at 309–10. This proposed product
standard would seek to set a maximum
nicotine level such that cigarettes and
certain other combusted tobacco
products could no longer create and
sustain this addiction among people
who smoke cigarettes and certain other
combusted tobacco products.
The proposed product standard
would limit the addictiveness of the
most toxic and widely used tobacco
products, which would have significant
public health benefits for all age groups.
The proposal would have cessation
benefits for adults who use cigarettes
and certain other combusted tobacco
products, most of whom want to quit
but are repeatedly unsuccessful because
of the highly addictive nature of these
products (see section IV.A of this
document). Because these products
would not create and sustain addiction,
users would be able to quit when they
would like, something many who use
these products currently do not have the
ability to do. Additionally, combusted
tobacco products at minimally addictive
or nonaddictive levels of nicotine would
remain on the market for those who
currently smoke and would like to
continue to do so.
It would also help prevent people
who experiment with cigarettes or
certain other combusted tobacco

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products (mainly youth) from moving
beyond experimentation, developing an
addiction to nicotine, and progressing to
regular use of combusted tobacco
products as a result of that addiction
(see section VIII.B of this document).
Reducing the number of people who
experiment with cigarettes or certain
other combusted tobacco products who
then transition to regular use of these
products would prevent severe adverse
health consequences of long-term
smoking at the individual level and
result in public health benefits at the
population level. Based on FDA’s
population health model, by the year
2100, in the United States,
approximately 48 million youth and
young adults who would have otherwise
initiated habitual cigarette smoking
would not as a result of the proposed
product standard. The model also
projects that more than 12.9 million
additional people who smoke cigarettes
would quit smoking cigarettes 2 1 year
after implementation of the proposed
product standard; this estimate
increases to 19.5 million additional
people within 5 years of
implementation (this includes people
who exclusively smoke cigarettes
quitting all tobacco products or
completely switching to noncombusted
tobacco product use, as well as people
who engage in dual use of cigarettes and
noncombusted tobacco products
quitting cigarette use). In addition, the
model estimates that, by the year 2060,
in the United States, this proposed
product standard would result in 1.8
million tobacco-related deaths averted,
rising to 4.3 million deaths averted by
the end of the century. The reduction in
premature deaths attributable to the
proposed product standard would result
in 19.6 million life years gained by 2060
and 76.4 million life years gained by
2100. For the reasons discussed in the
preamble, FDA finds that the proposed
product standard would be appropriate
for the protection of the public health.
As explained in section VIII.A., the
population health model uses inputs
derived from available empirical
evidence and expert opinion to estimate
the impact of this proposed rule. To
obtain expert opinion for the model
inputs, FDA conducted a formal expert
elicitation process in 2015 and repeated
it in 2018. FDA is conducting another
expert elicitation process and intends to
publish the results of this update for
public review and additional comment
2 For the purposes of this proposed rule, where
describing expected transition behaviors, we also
use the shorter phrase ‘‘quit smoking’’ to refer to
stopping use of combusted cigarettes.

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on this proposed standard in light of
that update.
B. Summary of the Major Provisions of
the Proposed Rule
There are currently no tobacco
product standards regulating nicotine in
tobacco products. The proposed rule
would establish a maximum level of
nicotine in cigarettes and certain other
combusted tobacco products. FDA
issued an Advance Notice of Proposed
Rulemaking regarding a potential
nicotine tobacco product standard
(Nicotine ANPRM), and the Agency
reviewed and analyzed the comments to
that ANPRM (83 FR 11818 (March 16,
2018)). FDA also conducted an
extensive and robust review of the
relevant scientific literature, as
discussed throughout this document.
FDA is proposing the following
provisions based on the comments
received and the Agency’s analysis of
relevant scientific literature.
Proposed scope—Given that
approximately 28 million adults and
380,000 youth in the United States
currently smoke cigarettes and the
toxicity and addictiveness of these
products, cigarettes are the tobacco
product category that causes the largest
amount of harm to public health in the
United States (Refs. 3 and 4). However,
if a product standard were to cover only
cigarettes, it is likely that a significant
number of addicted people who smoke
cigarettes would migrate to other similar
combusted tobacco products after the
standard went into effect to maintain
their nicotine exposure, thereby
undermining the public health benefits
of the standard (Ref. 5) (see also section
VI.B of this document). Therefore, to
increase the public health benefits, we
are proposing to cover the following
products under this proposed product
standard: Cigarettes (other than
noncombusted cigarettes, such as heated
tobacco products (HTPs 3) that meet the
definition of a cigarette), cigarette
tobacco, roll-your-own (RYO) tobacco,
cigars (including little cigars, cigarillos,
and large cigars but excluding premium
cigars 4), and pipe tobacco (other than
waterpipe tobacco 5). FDA requests
3 Tobacco products that meet the statutory or
regulatory definition of a cigarette but are not
combusted (do not exceed 350 °C) are categorized
as ‘‘heated tobacco products’’ (HTPs) for purposes
of FDA’s premarket review. HTPs that meet the
definition of a cigarette must be in compliance with
the applicable statutory and regulatory
requirements for cigarettes, unless otherwise noted
in a marketing authorization order (Ref. 6).
4 See section III.B.3 of this document.
5 Waterpipe tobacco (also known as hookah
tobacco) is a type of tobacco product that produces
smoke that people inhale when a hookah device is
heated. Hookah tobacco (also known as waterpipe

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comments, data, and research regarding
this proposed scope.
FDA is proposing to exclude
noncombusted cigarettes, such as HTPs
that meet the definition of a cigarette in
section 900(3) of the Federal Food,
Drug, and Cosmetic Act (FD&C Act) (21
U.S.C. 387(3)) from the scope of this
proposed product standard (proposed
§ 1160.3 includes a definition of
cigarette). Therefore, ‘‘cigarettes’’ in this
proposed rule refers to combusted
cigarettes, not HTPs. Based on FDA’s
experience with application review,
certain noncombusted cigarettes
produce fewer or lower levels of some
toxicants than combusted cigarettes.
FDA recognizes that tobacco products
exist on a continuum of risk, with
combusted cigarettes being the
deadliest, and that certain noncombusted cigarettes pose less risk to
individuals who use cigarettes or certain
other combusted tobacco products or to
population health than other products
meeting the definition of a cigarette.
Accordingly, FDA requests comments,
data, and research regarding the
proposal to exclude noncombusted
cigarettes from the scope of this
proposed rule, including any data that
could justify otherwise.
FDA also proposes to exclude
waterpipe tobacco from the proposed
product standard because, unlike
cigarette tobacco, pipe tobacco, RYO
tobacco, and cigars (other than premium
cigars), FDA believes there is little risk
of switching under the proposed
product standard. Waterpipes as
currently marketed and used generally
require substantial time for preparation
and use (i.e., an approximately 1-hour
session with waterpipes compared to 5–
7 minutes with cigarettes). In addition,
they are generally large and unwieldy
and thus ill-suited for mobile usage,
such as while driving or walking. FDA
requests comments, data, and research
regarding the proposal to exclude
waterpipe tobacco from the scope of this
proposed rule, including any data that
could justify otherwise.
FDA is also not including
noncombusted non-cigarette tobacco
products, such as electronic nicotine
delivery systems (ENDS) (which include
e-cigarettes) and smokeless tobacco
products, in the scope of this proposed
product standard. As discussed
throughout this document, nicotine is
the primary addictive constituent in
tobacco, maassel, shisha, narghile, or argileh)
typically contains a mixture of tobacco, sweeteners,
and flavoring. The hookah device (or waterpipe)
used to smoke the hookah tobacco works by passing
charcoal or electric heated air through the tobacco
mixture and ultimately through a water-filled
chamber (Ref. 7).

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tobacco products, and it is the nicotine
in such products that both creates and
sustains addiction and ultimately leads
to the significant adverse health effects
caused by these products. While these
effects raise concerns in the context of
any tobacco product—none of which is
without risk—at this time, FDA is
focusing this proposed rule on nicotine
levels in cigarettes and certain other
combusted tobacco products because
combusted tobacco products are
responsible for the majority of death and
disease due to tobacco use. FDA expects
that, if this proposed rule is finalized as
proposed, many people who smoke
cigarettes will quit smoking, either by
quitting all tobacco use or by completely
switching to a noncombusted tobacco
product. Those who switch completely
to use of a noncombusted tobacco
product may sustain their nicotine
dependence but may significantly
reduce their risk of tobacco-related
death and disease because switching
completely to a noncombusted tobacco
product would reduce exposure to the
chemical constituents created through
combustion, which are currently the
primary contributors of tobacco-related
harm (Ref. 8). Importantly, this action
would also help to prevent people who
experiment with cigarettes and cigars
(mainly youth) from moving beyond
experimentation, developing an
addiction to nicotine, and progressing to
regular use of combusted tobacco
products as a result of that addiction.
We request comments, data, and
research regarding the proposed scope
of this rule.
For further discussion regarding
considerations and request for
comments on the proposed scope of this
rule, see section IX.C of this document.
Proposed product standard for
nicotine—FDA is proposing to make
cigarettes and certain other combusted
tobacco products minimally addictive or
nonaddictive 6 by limiting the nicotine
yield of these products. We propose to
limit nicotine yield by setting a
maximum nicotine content level of 0.70
milligrams (mg) of nicotine per gram of
total tobacco in these tobacco products.
For comparison, the average nicotine
content in the top 100 cigarette brands
for 2017 is 17.2 mg/g of total tobacco
(Ref. 9). Nicotine yield is the amount of
6 FDA is using the term ‘‘nonaddictive’’
throughout this preamble specifically in the context
of the available data on very low nicotine content
cigarettes. We acknowledge the highly addictive
potential of nicotine itself depending upon the
route of delivery. As discussed elsewhere in this
preamble, questions remain with respect to the
precise level of nicotine in cigarettes that might
render them either minimally addictive or
nonaddictive for specific individual members or
segments of the population.

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nicotine in smoke, in other words, the
amount of nicotine to which a smoker
potentially is exposed. While nicotine
yield can be measured through
machine-generated smoking methods
(e.g., International Organization for
Standardization (ISO) machine smoking
method, Canadian Intense (CI) smoking
method, Federal Trade Commission
(FTC) smoking method), it can vary due
to a user’s compensatory behaviors—
e.g., inhaling more deeply, taking larger
puffs, and blocking cigarette features
designed to reduce nicotine yield—such
that users can increase the amount of
nicotine yield compared to the machinegenerated yield. In contrast, nicotine
‘‘content,’’ which refers to the amount of
nicotine present in tobacco filler, is not
affected by smoking behavior or
cigarette design features. Reducing the
nicotine content to the proposed 0.70
mg of nicotine per gram of total tobacco
limit in the finished tobacco products
subject to this proposed product
standard places an absolute maximum
limit on the amount of nicotine present
in tobacco smoke available for intake by
users of these products. There are many
different tobacco product characteristics
that can be manipulated to affect
nicotine yield, one of which is nicotine
content. Setting a limit on nicotine
content and measuring that content is
more effective in reducing yield (i.e., the
amount of nicotine the user is exposed
to) than setting a limit based on a direct
measurement of yield under
standardized smoking-machine
protocols because nicotine content
cannot be affected by the compensatory
behavior described above. Therefore,
limiting nicotine yield through a
maximum nicotine content level would
better achieve the public health benefits
that come from reducing the amount of
the nicotine to which a user is exposed
than would setting a limit based on a
measurement of the maximum machinemeasured yield of tobacco products. For
further discussion, see section VII.A.
The proposed limit of 0.70 mg of
nicotine per gram of total tobacco is
based on FDA’s analysis of studies
regarding the likely effects of reducing
nicotine, which shows that extended
exposure to very low nicotine content
(VLNC) combusted cigarettes is
associated with reduced addiction
potential, dependence levels, number of
cigarettes smoked per day and increased
quit attempts among people who
currently smoke cigarettes, without
increasing toxicant exposure, craving,
withdrawal, or compensatory smoking.
Throughout this preamble, ‘‘VLNC
cigarettes’’ refers to combusted
cigarettes that have been reported to

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contain ≤ 1.0 mg nicotine per gram of
total tobacco, ‘‘low nicotine content
(LNC) cigarettes’’ refers to cigarettes
with > 1.0 mg and < 11.4 mg nicotine
per gram of total tobacco, and ‘‘normal
nicotine content (NNC) cigarettes’’ refers
to cigarettes with ≥ 11.4 mg nicotine per
gram of total tobacco.7 FDA uses these
acronyms in places where we have
confirmed that the nicotine content of
the cigarettes referenced meets these
definitions. In documents that reference
nicotine content in tobacco, but do not
specify the levels of nicotine and
therefore cannot be confirmed to meet
these definitions, we have maintained
the full description that best reflects
what was used in the original document
(e.g., low nicotine content tobacco).
FDA is not seeking to require the
reduction of nicotine yields in any
tobacco product to zero, which would
violate section 907(d)(3) of the FD&C
Act (21 U.S.C. 387g(d)(3)). FDA requests
comments, data, and research regarding
this proposed maximum nicotine level.
Immediate nicotine reduction
approach—FDA is proposing an
immediate nicotine reduction (i.e.,
single target) approach to reach the
proposed maximum nicotine level
(rather than a gradual reduction, or
stepped-down, approach) to limit
additional toxicant exposure. Based on
studies involving VLNC cigarettes and
other reduced nicotine content (RNC)
cigarettes, we expect that there would
be very little or no compensatory
smoking (and, consequently, additional
limited toxicant exposure) with an
immediate reduction approach, as
opposed to a gradual reduction
approach which showed evidence of
increased compensatory smoking. As
such, an immediate reduction approach
would increase the benefits of the
proposed product standard. FDA also
notes that this immediate nicotine
reduction approach would reduce
manufacturing costs for those products
covered by the proposed standard
because manufacturers would not have
reason to formulate multiple products
and then prepare and submit premarket
review applications at each phase of a
gradual reduction approach. We request
comments, data, and information
regarding the selection of an immediate
reduction approach.
Analytical test method—To assist
FDA in determining compliance with
this rule, the proposed product standard
would require manufacturers to analyze
7 The term VLNC should not be confused with the
cigarette brand name ‘‘VLN;’’ ‘‘VLN’’ refers to
cigarette products authorized for marketing by FDA
in 2019. See https://www.fda.gov/media/133633/
download?attachment and https://www.fda.gov/
media/133635/download?attachment.

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the nicotine levels of cigarettes and
certain other combusted tobacco
products covered by the rule using an
analytical test method that has been
validated in an analytical test
laboratory. In addition, FDA is
proposing to require product testing
prior to commercial distribution in the
United States to prevent nonconforming
tobacco products from entering the
stream of commerce and reaching
consumers.
Sampling plan—The proposed
product standard would require tobacco
product manufacturers to design and
implement a sampling plan that covers
each batch of finished tobacco product 8
that they manufacture. This sampling
plan would be based on a valid
scientific rationale (such as
representative sampling) to ensure that
each product complies with the
proposed product standard. This
sampling plan would provide
procedures for the manufacturer to
select samples to demonstrate
conformance to the proposed product
standard requirement. The required
procedures would help ensure that
products that do not conform to the
product standard are not sold or
distributed to consumers.
Nonconforming tobacco product—
The proposed product standard would
require tobacco product manufacturers
to establish procedures for the control
and disposition of tobacco products that
do not conform to the requirements of
this rule. These procedures are
necessary to help prevent the
distribution of nonconforming tobacco
products by ensuring that all potential
nonconforming products are identified,
investigated, and segregated and that
appropriate disposition and followup
are taken for products determined to be
nonconforming. This proposed
requirement would ensure that any
reports of nonconforming products,
whether as a result of manufacturer
testing or otherwise, are examined and
investigated and that appropriate
measures are taken to ensure that
nonconforming products are not
distributed to consumers and to prevent
future nonconformity.
Manufacturing code—Currently, there
is no requirement for the use of a
8 For the purpose of this document, the term
‘‘finished tobacco product’’ refers to those products
subject to this proposed rule. FDA proposes to
define a ‘‘finished tobacco product’’ to mean a
tobacco product, including all components and
parts, sealed in final packaging (e.g., filters or filter
tubes sold to consumers separately or as part of kits)
or in the final form in which it is intended to be
sold to consumers. For a discussion of products
FDA proposes to include within the scope of this
product standard, see sections IX.C and X.A.1 of
this document.

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manufacturing code for tobacco
products. However, the proposed
regulation Requirements for Tobacco
Product Manufacturing Practice (TPMP)
(see https://www.federalregister.gov/
documents/2023/03/10/2023-04591/
requirements-for-tobacco-productmanufacturing-practice) includes a
requirement for a manufacturing code,
and this rulemaking’s provision is
modeled on the proposed TPMP
provision. The proposed product
standard would require the use of a
manufacturing code to serve as a
common identifier for production and
distribution records. The purpose of the
manufacturing code is to allow
manufacturers and FDA to identify the
production batch of a particular finished
product that has been released for
distribution. This information is
intended to help determine the
product’s history (e.g., batch production
records) and assist manufacturers and
FDA in the event of a nonconforming
tobacco product investigation and any
corrective actions to be taken by a
manufacturer as a result of the
investigation.
Recordkeeping requirements—To
assist FDA in determining compliance
with the rule and aid in nonconforming
product investigations, the proposed
product standard would require that
manufacturers establish and maintain
records regarding the results of testing
conducted on each batch to determine
conformance with the proposed
standard. In addition, this proposed
product standard would require that
manufacturers maintain records of
sampling plans and sampling
procedures, records related to
manufacturing controls, and all records
related to its analytical test method
validation. FDA also is proposing to
require that it be possible to identify the
production batch of a particular finished
product that has been released for
distribution.
Proposed effective date—FDA
proposes that any final rule that may
issue based on this proposed rule
become effective 2 years after the date
of publication of the final rule.
Therefore, after the effective date no
person could distribute, sell, or offer for
sale or distribution within the United
States finished tobacco products that are
not in compliance with part 1160 (21
CFR part 1160). Prior to the effective
date of any final rule that may issue
based on this proposed rule,
wholesalers, retailers, and related
entities would be able to sell available
stock of finished tobacco products were
not in compliance with part 1160 while
transitioning inventory in anticipation
of the effective date of the final rule;

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however, they would not be permitted
to sell off such stock after the effective
date. FDA believes this approach would
allow adequate time for developing any
necessary changes in technology or
inputs to comply with a finalized
product standard. It also would provide
sufficient time for tobacco product
manufacturers to submit, and FDA to
review, applications for new tobacco
products that comply with the finalized
product standard. Additionally, FDA
believes that this approach would allow
adequate time for making any changes
to tobacco purchasing choices and
curing methods, and for preparation or
changes needed in facilities and
processes. FDA requests comments and
data on this proposed effective date. For
further discussion regarding
considerations and request for
comments on the proposed effective
date of this rule, see section XI of this
document.
Given that any new tobacco products
that comply with this product standard
would be required to undergo premarket
review, FDA is considering options for
addressing any influx of applications.
C. Legal Authority
Section 907 of the FD&C Act
authorizes FDA to adopt tobacco
product standards, including product
standards that include provisions for
nicotine yields; for the reduction or
elimination of other constituents
(including smoke constituents) or
harmful components; respecting the
construction, components, ingredients,
additives, constituents (including smoke
constituents), and properties of tobacco
products; for the testing of tobacco
products; and for restricting the sale of
tobacco products to the extent
consistent with section 906 (21 U.S.C.
387f) (section 907(a)(3), (a)(4)(A)(i) to
(iii), and (a)(4)(B)(i) to (ii) and (iv) to
(v)). The FD&C Act also establishes
FDA’s authority to require tobacco
product manufacturers to establish and
maintain records in section 909 (21
U.S.C. 387i); authority related to
adulterated and misbranded tobacco
products in sections 902 and 903 (21
U.S.C. 387b and 387c); authority
regarding premarket review of new
tobacco products in section 910 (21
U.S.C. 387j); authority related to
prohibited acts in section 301 (21 U.S.C.
331); and FDA’s rulemaking and
inspection authorities in sections 701
and 704 (21 U.S.C. 371 and 374).
D. Costs and Benefits
The main quantified benefits come
from averted mortality and morbidity as
a result of reduced prevalence for
people who currently use combusted

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tobacco products, and reduced mortality
from reduced exposure to secondhand
smoke among people. Unquantified
benefits include medical cost savings,
productivity loss savings, reduced
exposure to thirdhand smoke, and
environmental impacts. We expect this
proposed rule, if finalized, to impose
costs on industry to follow the product
standard, on the broader economy to
repurpose land, labor, and capital, on
consumers impacted by the product

standard, and on FDA to enforce this
product standard. In addition to benefits
and costs, this rule would cause
transfers from the Federal Government
and State governments in the form of tax
revenue, from firms in the form of
reduced revenue, and transfers between
or within firms to cover shifts in user
fee obligations.
The annualized monetized benefits
over a 40-year time horizon far exceed
the annualized monetized costs over the
same time. We estimate that the

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Abbreviation/
acronym
3–HPMA ...............................
AI/AN ....................................
ANPRM ................................
BAP ......................................
CDC ......................................
CFR ......................................
CISNET ................................
CO ........................................
COHb ...................................
COPD ...................................
CORESTA ............................
CPD ......................................
CPS–I ...................................
CPS–II ..................................
CRM .....................................
DSM .....................................
ENDS ...................................
E.O. ......................................
FD&C Act .............................
FDA ......................................
FR .........................................
FTCD ....................................
FTND ....................................
GC–MS .................................
HHS ......................................
HPHCs .................................
HTP ......................................
IOM .......................................
LGBTQI+ ..............................
LNC ......................................
mg ........................................
MNWS ..................................
MRI .......................................
nAChR ..................................
NATS ....................................
NCI .......................................
NDSS ...................................
NHANES ..............................
NHIS .....................................
NHIS–LMF ............................
NIDA .....................................
NIH .......................................
NJATS ..................................
NLMS ...................................
NNAL ....................................
NNC ......................................
NNN ......................................
NPRM ...................................
NRC ......................................
NRT ......................................
NSDUH .................................
NYTS ....................................
OOS .....................................
PAH ......................................
PATH ....................................
PET ......................................
PD ........................................
QALYs ..................................

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annualized benefits over a 40-year time
horizon would be $1.1 trillion at a 2
percent discount rate, with a low
estimate of $0.27 trillion and a high
estimate of $1.2 trillion. Over a 40-year
time horizon, we estimate that the
annualized costs would be $2.07 billion
at a 2 percent discount rate, with a low
estimate of $0.7 billion and a high
estimate of $2.73 billion.
II. Table of Abbreviations/Commonly
Used Acronyms in This Document

What it means
3-hydroxypropyl mercapturic acid.
American Indians/Alaska Native.
Advance Notice of Proposed Rulemaking.
Benzo[a]pyrene.
Centers for Disease Control and Prevention.
Code of Federal Regulations.
Cancer Intervention and Surveillance Modeling Network.
Carbon monoxide.
Carboxyhemoglobin.
Chronic obstructive pulmonary disease.
Cooperation Centre for Scientific Research Relative to Tobacco.
Cigarettes per day.
Cancer Prevention Study I.
Cancer Prevention Study II.
CORESTA Recommended Method.
Diagnostic and Statistical Manual of Mental Disorders.
Electronic nicotine delivery systems.
Executive Order.
Federal Food, Drug, and Cosmetic Act.
Food and Drug Administration.
Federal Register.
Fagerstro¨m Test for Cigarette Dependence.
Fagerstro¨m Test for Nicotine Dependence.
Gas chromatography-mass spectrometry.
U.S. Department of Health and Human Services.
Harmful and potentially harmful constituents.
Heated tobacco product.
Institute of Medicine.
Lesbian, gay, bisexual, transgender, queer, and intersex.
Low nicotine content.
milligram.
Minnesota Nicotine Withdrawal Scale.
Magnetic resonance imaging.
Nicotinic acetylcholine receptor.
National Adult Tobacco Survey.
National Cancer Institute.
Nicotine Dependence Syndrome Scale.
National Health and Nutrition Examination Survey.
National Health Interview Survey.
National Health Interview Survey-Linked Mortality Files.
National Institute on Drug Abuse.
National Institutes of Health.
New Jersey Adult Tobacco Survey.
National Longitudinal Mortality Study.
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol.
Normal nicotine content.
N-Nitrosonornicotine.
Notice of proposed rulemaking.
National Research Council.
Nicotine replacement therapy.
National Survey on Drug Use and Health.
National Youth Tobacco Survey.
Out-of-specification.
Polycyclic aromatic hydrocarbon.
Population Assessment of Tobacco and Health.
Position emission tomography.
Product static ID number.
Quality-adjusted life years.

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Abbreviation/
acronym

QSU ......................................
RCT ......................................
RNC ......................................
RR ........................................
RYO ......................................
S–PMA .................................
SE .........................................
SES ......................................
STN ......................................
TNE ......................................
TPSAC .................................
TUS–CPS .............................
U.S. ......................................
VLNC ....................................
WISDM .................................
YRBS ....................................

What it means
Questionnaire of Smoking Urges.
Randomized clinical trial.
Reduced nicotine content.
Relative risk.
Roll-your-own.
S-phenylmercapturic acid.
Substantial Equivalence.
Socioeconomic status.
Submission tracking number.
Total nicotine equivalents.
Tobacco Products Scientific Advisory Committee.
Tobacco Use Supplement to the Current Population Survey.
United States.
Very low nicotine content.
Wisconsin Inventory of Smoking Dependence Motives.
Youth Risk Behavior Survey.

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III. Background
A. Need for the Regulation
Cigarettes are responsible for the
majority of tobacco-related death and
disease in the United States. Each year,
480,000 people die prematurely from a
smoking-attributable disease, putting a
substantial burden on the U.S.
healthcare system and causing massive
economic losses to society (Ref. 1). In
terms of a monetary measure of the
impact of cigarette smoking on the
public health, in 2018, cigarette
smoking cost the United States more
than $600 billion, including more than
$240 billion in healthcare spending
(Ref. 10), nearly $185 billion in lost
productivity from smoking-related
illnesses and health conditions (Ref. 10),
nearly $180 billion in lost productivity
from smoking-related premature death
(Refs. 1 and 10), and $7 billion in lost
productivity from premature death from
secondhand smoke exposure (Refs. 1
and 11). The mortality rate among
people who currently smoke cigarettes
is 2 to 3 times as high as that among
individuals who never smoked (Ref. 12).
Nicotine, the primary addictive
constituent in tobacco products, can be
delivered through a variety of products
along a continuum of risk, with
combusted tobacco products at the most
harmful end of this continuum. To
protect youth and reduce tobaccorelated disease and death, FDA utilizes
a comprehensive approach to tobacco
and nicotine regulation. Shortly after
FDA announced its comprehensive
approach in 2017 (https://www.fda.gov/
news-events/press-announcements/fdaannounces-comprehensive-regulatoryplan-shift-trajectory-tobacco-relateddisease-death), the Agency began a
public dialogue about lowering nicotine
levels in combusted cigarettes to
minimally addictive or nonaddictive
levels through achievable product

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standards. On March 16, 2018, FDA
issued a Nicotine ANPRM to seek input
on the potential public health benefits
and any possible adverse effects of
regulating nicotine yield by lowering
nicotine levels in cigarettes and invited
comments on many issues associated
with the development of a product
standard to establish a maximum
nicotine level (83 FR 11818). The
Nicotine ANPRM also acknowledged
that if FDA were to establish a nicotine
tobacco product standard that covered
only cigarettes, some number of people
who smoke cigarettes could migrate to
other similar combusted tobacco
products to maintain their nicotine
dependence (or engage in dual use with
other combusted tobacco products),
potentially reducing the positive public
health impact of such a rule. FDA
sought comments on whether the
standard therefore should cover other
combusted tobacco products. Based on
FDA’s scientific knowledge, extensive
research regarding VLNC cigarettes, and
comments submitted in response to this
Nicotine ANPRM, FDA is proposing a
tobacco product standard that would
regulate nicotine yield by establishing a
maximum nicotine level in cigarettes
and certain other combusted tobacco
products.
As the U.S. District Court for the
District of Columbia recognized in
United States v. Philip Morris USA, Inc.
et al., 449 F.Supp.2d 1 (D.D.C. 2006),
aff’d in relevant part, 566 F.3d 1095
(D.C. Cir. 2009), the tobacco industry
has long known that nicotine creates
and sustains addiction, and the industry
is dependent on maintaining this
addiction. Id. at 307. The court noted
how cigarette companies have engaged
in extensive research to understand how
nicotine operates within the human
body and then designed their cigarettes
to precisely control nicotine delivery
and provide nicotine doses to create and

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sustain addiction. Id. at 307–309.
Moreover, the court confirmed that
industry documents supported the
conclusion that these companies ‘‘knew
early on in their research that if a
cigarette did not deliver a certain
amount of nicotine, new smokers would
not become addicted, and ‘confirmed’
smokers would be able to quit.’’ Id. at
219. In fact, the tobacco industry has
had programs in place since the 1960s
to obtain ‘‘any level of nicotine desired’’
(Ref. 2). These companies sought to
identify the ‘‘optimum’’ dose needed to
‘‘satisfy’’ people who smoke cigarettes
and, thereby, assure their continued
smoking. Philip Morris 449 F.Supp.2d at
309–11. This proposed product standard
would seek to set a maximum nicotine
level requirement such that cigarettes
and certain other combusted tobacco
products would no longer be able to
create and sustain this addiction among
people who smoke cigarettes.
The proposed product standard
would limit the addictiveness of the
most toxic and widely used products,
which would have significant benefits
for all age groups. Adults who use
tobacco products, most of whom want to
quit, are often unsuccessful because of
the highly addictive nature of these
products (Ref. 13). Researchers estimate
that each year, only between 5.4 and 5.6
percent of adults who use cigarettes
successfully quit for good (Ref. 14).
Similar analysis of 2022 NHIS data
indicates that only 8.8 percent of adults
who formerly smoked cigarettes had
quit smoking cigarettes in the past year
(Ref. 4). Lowering nicotine to minimally
addictive or nonaddictive levels would
improve their ability to successfully quit
using the products within the proposed
scope of this rule. It also would prevent
people who experiment with cigarettes
and non-premium cigars, including
youth, from moving beyond
experimentation, developing an

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addiction to nicotine, and progressing to
regular use as a result of that addiction.
Furthermore, it is well-established that
secondhand tobacco smoke causes
premature death and disease in children
and in adults who do not smoke (Ref.
15 at p.11). It is estimated that exposure
to secondhand smoke caused 41,280
deaths per year in the United States
from 2005 to 2009 (Ref. 1 at Table 12.4).
This increased cessation and reduced
initiation, in turn, would result in a
significant decrease in harms from the
products to people who currently or
would otherwise use cigarettes and
certain other combusted tobacco
products, as well as harms to people
who do not use the products, including
harms caused by secondhand smoke to
both adults and children, harmful
perinatal effects due to parental tobacco
use, and fires.
Preventing people who do not smoke
cigarettes, particularly youth, from
regularly smoking cigarettes due to
nicotine addiction would allow them to
avoid the severe adverse health
consequences of smoking and would
result in significant public health
benefits. Without changes like those
proposed here, an estimated 3.66
million youth under the age of 18 who
were alive in 2018—and 2.54 million
youth who are alive in 2024, accounting
for the projected continued decline in
smoking prevalence—will die
prematurely later in life from a smokingrelated disease (Ref. 16). As a result of
the proposed product standard, many
youth and young adults would not be
subjected to the impacts of nicotine
addiction from cigarette smoking and
certain other combusted tobacco
products (which have a significantly
stronger effect on youth due, in part, to
their developing brains, as described in
sections IV.B and IV.C of this
document), nor would they suffer from
the adverse health effects and mortality
that these products cause.
Nicotine is powerfully addictive, and
youth and young adults 9 are
particularly susceptible to developing a
nicotine addiction. Multiple Surgeon
General’s Reports on smoking and
health have noted that almost 90
percent of adults who regularly smoke
cigarettes initiated smoking by age 18,
and 98 percent initiated smoking by age
26, which is notable given that 25 is the
approximate age at which the brain has
9 Though age ranges for youth and young adults
vary across studies, in general, ‘‘youth’’ or
‘‘adolescent’’ encompasses those ages 11–17, while
those who are ages 18–25 are considered ‘‘young
adults’’ (even though, developmentally, the period
between 18–20 years of age is often labeled late
adolescence); those ages 26 and or older are
considered ‘‘adults’’ (Ref. 17).

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completed development (Refs. 1, 17 to
19). The developing brain is more
vulnerable to nicotine dependence than
the adult brain is, and the earlier an
individual begins smoking the less
likely they are to quit (Ref. 20).
Generally, those who begin smoking
before the age of 18 are not aware of the
degree of addictiveness and the full
extent of the consequences of smoking
(Ref. 21). It is clear that many youth
who smoke cigarettes want to quit but
have difficulty doing so. An analysis of
data from the 2015 Youth Risk Behavior
Survey (YRBS) looking at youth
cigarette quit attempts found that 45.4
percent of high school students
currently smoking cigarettes had sought
to quit in the previous year (Ref. 22);
2020 National Youth Tobacco Survey
(NYTS) data were congruent, indicating
that 68.1 percent of middle and high
school students who smoke cigarettes
had sought to quit in the previous year
(Ref. 23).
More than half (52.2 percent) of U.S.
middle and high school students who
use cigarettes, cigars, smokeless
tobacco—including those with low
levels of use—report experiencing at
least one symptom of nicotine
dependence (Ref. 24). Notably, 12.7
percent of youth using tobacco products
1 to 2 days per month and 21.2 percent
of youth using tobacco products 3 to 5
days per month reported sometimes/
often/always feeling irritable or restless
when not using tobacco products for a
while, and 15.6 percent of youth using
tobacco products 1 to 2 days per month
and 32.0 percent of youth using tobacco
products 3 to 5 days per month reported
having strong cravings for a tobacco
product during the past 30 days (Ref.
24). Additionally, other researchers
analyzing data from the 2021 NYTS
found that a sizeable proportion of high
school students using tobacco products
in the past 30 days report symptoms of
nicotine dependence, including 27.2
percent reporting a strong craving for
tobacco use and 19.5 percent reporting
wanting to first use tobacco products
within 30 minutes of waking (Refs. 25
and 26). While prevalence rates of youth
use of noncombusted tobacco products
(e.g., ENDS) in recent years have
exceeded those of cigarettes and other
combusted tobacco products (Refs. 25
and 26), FDA expects that this proposed
product standard would have significant
benefits for youth by reducing the risk
that youth who experiment with
cigarettes and certain other combusted
tobacco products, or who may consider
using these products as an alternative to
noncombusted tobacco products, would

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progress to regular use of these products
as a result of nicotine dependence.
The adolescent and young adult brain
is more vulnerable to developing
nicotine dependence than the adult
brain is; data indicate that nicotine has
stronger rewarding effects in
adolescents than in adults (Ref. 17).
Adolescents who use tobacco and
initiated use at earlier ages were more
likely than those initiating at older ages
to report symptoms of tobacco
dependence, putting them at greater risk
for maintaining tobacco product use
into adulthood (Ref. 24). Additionally,
the earlier that individuals begin
smoking—and therefore the greater
amount of time that individuals
experience nicotine dependence—the
less likely they are to successfully quit
(Ref. 27). Evidence indicates that
exposure to substances such as nicotine
can disrupt brain development and have
long-term consequences for executive
cognitive functioning (such as decreased
attention and working memory and
increased impulsivity) and for the risk
of developing a substance use disorder
and various mental health problems
(particularly affective disorders such as
anxiety and depression) as an adult (Ref.
27). Furthermore, the 2010 Surgeon
General’s report noted that adolescents
report symptoms of dependence even at
low levels of cigarette smoking, and
thus may be particularly vulnerable to
addiction (Ref. 28). FDA expects that
this proposed product standard,
therefore, would have significant
benefits for youth and young adults by
reducing the risk that those who
experiment with cigarettes and certain
other combusted tobacco products
would progress to regular use as a result
of nicotine dependence.
Research studies involving VLNC
cigarettes—defined previously in this
document as cigarettes containing up to
1.0 mg of nicotine per gram of total
tobacco—demonstrate that setting the
maximum nicotine level we are
proposing here, would lead to a
reduction in nicotine dependence,
which would help people who smoke
cigarettes quit smoking. In studies that
immediately reduced the nicotine
content of cigarettes by switching
participants from usual brand cigarettes
to LNC or VLNC cigarettes, dependence
decreased in people who smoked
cigarettes who were not interested in
quitting compared to those who smoked
normal nicotine content (NNC) or usual
brand cigarettes for 6 weeks (Ref. 29), 10
weeks (Ref. 30), or 12 weeks (Ref. 31).
In smoking cessation studies in which
participants endorsed wanting to quit,
VLNC cigarettes were also associated

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with reductions in nicotine dependence
over time (Refs. 32 to 35).
FDA is issuing this proposal because
the tobacco products subject to this
proposed product standard remain
addictive due to the nicotine yield they
offer users and because combusted
tobacco products are responsible for the
majority of tobacco-related death and
disease (see section IV.D of this
document for a discussion regarding the
serious negative health effects of
smoking cigarettes and other combusted
tobacco products). Cigarettes have been
precisely designed to create and
maintain addiction among people who
smoke. United States v. Philip Morris
USA, Inc. et al., 449 F.Supp.2d 1, 307
(D.D.C. 2006). To protect the public
health, particularly youth, FDA is
proposing this standard, in part, to
ensure that people who smoke these
products would be less likely to: (1)
initiate regular use; (2) become addicted
to these products; and (3) suffer from
the many diseases and debilitating
effects, including death, caused by
combusted tobacco product use.
Similarly, FDA expects that the
proposed product standard would have
significant benefits for adults who use
combusted tobacco products, most of
whom want to quit but are often
unsuccessful because of the highly
addictive nature of these products (Ref.
13). Data from the 2022 National Health
Interview Survey (NHIS) and 2018–2019
Tobacco Use Supplement to the Current
Population Survey (TUS–CPS) indicate
that 67.7 and 76.6 percent, respectively,
of adults who smoke cigarettes wanted
to quit (Ref. 36), while 2022 NHIS data
(Ref. 4) and 2018–2019 TUS–CPS data
(Ref. 36) show that 53.3 and 51.3
percent, respectively, of adults who
smoke cigarettes in the United States
actually made a quit attempt within the
past year. However, analyses of NHIS
and TUS–CPS data for these years
indicate that only 8.8 and 7.5 percent of
adults had successfully quit smoking
cigarettes, respectively (Refs. 4 and 36).
Adults who smoke cigarettes may make
30 or more quit attempts before
succeeding (Ref. 37). FDA expects that
decreasing the nicotine yield of
cigarettes and certain other combusted
tobacco products covered by this rule,
by reducing nicotine content, so that
they are minimally addictive or
nonaddictive would likely help people
who smoke reduce their dependence on
combusted tobacco products, thereby
making it easier for them to quit
smoking. As discussed throughout this
document, FDA also expects that
decreasing the nicotine content in these
products, and thus the nicotine yield
offered to users, would prevent people

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who experiment with cigarettes and
cigars (mainly youth) from moving
beyond experimentation, developing an
addiction to nicotine, and progressing to
regular use as a result of that addiction.
Although many factors contribute to
an individual’s initial experimentation
with tobacco products, the addictive
nature of tobacco is the key reason
people progress to regular use, and
scientists agree that it is the presence of
nicotine that causes addiction and
sustains a person’s tobacco use (Refs. 1
HHS at p. 113 and 28). While nicotine
is the primary addictive chemical in
tobacco, sensorimotor stimuli (e.g.,
smell/taste of smoke; airway sensations;
holding the cigarette) repeatedly occur
during smoking (Ref. 38). These stimuli
often act as secondary or conditioned
reinforcers that contribute to the cycle
of nicotine dependence by motivating
and maintaining smoking behavior (Ref.
38). Once people who use tobacco
become addicted to nicotine, they
require nicotine to avoid withdrawal
symptoms. In the process of obtaining
their nicotine, people who use
combusted tobacco products are
exposed to an array of toxicants in
tobacco and tobacco smoke that lead to
a substantially increased risk of
morbidity and mortality (Ref. 28).
Because of their nicotine addiction,
many people who smoke cigarettes
struggle to stop using these toxic
tobacco products despite their stated
desire to quit (Ref. 28).
An advisory report from the World
Health Organization notes that the
ultimate health benefits of a nicotine
reduction strategy, like the one FDA is
proposing here, would require that the
standard cover other combusted tobacco
products—not just cigarettes (Ref. 39).
In alignment with this recommendation
from the World Health Organization,
this proposed rule would cover
combusted cigarettes and certain other
combusted tobacco products (i.e.,
cigarette tobacco, RYO tobacco, cigars
other than premium cigars, pipe
tobacco). The World Health
Organization report also noted that such
a strategy should be accompanied by the
provision of cessation treatments to help
people quit, including behavioral
support and nicotine replacement
therapy (NRT) or other medications
(Ref. 39). FDA remains committed to
facilitating the development and use of
therapeutic nicotine products for
tobacco product cessation and increased
availability of services alongside
enhanced outreach efforts to support
tobacco use cessation. For example,
FDA’s Nicotine Steering Committee,
which helps to develop and implement
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Agency, held a 21 CFR part 15 hearing
in early 2018 on the Agency’s approach
to evaluating the safety and efficacy of
NRT products, including how they
should be used and labeled (82 FR
56759 (November 30, 2017)). Also, in
May 2023, FDA’s Center for Drug
Evaluation and Research announced the
availability of a final guidance for
industry entitled ‘‘Smoking Cessation
and Related Indications: Developing
Nicotine Replacement Therapy Drug
Products,’’ which provides guidance to
assist sponsors in the clinical
development of NRT drug products,
including but not limited to those
intended for smoking cessation and
related chronic conditions (88 FR
26559, May 1, 2023; see https://
www.fda.gov/media/167599/download).
Additionally, as described further
below, the Agency is contributing to a
comprehensive effort coordinated by the
U.S. Department of Health and Human
Services (HHS or the Department) to
support tobacco use cessation.
Rendering cigarettes and certain other
combusted tobacco products minimally
addictive or nonaddictive through a
nicotine product standard would
address the principal reason that people
who smoke cigarettes have difficulty
quitting smoking. If this proposed
product standard is finalized, people
who use cigarettes and other combusted
tobacco products covered by this rule
would be unable to obtain enough
nicotine from those products to sustain
addiction no matter how they smoked
the products (e.g., more frequent
smoking, intensive puffing) (Refs. 32,
40, and 41), facilitating people who
currently smoke cigarettes to make more
successful quit attempts.10 At the same
time, combusted tobacco products at
minimally addictive or nonaddictive
levels of nicotine would remain on the
market for those who currently smoke
and would like to continue to do so.
FDA expects that, if this proposed
rule is finalized and a nicotine product
standard for cigarettes and certain other
combusted tobacco products is in place,
many people who smoke cigarettes will
either quit all tobacco-product use or
switch to a noncombusted tobacco
product. Those who switch completely
to use of a noncombusted tobacco
product may sustain their nicotine
dependence but may significantly
10 As stated throughout this preamble, in the
event that a nicotine product standard addresses
only cigarettes, FDA expects that, to maintain their
nicotine dependence, some number of people who
are addicted to cigarettes would likely migrate to
other similar combusted tobacco products (or
engage in dual use with such products) after the
product standard goes into effect, reducing the
benefits of the standard.

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reduce their risk of tobacco-related
death and disease because switching
completely to a noncombusted tobacco
product would reduce exposure to the
chemical constituents created through
combustion, which are the primary
contributors of tobacco-related harm
(Ref. 8).
The benefits of this rule have been
determined without taking into
consideration the impact of any
smoking cessation services that may be
coordinated by HHS, and are expected
to be significant. Also, FDA expects that
unassisted cessation attempts, i.e., those
made by people who smoke without
help, may be more successful in an
environment in which the product being
quit is no longer addictive as compared
to historic quitting success rates where
it has been easy to relapse to the same
highly addictive product. Nevertheless,
FDA recognizes that increasing and
improving cessation resources,
particularly in communities where
access to cessation resources have been
historically lacking, may provide an
opportunity to further increase the
expected benefits of this proposed
product standard and to enhance the
degree to which such benefits are
experienced by people in populations
that are disproportionately impacted by
combusted tobacco use. Accordingly,
FDA is contributing to a comprehensive
effort being coordinated by HHS to
support and accelerate cessation of
combusted tobacco products.11 With
input from subject matter experts from
across HHS Operating Divisions, the
Department has finalized the ‘‘HHS
Framework To Support and Accelerate
Smoking Cessation’’ (Framework). The
Framework aims to accelerate smoking
cessation and reduce smoking-related
disparities by building on current
activities and collaborations across the
Department. The Framework vision is to
ensure that every person in America has
access to comprehensive, evidencebased cessation treatment and can
benefit from HHS cessation supports,
programs, and policies. Specific
Framework goals are to: (1) reduce
smoking and cessation-related
disparities; (2) increase awareness and
knowledge related to smoking and
cessation; (3) strengthen, expand, and
sustain cessation services and supports;
(4) increase access to and coverage of
comprehensive, evidence-based
cessation treatment; (5) advance,
expand, and sustain surveillance and
11 See, for e.g., https://www.fda.gov/tobaccoproducts/ctp-newsroom/fda-and-nih-joint-publicmeeting-advancing-smoking-cessation-prioritiesregistration-open?utm_campaign=ctp-research&
utm_content=landingpage&utm_medium=email&
utm_source=govdelivery&utm_term=stratcomms.

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strengthen performance measurement
and evaluation; and (6) promote ongoing
and innovative research to support and
accelerate smoking cessation (https://
www.hhs.gov/about/news/2024/03/08/
hhs-announces-new-smoking-cessationframework-support-quitting.html). With
increased availability and accessibility
of services, more people who smoke
may be motivated to take advantage of
cessation resources, whether they smoke
cigarettes or other combusted tobacco
products. Additionally, FDA has
numerous processes and tools at its
disposal to communicate directly with
consumers, including communities that
are underserved by cessation services
and/or are disproportionately impacted
by tobacco use, and will continue to
evaluate the need for additional public
outreach, including targeted education
initiatives, in support of this proposed
rule. However, the Agency does not
have evidence to suggest that such an
effort is necessary at this time in order
to experience the public health benefits
of this proposed product standard.
For the reasons stated here and
throughout this document, FDA is
proposing this tobacco product standard
to: (1) reduce the risk of progression to
regular use and nicotine dependence for
those who experiment with such
tobacco products, especially youth and
(2) make it easier for people who are
addicted to cigarettes and certain other
combusted tobacco products and who
are interested in quitting to quit by
reducing the nicotine in these products
to minimally addictive or nonaddictive
levels. FDA expects that this proposed
product standard would significantly
reduce the morbidity and mortality
caused by smoking. Based on FDA’s
population health model, by the year
2100, in the United States,
approximately 48 million youth and
young adults who would have otherwise
initiated smoking would not start as a
result of the proposed product standard.
The model also projects that more than
12.9 million additional people who
smoke cigarettes would quit smoking
(including those who switch to
noncombusted tobacco products) 1 year
after implementation of the proposed
product standard, increasing to 19.5
million additional people who formerly
smoked cigarettes within 5 years of
implementation. Section XII discusses
that the main quantified benefits come
from averted mortality and morbidity, as
a result of tobacco use transitions,
including switching. In terms of
mortality benefits, the model considers
a higher risk for people who switch to
noncombusted products compared to
those who quit tobacco product use

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entirely. Specifically, the model
assumes that the risk for people who
switch to noncombusted product use is
8 percent higher than the risk for those
who quit tobacco use entirely. Details of
this approach can be found in the FDA’s
modeling document (Ref. 42). In
addition, the model estimates that, by
the year 2060, in the United States, this
proposed product standard would result
in 1.8 million tobacco-related deaths
averted, rising to 4.3 million deaths
averted by the end of the century (Ref.
42). The reduction in premature deaths
attributable to the proposed product
standard would result in 19.6 million
life years gained by 2060 and 76.4
million life years gained by 2100 (see
section VIII.A of this document for
further discussion of the model) (Ref.
42).
B. Relevant Regulatory History
In its implementation of the Family
Smoking Prevention and Tobacco
Control Act (Tobacco Control Act) (Pub.
L. 111–31) since its passage in 2009,
FDA has engaged in close study and
careful consideration of the scientific
evidence and complex policy issues
related to nicotine in cigarettes and
other combusted tobacco products. FDA
issued an ANPRM to solicit data and
information for consideration in
developing a tobacco product standard
to regulate nicotine yield by setting the
maximum nicotine level for cigarettes,
conducted a robust scientific assessment
related to a nicotine product standard
for combusted tobacco products,
developed a population health model to
assess the potential public health
impacts of such a product standard, and
sponsored research on a variety of
nicotine-related topics through contracts
and interagency agreements with
Federal partners, including the National
Institutes of Health (NIH).12 FDA has
considered the comments and
information received in response to the
ANPRM, scientific assessment, and
population health model in developing
this proposed rule. Please see the
remainder of this section for further
discussion.
1. ANPRM
In July 2017, FDA announced a
comprehensive approach to tobacco and
nicotine regulation to protect youth and
reduce tobacco-related disease and
death (Ref. 43). As part of the public
dialogue on the comprehensive
approach, in March 2018, FDA issued
three ANPRMs related to the regulation
12 Information on specific projects supported by
FDA is available at https://www.fda.gov/tobaccoproducts/tobacco-science-research/research.

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of nicotine in combusted cigarettes (83
FR 11818), flavors (including menthol)
in tobacco products (83 FR 12294,
March 21, 2018) (Flavors ANPRM), and
premium cigars (83 FR 12901, March 26,
2018). In addition, FDA announced the
availability of a draft concept paper
entitled ‘‘Illicit Trade in Tobacco
Products After Implementation of a
Food and Drug Administration Product
Standard,’’ and sought public comment
(83 FR 11754, March 16, 2018). This
paper analyzes the potential for illicit
trade markets to develop in response to
a tobacco product standard (Ref. 44).
The Nicotine ANPRM requested data
and information for consideration in
developing a tobacco product standard
to set a maximum nicotine level for
cigarettes to make them minimally
addictive or nonaddictive. Specifically,
FDA sought comments, evidence, and
other information regarding whether a
potential tobacco product standard
should cover tobacco products other
than cigarettes (e.g., cigarette tobacco,
RYO tobacco, some or all cigars, pipe
tobacco, waterpipe tobacco); what
maximum level of nicotine would be
appropriate for the protection of the
public health, in light of scientific
evidence about the addictive properties
of nicotine in cigarettes; whether such a
standard should propose either a single
target (i.e., an immediate reduction,
where the nicotine is reduced all at
once) or a stepped-down approach (i.e.,
a gradual reduction, where the nicotine
is reduced gradually over time) to reach
the desired maximum nicotine level;
whether such a product standard should
specify a method for manufacturers to
use to detect the level of nicotine in
their products; the technical feasibility
of current as well as more recent, novel
nicotine reduction techniques; and the
proper timeframe for implementation of
a possible nicotine tobacco product
standard to allow adequate time for
industry to comply. The Nicotine
ANPRM also requested comment on
possible negative effects that could
diminish the population health benefits
expected as a result of a nicotine
product standard, such as continued
combusted tobacco product use, where
people who currently use tobacco
products subject to a nicotine tobacco
product standard could turn to other
combusted tobacco products to maintain
their nicotine dependence, both in
combination with cigarettes (i.e., dual
use) or in place of cigarettes (i.e.,
switching); the potential for increased
harm due to continued VLNC cigarette
smoking with altered smoking behaviors
(e.g., increase in number of cigarettes
smoked, increased depth of inhalation);

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people seeking to add nicotine in liquid
or other form to their combusted
tobacco product; and whether illicit
trade could occur as a result of a
nicotine product standard and how that
could impact public health. Finally,
FDA also sought comments, data,
research results, and other information
regarding economic impacts of a
potential nicotine tobacco product
standard.
FDA received over 7,700 comments
on the Nicotine ANPRM, with
approximately 6,700 of those comments
submitted as part of 20 different
organized campaigns. The key ANPRM
areas of comments are covered in the
relevant sections in this document and
include the possible scope of products
covered by the rule (section IX.C),
technical achievability (section VII.E),
illicit trade (section IX.D), and
implementation/effective date (section
XI). Some of the issues raised in the
comments to the ANPRM are
highlighted below.
Comments generally in support of
setting a maximum nicotine level in
cigarettes stated that a nicotine product
standard would be appropriate for the
protection of the public health. In
particular, many comments argued that
reducing the nicotine content in
cigarettes to minimally addictive or
nonaddictive levels would be
appropriate for the following reasons:
(1) reduced nicotine content in
cigarettes will contribute to smoking
cessation, as well as decreased initiation
and addiction by people newly using
cigarettes and certain other combusted
tobacco products and youth and (2)
such increased cessation and decreased
initiation will reduce the instances of
preventable deaths and other negative
health effects caused by smoking. Some
comments also urged FDA to issue a
nicotine product standard as part of a
comprehensive package of tobacco
regulatory measures, including
increasing consumer access to reduced
risk products, regulating flavors in
tobacco products, taking action as soon
as possible, fully reviewing premarket
applications for new tobacco products,
and making effective smoking cessation
treatments and ongoing cessation
support accessible and affordable to
people who smoke cigarettes.
FDA received many comments
expressing concern about the effect of
nicotine on the adolescent brain and its
role in addicting those who experiment
with tobacco products, particularly
youth and young adults, leading them to
progress to regular use. Some comments
recommended extending the scope of a
nicotine product standard to
noncombusted tobacco products (e.g.,

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smokeless, ENDS) to prevent migration
to such products, particularly among
youth; a significant number of
comments urged FDA to extend the
scope of a nicotine product standard to
combusted tobacco products other than
cigarettes. Citing national survey data
trends and various recent studies,
numerous comments—including those
from public health associations,
government agencies, and advocacy
groups—asserted that including all
combusted tobacco products, not only
cigarettes, would prevent potential
youth initiation of, migration to, and
dual use with other combusted products
with higher nicotine content that may
be harmful to health, thus aligning with
the public health goals of a nicotine
product standard. Additionally, citing
studies relating to tobacco use patterns
by young people, a joint submission
from several nicotine and tobacco
researchers stated that adolescents who
use tobacco are particularly prone to
dual and multiple tobacco product use;
therefore, the potential for adolescents
to shift to other nicotine-containing
tobacco products underscores the need
for a nicotine reduction policy to cover
all combusted tobacco products. The
joint submission comment further stated
that if the scope of a nicotine product
standard only covered combusted
cigarettes, there is evidence from adult
studies that cigars—and in particular
little cigars—would be an attractive
substitute for full nicotine content
combusted cigarettes. These researchers
noted, if the scope of a proposed
nicotine product standard included
combusted cigarettes and other
combusted products, it would increase
the likelihood that people who use
combusted cigarettes, including youth
and young adults, who migrate to other
nicotine-containing products (rather
than quit), would transition to
noncombusted products, thereby
increasing the health benefits of the
policy.
FDA also received comments from
individuals, advocacy groups, and
members of the tobacco industry
generally opposing efforts to reduce
nicotine levels in cigarettes to
minimally addictive or nonaddictive
levels. These comments generally stated
that such a regulation would stifle free
enterprise or would negatively limit
consumer freedom of choice and that
the regulation would result in a de facto
ban on cigarettes that would have a
devastating impact on tobacco farming,
as well as the manufacturing,
distribution, and retail sectors. Some
comments discussed the technical
feasibility of achieving lower nicotine

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levels. Some comments opposed to a
nicotine product standard stated that
there is not enough scientific research to
support reducing nicotine in cigarettes.
Other comments argued that FDA
should instead focus on giving adults
who smoke cigarettes access to a wider
choice of less harmful tobacco products
and truthful information about the
benefits of switching to those products,
as well as focus resources on a plan to
reduce harm through proven strategies
to prevent initiation and encourage
cessation.
FDA has reviewed and closely
considered the comments to the
Nicotine ANPRM, as well as additional
evidence and information not available
at the time of the Nicotine ANPRM, in
developing this proposed rule.
2. Scientific Review
As the body of evidence has
continued to grow, FDA undertook a
robust systematic review of the
scientific evidence regarding the likely
effects of reducing nicotine in
combusted tobacco products. This
review, entitled ‘‘The Science of a
Nicotine Standard for Combusted
Tobacco Products’’ (Ref. 45), covers
peer-reviewed, publicly available
literature and focuses on the likely
effects of reducing nicotine in
combusted tobacco products. This
scientific assessment has been peer
reviewed by independent external
experts. Taking into consideration
comments from this peer review (Ref.
46), FDA revised the scientific
assessment, and the final peer-reviewed
document is available in the docket for
this proposed rule (Ref. 45).
Additionally, this final peer-reviewed
document and other related documents
such as FDA’s response to the peer
review comments can be found at
https://www.fda.gov/science-research/
peer-review-scientific-information-andassessments/completed-peer-reviews.
FDA’s peer reviewed scientific
assessment examined the effects of
reducing the level of nicotine in
combusted tobacco products on use
behavior, dependence, and toxicant
exposure, as well as the knowledge,
beliefs, and perceptions around nicotine
and VLNC cigarettes. This scientific
review found that the totality of the
evidence supports that extended
exposure to combusted cigarettes
containing VLNC tobacco filler is
associated with reduced addiction
potential, dependence levels, and
number of cigarettes smoked per day,
and increased quit attempts among
people who currently smoke cigarettes,
without evidence of increased toxicant
exposure, craving, withdrawal, or

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compensatory smoking. The review also
determined that if FDA were to establish
a nicotine product standard that covered
only cigarettes, a portion of people who
are currently addicted to cigarettes
would likely migrate to other, similar
combusted tobacco products to maintain
their nicotine dependence (or engage in
dual use without substantially reducing
their combusted tobacco product use),
thereby reducing the positive public
health impact of such a rule. Based on
FDA’s review of the literature on
combusted tobacco products, including
cigarettes, cigarette tobacco, RYO
tobacco, cigars, and pipe tobacco, the
final scientific assessment concluded
that use of any of these combusted
products is sufficient to create or sustain
nicotine dependence and would
therefore continue to expose people
who use these products to toxicants.
Further, FDA’s scientific assessment
concluded that the establishment of a
maximum nicotine level in combusted
tobacco products that would render
them minimally addictive or
nonaddictive could increase the
likelihood of successful quit attempts
and help prevent people who
experiment with cigarettes and cigars
(mainly youth) from progressing to
regular use, thereby significantly
reducing the morbidity and mortality
caused by smoking. FDA has considered
the scientific assessment conclusions in
the development of this proposed
product standard.
In addition, to assess the potential
public health impacts of a nicotine
product standard, FDA developed a
population health model using inputs
derived from available empirical
evidence and expert opinion to estimate
the impact of changes in tobacco
product initiation, cessation, switching,
and dual use on tobacco use prevalence,
morbidity, and mortality in the United
States. Details of this modeling
approach have been previously
published in two peer-reviewed
publications (Refs. 47 and 48), which
describe the overall model in terms of
the inputs, transition behaviors, and
outputs that it contains, along with
results from simulation studies. In
preparation for this proposed product
standard, FDA updated a previouslypublished model (Ref. 47), which
describes the impact of a potential
product standard that limits the level of
nicotine in cigarettes, RYO tobacco,
non-premium cigars, and pipe tobacco
so that they are minimally addictive or
nonaddictive. In this updated modeling
document, entitled ‘‘Methodological
Approach to Modeling the Potential
Impact of a Nicotine Product Standard

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on Tobacco Use, Morbidity, and
Mortality in the U.S.’’ (Ref. 42), we
estimated the potential impacts of a
nicotine product standard by modeling
a baseline scenario of use of cigarettes
and noncombusted tobacco products
including smokeless tobacco, ecigarettes, and HTPs. These product
classes (cigarettes and noncombusted
products) were selected because of the
magnitude of population health effects
from cigarette smoking and the
likelihood of product switching to
noncombusted products, especially ecigarettes. Estimates of changes in
mortality from other exposures
including non-premium cigar and pipe
tobacco use are not produced directly by
the model but are derived from model
outputs instead. We then compared the
baseline scenario to a product standard
scenario characterized by the
introduction of a potential nicotine
product standard that would apply to
cigarettes, cigarette tobacco, RYO
tobacco, non-premium cigars, and pipe
tobacco. FDA’s modeling framework
and methodological approach and the
associated data inputs and assumptions
have been peer reviewed by
independent external experts. Taking
into consideration comments from this
peer review (Ref. 49), FDA revised the
modeling document, and the final
modeling document is available in the
docket for this proposed product
standard (Ref. 42). FDA’s modeling
work informed the development of this
proposed product standard.
Additionally, the modeling document,
model code, and inputs are publicly
available at https://www.fda.gov/
science-research/peer-review-scientificinformation-and-assessments/
completed-peer-reviews. Further
discussion of FDA’s estimates of the
public health impact of this proposed
product standard can be found in
section VIII of this document.
3. Premium Cigars
On August 9, 2023, the U.S. District
Court for the District of Columbia issued
an order vacating FDA’s rule deeming
tobacco products to be subject to FDA’s
tobacco product authorities ‘‘insofar as
it applies to premium cigars.’’ 13 Cigar
13 For purposes of its ruling, the court specified
that a premium cigar is a cigar that: (1) is wrapped
in whole tobacco leaf; (2) contains a 100 percent
leaf tobacco binder; (3) contains at least 50 percent
(of the filler by weight) long filler tobacco (i.e.,
whole tobacco leaves that run the length of the
cigar); (4) is handmade or hand rolled (i.e., no
machinery was used apart from simple tools, such
as scissors to cut the tobacco prior to rolling); (5)
has no filter, nontobacco tip, or nontobacco
mouthpiece; (6) does not have a characterizing
flavor other than tobacco; (7) contains only tobacco,

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Ass’n of Am. v. FDA, No. 16–cv–01460,
2023 WL 5094869 (D.D.C. Aug. 9, 2023),
appeal docketed, No. 23–5220 (D.C. Cir.
argued Sept. 13, 2024). The government
has appealed this decision. When the
deemed status of premium cigars is
resolved, FDA will consider any
impacts with respect to this proposed
rule and take additional steps as
warranted, including for example, by
reopening the comment period and/or
issuing a supplemental notice of
proposed rulemaking. References to
premium cigars in this document serve
merely to clarify the current proposed
scope of products covered, evaluate the
scientific evidence related to nonpremium cigars, and describe FDA’s
approach to modeling the projected
public health impacts of this proposed
standard.
C. Legal Authority

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1. Product Standard Authority
The Tobacco Control Act was enacted
on June 22, 2009, amending the FD&C
Act and providing FDA with the
authority to regulate tobacco products.
Section 901 of the FD&C Act (21 U.S.C.
387a) granted FDA the authority to
regulate the manufacture, marketing,
and distribution of cigarettes, cigarette
tobacco, RYO tobacco, and smokeless
tobacco to protect the public health and
to reduce tobacco use by youth. The
Tobacco Control Act also gave the
Agency authority to conduct rulemaking
to ‘‘deem’’ any other tobacco products
subject to chapter IX of the FD&C Act
(21 U.S.C. 387 to 387t). In 2016, FDA
issued a final rule deeming products
meeting the statutory definition of
‘‘tobacco product’’ (including cigars and
pipe tobacco), except accessories of the
newly deemed products, to be subject to
chapter IX of the FD&C Act, as amended
by the Tobacco Control Act (81 FR
28974) (deeming final rule).
Among the tobacco product
authorities provided to FDA is the
authority to adopt tobacco product
standards where FDA determines that
such standard is appropriate for the
protection of the public health (section
907(a)(3)(A) of the FD&C Act). To
establish a tobacco product standard,
section 907(a)(3)(A) and (B) of the FD&C
Act requires that FDA find that the
standard is appropriate for the
protection of the public health, taking
into consideration scientific evidence
concerning:
• The risks and benefits to the
population as a whole, including users
water, and vegetable gum with no other ingredients
or additives; and (8) weighs more than 6 pounds per
1,000 units.

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and nonusers of tobacco products, of the
proposed standard;
• The increased or decreased
likelihood that existing users of tobacco
products will stop using such products;
and
• The increased or decreased
likelihood that those who do not use
tobacco products will start using such
products.
2. Authority To Establish a Maximum
Nicotine Level and Related Provisions
Section 907 of the FD&C Act
authorizes FDA to adopt tobacco
product standards that are appropriate
for the protection of the public health,
including expressly authorizing FDA to
adopt product standards with
provisions for nicotine yields; for the
reduction or elimination of other
constituents (including smoke
constituents) or harmful components;
and respecting the construction,
components, ingredients, additives,
constituents (including smoke
constituents), and properties of tobacco
products (section 907(a)(3), (a)(4)(A)(i)
to (iii), and (a)(4)(B)(i)). This includes
the authority to issue a new product
standard to establish a maximum level
of nicotine in tobacco products.
FDA is proposing to limit nicotine
yield by setting a maximum nicotine
content level for finished cigarettes and
certain other finished combusted
tobacco products not to exceed 0.70 mg
of nicotine per gram of total tobacco.
FDA is not seeking to require the
reduction of nicotine yields in any
tobacco product to zero, which is
prohibited under section 907(d)(3) of
the FD&C Act. To ensure that tobacco
products subject to the product standard
comply with the proposed maximum
nicotine level, FDA also is including
provisions that would require
manufacturers to test their products
using an analytical test method for
conformance with the maximum
nicotine level pursuant to section
907(a)(4)(B)(ii) and (iv) of the FD&C Act.
3. Sale and Distribution Restrictions
Section 907(a)(4)(B)(v) of the FD&C
Act states that product standards shall,
where appropriate for the protection of
the public health, include provisions
requiring that the sale and distribution
of tobacco products be restricted but
only to the extent that the sale and
distribution of a tobacco product may be
restricted under section 906(d) of the
FD&C Act. Similar to section 907,
section 906(d) of the FD&C Act gives
FDA authority to require restrictions on
the sale and distribution of tobacco
products by regulation if the Agency
determines that such regulation would

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be appropriate for the protection of the
public health. The finding as to whether
a regulation is appropriate for the
protection of the public health must be
determined with respect to the risks and
benefits to the population as a whole,
including users and nonusers of the
tobacco products, and must take into
account:
• The increased or decreased
likelihood that existing users of tobacco
products will stop using such products;
and
• The increased or decreased
likelihood that those who do not use
tobacco products will start using such
products (see section 906(d)(1) of the
FD&C Act).
Under these authorities and section
701 of the FD&C Act, which provides
FDA with the authority to promulgate
regulations for the efficient enforcement
of the FD&C Act, FDA is proposing
provisions that would restrict the
manufacture, sale, and distribution of
cigarettes and certain other combusted
tobacco products that are not in
compliance with this standard. These
provisions are not intended to restrict
the manufacture of cigarettes intended
for export. Consistent with section
801(e)(1) of the FD&C Act (21 U.S.C.
381(e)(1)), a tobacco product intended
for export shall not be deemed to be in
violation of section 907 of the FD&C Act
or this product standard, if it meets the
criteria enumerated in section 801(e)(1)
of the FD&C Act, including not being
sold or offered for sale in domestic
commerce. These provisions are critical
to maintain the purpose of the standard
by helping to ensure that the tobacco
products conform to the proposed
maximum nicotine level when used by
consumers.
FDA is also proposing, under these
authorities and others described herein
regarding testing and recordkeeping, a
requirement that the labels of tobacco
products covered under this proposed
product standard contain a
manufacturing code to identify, among
other things, the date of manufacture of
a production batch, so that FDA can
determine whether a product on store
shelves is in conformance with the
proposed product standard. The
proposed manufacturing code would
allow manufacturers and FDA to
identify the production batch of a
particular finished product that has
been released for distribution. This
information is intended to help
determine the product’s history (e.g.,
batch production records) and assist
manufacturers and FDA in the event of
a nonconforming tobacco product
investigation and any corrective actions
to be taken by a manufacturer as a result

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of the investigation. The manufacturing
code must also contain an ‘‘-NS’’
designation. The ‘‘-NS’’ designation will
enable retailers to readily identify that
a finished tobacco product conforms
with this standard. Finished tobacco
products that do not have this
designation do not conform to this
standard. The manufacturing code
information also would aid FDA in
ensuring compliance with this proposed
product standard by clearly identifying
those products that conform to the
standard and linking those products to
records that substantiate their
conformance.
4. Testing Requirements
This proposal contains provisions
regarding testing requirements pursuant
to sections 907(a)(4)(A)(iii) and
907(a)(4)(B) of the FD&C Act to help
ensure that finished cigarettes and
certain other finished combusted
tobacco products conform to the
requirements of the proposed product
standard before they are distributed to
consumers.
Section 907(a)(4)(A)(iii) states that
product standards shall include
provisions that are appropriate for the
protection of the public health,
including provisions, where
appropriate, relating to any requirement
under section 907(a)(4)(B) of the FD&C
Act. Section 907(a)(4)(B)(ii) of the FD&C
Act, in turn, provides that a product
standard shall, where appropriate for
the protection of the public health,
include provisions for testing the
tobacco product. In addition, section
907(a)(4)(B)(iv) of the FD&C Act
provides that, where appropriate for the
protection of the public health, a
product standard shall include
provisions requiring that the results of
test(s) required under section
907(a)(4)(B)(ii) show that the product is
in conformity with the portions of the
standard for which the test(s) were
required. FDA is proposing testing
requirements because it finds that such
requirements are appropriate for the
protection of the public health.
Consistent with these statutory
provisions, proposed §§ 1160.12,
1160.14, and 1160.16 would establish
product testing and sampling plan
requirements. Proposed § 1160.12
would require that a manufacturer
conduct testing on each batch of
finished cigarettes and certain other
finished combusted tobacco products to
determine whether the products
conform to the proposed maximum
nicotine level requirement and would
also require the manufacturer to
document all testing. Proposed
§ 1160.14 would require manufacturers

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to use an analytical test method and to
demonstrate that the test method was
validated in an analytical test
laboratory. Proposed § 1160.16 would
require that manufacturers design and
implement a sampling plan for finished
cigarettes and certain other finished
combusted tobacco products to ensure
the batch consistently conforms to the
proposed maximum nicotine level.
To support these proposed
requirements, proposed § 1160.18(b)
would require each tobacco product
manufacturer to investigate all potential
nonconforming tobacco products to
determine if the product is
nonconforming. For example, if any
representative samples from a batch of
finished cigarettes or certain other
finished combusted tobacco products
are determined to be out of conformance
or if FDA notifies a tobacco product
manufacturer that a finished tobacco
product in commercial distribution does
not conform to the requirements of this
part, the manufacturer must conduct an
investigation to determine the extent of
the nonconformity and locations to
which nonconforming tobacco products
have been distributed. This proposed
requirement would ensure that any
reports of nonconforming products,
whether as a result of manufacturer
testing or otherwise, are examined and
investigated and that appropriate
measures are taken to ensure that
nonconforming products are not
distributed to consumers and to prevent
future nonconformity.
5. Recordkeeping
Section 909 of the FD&C Act
authorizes FDA to require tobacco
product manufacturers to establish and
maintain records, make reports, and
provide such information as the Agency
may by regulation reasonably require to
assure that a tobacco product is not
adulterated or misbranded and to
otherwise protect public health.
FDA is proposing a requirement that
manufacturers maintain certain records,
including the results of batch testing
and analyses conducted to determine
conformance with the proposed product
standard, records of sampling plans and
sampling procedures, records related to
manufacturing controls, and all records
related to the analytical test method
used to assess finished cigarettes and
certain other finished combusted
tobacco products for conformance with
the proposed maximum nicotine level
requirement. FDA is also proposing to
require that manufacturers use a
manufacturing code, from which the
Agency must be able to identify the
production batch of finished cigarettes
and certain other finished combusted

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tobacco products that have been
released for distribution. The
maintenance of these records for the
time period specified in this proposed
product standard is necessary to help
ensure that such tobacco products are in
conformance with the proposed product
standard and are not adulterated or
misbranded, consistent with the
authority provided in section 909 of the
FD&C Act. FDA has authority to inspect
manufacturers, including access to these
records, under, among other authorities,
section 704 of the FD&C Act. In
addition, the recordkeeping and record
access requirements would help FDA
with the efficient enforcement of the
Act, consistent with the rulemaking
authority provided by section 701(a) of
the FD&C Act.
IV. Nicotine in Cigarettes and Other
Combusted Tobacco Products:
Addiction, Initiation, Dependence,
Cessation, Relapse, Health Effects, and
Consumer Perceptions
Tobacco products are addictive,
primarily due to the presence of
nicotine, and the magnitude of public
health harm caused by tobacco products
is inextricably linked to their addictive
nature (Ref. 50 at p. xi). Some evidence
suggests that nicotine is more addictive
than many other addictive substances.
For example, one study showed the
probability of transitioning from first
use to dependence was 68 percent for
nicotine, but less than 23 percent for
alcohol, cocaine, and cannabis (Ref. 51).
While cigarettes are the most widely
used tobacco products among adults,
other combusted tobacco products that
are possible targets of product migration
(i.e., alternatives that allow people who
smoke cigarettes to maintain their
nicotine addiction) or dual use have
similar adverse health effects, and also
cause nicotine dependence (Refs. 52 and
53). For example, persons who use
cigars and pipe tobacco are still subject
to the addictive effects of nicotine
through nicotine absorption (and to the
health impacts of long-term use that
may follow from regular use due to
addiction) even if they report that they
do not inhale (Refs. 54 to 56).
A. Nicotine Is Addictive
The scientific evidence is clear that
nicotine is the primary chemical in
tobacco products that causes addiction
through its psychoactive and reinforcing
effects (Ref. 57). Since 1988, the U.S.
Surgeon General has determined that
there is a causal relationship between
smoking and addiction to nicotine (Refs.
1 and 57), and the earlier that
individuals begin smoking, the less
likely they are to successfully quit (Ref.

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27). Upon inhaling smoke from a
burning cigarette, nicotine is absorbed
into the lungs and rapidly travels to the
brain. Once in the brain, nicotine
produces its initial effects by binding to
nicotinic receptors—the primary targets
for nicotine in the brain—and inducing
release of the chemical dopamine (Refs.
58 and 59). Dopamine plays a major role
in the pleasurable and reinforcing
effects of smoking that promote
continued use (Refs. 58 and 59).
Nicotine addiction occurs as the result
of repeated exposure to nicotine, which
induces changes in the brain (Refs. 58
to 60). Addiction to nicotine can lead to
symptoms of nicotine dependence,
which may include tolerance to the
effects of nicotine, withdrawal
symptoms upon cessation of use, and
craving cigarettes (Refs. 1 and 58).
The addiction potential of a nicotine
delivery system varies as a function of
its total nicotine dosing capability, the
speed at which it can deliver nicotine,
the rate of absorption, its palatability
and sensory characteristics, how easy it
is for the person using the product to
extract nicotine, and its cost (Ref. 61).
The amount of nicotine delivered and
the means through which it is delivered
can either reduce or enhance a product’s
potential for abuse and physiological
effects (Ref. 28 at p.113). Quicker
delivery, higher rate of absorption, and
higher resulting concentration of
nicotine increase the potential for
addiction (Ref. 28 at p.113). A cigarette
is an inexpensive and extremely
effective nicotine delivery system that
maximizes the cigarette’s addicting and
toxic effects (Ref. 61).
Tobacco use disorder is a psychiatric
disorder, defined by the Diagnostic and
Statistical Manual of Mental Disorders
(DSM) as being characterized by
tolerance to the effects of tobacco
products, withdrawal symptoms that are
mitigated by the self-administration of
nicotine-containing products, and
unsuccessful attempts at reducing or
quitting the use of nicotine-containing
products (Ref. 62). Researchers consider
several behaviors indicative of a
substance with addictive properties.
These behaviors include reinforcement,
tolerance, withdrawal, and craving—all
of which support the fact that nicotine
is the primary addictive constituent in
tobacco products. The scientific
evidence is clear that nicotine is the
primary chemical in tobacco products
that causes and maintains addiction.
1. Reinforcement
The reinforcement threshold for
nicotine can be defined as the lowest
nicotine level that would maintain or
increase nicotine self-administration

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behavior. Currently, most marketed
cigarettes are above that threshold;
people who smoke cigarettes develop
and maintain their addiction through
continued smoking (Refs. 17 and 63).
Evidence supports that VLNC cigarettes
(see table 1 of this document) are below
that threshold, as studies show a
reduction in the level of addiction based
on dependence scales (Ref. 32) and
cigarettes per day (CPD) (Refs. 32, 64,
and 65). The maximum nicotine level
included in this proposed product
standard is based on FDA’s analysis of
studies regarding the likely effects of
reducing nicotine, which demonstrates
that extended exposure to VLNC
cigarettes, which result in very low
nicotine yield that cannot be overcome
by use behaviors, is associated with
reduced addiction potential,
dependence levels, number of cigarettes
smoked per day, and increased quit
attempts among people who currently
smoke cigarettes, without evidence of
increased toxicant exposure, craving,
withdrawal, or compensatory smoking
(Ref. 45).

time course are consistent with most
prototypical addictive substances (e.g.,
alcohol, benzodiazepines, opioids,
amphetamines, cocaine, caffeine) (Ref.
74). While some have asserted that
people smoke cigarettes as a ‘‘tool’’ or
‘‘resource’’ that provides them with
needed ‘‘psychological benefits,’’ such
as increased mental alertness and
anxiety reduction (Ref. 75), this view is
not borne out by the scientific evidence.
In fact, the claimed ‘‘psychological
benefits’’ (i.e., increased mental
alertness, anxiety reduction, coping
with stress) that have been ascribed to
a smoking ‘‘habit’’ are actually
symptoms of withdrawal suppression
(Ref. 76). Craving or urge is described as
a motivation for substance use, which is
seen in people who use nicotine (Refs.
77 to 79). Although craving is often
characterized as a symptom of nicotine
and tobacco withdrawal, it is also a
prominent symptom of nicotine
dependence (Ref. 72), and it can occur
in the absence of other withdrawal
symptoms.

2. Tolerance
Tolerance is defined as a state in
which, after repeated exposure, a
substance produces less of an effect than
previously (Ref. 66) and increasing
amounts are required to achieve the
effect observed with the first exposure.
Both clinical and preclinical research
has shown that nicotine has euphoric
effects, produces a ‘‘pleasurable buzz,’’
and directly enhances positive affect or
indirectly increases the reward value of
pleasurable situations (Refs. 67 to 70).
With repeated exposure to nicotine,
neuroadaptation occurs to some of these
positive effects, and symptoms of
craving and withdrawal begin during
periods of abstinence (Ref. 58). Nicotine
addiction results from a combination of
positive reinforcement from smoking
and avoidance of these withdrawal
symptoms (Ref. 58). Evidence of
tolerance in people who smoke
cigarettes is demonstrated as they tend
to progressively increase the number of
cigarettes they smoke over a period of
several years before plateauing to a
relatively constant level of use (Ref. 71).

4. Nicotine Use Is an Addiction, Not a
Habit

3. Withdrawal and Craving
Nicotine produces a characteristic
withdrawal syndrome manifested by
irritability/anger/frustration, anxiety,
depressed mood, difficulty
concentrating, increased appetite,
insomnia, and restlessness (Ref. 72).
Symptoms typically emerge within the
first 1–2 days following abstinence,
peak within the first week, and last 2–
4 weeks (Ref. 73). The symptoms and

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A few individual reports have
challenged the conclusion that nicotine
is the constituent in tobacco products
that causes addiction, stating that
nicotine only causes habitual behavior
(Refs. 67 and 75), and that the craving
associated with nicotine is determined
by nonpharmacological factors that are
disassociated from smoking withdrawal
(Ref. 80). However, nicotine has been
extensively studied and the evidence
overwhelmingly demonstrates that
nicotine is an addictive drug and the
fundamental reason that individuals
continue using tobacco products (Refs.
57 and 28). Since 1988, the U.S.
Surgeon General has concluded that
nicotine is the substance in tobacco
products that causes addiction through
its psychoactive effects, reinforcing
effects, tolerance, and physical
dependence/withdrawal, and that
nicotine use is not habitual (Ref. 57).
The tobacco industry also has
acknowledged that nicotine is addictive
(Refs. 81 and 82).
For these reasons, FDA concludes that
the addictiveness of nicotine in tobacco
products leads to regular use (even
when people wish to quit), which is at
the root of tobacco-related disease and
death from cigarettes and certain other
combusted tobacco products.

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Federal Register / Vol. 90, No. 10 / Thursday, January 16, 2025 / Proposed Rules
B. The Developing Brain’s Vulnerability
to the Effects of Nicotine Leads to
Progression to Regular Cigarette Use
Among Youth and Young Adults Who
Experiment
Youth and young adults are
particularly susceptible to developing
an addiction to nicotine. Due to the
brain’s ongoing development during
adolescence and young adulthood—
until about age 25—it is more
vulnerable to nicotine’s effects than the
adult brain is (Refs. 83 to 85). The 1994,
2012, 2014, and 2020 Surgeon General’s
Reports on smoking and health note that
almost 90 percent of adults who
currently and regularly smoke initiated
smoking by age 18, and 98 percent
initiated smoking by age 26, which is
notable given that 25 is the approximate
age at which the brain has completed
development (Refs. 1, 17 to 19). The
developing brain is more vulnerable to
developing nicotine dependence than
the adult brain is, and the earlier an
individual begins smoking the less
likely they are to quit (Ref. 20). The
maximum nicotine level requirement
included in this proposed product
standard to regulate nicotine yield
would make cigarettes and certain other
combusted tobacco products minimally
addictive or nonaddictive, limiting the
number of youth and young adults who
progress from experimentation to
regular use and reducing their risk for
smoking-related diseases.
There are three primary stages that
occur as an individual transitions from
never smoking to smoking cigarettes
regularly: initiation, experimentation,
and regular use. An individual initiates
smoking once he or she first tries a
cigarette, even one or two puffs (Ref.
17). The vast majority of smoking
initiation occurs during adolescence
(Ref. 17). Initiation can progress to
experimentation, where individuals
continue to occasionally try cigarettes,
but do not smoke every day, and then
to smoking regularly (i.e., smoking daily
or on most days) (Ref. 17).
Adolescence is a period of
development when individuals who
experiment with tobacco products are
more susceptible to transitioning to
regular use and developing addiction to
nicotine. Data from the 2024 NYTS
found that 10.1 percent of high school
students and 5.4 percent of middle
school students reported current use of
any tobacco product (Ref. 3). Each day,
approximately 1,200 youth (ages 18 and
below) try their first cigarette (Ref. 86 at
Table A.13A). The transition to regular
cigarette use (i.e., smoking on ≥20 of the
past 30 days) can occur relatively
quickly and can be achieved by smoking

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as few as 100 cigarettes (Ref. 17).
Longitudinal and nationally
representative cross-sectional data
indicate that an established pattern of
cigarette use—including those who
‘‘rapidly escalate’’ to regular use—
typically occurs by early adulthood
(ages 20–22) (Refs. 87 and 88). The
Centers for Disease Control and
Prevention (CDC) and other researchers
have estimated that 30 percent or more
of people who experiment with
cigarettes transition to regular cigarette
use (Refs. 89 to 92). Researchers applied
the 30 percent estimate to the number
of adolescents who were at the early
experimentation stage in 2000,
translating to approximately 2.9 million
of these adolescents who have or will
become people who regularly smoke
cigarettes (Ref. 91). Based on the
number of persons under the age of 18
in 2012 in the United States, the U.S.
Surgeon General estimated that
17,371,000 of that group would begin
smoking cigarettes regularly and
5,557,000 will die from a smokingrelated disease (Ref. 1 at Table 12.2.1).
These concerningly high numbers speak
to the extreme vulnerability of youth
and young adults to the health harms of
tobacco use resulting from addiction to
nicotine.
Nicotine addiction is a critical factor
in the transition of people who smoke
cigarettes from experimentation to
regular smoking and in the continuation
of smoking for those who want to quit
(Ref. 28 at p.113, Ref. 1). Although the
majority of adolescents who smoke
daily meet the criteria for nicotine
dependence, one study found that the
most susceptible youth lose autonomy
(i.e., independence in their actions)
regarding tobacco within 1 or 2 days of
first inhaling from a cigarette (Refs. 93
and 94). Another study found that 19.4
percent of adolescents (initially ages 12–
13 and followed over 6 years) who
smoked weekly were dependent on
nicotine (Ref. 95). In a study regarding
nicotine dependence among adolescents
who recently initiated smoking (9th and
10th grade students), adolescents who
smoked cigarettes at the lowest levels
(i.e., smoking on only 1 to 3 days of the
past 30 days) experienced nicotine
dependence symptoms such as loss of
control over smoking (42 percent) and
irritability after not smoking for a while
(23 percent) (Ref. 96). Researchers in a
4-year study of 6th grade students also
found that ‘‘[e]ach of the nicotine
withdrawal symptoms appeared in some
subjects prior to daily smoking’’ (Ref.
93) (emphasis added). Ten percent of
the study participants showed signs of
tobacco dependence within 1 or 2 days

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of first inhaling from a cigarette, and
half had done so by the time they were
smoking seven cigarettes per month
(Ref. 93).
Similarly, researchers have found that
among the 3.9 million middle and high
school students who reported current
use of tobacco products (including
cigarettes and cigars) in 2012, 2 million
of those students—including those who
used intermittently (e.g., smoking
cigarettes on a monthly basis)—reported
at least one symptom of dependence
(Ref. 24). Other researchers analyzing
data from the 2021 NYTS found that a
sizeable proportion of high school
students using tobacco products in the
past 30 days report symptoms of
nicotine dependence, including 27.2
percent reporting a strong craving for
tobacco use and 19.5 percent reporting
wanting to first use tobacco products
within 30 minutes of waking (Ref. 25).
Overall, these findings demonstrate that
youth and young adults who experiment
with cigarettes (and other tobacco
products) are particularly vulnerable to
the effects of nicotine on progression to
regular use and dependence, leading to
maintained tobacco product use into
adulthood.
C. Youth and Adult Cigarette Smoking
Cessation and Relapse
Like adults, many youths who smoke
cigarettes want to quit but have
difficulty doing so. An analysis of data
from the 2015 YRBS looking at youth
cigarette quit attempts found that 45.4
percent of high school students
currently smoking cigarettes had sought
to quit in the previous year (Ref. 22);
2012 NYTS data were congruent,
indicating that 51.5 percent of middle
and high school students who smoke
cigarettes had sought to quit all tobacco
use in the previous year (Ref. 22).
For adults who smoke who report quit
attempts, few are successful. As of 2019,
researchers estimate that only between
5.4 and 5.6 percent of people who
smoked cigarettes successfully quit for
good, according to data from the NHIS
and National Survey on Drug Use and
Health (NSDUH), respectively (Ref. 14).
According to recent data regarding adult
quit attempts, analyses of 2022 NHIS
and 2018–2019 TUS–CPS data indicate
that 67.7 and 76.6 percent of adults,
respectively, who smoke cigarettes were
interested in quitting (Refs. 4 and 36),
while the 2022 NHIS data and 2018–
2019 TUS–CPS data show that only 53.3
and 51.3 percent, respectively, of U.S.
adults who smoke actually made a quit
attempt within the past year (Refs. 4 and
36). Analyses of 2022 NHIS and 2018–
2019 TUS–CPS data indicates that only
8.8 and 7.5 percent of adults who

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formerly smoked cigarettes had
successfully quit smoking cigarettes,
respectively (Ref. 4 and 36). Adults who
smoke may make 30 or more quit
attempts before succeeding (Ref. 37).
Some population groups are less
successful than others: for example,
adults with education levels at or below
the equivalent of a high school diploma
have the highest smoking prevalence
levels but the lowest quit ratios (i.e., the
ratio of persons who have smoked at
least 100 cigarettes during their lifetime
but do not currently smoke to persons
who report smoking at least 100
cigarettes during their lifetime) (Ref. 97).
Nicotine addiction and associated
withdrawal symptoms make it difficult
for people who smoke cigarettes to quit,
and quit rates rarely exceed 25 percent
(Ref. 98).
Relapse is the principal limiting factor
in the transition from smoking to
nonsmoking status (Ref. 28). Relapse
refers to the point after an attempt to
stop smoking when a person’s tobacco
use again becomes ongoing and
persistent (Ref. 28 citing Brandon et al.,
1986). Most people who relapse do so
soon after their quit attempt (Ref. 28).
One study found that 80 to 90 percent
of individuals who were smoking at 6
months following a quit attempt had
resumed smoking within 2 weeks
following their quit attempt (Ref. 99).
However, even those who quit smoking
for longer periods of time frequently
relapse. Long-term studies of
individuals trying to quit smoking
reveal that 30 to 40 percent of those who
quit smoking for 1 year eventually
relapsed (Ref. 99). In addition, one
study following 840 participants for
more than 8 years found that
approximately one-half of people who
smoke who stopped smoking for 1 year
relapsed to regular smoking within the
subsequent 7 years (Ref. 100).
Researchers have found that a higher
frequency of smoking is associated with
earlier lapses after cessation (e.g.,
smoking on the first day of cessation or
within the first 2 weeks), which in turn
is strongly associated with an increased
risk of relapse, and is also associated
with more severe withdrawal symptoms
and earlier relapse after an attempt to
quit smoking (Ref. 28 at p.119). These
findings confirm the powerful addictive
properties of nicotine in tobacco
products, a principal factor limiting the
ability to quit for a person who uses
combusted tobacco products, and
further underscore the public health
importance of decreasing the
addictiveness of these products by
decreasing nicotine yield, particularly
for youth and young adults who

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experiment with smoking and for
people currently smoking and who hope
to quit.
D. Smoking Cigarettes and Other
Combusted Tobacco Products Causes
Serious Negative Health Effects
Nicotine is a powerfully addictive
chemical. The effects of nicotine on the
central nervous system occur rapidly
after absorption (Ref. 57 at p.12). People
who use cigarettes and other combusted
tobacco products absorb nicotine readily
from tobacco smoke through the lungs
(Ref. 57 at p. iii), and, from the lungs,
nicotine is then rapidly transmitted to
the brain (Ref. 57 at p.13). In the case
of cigars, nicotine is also absorbed
through the mouth. With regular use,
nicotine levels accumulate in the body
during the day from tobacco product use
and the nicotine persists overnight,
allowing for continuous exposure
throughout the entire 24-hour period
(Ref. 57 at p.38). While mild nicotine
intoxication can occur among people
who are smoking for the first time (Ref.
57 at p. 15–16), tolerance to the effects
of nicotine develops rapidly.
Cigarette smoking is responsible for
480,000 premature deaths every year
from many diseases, puts a substantial
burden on the U.S. healthcare system,
and causes massive economic losses to
society (Ref. 1 at p. 659–666). In terms
of a monetary measure of the impact of
cigarette smoking on the public health,
in 2018 smoking cost the United States
more than $600 billion, including more
than $240 billion in healthcare spending
(Ref. 10), nearly $185 billion in lost
productivity from smoking-related
illnesses and health conditions (Ref. 10),
nearly $180 billion in lost productivity
from smoking-related premature death
(Refs. 1 and 10), and $7 billion in lost
productivity from premature death from
secondhand smoke exposure (Refs. 1
and 11). Current evidence shows that,
while nicotine itself is not the direct
cause of most smoking-related diseases,
addiction to the nicotine in tobacco
products is the proximate driver of
tobacco-related death and disease
because it sustains tobacco use even
when people who smoke want to quit
(which most people who smoke report
wanting to do) (Refs. 1, 13, 28, 58, and
61). Inhalation of smoke from cigarettes
and other combusted tobacco products
exposes people who use the products to
over 7,000 chemicals, many known to
be hazardous to health and lead to
disease (Ref. 28). According to the 2014
Surgeon General’s Report, which
summarizes thousands of peer-reviewed
scientific studies and is itself peerreviewed, smoking remains the leading
preventable cause of disease and death

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in the United States, and cigarettes have
been shown to cause an ever-expanding
number of diseases and health
conditions (Ref. 1). Every year, cigarette
smoking is the primary causal factor for
163,700 deaths from cancer, 160,600
deaths from cardiovascular and
metabolic diseases, and 131,100 deaths
from pulmonary diseases (Ref. 1 at
p.659). In the United States, about 87
percent of all lung cancer deaths, 32
percent of coronary heart disease
deaths, and 79 percent of all cases of
chronic obstructive pulmonary disease
(COPD) are attributable to cigarette
smoking (Ref. 1). Smoking during
pregnancy can result in negative
outcomes for a newborn baby, such as
low birth weight, lungs that fail to
develop properly, birth defects such as
cleft lip and/or cleft palate, and Sudden
Infant Death Syndrome (Ref. 101). As
stated in the 2014 Surgeon General’s
Report, ‘‘[c]igarette smoking has been
causally linked to diseases of nearly all
organs of the body, to diminished health
status, and to harm to the fetus . . .
[and] the burden of death and disease
from tobacco use in the United States is
overwhelmingly caused by cigarettes
and other combusted tobacco products’’
(Ref. 1 at p.7).
Tobacco and cigarette smoking-related
morbidity and mortality also have been
experienced differentially across
different sociodemographic
characteristics, such as race, ethnicity,
socioeconomic status, educational
attainment, mental health status, and
homelessness. Black 14 adults, and in
particular Black men, experience the
highest rates of incidence and mortality
from many tobacco-related cancers,
such as lung and bronchus cancer and
head and neck cancer, compared to
those from other racial and ethnic
groups (Refs. 102 to 104). Deaths from
other tobacco-related conditions such as
heart disease, stroke, and hypertension
are higher among Black individuals
compared to other racial and ethnic
groups regardless of tobacco use status
(Refs. 105 to 110). Compared to persons
identifying as non-Hispanic White,
Hispanic and Black persons smoke
fewer cigarettes (Refs. 111 to 113) and
are more likely to be people who do not
smoke daily (Refs. 111 and 114), yet
14 Throughout this document, FDA uses both the
terms ‘‘Black’’ and ‘‘African American.’’ The term
‘‘African American’’ is used to describe or refer to
a person of African ancestral origins or who
identifies as African American. ‘‘Black’’ is used to
broadly describe or refer to a person who identifies
with that term. Though these terms may overlap,
they are distinct concepts (e.g., a Black person may
not identify as African American). As a result, FDA
relies on the specific term used by researchers when
citing to specific studies. FDA uses the term
‘‘Black’’ when not citing to a specific study.

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have greater risk of lung cancer
morbidity and mortality (Refs. 1, 115 to
118). Additionally, American Indian/
Alaska Native (AI/AN) populations have
the highest cigarette use prevalence
(Refs. 119 to 121) and are more likely to
suffer disproportionate rates of tobaccorelated death (Ref. 119). An analysis of
2001–2009 mortality data for people
living in the Indian Health Service
Contract Health Service Delivery Area
counties in the United States indicated
that age-adjusted death rates, smokingattributable fractions, and smokingattributable mortality for all-cause
mortality were statistically significantly
higher among AI/AN populations than
among White populations for adult men
and women aged 35 years and older
(Ref. 122). Cigarette smoking caused 21
percent of ischemic heart disease, 15
percent of other heart disease, and 17
percent of stroke deaths in AI/AN men,
compared with 15 percent, 10 percent,
and 9 percent, respectively, for White
men (Ref. 122). Among AI/AN women,
smoking caused 18 percent of ischemic
heart disease deaths, 13 percent of other
heart disease deaths, and 20 percent of
stroke deaths, compared with 9 percent,
7 percent, and 10 percent, respectively,
among White women (Ref. 122). Some
Asian populations, Native Hawaiians,
and other Pacific Islander populations
also suffer from disproportionate rates
of tobacco-related mortality as
compared to non-Hispanic White
persons (Refs. 115, 117, 123, and 124).
Disparities in tobacco-related
morbidity and mortality have also been
observed for additional population
groups that have higher levels of
tobacco use. Those with low household
income and/or educational attainment
bear a disproportionate burden of
myocardial infarction prevalence and
coronary heart disease-related mortality
(Ref. 125). National Health and
Nutrition Examination Survey
(NHANES) data from 2007 to 2010
indicate that prevalence of co-occurring
obesity and smoking was linearly
associated with educational attainment
as women with the lowest levels of
education had greater likelihood of
being obese and smoking than women
with the highest levels of education
(Ref. 126). Some research also indicates
that race/ethnicity status interacts with
the effects of higher educational
attainment on the likelihood of current
smoking. The protective effect of higher
education against current smoking was
shown to be a stronger effect for White
as compared to Black respondents (Ref.
127). Research has also demonstrated
that individuals with behavioral health
conditions and other medical

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comorbidities have higher prevalence of
combusted tobacco use compared to
those without these conditions (Refs.
128 and 129) and have increased risk of
tobacco-related morbidity and mortality
(Refs. 120, 130, and 131). Inpatient
hospital admission data from 1990 to
2005 from California indicate that
approximately half of the deaths in
those who had been hospitalized for
schizophrenia, bipolar disorder, or
major depressive disorder were due to
diseases causally linked to tobacco use
(Ref. 130) and that the majority of
deaths for those hospitalized for opioidrelated conditions were related to
tobacco and alcohol, not to opioids (Ref.
132). Tobacco-related cancers are a
leading cause of death among adults
experiencing homelessness (Ref. 133).
While cigarette smoking and exposure
to cigarette smoke are responsible for
significant mortality—480,000
premature deaths annually, as
previously stated—this estimate does
not include deaths caused by other
tobacco products, such as cigars and
pipes (Ref. 1 at p. 665).15 Additionally,
for every person who dies from a
smoking-related disease in the United
States, approximately 30 more people
will suffer from at least one smokingrelated disease (Ref. 1).
Inhalation of the chemicals produced
by combustion results in numerous
adverse health outcomes through
mechanisms that include DNA damage,
inflammation, and oxidative stress (Ref.
28). The three leading causes of
smoking-attributable death for people
who currently and formerly smoke
cigarettes are lung cancer, heart disease,
and COPD (Ref. 1 at p. 660). Cigarette
smoking results in a chronic
inflammatory state in the cardiovascular
system that is known to be a powerful
predictor of cardiovascular events
including heart disease (Ref. 28). For
COPD, although studies have shown
that the disease can be almost
completely prevented with the
elimination of smoking (Ref. 63), for
those who have already developed the
disease, evidence indicates that the
related morbidity persists long after
cessation of smoking (Ref. 28). In
addition, it has been established that
more than 85 percent of lung cancers are
due to smoking, and lung cancer is the
15 Regular cigar smoking was responsible for
approximately 9,000 premature deaths and more
than 140,000 years of potential life lost among
adults aged 35 years or older in 2010 (Ref. 134). The
2014 Surgeon General’s Report states that the
methodology for estimating the current population
burden for use of combusted tobacco products other
than cigarettes remains under discussion, but the
number of added deaths is expected to be in the
thousands per year (Refs. 1 and 135).

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country’s leading cause of cancer death
(Refs. 1, 28, 63, and 136).
Cigarettes and other combusted
tobacco products also have deadly
effects on people who do not smoke
because they produce secondhand
smoke. It is well-established that
secondhand tobacco smoke causes
premature death and disease in children
and in adults who do not smoke (Ref.
15 at p.11). Secondhand smoke
exposure is currently estimated to be
responsible for over 41,000 deaths
annually in the United States (Ref. 1).
For example, an estimated 7,300 lung
cancer deaths and nearly 34,000
coronary heart disease deaths annually
can be attributed to secondhand smoke
(Ref. 1). Additionally, productivity
losses due to secondhand smokeattributable deaths are estimated to cost
the United States $5.6 billion each year
(Ref. 1).
Secondhand smoke is particularly
harmful to children. For instance, the
2014 Surgeon General’s Report
estimated that each year, secondhand
smoke is associated with 150,000 to
300,000 lower respiratory tract
infections in infants and children under
18 months of age, 790,000 doctor’s
office visits related to ear infections, and
202,000 asthma cases (Refs. 1 and 137).
In addition, thirdhand smoke—the
chemical residue from combusted
tobacco smoke that can become
embedded in the environment (e.g.,
carpet, dust)—results in exposure to
harmful constituents such as tobacco
specific nitrosamines (Ref. 138).
Exposure to thirdhand smoke is
especially concerning for young
children given their size and behaviors,
like crawling on the ground and
frequently putting their hands in their
mouths.
Additionally, the burden of
secondhand smoke exposure is
experienced disproportionately among
members of some racial and ethnic
groups and people with lower
household income and educational
attainment. Among people who do not
smoke, ages 3 and older, findings from
2011 to 2018 NHANES data indicate
that non-Hispanic Black respondents
and those living below the poverty level
had the highest levels of secondhand
smoke exposure compared to people of
other races and those living above the
poverty level, respectively; these
disparities persisted across all years of
the study analysis from 2011 to 2018
(Ref. 139). From 1999 to 2012, the
percentage of persons who do not smoke
(ages 3 and older) with detectable serum

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cotinine 16 levels (defined in the study
as levels ≥0.05 nanogram per milliliter
to indicate secondhand smoke
exposure) declined across all racial and
ethnic groups (Ref. 141). However, a
higher proportion of non-Hispanic Black
individuals who do not smoke
continued to have detectable serum
cotinine levels, compared to Hispanic
and non-Hispanic White individuals
who do not smoke. For example, in
2017–2018, nearly 50 percent of nonHispanic Black people who do not
smoke had detectable serum cotinine
levels, compared with 22 percent of
non-Hispanic White and 17 percent of
Mexican American people who do not
smoke (Ref. 141). Moreover, disparities
in trends in detectable serum cotinine
levels among people who do not use
cigarettes over time have been observed
on the basis of race/ethnicity. One
analysis of NHANES data and found
that from 1999 to 2012 among children
ages 3–11, comparable levels of decline
were observed among non-Hispanic
White (percentage change: 41.2 percent)
and Mexican American (percentage
change: 39.0 percent) youth, but a lesser
decline was observed among nonHispanic Black youth (percentage
change: 19.8 percent) (Ref. 141). A more
recent analysis of NHANES data also
indicated that, between 2011 and 2018,
the percentage of people who do not use
cigarettes with detectable serum
cotinine levels increased among nonHispanic Black youth ages 12–19 but
remained stagnant among non-Hispanic
White youth of the same ages (Ref. 142).
Moreover, there is also some scientific
evidence supporting disparities in
secondhand smoke exposure by sexual
orientation. An analysis of NHANES
data from 2003–2010 found that
secondhand smoke exposure (defined as
a serum continine 17 levels ≥0.05
nanogram per milliliter) differed by
sexual orientation among women 20–59
years of age (Ref. 143). This study found
that among women 20–59 years of age,
secondhand smoke exposure was higher
among non-smoking women who
identified as lesbian (56.2 percent) or
who reported a lifetime experience with
a same-gender partner (47.7 percent)
than those women who identified as
exclusively heterosexual (33.0 percent;
p<0.001) (Ref. 143). However, among
men 20–59 years of age, exposure to
secondhand smoke did not significantly
differ by sexual orientation.
16 Cotinine is an alkaloid found in tobacco leaves
and is the main metabolite of nicotine. Measuring
cotinine in people’s blood is a reliable way to
determine exposure to nicotine for both people who
smoke and those exposed to environmental tobacco
smoke (Ref. 140).

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Disparities in the secondhand smoke
exposure are found across various
environmental settings. These
disparities speak to the interrelated
influences of individual factors (e.g.,
age, race and ethnicity, sexual
orientation, income) and existing
inequities in places where members of
communities disproportionally
impacted by tobacco-related health
disparities are likely to reside, spend
time, and work (Refs. 53 and 120). For
example, an analysis of NHANES data
from 2017–2018 found that 87.8 percent
of non-smoking persons 3 years of age
and older who lived with someone who
smoked inside the home was exposed to
secondhand smoke based on serum
cotinine values of 0.05–10.00 nanogram
per milliliter compared to 21.4 percent
of non-smoking persons 3 years of age
and older not living with someone who
smoked inside the home (Ref. 142). In
terms of race and ethnicity, findings
drawn from the 2013–2016 NHANES
data indicate that compared to nonHispanic White respondents, nonHispanic Black respondents had higher
odds of secondhand smoke exposure in
homes other than their own (Ref. 144).
An analysis of NYTS data indicates that
non-Hispanic Black and non-Hispanic
White students both had higher
prevalence of secondhand smoke
exposure at home and in vehicles than
Hispanic and non-Hispanic other race/
ethnicity students (Ref. 145). While
secondhand smoke exposure in homes
and vehicles declined from 2011 to
2018, secondhand smoke exposure in
homes among non-Hispanic Black
students did not change (Ref. 145).
Additionally, a study using data from
Wave 1 (2013–2014) of the Population
Assessment of Tobacco and Health
(PATH) Study found that the odds of
exposure to secondhand smoke at home
were higher for Black adults (OR=1.12,
95 percent CI:1.00–1.24; p-value=0.042)
than White adults; and higher for those
adults who self-identified as being
LGBT (OR=1.30, 95 percent CI:1.11–
1.52; p-value=0.001) than for
heterosexual adults (Ref. 146). Home
smoking bans (i.e., when people decide
to have their own rules that restrict or
ban smoking inside their own home)—
can reduce secondhand smoke
exposure. For example, a study using
data from the 2009–2010 National Adult
Tobacco Survey (NATS) found the
prevalence of exposure to secondhand
smoke varied based on the presence (or
absence) of smokefree rules in the home
(Ref. 147). This study found that overall,
1.4 percent of people who did not
smoke and had a smokefree rule at
home were exposed to secondhand

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smoke in their homes in the past 7 days,
compared with 43.9 percent of people
who did not smoke and did not have a
smokefree rule at home (Ref. 147). A
similar pattern was observed across age
groups, race and ethnicity, and levels of
educational attainment. For example, a
higher percentage of Black and Hispanic
people were exposed to secondhand
tobacco smoke in homes with and
without smokefree rules than White
people. Additionally, a study using
1995–2007 TUS–CPS data found that
among two parent households, higher
levels of parental educational level and
annual household income were
associated with the higher reporting of
a complete home ban as compared to
lower levels of parental educational and
annual household income (Ref. 148).
Such findings emphasize the degree to
which certain aspects of disadvantage
(such as lower family income, lack of
access to single-family housing, or lack
of autonomy over the home
environment) may compound tobaccorelated health disparities.
Individuals who live in multi-unit
housing, including apartments, are
particularly susceptible to involuntary
secondhand smoke exposure in the
home, as secondhand smoke can
infiltrate throughout a building along
various pathways (Refs. 149 to 153).
Exposures to secondhand smoke in
multi-unit housing are potentially
concerning given a study drawing on
the 2013–2014 National Adult Tobacco
Survey (NATS) found that tobacco use
was higher among adults living in
multi-unit housing (24.7 percent) than
those in single-family housing (18.9
percent) (Ref. 154). This study also
found that smoke-free home rules (i.e.,
home smoking bans) were higher among
adults living in single-family housing
(86.7 percent) than those in multi-unit
housing (80.9 percent) (Ref. 154).
However, more than a third (34.4
percent) of multi-unit housing residents
with home smoking bans have
experienced secondhand smoke
incursions (Ref. 154). Recent estimates
indicate that approximately 80 million
residents in the United States are
currently living in some type of multiunit housing (Ref. 150). Among those
living in multi-unit housing with a
home smoking ban, an estimated 27.6–
28.9 million are exposed to secondhand
smoke incursions from neighboring
units and/or shared common areas (Ref.
150). Moreover, a 2013 nationally
representative study conducted among
U.S. adults living in multi-unit housing
found that 25.2 percent of non-smoking
residents who had no smoking in the
home for at least 3 months and who also

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had a child in the home had a recent
secondhand smoke incursion into their
unit; 99 percent of these residents also
reported being bothered by the
incursion (Ref. 155). Multi-unit housing
secondhand smoke incursions have also
been found to be greater among specific
populations that are already
disproportionately burdened by
tobacco-related disease and death,
including women, younger adults, and
non-Hispanic Black, Hispanic, and
lower income populations (Ref. 154).
Workplace secondhand smoke
exposure has also been shown to vary
across population groups. A study using
data from the 2009–2010 NATS show
the prevalence of secondhand smoke
exposure from employed nonsmoking
adults was higher among males, nonHispanic Black, Hispanic, and AI/AN
people compared with White people,
and people with low education and low
income (Ref. 156). Similarly, data from
the 2010 and 2015 NHIS show that
exposure to secondhand smoke in the
workplace was disproportionately high
among non-Hispanic Black respondents,
Hispanic respondents, and workers with
low education and low income (Ref.
157). Additionally, the study findings
indicated that ‘‘blue-collar workers’’
(defined as those who performed
manual labor such as manufacturing,
mining, sanitation, and construction)
experienced higher prevalence of
secondhand smoke exposure compared
to ‘‘white-collar workers’’ (defined as
those who primarily work in an office,
with computer and desk setting, and
perform professional, managerial, or
administrative work) (Ref. 157).
The disparities observed in tobacco
use, as well as disparities in
secondhand smoke exposure, contribute
to the disparities in tobacco-related
morbidity and mortality experienced by
some population groups. This proposed
product standard is anticipated to
reduce smoking-related morbidity and
mortality for the population as a whole,
including these populations that use
tobacco or are exposed to secondhand
smoke at disproportionately high levels.
Other combusted tobacco products,
particularly those that could serve as
alternatives to cigarettes if people who
smoke cigarettes no longer had access to
normal nicotine cigarettes (NNC), cause
similar negative health effects. For
example, cigar smoke contains many of
the same harmful constituents as
cigarette smoke, and cigar smoke may
have even higher levels of several
harmful compounds compared to
cigarette smoke (Refs. 1, 134 and 158).
For example, cigar smoke contains
higher amounts of carcinogenic,
tobacco-specific N-nitrosamines than

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cigarette smoke due to the relatively
high concentration of nitrate in cigar
tobacco, which leads to formation of
cancer-causing nitrosamines during the
fermentation process (Refs. 1; 53 at
Chapter 3; and 158). Researchers have
found urinary concentrations of 4(methylnitrosamino)-1-(3-pyridyl)-1butanol (NNAL) (a hazardous tobaccospecific nitrosamine) measured in
people who smoke cigars daily to be as
high as those measured in people who
smoke cigarettes daily (Refs. 159 and
160). Like exposure to cigarette smoke,
exposure to higher levels of cigar smoke
for longer time periods increases the
adverse health risks caused by cigar
smoking (Ref. 28).
Consequently, there is a long-standing
body of research, including reports from
the U.S. Surgeon General and National
Cancer Institute (NCI), demonstrating
that cigar use causes serious adverse
health effects (Ref. 53 at p.119–155;
Refs. 55; 161, and 162). NCI’s Smoking
and Tobacco Control Monograph No. 9
(‘‘Cigars: Health Effects and Trends’’),
which provides a comprehensive, peerreviewed analysis of the trends in cigar
smoking and potential public health
consequences, as well as other research,
demonstrates that cigar smoking leads to
an increased risk of oral, laryngeal,
esophageal, pharyngeal, and lung
cancers, as well as coronary heart
disease and aortic aneurysm, with the
magnitude of risk a function of the
amount smoked and depth of inhalation
(Ref. 53 at p.119–155). Likewise, a
systematic review of the mortality risks
associated with cigar smoking that
identified 22 studies found that people
who regularly smoke cigars are at
increased risk for many of the same
diseases as people who smoke
cigarettes, including oral, laryngeal,
esophageal, and lung cancer;
cardiovascular diseases; and COPD (Ref.
163).
Research indicates that most people
who smoke cigars do inhale some
amount of smoke, even when they do
not intend to inhale, and are not aware
of doing so (Refs. 54 and 55). Even when
people who smoke cigars do not breathe
smoke into their lungs, they are still
subject to the addictive effects of
nicotine through nicotine absorption
(Refs. 55 and 56). This nicotine
absorption occurs because cigar smoke
dissolves in saliva, allowing the person
smoking the cigar to absorb sufficient
nicotine by holding the smoke in their
mouths, even if the smoke is not inhaled
(Refs. 53, 56, and 164). Cigar and/or
pipe smoking causes cancers of the lung
and upper aerodigestive tract, including
the oral cavity, oropharynx,
hypopharynx, larynx and esophagus

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(Ref. 158). Additional evidence suggests
that cigar and/or pipe smoking is
causally associated with cancers of the
pancreas, stomach, and bladder (Ref.
165). People who smoke cigars also have
increased risks for coronary heart
disease and COPD compared with
people who never used tobacco (Ref.
166).
One study using NATS data from
2009 to 2010 found that regular cigar
smoking (defined as use on at least 15
of the past 30 days) was responsible for
approximately 9,000 premature deaths
and more than 140,000 years of
potential life lost among adults aged 35
years or older in 2010 (Ref. 134). A
study of healthcare expenditures from
2000 to 2015 found that cigarattributable healthcare expenditures for
adults totaled $1.75 billion per year,
with $284 million attributed to
exclusive cigar smoking and $1.5 billion
attributed to poly tobacco use (i.e., use
of multiple tobacco products) involving
cigar smoking plus cigarette or
smokeless tobacco use (Ref. 167). In
addition, overall mortality rates for all
people who smoked cigars (i.e., those
who report inhaling as well as those
who report not inhaling cigar smoke) are
higher than rates for those who have
never smoked, although they are
generally lower than the rates observed
for people who smoke cigarettes (Ref. 53
at p. 112). In an analysis of National
Longitudinal Mortality Study (NLMS)
data, researchers also found that the risk
of dying from tobacco-related cancers is
higher for people who currently
exclusively use pipe tobacco and those
who currently exclusively smoke cigars
than for those who reported never using
combusted tobacco products (Ref. 168).
Another similar analysis using the
restricted-use National Health Interview
Survey-Linked Mortality Files (NHIS–
LMF), following participants for
mortality from 2000 through 2015,
observed that people who currently
smoked cigars daily had elevated risk of
all-cause mortality compared to those
who had never used tobacco (Ref. 169).
In addition, researchers studying people
who smoke cigars in 2009 and 2010
found that the average person who
smokes cigars or pipes loses
approximately 15 life years (Ref. 134).
Disparities in cigar-related health
outcomes have also been observed by
gender and race/ethnicity. Likely due to
the greater prevalence of cigar use
among men versus women, one analysis
observed a significantly greater number
of years of potential life lost for men
than women (117,440 for men; 22,284
for women) associated with cigar use, as
well as disparate monetary losses
associated with cigar use ($19.5 billion

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for men; $3.4 billion for women) based
on the value of a statistical life year (Ref.
134). Studies have shown that levels of
nicotine and other carcinogens in cigars
can be higher than those in cigarettes
and may be at levels that lead to
increased risk of morbidity and
mortality from conditions such as
cancer, cardiovascular disease, and
COPD (Refs. 134, 163, and 164). The
prevalence of cigar smoking among AI/
AN populations is lower than
prevalence among Black populations,
but higher than among Hispanic and
Asian populations (Refs. 120 and 121),
contributing to the disproportionate
prevalence of lung cancer and
cardiovascular diseases in these
populations (Refs. 170 and 171).

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E. Tobacco Product Marketing Has
Contributed to Disparities in Use and
Health Outcomes
Tobacco companies have long
understood the complexities of nicotine
addiction (Ref. 172) and have
capitalized on the psychological and
sociological aspects of tobacco use to
market their products
disproportionately to specific
populations, such as youth and young
adults, some racial and ethnic
populations, individuals who identify
as lesbian, gay, bisexual, transgender,
queer, and intersex (LGBTQI+),17 those
with lower household income and
educational attainment, and individuals
with behavioral health conditions (Refs.
173 and 174). For example, retail
advertising for tobacco products is more
common in neighborhoods with greater
proportions of Black residents and in
lower income neighborhoods (Refs. 175
to 179). Storefront and outdoor tobacco
marketing, as well as point-of-sale
marketing, are all disproportionately
present in Black, Hispanic/Latino, AI/
AN, and low-income communities (Refs.
175, 179, 180 to 187). Higher exposure
to tobacco advertisements and retailing
is associated with tobacco use
susceptibility and tobacco use among
youth, with observed disparities
impacting youth who are Black,
Hispanic, or lower socioeconomic status
(Refs. 188 to 192). For example, a
systematic review of 35 studies found
that a higher density of tobacco retailers
near the home is associated with
17 Throughout this document, FDA uses the term
‘‘LGBTQI+’’ broadly when referring to lesbian, gay,
bisexual, transgender, queer, and intersex
communities. When we describe findings from the
published literature, we refer specifically to the
groups that are studied. For example, some authors
examine tobacco-related outcomes for members
who identify as lesbian, gay, bisexual, or
transgender only; as such, the data are limited to
those who identify as LGBT, and authors interpret
the findings for those specific groups.

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increased combustible tobacco product
use among youth (Ref. 193).
Industry marketing tactics have also
included the incorporation of culturespecific imagery, traditional practices,
and events that target specific racial and
ethnic groups. For instance, tobacco
companies have sponsored cultural
events such as Cinco de Mayo
celebrations, Chinese New Year
celebrations, and activities related to
Black History Month (Refs. 173 and 194)
and have used the cultural significance
of traditional tobacco to validate the
authenticity of commercially available
cigarettes, exploiting the traditions of
Native people to encourage cigarette use
(Ref. 195). Tobacco industry documents
show that tobacco companies have
strategically marketed their products to
women with lower income, particularly
Black and Hispanic women, (Ref. 196),
people experiencing homelessness and
people with mental illness (Refs. 197
and 198), and the LGBTQI+ community
(Refs. 199 to 201). Research also
demonstrates that since at least the
1960s, the tobacco industry has made
strategic donations to organizations
representing and affiliated with these
communities (Refs. 120, 202 to 205).
Internal industry documents reveal that
at least one tobacco company
considered such donations to be a ‘‘quid
pro quo,’’ because they could result in
the normalization of tobacco use,
development of brand loyalty, and
opposition to health-protective tobacco
control policies (Ref. 206).
The industry’s practices have resulted
in long-term consequences for
communities. Tobacco marketing
influences social norms around tobacco
use, making it more socially acceptable
and increasing the likelihood of use
(Refs. 207 to 209). In communities
where the tobacco industry has
disproportionately marketed to
historically marginalized populations
over decades, these social norms are
transferred through peers and family
generations, perpetuating the use of
harmful combusted tobacco products,
and contributing to present-day tobaccorelated health disparities in these
populations (Refs. 207, 210, and 211).
Moreover, recent scientific evidence
indicates that tobacco companies
continue to target populations that
experience tobacco-related health
disparities with tobacco marketing
(Refs. 178, 180, 191, 207, 212 to 226).
Although targeted marketing is only
one factor in the development and
perpetuation of combusted tobacco
product use and related harms, it
contributes to disparities that affect
public health and are of great concern
to FDA. Advancing health equity is a

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policy priority and an important
component of fulfilling FDA’s mission
to protect and promote public health.
FDA and the Federal Government
recognize the advancement of health
equity as ‘‘both a moral imperative and
pragmatic policy,’’ as Executive Order
13995 states. Considerations related to
health equity helped inform FDA’s
decision to prioritize this proposed
product standard.
F. Consumer Knowledge, Attitudes,
Beliefs, and Perceptions About Nicotine
The science on consumer knowledge,
attitudes, beliefs, and perceptions about
nicotine demonstrates that a majority of
consumers correctly understand that
nicotine is the substance in cigarettes
that causes addiction. Nationally
representative studies that examined
nicotine addiction beliefs in the general
population reported that the belief that
nicotine is addictive was endorsed by
approximately 85.8 percent of the
population, and the belief that nicotine
is responsible for driving continued
cigarette use was endorsed by
approximately 82.9 percent of the
population (Refs. 227 to 233). A
nationally representative survey found
that 88 percent of people who currently
smoke cigarettes and 91 percent of
people who use e-cigarettes agreed that
nicotine makes people want to smoke
(Ref. 227). A nationally representative
study of youth suggests that about 77.1
percent of respondents believe that
nicotine definitely or probably causes
addiction (Ref. 234).
However, in contrast to high rates of
correct beliefs about the addictiveness
of nicotine, there are high rates of
incorrect beliefs about the harms of
nicotine. Studies that examined nicotine
harm beliefs in the general population
reported that the belief that nicotine
causes cancer was endorsed by 40 to 78
percent of adult participants (Refs. 227,
228, 232, 233, 235 to 245). Additionally,
a nationally representative study of
youth suggests that about 74.7 percent
believe that nicotine definitely or
probably causes cancer (Ref. 234).
Multiple nationally representative
studies that examined nicotine harm
perceptions by tobacco use status found
that 52 to 61 percent of people who
currently use cigarettes and up to 84
percent of people who do not use
cigarettes endorsed the belief that
nicotine itself causes cancer or that
nicotine is the major contributing
constituent in cigarettes that causes
cancer (Refs. 228, 241, and 245). A more
recent qualitative study of people who
currently use little cigars and cigarillos
suggests that the misperception that
nicotine has significant adverse health

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effects is also common among people
who use these products (Refs. 228, 241,
245, and 246). Although nicotine creates
and sustains addiction and therefore is
the driver of the death and disease
associated with smoking, it is the
repeated exposure to toxicants from
tobacco products that directly causes
most of the serious health effects among
those who use tobacco products,
including fatal lung diseases, such as
COPD, and cancer (Ref. 28).
Consumer misperceptions regarding
the harms associated with nicotine may
lead to inaccurate judgments about the
risks of using products that contain
nicotine, including NRT. For example,
individuals who hold a misperception
about nicotine may be less likely to use
NRT as a smoking cessation aid.
Furthermore, there is evidence that
misperceptions of nicotine harm vary by
gender, ethnicity, and age, and may
contribute to unequal health outcomes
(Ref. 233). FDA recognizes the
importance of addressing nicotine
misperceptions in the context of a
proposed product standard that limits
the level of nicotine in cigarettes and
certain other combusted tobacco
products in order to make those
products minimally addictive or
nonaddictive. FDA will continue to
conduct research and develop
communication tools (e.g., consumer
outreach, public education initiatives,
engagement with interested parties) to
ensure that consumers are informed of
the risks of using tobacco products that
contain nicotine, including the products
covered under this proposed product
standard.

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V. History and Perceptions of VLNC
Cigarettes
A. History of LNC and VLNC Cigarettes
Tobacco companies had the technical
expertise to manipulate the nicotine
content in tobacco as early as the 1920s
and then began to market products that
may have met very low nicotine content
(VLNC) 18 cigarette levels throughout
the late 1970s and early 1980s (Ref.
247). As discussed above, the term
‘‘VLNC cigarettes’’ generally refers to
combusted cigarettes that have been
reported to contain ≤1.0 mg nicotine per
gram of total tobacco. For a detailed
discussion of the scientific evidence
that supports the technical achievability
of this proposed product standard, see
section VII.E of this document. In this
18 As previously noted in footnote 7, the term
VLNC should not be confused with the cigarette
brand name ‘‘VLN;’’ ‘‘VLN’’ refers to cigarette
products authorized for marketing by FDA in 2019.
See https://www.fda.gov/media/133633/download?
attachment and https://www.fda.gov/media/
133635/download?attachment.

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section, we describe some of the
industry’s early and continuing efforts
to develop VLNC cigarettes.
Some of the earliest VLNC cigarettes
studied by academic researchers were
produced by Philip Morris and
marketed under the brand name ‘‘Next,’’
which was reported to contain 0.4 mg
nicotine per gram of total tobacco (Ref.
248). Later, the National Institute on
Drug Abuse (NIDA) contracted with the
Ultratech/Lifetech Corporation 19 to
produce VLNC cigarettes for research
purposes only (Refs. 249 and 250). The
two types of cigarettes produced were:
(1) 8.0–10.3 mg nicotine per gram of
total tobacco and (2) 0.6–0.7 mg nicotine
per gram of total tobacco (Ref. 250).
Commercially available Quest
cigarettes were produced and marketed
by Vector Tobacco in the early 2000s
and utilized genetically engineered
tobacco to create cigarettes with three
distinct nicotine content levels (i.e.,
Quest 1 (12.7 mg/g), Quest 2 (7.3 mg/g),
Quest 3 (0.9 mg/g)) (table 1). These
cigarettes were used in much of the
VLNC research conducted prior to the
development of SPECTRUM Nicotine
Research Cigarettes; they are no longer
on the market. Philip Morris also
manufactured cigarettes with varying
nicotine levels for research only (Ref.
251). In a public statement issued on
July, 2018, 22nd Century Group, Inc.
stated that they were already using
genetic engineering and plant breeding
to produce VLNC tobacco for cigarettes
(Ref. 252). In 2014, the company was
granted patents for its process to
dramatically reduce the nicotine in
tobacco plants (Ref. 253). This tobacco
has been used to generate low nicotine
content research cigarettes, produced
and distributed by RTI International,
under a contract with the NIDA Drug
Supply Program (Ref. 254). 22nd
Century Group, Inc. acts as a vendor for
RTI for this contract, manufacturing
SPECTRUM Nicotine Research
Cigarettes that were reported to contain
0.4 mg nicotine per gram of tobacco
(Ref. 254), and they also manufacture
cigarettes with other reduced levels of
nicotine. These SPECTRUM Nicotine
Research Cigarettes are similar in many
sensory characteristics to NNC
cigarettes, but with VLNC (Refs. 255 and
256).
In 2019, 22nd Century Group, Inc.
received FDA marketing authorization
and, in 2021, received exposure
modification orders for their VLNC
cigarettes under the names VLN King
and VLN Menthol King. VLN cigarettes
19 Both Ultratech and Lifetech have been reported
as being the company through which NIDA
manufactured research cigarettes.

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are currently being marketed and sold to
consumers in select U.S. markets as
cigarettes with 95 percent less nicotine
than conventional cigarettes. From
January 1, 2023, to November 22, 2024,
22nd Century VLN cigarette dollar sales
accounted for less than 0.001 percent of
total cigarette dollar sales in any 4week
period. Menthol flavored 22nd Century
VLN cigarettes over the same time
accounted for less than 0.001percent of
any 4-week menthol flavored cigarette
dollar sales.20
Currently, these are the only
authorized VLNC cigarettes. As we
discuss in other parts of this document
(see section VII.E), we believe the
scientific evidence supports the
technical achievability of the proposed
standard; additionally, the tobacco
industry and consumer product
companies have developed a range of
brands with differing nicotine levels.
Thus, it appears there would be
opportunities for any manufacturer who
chooses to enter the market for products
covered by this proposed product
standard.
Although many of the studies
discussed in this section investigated
the effects of VLNC cigarettes, some
studies also investigated the effects of
cigarettes with higher levels of nicotine,
often as comparators. Table 1 displays
the reduced nicotine content cigarettes
that were administered in studies
summarized in this document and their
reported nicotine levels. The nicotine
content values in table 1 are
approximate, and they are primarily
based on published reports from the
peer-reviewed scientific literature. Most
studies that investigated the clinical
effects of reduced nicotine content
cigarettes did not chemically analyze
the study cigarettes. For example, many
studies that examined the effects of
VLNC SPECTRUM Nicotine Research
Cigarettes did not chemically
characterize these cigarettes, but the
authors of these studies reported that
the nicotine content of the cigarettes
was 0.4 mg nicotine per gram of
20 FDA’s own analyses, calculations and
conclusions informed in part by the NielsenIQ
Retail Measurement Service (RMS) data through
NielsenIQ’s RMS for the tobacco product category
‘‘Cigarettes’’ for the time period January 1, 2023
through November 2, 2024 for Total US Expanded
All Outlets Combined (xAOC) and convenience
stores are those of FDA and do not reflect the views
of NielsenIQ. NielsenIQ is not responsible for, had
no role in, and was not involved in analyzing and
preparing the results reported herein, or in
developing, reviewing, or confirming the research
approaches used in connection with this report.
NielsenIQ RMS data consist of weekly purchase and
pricing data generated from participating retail store
point-of-sale systems in all U.S. markets. See
https://NielsenIQ.com/global/en/ for more
information.

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tobacco. The actual nicotine content of
these cigarettes is expected to vary
around this value. For example, the
results of one study that chemically
characterized SPECTRUM Nicotine
Research Cigarettes showed that the
nicotine content of the sampled VLNC
cigarettes ranged between 0.28 and 0.33
mg nicotine per gram (Ref. 256), which

is lower than the 0.4 mg nicotine per
gram level typically reported in the
literature. In 22nd Century Group, Inc.’s
modified risk tobacco product
applications, the company reported that
after 9 years of sampling by the
company, the average nicotine content
of its genetically engineered VLNC
tobacco is 0.6 mg nicotine per gram of

total tobacco, with a range of 0.4 to 0.7
mg nicotine per gram of total tobacco. It
is likely that the Quest and SPECTRUM
Nicotine Research Cigarettes, used
throughout the scientific literature, also
contained between 0.4 to 0.7 mg
nicotine per gram of total tobacco (Ref.
257).

TABLE 1—NICOTINE CONTENT FOR NORMAL, LOW, AND VERY LOW NICOTINE CONTENT CIGARETTES USED IN THE
RESEARCH STUDIES CITED IN THIS DOCUMENT
Brand

Manufacturer

Nicotine
content
category

Magic 1 .............................................................................................
Next 2 ...............................................................................................
Philip Morris 1 mg 3 .........................................................................
Philip Morris 2 mg 3 .........................................................................
Philip Morris 4 mg 3 .........................................................................
Philip Morris 8 mg 3 .........................................................................
Philip Morris 12 mg 3 .......................................................................
Quest 1 ............................................................................................
Quest 2 ............................................................................................
Quest 3 ............................................................................................
SPECTRUM 0.4 mg (NRC102–NRC105) 4 .....................................
SPECTRUM 1.3 mg (NRC200, NRC201) 5 ....................................
SPECTRUM 2.4 mg (NRC300, NRC301) 5 ....................................
SPECTRUM 5.2 mg (NRC400, NRC401) 5 ....................................
SPECTRUM 15.8 mg (NRC600, NRC601) 5 ..................................
Ultratech/Lifetech denicotinized 6 ....................................................
Ultratech/Lifetech nicotine 6 .............................................................
Xodus 7 ............................................................................................

22nd Century Group, Inc ............................
Philip Morris International ...........................
Philip Morris Tobacco Company ................
Philip Morris Tobacco Company ................
Philip Morris Tobacco Company ................
Philip Morris Tobacco Company ................
Philip Morris Tobacco Company ................
Vector Group Ltd ........................................
Vector Group Ltd ........................................
Vector Group Ltd ........................................
22nd Century Group, Inc ............................
22nd Century Group, Inc ............................
22nd Century Group, Inc ............................
22nd Century Group, Inc ............................
22nd Century Group, Inc ............................
Ultratech Inc./Lifetech Corp ........................
Ultratech Inc./Lifetech Corp ........................
22nd Century Ltd., LLC ..............................

VLNC ......
VLNC ......
VLNC ......
LNC .........
LNC .........
LNC .........
NNC ........
NNC ........
LNC .........
VLNC ......
VLNC ......
LNC .........
LNC .........
LNC .........
NNC ........
VLNC ......
LNC .........
LNC .........

Nicotine content
(mg/g)
* 1.0
* 0.4
* 0.7–0.9
* 2.1–2.4
* 5.0–5.6
* 9.3–10.6
* 14.4–14.7
* 12.7
* 7.3
* 0.9
0.4–0.7
0.9–1.3
1.9–2.4
4.6–5.2
15.5–17.3
* 0.6–0.7
* 8.0–10.3
* 1.2–1.7

Abbreviations: VLNC: ≤1.0 mg nicotine per gram of total tobacco; LNC: >1.0 mg and <11.4 mg nicotine per gram of total tobacco; NNC: ≥11.4
mg nicotine per gram of total tobacco.
1 Nicotine content from (Ref. 31).
2 Nicotine content from (Ref. 248).
3 Nicotine content from (Refs. 258 and 259).
4 Nicotine content from (Ref. 257).
5 Nicotine content from (Ref. 29) (supplement).
6 Nicotine content estimated by FDA based on nicotine yield data from (Ref. 250).
7 Nicotine content from (Ref. 41).
* For these cigarettes, FDA calculated milligrams of nicotine per gram of total tobacco based on reports of milligrams of nicotine per cigarette.
Calculations were based on an estimate of 0.7 grams of tobacco per cigarette.

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B. Consumer Knowledge, Attitudes,
Beliefs, and Perceptions Regarding
VLNC Cigarettes and FDA Regulation of
Levels of Nicotine in Tobacco
In this section we describe the science
related to consumer knowledge,
attitudes, and beliefs about reduced
nicotine content (RNC) 21 cigarettes and
consumers’ perceptions about a
hypothetical policy reducing nicotine
levels in cigarettes and certain
combustible tobacco products. These
concepts are important because they are
21 RNC cigarettes in this context refers to any
cigarette with a lower amount of nicotine than NNC
cigarettes. FDA notes that studies focusing on
consumer perceptions of RNC cigarettes typically
do not differentiate between RNC, LNC, and VLNC
cigarettes. However, when describing studies that
focus on consumer behavior and perceptions of
VLNC cigarettes specifically, FDA uses the term
VLNC cigarettes. FDA notes that studies in this
domain typically use consumer perceptions of RNC
cigarettes to form conclusions about consumer
perceptions about VLNC cigarettes and FDA’s
proposed reduction of nicotine more broadly.

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associated with the behavioral
responses consumers believe they
would take if such a policy is in effect.
The science on consumer knowledge,
attitudes, beliefs, and perceptions about
RNC cigarettes demonstrates that a
majority of consumers perceive that
RNC cigarettes are equally or more
harmful than NNC cigarettes. Nationally
representative studies suggest that 50 to
71 percent of consumers perceive RNC
cigarettes to be as or more harmful to
health than NNC cigarettes, while 25 to
35 percent perceive them to be less
harmful than NNC cigarettes (Refs. 260
to 262). Recent nationally representative
findings estimate that between 12 and
25 percent of people who smoke or use
e-cigarettes believe RNC cigarettes are
less harmful than NNC cigarettes (Refs.
227 and 236). In studies where
participants actually use VLNC
cigarettes, they tend to perceive them as
significantly less harmful to health and

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less likely to cause cancer than NNC
cigarettes (Refs. 230, 263 to 265).
Furthermore, there is evidence that
perceptions about the harms of VLNC
cigarettes relative to NNC cigarettes vary
by race and age (Refs. 236, 266 to 268).
The science on consumer knowledge,
attitudes, beliefs, and perceptions about
RNC cigarettes also demonstrates that
there are widespread misperceptions
about the addictiveness of RNC
cigarettes relative to NNC cigarettes.
Studies that use nationally
representative surveys report that 60 to
77 percent of consumers incorrectly
believe that RNC cigarettes are equally
or more addictive than NNC cigarettes
(Refs. 260 and 261). Tobacco use status
does not appear to significantly change
misperceptions about the addictiveness
of RNC cigarettes (Ref. 228).
A 2019 nationally representative
study of consumer support for a policy
‘‘requiring cigarette makers to lower the

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VI. Rationale for Products Covered by
the Proposed Product Standard
FDA has reviewed and closely
considered the comments to the
Nicotine ANPRM, as well as additional
evidence and information not available
at the time of the ANPRM, in
developing the scope of products for
this proposed product standard.
Specifically, we considered several
factors, such as the strength and breadth
of the available data on the likely effects
of reducing nicotine derived from
studies of VLNC cigarettes; current
prevalence and initiation rates for
different classes of tobacco products; the
available data on product toxicity,
addictiveness, and appeal; product use
topography 22 (including quantity,

intensity, and duration of use); and the
potential for migration to different
products. These data indicate that
reduction of nicotine in cigarettes
would reduce addiction potential,
dependence levels, number of cigarettes
smoked per day, and increase quit
attempts among people who currently
smoke cigarettes. In light of these data,
FDA also expects that reduction of
nicotine would prevent people who
experiment with cigarettes and cigars
from developing an addiction to tobacco
and progressing to regular tobacco use.
This proposed product standard is
intended to address one of our nation’s
greatest public health challenges: the
death and disease caused by combusted
tobacco use. Approximately 480,000
people die every year from smoking
cigarettes (Ref. 1 at p. 659) and another
9,000 die from smoking cigars (Ref. 1 at
p. 659; Ref. 134). Cigarettes are the
tobacco product category that causes the
greatest amount of harm to the public
health as a result of the prevalence of
cigarette use among adults and cigarette
toxicity and addictiveness. This
proposed product standard is expected
to increase cessation and switching to
potentially less harmful tobacco
products and prevent people who are
experimenting with use—mainly youth
and young adults—from transitioning to
regular use of cigarettes. However, if the
product standard were only to cover
cigarettes, it would likely be less
effective. Specifically, a significant
number of people who are addicted to
smoking cigarettes would likely migrate
to similar combusted tobacco products
after the standard went into effect to
maintain their nicotine exposure,
thereby undermining the significant
health benefits of the proposed product
standard (Ref. 5) (see also section VI.B
of this document for further discussion
of the potential for non-cigarette
combusted tobacco product switching).
Therefore, to increase public health
benefits, FDA also is proposing to cover
certain other combusted tobacco
products in addition to cigarettes.
Based on these considerations, FDA is
proposing to cover the following
products under this product standard:
• Cigarettes (other than
noncombusted cigarettes, such as HTPs
that meet the definition of a cigarette),
• Cigarette tobacco,
• RYO tobacco,
• Cigars (including little cigars,
cigarillos, and large cigars but excluding
premium cigars), and

22 Smoking topography measures provide data on
various aspects of smoking behavior, including
number of puffs per cigarette, total time spent

smoking, puff volume (i.e., puff size), puff velocity
(i.e., puff intensity), puff duration, and inter-puff
interval (i.e., length of time between puffs).

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nicotine levels in cigarettes so that they
are less addictive’’ reported that 81
percent of study participants favored the
policy (52.4 percent strongly favored,
28.6 somewhat favored) and 19 percent
opposed the policy (10.3 percent
somewhat opposed, 8.7 percent strongly
opposed) (Ref. 269). However, consumer
misperceptions about the harm and
addictiveness of reduced nicotine
content combustible tobacco products
impact understanding of the purpose of
a reduced nicotine product standard.
For example, respondents in some
studies did not understand why FDA
would choose to remove nicotine from
cigarettes or little cigars and cigarillos
but not remove other chemicals that are
harmful (Ref. 229, 270, and 271).
Respondents also stated that they
believed other chemicals besides
nicotine make cigarettes addictive, and
that removing nicotine from cigarettes
would not eliminate their addictiveness
(Refs. 229 and 270). Misperceptions may
also serve as potential determinants of
consumer responses to a reduced
nicotine product standard. For example,
one study suggests that misperceptions
among people who smoke regarding the
harm of RNC cigarettes is correlated
with quit intentions in responses to a
hypothetical government policy
reducing most of the nicotine in
cigarettes (Ref. 267). FDA recognizes the
importance of addressing consumers’
misperceptions about the relative harm
and addictiveness of VLNC cigarettes as
compared to other products. FDA will
continue to conduct research (e.g.,
assess changes over time in knowledge,
attitudes, and perceptions relative to
tobacco product characteristics
including nicotine content) to inform
regulatory decisions and other actions.

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• Pipe tobacco (other than waterpipe
tobacco).
FDA has determined that research
regarding the public health impacts of
potential maximum nicotine level
policies applies across the tobacco
products covered under this proposed
product standard. As discussed in
greater detail in section VII.B.12 of this
document, given that cigarette tobacco,
RYO tobacco, and pipe tobacco can be
effectively used in cigarettes, the VLNC
cigarette research discussed in this
proposed rule applies to these products,
and any expected benefits that would
accrue as a result of instituting the
proposed product standard for cigarettes
would also be expected to accrue for
these product categories. FDA also
concludes that the VLNC cigarette
research applies to cigars, given the
similarities between cigarettes and most
cigars (e.g., use topography). For further
discussion of FDA’s findings that VLNC
cigarette research applies to other
covered products under this proposed
product standard, see section VII.B.12 of
this document. In addition, as discussed
in section VI.A.3 of this document, FDA
finds that the non-cigarette combusted
products within the proposed scope of
this rule (i.e., RYO tobacco, cigars, pipe
tobacco) could function as acceptable
substitutes for many people who smoke
cigarettes while exposing them to
similar risks and toxicity as cigarettes.
As discussed in section VIII of this
document, FDA finds that the proposed
product standard, with this scope, is
appropriate for the protection of the
public health and would provide
substantial benefits for people who
currently use cigarettes and certain
other combusted tobacco products and
for people who experiment with
cigarettes and cigars and people who do
not use such tobacco products. FDA
seeks comments on this proposed scope,
particularly on how it may affect youth
initiation and use of combusted tobacco
products.
A. Prevalence and Abuse Potential of
Cigarettes and Other Combusted
Tobacco Products
Cigarettes, the most frequently used
tobacco products, are the tobacco
product category that causes the greatest
burden of harm to public health given
that approximately 28 million adults
and 380,000 youth currently smoke
cigarettes (Ref. 3); the toxicity and
addictiveness of these products; and the
resulting tobacco-related disease and
death across the population, including
among people who do not smoke.
Cigarettes are highly addictive and
harmful tobacco products; however, the
other combusted tobacco products

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covered in this proposed product
standard are similarly addictive and
harmful. If the proposed product
standard covered only cigarettes, some
number of people who smoke cigarettes
and are addicted to nicotine would
likely migrate to similar combusted
tobacco products to maintain their
nicotine exposure (or engage in dual use
with other similar combusted tobacco
products), thus reducing the positive
public health impact of this proposed
product standard.
Regulating the nicotine yield of
cigarettes and certain other combusted
tobacco products through setting a
maximum nicotine level for them would
make these dangerous combusted
products minimally addictive or
nonaddictive, making cessation easier
and helping to prevent people who are
experimenting with smoking from
developing nicotine dependence and
progressing to regular use. As stated
elsewhere in this document, FDA’s
approach in proposing this product
standard for cigarettes and certain other
combusted tobacco products protects
public health by reducing combusted
tobacco product use (and therefore
reducing exposure to harmful toxicants
created through combustion) by making
it considerably easier for people who
want to quit cigarette use to quit all
tobacco products or switch to
potentially less harmful, noncombusted
tobacco products which remain
available. Therefore, to increase the
public health benefits, FDA is focusing
this proposed rule on nicotine levels in
cigarettes and certain other combusted
tobacco products because combusted
products are responsible for the majority
of death and disease due to tobacco use.
1. Cigarettes
Data from the 2024 NYTS indicate
that 1.7 percent of high school students
(approximately 250,000) and 1.1 percent
of middle school students
(approximately 120,000) reported
current use of cigarettes (i.e., smoked at
least once during the past 30 days) (Ref.
3). In addition, 11.6 percent of adults
reported that they currently smoked
cigarettes in 2022 (i.e., smoked at least
100 cigarettes during their lifetime and
now smoke cigarettes every day or some
days); this means an estimated 28.8
million adults in the United States
currently smoke cigarettes (Ref. 4).
Although cigarette smoking is present in
all population groups in the United
States, the prevalence of cigarette use
differs based on sociodemographic
characteristics.
Findings from the 2024 NYTS show
that, among middle and high school
students, 1.4 percent of non-Hispanic

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White students, 0.9 percent of nonHispanic Black students, and 1.6
percent of Hispanic students currently
smoked cigarettes (Ref. 3). Additionally,
data from the 2022 NHIS show
differences in smoking prevalence on
the basis of race/ethnicity among adults
(age 18 and over). Specifically, 4.6
percent of non-Hispanic Asian, 8.0
percent of Hispanic, 12.7 percent of
non-Hispanic White, 14.2 percent of
non-Hispanic Black, 19.3 percent of
non-Hispanic AI/AN, and 11.9 percent
of non-Hispanic Other participants
reported current cigarette smoking (Ref.
272). Data from the 2005 and 2015 NHIS
also indicate that the prevalence of
cigarette smoking has statistically
significantly declined over this time
period for non-Hispanic white, Black,
Asian, and AI/AN adults and Hispanic
adults (Ref. 273).
Data from an analysis of the 2005 and
2015 NHIS indicate that the prevalence
of smoking has declined significantly
over that time period among both adult
male and female participants (29.9 and
25.2 percent relative decrease,
respectively) (Ref. 273). Currently,
according to data from the 2022 NHIS,
smoking remains more prevalent among
males (13.2 percent) as compared to
females (10.0 percent) in the United
States (Ref. 272).
Study findings indicate that
individuals who identify as lesbian, gay,
or bisexual are more likely to report
smoking cigarettes as compared to those
who identify as heterosexual (Refs. 274
to 277). Among adults in the 2022 NHIS,
cigarette smoking among persons
identifying as lesbian, gay, and bisexual
was 12.8 percent and among those
identifying as heterosexual/straight it
was 11.6 percent (Ref. 272), and
smoking was more prevalent among
youth identifying as lesbian, gay, and
bisexual (7.0 percent) in the 2020 NYTS
than among those ‘‘not sure’’ of their
sexual identity (3.5 percent) or youth
identifying as heterosexual (2.7 percent)
(Ref. 275). Current tobacco use for
lesbian, gay, bisexual, and transgender
youth in the 2022 NYTS was reported
for ‘‘any’’ tobacco use (i.e., current use
of one or more of the following: ecigarettes, cigarettes, cigars, smokeless
tobacco, hookah, HTPs, nicotine
pouches, pipe tobacco, or bidis), but not
for individual tobacco products (Ref.
278). Pooled data from the 2015 to 2019
NSDUH indicate that compared to
heterosexual/straight respondents,
respondents who identified as gay
males, lesbian/gay females, or bisexual
females reported higher prevalence of
past 30-day smoking (Ref. 279).
Additionally, in data from the 2015/
2016 NSDUH, relative to same-age

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heterosexual men, lifetime rates of daily
cigarette smoking were significantly
elevated among gay men ages 18–25 (30
percent versus 23 percent) and ages 35–
49 years (44 percent versus 38 percent)
(Ref. 277). Similarly, relative to sameage heterosexual women, lifetime daily
cigarette smoking was significantly
greater among lesbian/gay women ages
18–25 (37.7 percent versus 16.3
percent), ages 26–34 (42.2 percent
versus 30.3 percent), and ages 35–49
(42.7 percent versus 32.6 percent) (Ref.
277).
As evidenced in a systematic review
and meta-analysis (Ref. 280), studies
have consistently shown a relationship
between socioeconomic status and the
prevalence of cigarette smoking, such
that greater levels of educational
attainment and greater total family
income are inversely associated with the
prevalence of smoking. Specifically, in
2021 NHIS data, the prevalence of
cigarette smoking was 18.3 percent for
adults with a low income, 12.3 percent
for those with a medium income, and
6.7 percent for those with a high income
(Ref. 274). Similarly, by and large, there
is an inverse relationship between
educational attainment and the
prevalence of smoking. For instance,
according to the 2021 NHIS, the
prevalence of smoking was 20.1 percent
among adults with some high school
education but no degree, 30.7 percent
among persons with a general
equivalency degree, 17.1 percent among
those with a high school diploma, 13.7
percent among persons with an
associate’s degree, 5.3 percent among
those with an undergraduate degree,
and 3.2 percent among persons who had
received a graduate degree (Ref. 274).
The prevalence of cigarette smoking is
also higher among adults with mental
health symptoms or substance use
disorder (Refs. 281 to 284). Findings
from the 2022 NHIS show that 27.2
percent of persons reporting severe
generalized anxiety disorder (GAD)
currently smoke cigarettes, as compared
with 10.1 percent who report no or
minimal GAD (Ref. 272). Similarly, 27.1
percent of adults who report severe
depression currently smoke cigarettes,
versus 10.1 percent among those who
report no or minimal depression (Ref.
281). Additionally, findings from the
2021 NHIS show that 28.1 percent of
persons reporting serious psychological
distress also reported smoking
cigarettes, compared to 10.9 percent of
persons not reporting serious
psychological distress (Ref. 274).
Analyses of data from the 2015 NSDUH
for individuals aged 12 years and over
also show that cigarette smoking is
significantly more prevalent among

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persons who use cannabis (daily
cannabis use: 54.6 percent; nondaily
cannabis use: 40.2 percent) as compared
to those who do not use cannabis (15.1
percent) (Ref. 282). An analysis of 2016
NSDUH data indicates that cigarette
smoking is more than twice as prevalent
among persons with alcohol use
disorder, as compared to those without
(37.8 percent versus 16.3 percent) (Ref.
283), while data from the 2014 NSDUH
show that the prevalence of cigarette
smoking is also more than twice as high
among persons with mental health and/
or substance use problems than among
persons without (38.5 percent versus
15.4 percent) (Ref. 284).
2. Cigars
Cigar smoke contains many of the
same constituents as cigarette smoke,
including nicotine, many of which can
cause significant harm to those who use
cigars (Ref. 53). According to the 2024
NYTS, 330,000 middle and high school
students,23 including 1.5 percent (an
estimated 230,000) of high school
students (grades 9–12) and 0.8 percent
(an estimated 80,000) of middle school
students (grades 6–8), had smoked a
cigar (cigar, cigarillo, or little cigar) on
at least 1 day during the past 30 days
(Ref. 3). Overall, the prevalence of cigar
smoking among middle and high school
students is comparable to the
prevalence of cigarette smoking, with
1.7 percent (an estimated 250,000) of
high school students and 1.1 percent (an
estimated 120,000) of middle school
students having smoked cigarettes on at
least 1 day during the past 30 days (Ref.
3). Cigars are also a popular tobacco
product among adults. In the 2022
NHIS, 3.7 percent of adults aged 18 or
older reported currently using cigars
some or every day, behind cigarettes
(11.6 percent) and e-cigarettes (6.0
percent) (Ref. 272).
Evidence from national surveys—
including the Monitoring the Future
study and NSDUH—indicate that,
similar to cigarettes, cigar use has been
on the decline among U.S. youth and
adults in recent years (Refs. 285 to 287).
However, among youth, this decrease
has not been equitably experienced. The
popularity of cigar use is
disproportionately high among groups
such as lesbian, gay, and bisexual youth
and young adults (3.2 percent among
transgender youth, 3.2 percent among
sexual minority females, and 3.9 percent
23 The weighted population estimate reported in
the scientific publication is 500,000 students. As
noted in the scientific publication, overall
population estimates might not sum to
corresponding population estimates because of
rounding or inclusion of students who did not selfreport sex, race and ethnicity, or grade level.

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among sexual minority males) (Ref.
288), and youth with disabilities (7.0
percent among those who reported
using little cigars and 2.6 percent among
those who reported using large cigars)
(Ref. 289). Cigar smoking also occurs
disproportionately among specific
populations of adults as well, with
greater prevalence of cigar smoking
reported among non-Hispanic Black
adults (5.1 percent) (Ref. 274),
individuals of lower educational
attainment and lower annual household
income (Refs. 290 and 291), and
LGBTQI+ adults (Refs. 292 to 296).
Additionally, when comparing data
from 2011 to 2019, while past month
cigarette smoking and cigar use were
both statistically significantly lower in
young adults (ages 18–25), the absolute
and relative declines in cigar use were
less than the declines in cigarette use
(33.5 percent in 2011 to 17.5 percent in
2019 for cigarettes; 10.9 percent in 2011
to 7.7 percent in 2019 for cigars) (Ref.
286). For adults (ages 26 or older),
cigarette use in 2011 was statistically
significantly higher compared to in
2019; however, cigar use remained
relatively stable and did not
significantly change (21.9 percent in
2011 to 18.2 percent in 2019 for
cigarettes; 4.2 percent in 2011 to 4.0
percent in 2019 for cigars) (Ref. 286).
The 2023 NSDUH found that among
adults ages 26 or older in 2019, 1,847
individuals initiated cigar use each day,
considerably more than the 282 who
initiated cigarette smoking each day in
that year (Ref. 86).
While these data indicate a high
burden of current cigar smoking, the
true prevalence of cigar use is likely
higher. Little cigars often closely
resemble cigarettes, given their shape,
size, filters, and packaging, and are
perceived by many as being healthier
than cigarettes (Refs. 297 and 298).
Several studies have shown that youth
tend to underreport cigar smoking if
brand name identifiers are not provided
(Refs. 299 to 301). For example, in one
study of Virginia high school students,
the reported prevalence of cigar use
nearly doubled after accounting for
students who reported smoking Black &
Mild (a brand name of cigarillos); in the
original survey results, more than half of
the students who used Black & Mild
cigarillos did not report using cigars,
cigarillos, or little cigars (Ref. 299).
Research indicates that most people
who smoke cigars unknowingly inhale
some amount of smoke, including
people who smoke cigars who report
that they do not inhale (Refs. 54 and 55).
Youth more commonly use cigarillos
and little filtered cigars that are
designed to be inhaled, which may

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increase their risk of poor health
outcomes as well as addiction (Refs. 53
and 163). Even if people who smoke
cigars do not breathe or inhale smoke
into their lungs, they are still subject to
nicotine’s addictive effects through
buccal (oral) absorption of nicotine or
nicotine absorption through the lips due
to cigar tobacco’s alkalinity, as well as
other harmful health effects (Refs. 55,
56, 302 and 303). Cigar smoke dissolves
in saliva and makes it possible for
people who smoke cigars to absorb
sufficient amounts of nicotine to create
dependence even if the user does not
inhale (Ref. 56).
Nicotine can exist in protonated and
freebase (unprotonated) forms. In the
freebase form, it is most addictive
because it is readily absorbed by the
buccal mucosa, respiratory tissues, skin,
and the gastrointestinal tract (Refs. 28
and 57). Freebase nicotine amounts are
generally higher in cigars than cigarettes
due to the higher pH of cigar smoke
(Ref. 53). Nicotine absorbed across the
buccal mucosa, the mouth’s membrane
lining, can provide sustained amounts
of freebase nicotine to the person using
the tobacco product (Ref. 53). Cigars can
deliver nicotine much like chewing
tobacco or oral snuff, with nicotine
extraction absorbed directly through the
buccal mucosa and lips (Ref. 53).
A 1998 NCI Monograph chapter (NCI
Monograph 9) on cigar pharmacology
and abuse potential concluded that the
nicotine delivery characteristics and
daily patterns of smoking among people
who smoke cigars indicate that cigars
produce dependence (Refs. 53 and 164).
Since the publication of NCI Monograph
9, several in-person laboratory studies,
where participants use products under
observation and have outcome measures
assessed, have provided additional
evidence to support that nicotine
exposure from cigar smoking is
sufficient to create or sustain nicotine
dependence among people who use
cigars. Through cigar smoke, nicotine
can be absorbed by inhalation (like
cigarettes) or through the buccal mucosa
(like smokeless tobacco). Multiple
studies found that people who smoke
cigars inhale (as evidenced by carbon
monoxide (CO) levels and smoking
topography) and that plasma nicotine
levels are similar to those of people who
smoke cigarettes (Refs. 304 to 308).
Furthermore, using the Questionnaire of
Smoking Urges, a commonly used
measure of tobacco craving, several
studies found that cigars reduce craving
and urge to smoke to a similar
magnitude as cigarettes (Refs. 306 to
308). Cigars have also been shown to
decrease acute nicotine withdrawal

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symptoms (e.g., craving, anxiousness)
(Ref. 304).
Several additional studies have used
epidemiological data to compare
nicotine dependence levels among
people who use multiple tobacco
products (i.e., poly tobacco use), people
who exclusively use cigarettes, and
people who exclusively use cigars (Refs.
309 to 311). The data show that a
significant proportion of people who
exclusively use cigars display
characteristics of tobacco dependence
such as craving (Ref. 309); however,
people who use multiple tobacco
products and people who exclusively
use cigarettes showed the highest levels
of dependence, followed by people who
exclusively use cigars (Refs. 309 to 311).
3. Loose Tobacco (Pipe and RYO
Tobacco)
Laboratory and survey studies have
provided evidence to conclude that
RYO and pipe tobacco smoking is
sufficient to create or sustain nicotine
dependence among people who use
RYO or pipe tobacco (Ref. 312). Studies
show that people who use RYO and
pipe tobacco inhale (as evidenced by
smoking topography) (Refs. 312 to 314)
and plasma nicotine levels are similar to
those of people who smoke factorymade cigarettes (Ref. 313). Furthermore,
RYO tobacco reduces craving and urge
to smoke at a similar magnitude and is
rated similarly with regard to subjective
appeal as factory-made cigarettes (Ref.
313). Evidence also suggests that RYO
tobacco is at least as harmful to health
as factory-made cigarettes (Refs. 315 to
318).
According to data from the 2024
NYTS, 0.5 percent of high school
students (or approximately 70,000
students) reported using pipe tobacco
within the previous 30 days and 0.5
percent of middle school students (or
approximately 50,000 students) reported
pipe tobacco use in the prior 30 days
(Ref. 3). Data from the 2021 NHIS
indicated that 0.9 percent of adults ages
18 and older (or approximately 2.3
million adults) currently used pipes
(Ref. 274). However, FDA notes that
pipe tobacco prevalence data are likely
an underestimate, as the NIHS survey
does not include the number of people
who use pipe tobacco to roll their own
cigarettes.24 There is also evidence that
young adults who smoke cigarettes are
24 People who smoke RYO and pipe tobacco are
susceptible to similar negative health consequences
as people who smoke traditional cigarettes. While
there is a paucity of research examining RYO and
pipe tobacco use, FDA is not aware of any data
indicating that RYO cigarettes or pipe tobacco are
associated with fewer adverse health consequences
than traditional cigarettes.

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engaging in RYO use for financial
reasons (Ref. 319). Studies of RYO
tobacco use among youth are limited,
but prevalence of RYO tobacco use
among U.S. middle and high school
students in the 2012 NYTS was 3.4
percent (Ref. 320).
The lack of data on RYO and pipe
tobacco use and the limitations in how
national surveys assess loose tobacco
use impact our ability to draw
conclusions regarding appeal of loose
tobacco among youth and adults at this
time. However, if such products were
not included within the scope of this
proposed product standard, some
number of people who smoke cigarettes
and/or cigars and are addicted to
nicotine would likely easily migrate to
such products to maintain their nicotine
exposure given that RYO and pipe
tobacco have the same addictive
properties and health consequences as
factory-made cigarettes (Refs. 168 and
321). For example, more people who
smoke cigarettes could use RYO or pipe
tobacco to make NNC cigarettes (or
engage in dual use with certain other
combusted tobacco products), reducing
the positive public health impact of this
proposed product standard (see section
VI.B.1 of this document) (Ref. 322).
Taken together, these data
demonstrate that if FDA did not include
certain other combusted tobacco
products within the scope of this
proposed product standard, many
people who smoke cigarettes likely
would migrate to, or increase use of,
such other tobacco products in an
attempt to replace or supplement the
reduction of nicotine in their VLNC
cigarettes.
B. Potential for Non-Cigarette
Combusted Tobacco Product Switching
Nicotine can be delivered through
products that represent a continuum of
risk, with combusted tobacco products
at the most harmful end of this
continuum. FDA’s approach in
proposing this product standard for
cigarettes and certain other combusted
tobacco products protects public health
by reducing combusted tobacco product
use (and therefore reducing exposure to
harmful toxicants created through
combustion) while potentially less
harmful, noncombusted tobacco
products remain available for people
who have not quit all tobacco products.
FDA expects that, if this proposed rule
is finalized and a nicotine product
standard for cigarettes and certain other
combusted tobacco products is in place,
many people who smoke cigarettes will
either quit smoking or switch to a
noncombusted tobacco product. Those
who switch completely to use of a

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noncombusted tobacco product may
sustain their nicotine dependence and
may significantly reduce their risk of
tobacco-related death and disease to the
extent that the products they switch to
result in less harm. That is, while
dependence on any tobacco product
remains a health concern, nicotine alone
is not directly responsible for tobaccorelated cancer, lung disease, and heart
disease (Ref. 323). Switching completely
to a noncombusted tobacco product
would reduce exposure to the chemical
constituents created through
combustion, which are the primary
contributors of combusted tobaccorelated harm (Refs. 28 and 324).
However, as discussed throughout
this document, if a nicotine tobacco
product standard were to apply to
cigarettes only, it likely would have
substantially less impact on improving
health outcomes for people who use
tobacco products. Specifically, FDA
expects that, to maintain their nicotine
exposure, some people who smoke
cigarettes and are addicted to nicotine
would likely migrate to other combusted
tobacco products (or begin to engage in
dual use with such other products) with
similar toxicological risks after such a
cigarette-only standard was in effect.
FDA also would expect that people who
use non-cigarette combusted tobacco
products would continue their existing
use patterns, thereby maintaining their
risk of tobacco-related death and
disease. To ensure maximum benefits
for this nicotine tobacco product
standard, FDA is proposing that it apply
to cigarettes and certain other
combusted tobacco products.
1. Tobacco Product Switching in
Behavioral Intention and Clinical
Studies
Studies involving people who
currently use cigarettes predict a range
of tobacco use behaviors in response to
a nicotine product standard. When
presented with a hypothetical nicotine
reduction policy, most people who use
cigarettes report that they would
continue to smoke VLNC cigarettes or
use other combusted tobacco products,
or that they would quit; only a small
portion report that they would consider
switching to a noncombusted tobacco
product (Refs. 262 and 264). One
experimental study using a nationally
representative sample examined the
intended behaviors of people who
currently smoke cigarettes if a nicotine
product standard were put in place;
overall, 30.5 percent of the participants
intended to quit using all tobacco
products, 5.8 percent intended to switch
to noncombusted tobacco products, and
61.0 percent indicated they would

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smoke VLNC cigarettes or other
combusted tobacco products (Ref. 262).
An in-depth qualitative study assigned
a small number of people who use
cigarettes to use VLNC cigarettes for 5
days, then examined their intended
behaviors in response to a nicotine
product standard (Ref. 264). Most
participants reported that if a product
standard was put in place, they would
use VLNC cigarettes if they were the
only cigarettes available, and a few said
that they would use VLNC cigarettes to
reduce their smoking over time to
eventually quit. Some participants
discussed the possibility of switching to
ENDS or other combusted products if a
product standard was put in place. Selfreported intentions to use tobacco
products are a useful predictor of
individuals’ future tobacco use behavior
(Refs. 325 and 326) and these two
studies support FDA assessments of the
likelihood of switching in response to
the nicotine product standard.
In clinical studies that investigated
the effects of VLNC cigarettes,
researchers typically instructed
participants assigned to VLNC cigarette
groups to use only study-provided
cigarettes (i.e., to refrain from using
usual brand cigarettes or other tobacco
products during experimental
conditions). Noncompliance with these
instructions during a clinical trial may
also indicate the likelihood that people
who smoke VLNC cigarettes would use
alternative nicotine-containing products
if a nicotine product standard is
implemented. Several studies reviewed
in this document assessed biochemical
or self-reported measures of VLNC
cigarette noncompliance (i.e., ongoing
NNC cigarette or other tobacco product
use) and showed high levels of
noncompliance with smoking only
VLNC cigarettes during the study. Since
participants were provided with VLNC
cigarettes at no cost and continued to
use non-study provided tobacco
products (particularly NNC cigarettes),
these data suggest that VLNC cigarettes
have lower appeal and abuse potential
compared to NNC cigarettes (Refs. 327
to 331). These findings suggest that once
a nicotine product standard covering
solely cigarettes is in place and VLNC
cigarettes are the only cigarettes
available, people are likely to use
alternative nicotine-containing products
including other combusted products.
However, if cigarettes and certain other
combusted products are covered by a
product standard, people who use
combusted products are likely to use
non-combusted products, therefore
benefitting public health.
A clinical study conducted to
compare the use of alternative nicotine-

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containing products (i.e., smokeless
tobacco, ENDS, NRT, cigars, cigarillos)
and smoking behavior in 136 people
who smoked cigarettes and were
unwilling to quit randomly assigned
participants to one of three conditions
and instructed them to use only studyassigned tobacco products for 8 weeks
(Ref. 5). The ‘‘LNC1’’ group received
LNC cigarettes combined with
noncombusted tobacco products (i.e.,
smokeless tobacco, ENDS, NRT) and
combusted non-cigarette tobacco
products (i.e., cigars, cigarillos), the
‘‘LNC2’’ group received LNC cigarettes
combined with only noncombusted
tobacco products, and the NNC cigarette
group received NNC cigarettes
combined with noncombusted and
combusted non-cigarette products.
Participants who received LNC
cigarettes (both the LNC1 and LNC2
groups) used more alternative
combusted tobacco products and more
noncombusted tobacco products (the
LNC2 group) than participants in the
NNC cigarette group. However, these
participants also smoked fewer total
combusted tobacco products and had
more quit attempts than participants in
the NNC cigarette group. The findings
from this study demonstrate that when
people who smoke cigarettes are
switched to LNC cigarettes and
provided with alternative sources of
nicotine, they will readily use the
alternative sources of nicotine.
Moreover, the LNC cigarette group (the
LNC2 group) that had access to
noncombusted nicotine sources only
(i.e., smokeless tobacco, ENDS, NRT)
had statistically significantly lower
biomarker levels of certain harmful
constituents (N-Nitrosonornicotine
(NNN) and NNAL) than those who
continued to smoke NNC cigarettes and
had access to noncombusted and
combusted non-cigarette products (the
LNC1 group) (Ref. 5). The NNN and
NNAL biomarker levels in the LNC1
group with access to both combusted
and noncombusted tobacco products
resembled the NNC group (Ref. 5).
Taken together, these findings suggest
that if the proposed product standard
reduces the nicotine level in cigarettes
only, but people who smoke cigarettes
still have access to other NNC
combusted tobacco products, they likely
would substitute with the NNC
combusted tobacco products. This
behavior would negate a significant
proportion of the public health impact
of the product standard. If other
combusted tobacco products also are
covered by this proposed product
standard, however, data suggest that
people who smoke cigarettes would

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likely switch from combusted tobacco
product use to potentially less harmful
tobacco products. For further discussion
of switching to a potentially less
harmful nicotine delivery product, see
section VIII.D.3 of this document.
2. Cigarette Price Increases
Studies investigating the effects of
changes in cigarette prices on product
substitution may also be used as an
indicator of potential product switching
in response to the proposed nicotine
tobacco product standard, because a
reduction in nicotine content could be
conceptualized as an increase in the
unit price of nicotine, as the cost to
consumers is increased per unit of
nicotine (Ref. 332). Therefore, studies
assessing cigarette taxation may be
useful because they are assessing the
influence of changes in the unit price of
cigarettes, through increases in cost, on
behavior among people who use the
products. Price increases, including
taxation, represent one of the most
effective tobacco control policies
associated with significant declines in
overall tobacco consumption as well as
reductions in youth initiation rates (Ref.
333). However, taxation and price
increases are also associated with a
range of tax avoidance behaviors, such
as substitution with a less expensive
product, purchasing from low or
untaxed sources, or purchasing in bulk
(Ref. 334), and this behavior is more
likely to occur among people who
smoke and are of lower socioeconomic
status (Ref. 335). It is this potential
substitution that FDA is seeking to
mitigate by proposing to cover certain
other combusted tobacco products in
addition to cigarettes. FDA expects that
by reducing the nicotine in cigarettes
and certain other combusted tobacco
products through this proposed product
standard, the effect on people who
smoke will be similar to increasing the
price, and, as is seen in examples of
taxation and price increases, people
who smoke would likely turn to
alternative sources of nicotine.
An epidemiological study used data
from the 2001 and 2002 New Jersey
Adult Tobacco Survey (NJATS) to
determine whether people who smoke
cigarettes switched to cigars following
an increase in the state cigarette excise
tax (U.S. $0.80 to U.S. $1.50 per pack)
(Ref. 336). In 2001, the cigarette
smoking prevalence in New Jersey was
22.1 percent. Following a large cigarette
excise tax increase, the cigarette
prevalence decreased to 18 percent (Ref.
336). There were no statistically
significant differences in the cigar
smoking prevalence between 2001 and
2002; however, ever cigar use increased

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statistically significantly for people who
currently smoked cigarettes (50.9
percent versus 60.3 percent,
respectively) and increased slightly for
people who recently quit smoking (48.4
percent versus 56.4 percent,
respectively). In 2001, people who
currently smoked cigarettes had the
highest prevalence of current cigar use
(13.9 percent), while people who had
recently quit cigarette use had the
lowest prevalence (2.6 percent). In
contrast, in 2002, while people who
currently smoked cigarettes again
reported the greatest prevalence of
current cigar use (13.2 percent), people
who had recently quit cigarette smoking
had the second highest prevalence of
current cigar use (11.1 percent). The
authors concluded that after a cigarette
excise tax increase, a small but notable
proportion of people who had recently
quit cigarette smoking tried cigars,
substituted cigars for cigarettes, or
continued using combusted tobacco
products in the form of cigars (Ref. 336).
Additional indirect evidence assessing
trends in internet searches following the
2009 U.S. Federal tobacco tax increase
showed that after the tax was
announced, search queries increased for
both combusted and noncombusted
non-cigarette tobacco products (Ref.
337).
Similarly, several studies assessed
changes in loose tobacco sales following
a large tax increase in RYO tobacco and
found decreases in RYO tobacco sales
and increases in pipe tobacco sales as
soon as the tax rate changed (Refs. 322,
338 to 340). Researchers analyzing
publicly available Federal excise tax
data from 2000 to 2015 found that total
RYO tobacco sales statistically
significantly decreased by 70.0 percent;
however, total pipe tobacco sales
increased by 556.4 percent (Ref. 340).
Another study found a similar increase
in pipe tobacco sales and decrease in
RYO tobacco sales in response to tax
differences between the products;
however, self-reported pipe tobacco use,
assessed via the NSDUH, remained
consistent, and RYO consumption
increased (Ref. 338). The authors
suggested that people who smoke
cigarettes may have bought loose
tobacco labeled as pipe tobacco for use
as RYO cigarettes as a tax avoidance
strategy. These data suggest that
following the implementation of a new
tobacco control policy, manufacturers
may modify their products and a
significant proportion of consumers may
modify their behavior to adapt to the
changes (e.g., switching to a similar
combusted tobacco product if a final
nicotine tobacco product standard

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covered cigarettes only), which would
reduce the rule’s potential public health
effects. If cigarettes were the only
product covered by the proposed
product standard, a proportion of
people who smoke cigarettes would
likely to turn to certain other combusted
products, thereby reducing the
significant public health impact of this
rule. Similarly, people who use certain
other combusted products would not be
affected by the reduction in nicotine in
cigarettes and would also not benefit.
Further, if cigarettes were the only
product covered by the proposed
product standard, the negative health
effects of second- and thirdhand smoke
from these other combusted products
would still affect other non-smoking
individuals exposed to these combusted
products. However, if these certain
other combusted products are covered,
then the alternative products for those
who switch (instead of quitting) likely
would not be combusted, therefore
benefitting public health.
3. Behavioral Economics Data
Behavioral economics utilizes
principles of psychology and economics
to predict purchasing behavior as a
function of different market constraints
(Ref. 341). Several studies have used
real or hypothetical scenarios to
investigate the impact of a change in
price or availability of a given tobacco
product on subsequent purchasing or
use of another tobacco product.
Purchasing behaviors observed in
behavioral economics studies have been
shown to be concordant with actual
tobacco consumption and real purchase
estimates (Refs. 342 to 344).
Studies have used retail sales data to
investigate tobacco substitution as a
function of price (Refs. 345 to 347). One
study investigated relationships
between purchasing patterns and price
of cigarettes and little cigars. In 2013, a
pack of little cigars was approximately
32 to 37 percent less expensive than a
pack of cigarettes (Ref. 345). A 10
percent increase in the price of little
cigars was associated with a 31.7
percent decrease in per capita little cigar
sales, while a 10 percent increase in the
price of cigarettes was associated with a
27.3 percent increase in per capita little
cigar sales. The authors concluded that
people who smoke cigarettes are price
sensitive and avoided the higher cost of
cigarettes by switching to little cigars.
Another study estimated demand for
cigarettes, little cigars/cigarillos, large
cigars, e-cigarettes, smokeless tobacco,
and loose tobacco using Nielsen’s
Convenience Track retail scanner
database (Ref. 347). In this study, a 10
percent increase in the price of

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cigarettes resulted in an 18.6 percent
increase in e-cigarette demand, showing
that e-cigarettes substituted for
cigarettes (Ref. 347). Although, in this
study, large cigars, smokeless tobacco,
and loose smoking tobacco were not
associated with increased use in
response to increasing cigarette prices,
Nielsen retail sales data that were
analyzed in another study showed that
little cigars, RYO tobacco, and pipe
tobacco each serve as substitutes for
cigarettes (Ref. 346).
Studies have also used hypothetical
purchase tasks to investigate responses
by people who smoke cigarettes to
potential tobacco policy changes or
price increases (Refs. 348 and 349). One
study used a simulated tobacco
marketplace to measure purchasing
behaviors among people who smoke
cigarettes (Ref. 349). Participants could
purchase cigarettes, e-cigarettes,
cigarillos, gum, dip, lozenges, and snus.
When cigarette prices increased, ecigarette purchasing statistically
significantly increased (Ref. 349). A
study conducted in the Netherlands
utilized a similar hypothetical tobacco
marketplace to investigate hypothetical
purchases for VLNC cigarettes as a
function of varying scenarios (Ref. 348).
Most relevant was the scenario where
participants made hypothetical
purchases for VLNC cigarettes, ecigarettes, and NRT in a marketplace
where NNC cigarettes were unavailable.
VLNC cigarettes had the highest rate of
purchase, followed by e-cigarettes, and
then NRT. Approximately 20 percent of
participants reported that they would
not purchase any of the products if NNC
cigarettes were unavailable (Ref. 348).
These data demonstrate that people
who smoke cigarettes are willing to shift
consumption toward both
noncombusted and combusted noncigarette tobacco products in times of
economic or product constraint.
Moreover, this evidence supports the
conclusion that many people who
smoke cigarettes likely would switch to
other combusted tobacco products that
contain nicotine if a nicotine product
standard covered only cigarettes. Of
additional concern is the potential for
increased combusted non-cigarette
tobacco product substitution among
certain populations that may be price
sensitive, such as individuals with low
socioeconomic status compared to those
with higher socioeconomic status (Ref.
335). One study showed that
individuals of low socioeconomic status
are 85 percent more likely to report
using discount brands/RYO compared
to participants with higher
socioeconomic status (SES) in order to
avoid an increase in the cost of their

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preferred product, combusted cigarettes,
and therefore, these individuals have a
history of and comfort with switching to
alternative combusted products when
available at a lower cost (Ref. 335).
Given that the research highlighted
above has shown that a change in the
availability of a tobacco product
influences subsequent purchasing or use
of other tobacco products, FDA is
concerned that if the proposed nicotine
product standard is limited to cigarettes,
a large portion of individuals will seek
out alternative sources of nicotine by
using other combusted tobacco products
if those products are not included
within the scope of this rule.

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VII. Discussion of Nicotine-Related
Topics
A. Approach To Limiting User Exposure
to Nicotine
Nicotine is the primary addictive
constituent in all tobacco products,
including cigarettes. FDA is proposing a
tobacco product standard that would
limit nicotine yield by establishing a
maximum nicotine level in cigarettes
and certain other combusted tobacco
products to make these products
minimally addictive or nonaddictive,
using the best available science to
determine a level that is appropriate for
the protection of the public health.
After consideration of the scientific
literature, comments submitted in
response to the Nicotine ANPRM, and
the measured levels of nicotine content
in research cigarettes (as reported in the
literature, as well as in information
submitted to FDA from industry), FDA
is proposing that the maximum nicotine
level in cigarettes and certain other
combusted tobacco products not exceed
0.70 mg of nicotine content per gram of
total tobacco in order to limit user
exposure to nicotine.
Nicotine ‘‘yield’’ is the amount of
nicotine in smoke, in other words, the
amount of nicotine to which a smoker
potentially is exposed. Nicotine yield is
measured by a machine-generated
protocol where the product is smoked
by a machine in a prescribed manner
and the smoke is collected in order to
measure nicotine with another
instrument, such as a gas
chromatograph. Nicotine content refers
to the total amount of nicotine present
in the tobacco filler and is typically
conveyed as either milligrams of
nicotine per gram of total tobacco or
milligrams of nicotine per product. The
nicotine content of a tobacco product
serves as a ceiling on nicotine yield, as
it denotes the maximum amount of
nicotine that a user can be exposed to
when they smoke the cigarette or other

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tobacco product, and it cannot be
manipulated by user behavior.
Setting a limit on nicotine content
and measuring that content is more
effective in reducing yield (i.e., the
amount of nicotine the user is exposed
to) than setting a limit based on a direct
measurement of yield under
standardized smoking-machine
protocols. This is because the way yield
is measured by smoking machines does
not accurately capture the amount of
nicotine that is taken in by a person
using the tobacco products. For
example, manufacturers have developed
‘‘low-yield’’ cigarettes designed to
markedly reduce yield results as
measured by the Federal Trade
Commission (FTC) testing method (Ref.
350). They decreased yields by
manipulating various characteristics of
the cigarettes (e.g., decreasing the length
of the available tobacco column,
increasing the burn rate of the column,
increasing filter efficiency, increasing
air dilution in mainstream smoke,
decreasing density of tobacco, or
changing the concentration of nicotine
in the tobacco) (Ref. 350 at Table 2–2).
Many of these design changes led to the
amount of nicotine measured in the
machine-generated yield being different
from—and less than—the amount of
nicotine received by the smoker (Ref.
350). This disconnect is a result of
smoking compensatory behaviors, such
as smoking more cigarettes per day,
increasing the number of puffs (with a
smoker’s last few puffs on a cigarette
delivering disproportionately more
nicotine than delivered in a smoking
machine’s standardized number of
puffs), increasing puff volume and
frequency, inhaling more deeply, and
covering ventilation holes with fingers
or lips, that enable smokers to
overcome, intentionally or
unintentionally, many of these design
changes and, thereby, increase the
amount of their nicotine intake
compared to the machine-generated
yield. They often do this to obtain
adequate nicotine to satisfy their
nicotine cravings (Ref. 350).
While standardized smoking machine
puffing regimes in a controlled
laboratory environment are effective in
producing reproducible measurements
of nicotine yield, as noted above, human
behavior—how people smoke, including
in response to cigarette-design
features—influences the nicotine intake
from a cigarette and can overcome
features of a cigarette that lowered the
machine-generated nicotine yield. For
example, combusted cigarettes that were
once referred to as ‘‘light’’ cigarettes
achieved a reduction in machinemeasured nicotine yield (e.g., ISO

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machine smoking method, CI smoking
method, FTC smoking method) through
a variety of design changes to the
cigarette, including the use of
ventilation holes—although the actual
nicotine content of the tobacco filler
was not low. These design changes led
to lower tar and nicotine yields in
machine-generated smoke, and
therefore, these products were labeled
and marketed as low nicotine yield or
‘‘light,’’ ‘‘low,’’ or ‘‘mild’’ cigarettes.
However, often unconsciously cigarette
users could and did modify their use
behaviors to compensate for these
design changes and extract more
nicotine from the products compared to
the machine-generated yields, often to
levels comparable to conventional
cigarettes. For example, cigarette makers
generally design cigarettes with
ventilation holes far enough down the
cigarette that they are not blocked
during the FTC smoking test, but are
easily blocked by users’ fingers or
mouths, and larger or more frequent
puffs could be taken by consumers (Ref.
351). Through such compensatory
smoking behaviors, cigarette users were
able to overcome the changes in
ventilation in these products, resulting
in no benefit to public health (Ref. 350).
There is ample research demonstrating
that people who use ventilated
cigarettes change their smoking
behavior to increase their smoke intake,
including taking larger puffs, inhaling
more deeply, taking more frequent
puffs, or increasing the number of
cigarettes they smoke per day 25 (Refs.
350 to 361). As a result, evidence shows
that many people are exposed to higher
yields of smoke constituents, including
nicotine, than the yields estimated by
standardized smoking machine methods
(Refs. 362 to 364). Further, researchers
have reviewed the extensive body of
literature on filter ventilation and health
effects and concluded that there is
strong evidence to suggest that filter
ventilation has contributed to the rise in
lung adenocarcinomas among people
who smoke (Ref. 365). Studies that
measure nicotine pharmacokinetics
have also found that the relative
percentage of free nicotine in smoke
may increase with percent of filter
ventilation (Ref. 366), which suggests
that greater filter ventilation may expose
smokers to greater free nicotine levels
that can lead to greater total nicotine
exposure while smoking as this form of
nicotine is more easily absorbed by the
body.
25 See section VII.B 4., Smoking Topography, of
this document for further discussion of
compensatory smoking and VLNC cigarettes.

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In contrast, reducing the nicotine
content in cigarettes and certain other
combusted tobacco products places an
absolute maximum limit on the amount
of nicotine that can be extracted (i.e.,
yielded) by the user. VLNC cigarettes, in
contrast to low nicotine yield cigarettes
generated by other design changes, are
associated with minimal and transient
compensatory smoking because people
who smoke these cigarettes are unable
to obtain adequate amounts of nicotine
through these behaviors; therefore, they
stop trying to do so. In sum, limiting
nicotine yield through a maximum
nicotine content level would be more
effective in achieving the public health
benefits that come from reducing the
amount of the nicotine to which a user
is exposed than would setting a limit
based on a measurement of the
maximum yield of tobacco products.26

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B. Scientific Evidence Supports the
Target Level of Nicotine
Many studies have investigated the
effects of VLNC cigarettes on behavioral
outcomes, including smoking cessation,
use behaviors, biomarkers of exposure,
and physiological effects. Findings from
these studies are discussed in this
section, and they suggest that
individuals who smoke VLNC cigarettes
with nicotine levels similar to what
FDA is proposing here are more likely
to make a quit attempt, reduce smoking,
demonstrate reduced exposure to
harmful and potentially harmful
constituents (HPHCs), and demonstrate
similar or reduced physiological
responses to cigarettes relative to
individuals who smoke usual brand or
NNC cigarettes. Results from these and
other studies suggest that switching to
VLNC cigarettes does not lead to
compensatory smoking (see this section
and VII.B.4 of this document for further
discussion of compensatory smoking).
Therefore, the data reported in the
scientific literature support a tobacco
product standard limiting nicotine yield
by setting a maximum nicotine content
level in cigarettes and certain other
combusted tobacco products to a
maximum of 0.70 mg of nicotine per
gram of total tobacco. FDA believes that
this maximum nicotine level would
provide the appropriate flexibility to
account for variations in tobacco
growing seasons and variations in
analytical testing. FDA requests
26 Consistent with the proposed limit on nicotine
content, FDA is also proposing testing for nicotine
content only, rather than both content and yield.
This testing requirement is less burdensome yet still
effective in measuring the maximum nicotine yield,
i.e., the maximum amount of nicotine to which a
user can be exposed.

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comments, data, and research regarding
this proposed maximum nicotine level.
1. Origin of the Proposed Product
Standard
In 1994, Benowitz and Henningfield
proposed the idea of Federal regulation
of nicotine content in combusted
tobacco products to a level too low to
sustain addiction (Ref. 367). They
considered the smoking habits of a
small population of people who smoke
cigarettes intermittently and who
demonstrate reduced nicotine
dependence (a group sometimes referred
to as tobacco ‘‘chippers’’) to inform
indirect estimates of a nicotine level
that they proposed would be too low to
sustain addiction in most people who
smoke cigarettes. Chippers are typically
characterized by smoking five or fewer
CPD, with limited or no withdrawal
symptoms, and by being able to skip
smoking for days at a time (Ref. 368).
Based on their estimates of nicotine
exposure among chippers, the
researchers proposed a level of nicotine
per cigarette—approximately 0.5 mg of
nicotine per cigarette—that should be
low enough to prevent or limit the
development of nicotine addiction in
most young people. The nicotine level
proposed by Benowitz and Henningfield
was an initial estimation based on
observational data, and there is
individual variability in dose sensitivity
to all addictive substances; however, the
initial estimate posed by Benowitz and
Henningfield paved the way for
subsequent prospective clinical studies
designed to evaluate the addiction
potential of VLNC cigarettes.
Several brands of commercial and
research cigarettes were manufactured
to contain a nicotine content similar to
that originally proposed by Benowitz
and Henningfield (see table 1 of this
document). Using these cigarettes,
researchers have consistently
demonstrated that VLNC cigarettes have
reduced addiction potential compared
to NNC cigarettes.
22nd Century Group Inc., the
company that developed SPECTRUM
Nicotine Research Cigarettes and whose
genetically engineered tobacco was used
to make Quest cigarettes, submitted
modified risk tobacco product
applications to FDA that reported that
the actual average value of nicotine
content in its genetically engineered
VLNC tobacco is 0.6 mg nicotine per
gram of total tobacco, with a range of 0.4
to 0.7 mg nicotine per gram of total
tobacco (see section V.A of this
document for a discussion of the history
of LNC and VLNC cigarettes, including
the SPECTRUM Nicotine Research

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Cigarettes).27 The natural variation of
this agricultural product resulted in the
slight variation in the nicotine content
of the tobacco filler within the
company’s internal range of acceptable
values. The average value and range
were compiled by the company from 9
years of sampling data of the genetically
engineered tobacco that was used to
make SPECTRUM and Quest cigarettes.
It is likely that the cigarettes used
throughout the scientific literature,
reported as having 0.4 mg nicotine per
gram of total tobacco, may have, in
actuality, been between 0.4 and 0.7 mg
of nicotine per gram of total tobacco.
This range is consistent with the
scientific evidence to support a
minimally addictive or nonaddictive
level of nicotine content in cigarettes
and certain other combusted tobacco
products, and FDA took these data from
22nd Century Group Inc.’s VLNC
cigarettes into consideration when
determining the appropriate, technically
feasible maximum level of nicotine
content to propose in this product
standard.
2. Smoking Cessation
A number of studies investigated the
effects of VLNC or LNC cigarettes alone
or in combination with NRT on smoking
cessation among people who smoke but
are interested in quitting (Refs. 32, 35,
41, 369 to 373) and those uninterested
in quitting (Refs. 31, 40, 258, and 374).
As stated throughout this document,
most adults who use tobacco products
wish to quit but are unsuccessful
because of the highly addictive nature of
these products (Refs. 1, 13, 28, 58, and
61) (see section IV.A of this document
for a discussion of the addictiveness of
nicotine). Taken together, results from
these studies demonstrate that people
who smoke and are interested in
quitting who are given VLNC cigarettes
are more likely to achieve initial
smoking abstinence compared to those
who continue to smoke their usual
brand or NNC cigarettes. In addition,
provision of NRT and/or behavioral
intervention with VLNC cigarettes may
further increase smoking cessation
among individuals interested in quitting
(Ref. 19).
Research demonstrates the benefits of
VLNC cigarettes for those people who
smoke and are interested in quitting. In
one of the clinical trials that has
examined the effects of VLNC cigarettes
27 On December 23, 2021, FDA issued exposure
modification orders to 22nd Century Group Inc. for
VLN King and VLN Menthol King combusted,
filtered cigarettes. See https://www.fda.gov/tobaccoproducts/advertising-and-promotion/22nd-centurygroup-inc-modified-risk-tobacco-product-mrtpapplications.

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alone on smoking cessation in people
who smoke cigarettes who were
interested in quitting, 165 people who
smoke were randomized to use LNC
cigarettes, VLNC cigarettes, or 4 mg
nicotine lozenges for 6 weeks (Ref. 32).
While there were no statistically
significant differences between groups
in CO-verified point prevalence
abstinence (i.e., quit) rates at 1–4-week
followup visits, abstinence rates at the
week 6 followup visit were statistically
significantly higher in the VLNC
cigarette group (47.2 percent) and
nicotine lozenge group (36.7 percent)
relative to the LNC cigarette group (23.1
percent) (Ref. 32). In another
randomized clinical trial (RCT), 346
people who smoked and were interested
in quitting were randomized to receive
6 weeks of (1) a combination of VLNC
cigarettes (nicotine was gradually
reduced from NNC to LNC to VLNC
cigarettes every 2 weeks) and nicotine
patch (VLNC cigarettes + NRT); (2)
VLNC cigarettes and a placebo patch
(VLNC cigarettes only); or (3) NNC
cigarettes and NRT after their quit date
(NNC cigarettes + NRT) (Ref. 369).
Following their quit date at week 7, the
VLNC cigarettes + NRT group continued
to receive NRT, the VLNC cigarettes
only group received placebo patches,
and the NNC cigarettes + NRT group
was provided with NRT during weeks
7–10. Biochemically confirmed
continuous abstinence rates were 32.8
percent in the VLNC cigarettes + NRT
group, 16.4 percent in the VLNC
cigarettes only group, and 21.9 percent
in the NNC cigarettes + NRT group (Ref.
369), suggesting that the combination of
VLNC cigarettes and NRT is more
effective at promoting continuous
abstinence than VLNC cigarettes alone.
However, abstinence at 3- and 6-month
followups could not be adequately
assessed due to attrition (Ref. 369).
Many other studies conducted in
individuals interested in quitting
investigated the effects of LNC or VLNC
cigarettes combined with NRT (Refs. 41,
35, 371 to 373, and 375). For example,
in a study conducted in New Zealand,
1,410 callers to a quitline were
randomized to receive VLNC cigarettes
with usual quitline care (8 weeks of
NRT and behavioral support via a
quitline) or usual care alone (Ref. 373).
Six months after the quit date, 7-day
point-prevalence abstinence rates 28
were statistically significantly greater in
participants using VLNC cigarettes with
28 Seven-day point prevalence abstinence is a
measure of, in this case, tobacco cessation outcomes
for quitlines. At a given point in time (in this case,
6 months after the quit date), study participants are
asked whether they have used cigarettes or other
forms of tobacco in the past 7 days.

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usual quitline care (33 percent)
compared to the group who received
usual quitline care alone (28 percent).
Continuous abstinence rates at month 6
also were statistically significantly
higher for participants who received
VLNC cigarettes with usual quitline care
(23 percent) compared to those who
received usual quitline care alone (15
percent). Likewise, in another study, 98
persons who reported heavy smoking
(i.e., greater than or equal to 20 CPD)
received either VLNC cigarettes and a 21
mg nicotine patch or NNC cigarettes for
2 weeks prior to quitting (Ref. 372).
After the quit date, all study
participants wore nicotine patches for
up to 8 weeks. Participants who smoked
VLNC cigarettes and received patches
reported less frequent and less intense
cravings during the 2 weeks before and
after the quit date, suggesting that use of
VLNC cigarettes plus NRT may aid in
cessation by reducing cigarette craving
during a quit attempt. Participants in
the VLNC cigarettes + NRT group had a
higher self-reported quit rate compared
to those in the NNC cigarettes + NRT
group at 3 months (43 percent vs. 34
percent, respectively) and 6 months (28
percent vs. 21 percent, respectively), but
these quit rates did not differ
statistically significantly between
groups, likely due to a small sample size
precluding sufficient statistical power.
Several other studies have
investigated the effects of VLNC or LNC
cigarettes on smoking cessation among
individuals uninterested in quitting
(Refs. 31, 40, 258 and 374). In an RCT,
participants received either NNC
cigarettes or VLNC cigarettes (doubleblinded, i.e., neither the participants nor
the researchers knew which type of
cigarette participants received), and
either received or did not receive a
transdermal nicotine patch (open-label,
i.e., participants and researchers were
aware of whether participants received
NRT) for 7 weeks. At week 7,
participants were provided a daily
descending monetary bonus for
refraining from using any cigarettes.
Participants randomized to receive NRT
were encouraged to continue using their
patches. Although participants who
received VLNC cigarettes smoked
statistically significantly fewer total
CPD than participants who received
NNC cigarettes, during the abstinence
period, no groups differed statistically
significantly from the NNC cigaretteonly group in time to lapse or number
of days abstinent; however, these results
were likely influenced by low
adherence to VLNC cigarette use in this
study (Ref. 376). In another series of
studies, participants received gradually

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reduced nicotine content cigarettes over
a period of 6 months, beginning with
NNC cigarettes and ending with VLNC
cigarettes (Refs. 258 and 374). In the
first study, a statistically significantly
greater proportion of participants who
received VLNC cigarettes considered
quitting at the end of the study,
compared to those in a control group
who smoked their usual brand cigarettes
throughout the study (Ref. 258). In a
followup study in which a subset of
participants was followed for 2 years,
cotinine levels in the gradual nicotine
reduction group rose to baseline levels
or levels similar to those of the control
group after 12 months during which
both groups could freely smoke usual
brand cigarettes (Ref. 374). Although 7.5
percent of participants in the gradual
reduction group quit smoking,
compared to only 2 percent of
participants in the usual brand control
group, this difference was not
statistically significant (Ref. 374). In
another study, 33 participants were
randomized to receive VLNC cigarettes
or to continue to smoke their usual
brand cigarettes for 12 weeks (Ref. 31).
The availability of VLNC cigarettes
increased quit attempts in people who
smoked cigarettes and had no intention
of quitting (Ref. 31).
Furthermore, several extended
duration VLNC studies demonstrated
how VLNC cigarettes can increase
cessation by assessing self-reported quit
attempts as a secondary study aim.
While one study showed no statistically
significant differences in quit rates
among people who smoke cigarettes on
a nondaily basis who used VLNC or
NNC cigarettes for 10 weeks (Ref. 377),
other studies showed that participants
who smoked VLNC cigarettes were more
likely to report a quit attempt after 6
weeks of use (Ref. 29) and had a greater
number of cigarette-free days after 12
(Ref. 378) and 18 weeks (Ref. 379)
compared to those who smoked NNC
cigarettes. However, a secondary
analysis of the 18 week study (Ref. 379)
found that there were no significant
differences in quit rates or intention to
quit at the 6-month followup timepoint
(Ref. 380).
Among the studies evaluating
smoking cessation following VLNC
cigarette use, few utilized a randomized
controlled trial design, and results were
sometimes inconsistent, particularly
related to long-term followup. However,
the weight of evidence from these
studies suggests that among people who
smoke and are interested in quitting,
using VLNC cigarettes can facilitate
initial smoking abstinence, particularly
when used along with NRT and/or
behavioral intervention. Among people

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who smoke but are uninterested in
quitting, VLNC cigarette use did not
increase quit rates; however, it did
increase quit attempts. It is important to
note that studies evaluating smoking
cessation following VLNC cigarette use
took place in an environment where
NNC cigarettes and other combusted
tobacco products remained readily
available. For this reason, the available
data likely underestimates the
likelihood of increased cessation rates
following the implementation of a
nicotine product standard because NNC
cigarettes would no longer be available,
making relapse to these cigarettes no
longer possible.
3. Cigarettes Per Day (CPD)
One concern raised by some with
regard to a reduced nicotine policy is
whether people who smoke might alter
their smoking behavior by smoking
additional cigarettes in order to attempt
to compensate for the lower amounts of
nicotine, but studies show that extended
use of VLNC cigarettes does not produce
increases in CPD. Researchers typically
assess CPD via participant self-reporting
or by counting cigarette filters or packs
returned by participants. By measuring
CPD during an extended exposure trial,
researchers can determine whether
switching to VLNC cigarettes produces
changes in CPD compared to usual
brand or NNC cigarette conditions.
Research conducted in the absence of
the proposed standard shows that
switching to LNC or VLNC cigarettes
can produce modest decreases in CPD.
However, as noted previously, studies
evaluating changes in CPD following
VLNC cigarette use took place in an
environment where NNC cigarettes and
other combusted tobacco products
remained readily available, likely
underestimating the potential
reductions in CPD following
implementation of a nicotine product
standard because NNC cigarettes and
other combusted tobacco products
would no longer be legally available.
These findings suggest that, if the
proposed product standard were
finalized and implemented, people who
smoke VLNC cigarettes would not
increase CPD to compensate for reduced
nicotine exposure, and FDA expects that
for many CPD would decrease over
time.
Many studies measured VLNC CPD
under conditions of extended exposure
(e.g., several consecutive weeks or
longer). These studies varied in sample
size, duration of exposure, average CPD
requirements to enter the study,
participants’ intentions to quit smoking,
and the method in which participants
transitioned from usual brand cigarettes

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to VLNC cigarettes (i.e., gradual versus
immediate reduction in nicotine
content). Despite these differences in
study methods and participant
characteristics, nearly all the studies
came to a similar conclusion: relative to
usual brand or NNC cigarette
conditions, CPD was similar (i.e., there
was no compensatory smoking) (Refs.31,
35, 329, 369, 374, 381 to 385,) or lower
in VLNC cigarette conditions (Refs. 29,
32, 41, 265, 386, and 387). Notably,
studies that found lower CPD while
participants smoked VLNC cigarettes
tended to have larger sample sizes (Refs.
29 and 379), which may have had more
statistical power to detect relatively
small but consistent differences in CPD
across conditions.
One limitation of some studies that
examined the effects of VLNC cigarette
smoking on CPD is that comparisons
between VLNC CPD and usual brand or
NNC CPD were made without taking
into account the number of non-study
cigarettes smoked per day in
experimental conditions. A measure of
‘‘total CPD’’ in VLNC cigarette
conditions would include the number of
study-assigned VLNC cigarettes plus the
number of usual brand or non-study
cigarettes smoked by participants who
were not fully compliant with study
procedures. Few studies have compared
total CPD across VLNC and usual brand
or NNC cigarette conditions. However,
one study found that, relative to usual
brand and NNC cigarette conditions, the
combination of study- and non-studyassigned CPD was lower in VLNC and
LNC cigarette conditions when nicotine
content was less than or equal to 2.4 mg
nicotine per gram of total tobacco, and
that those participants who used VLNC
cigarettes (i.e., 0.4 mg nicotine per gram
of total tobacco), demonstrated reduced
use and dependence with minimal
evidence of withdrawal-related
discomfort or safety concerns (Ref. 29).
Another study found that fewer
combusted tobacco products were
smoked during LNC cigarette conditions
relative to an NNC cigarette condition
(Ref. 5). A study where participants
were confined to a hotel in order to
limit their access to non-study products
assessed the potential effects of VLNC
cigarettes on compensatory smoking
behaviors (Ref. 388). Participants
completed two 4-night stays; during
their first stay, they were randomized to
receive either NNC or VLNC cigarettes
and were randomized to the other group
during their second stay. Furthermore,
participants were given an ‘‘account
balance’’ where they could purchase
study cigarettes from a ‘‘cigarette store’’
during the study. Investigators found

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that by the end of the four night stays
the number of cigarettes participants
smoked did not differ statistically
significantly between the NNC and
VLNC cigarette groups, indicating that
people who smoke may not engage in
compensatory smoking behavior when
only VLNC cigarettes are available (Ref.
388). Another study compared the
effects of VLNC and NNC cigarettes on
CPD in people who smoke who
inhabited a residential research facility
throughout the study. The results
showed that when participants had
access to only VLNC cigarettes for 11
days, they smoked statistically
significantly fewer CPD than those who
had access to only NNC cigarettes (Ref.
64).
Taken together, these studies indicate
that extended use of VLNC cigarettes
does not produce increases in CPD in an
attempt to compensate for the reduced
nicotine levels. FDA expects that this
may result in reductions in CPD among
people who do not quit, particularly in
an environment where NNC cigarettes
are not legally available.
4. Smoking Topography
Smoking topography refers to various
aspects of smoking behavior, including
number of puffs per cigarette, total time
spent smoking, puff volume (i.e., puff
size), puff velocity (i.e., puff intensity),
puff duration, and inter-puff interval
(i.e., length of time between puffs).
Although some of these outcomes (e.g.,
puffs per cigarette) can be measured via
direct observation, smoking topography
is typically assessed with an electronic
puff topography unit attached directly
to a cigarette. Smoking topography
measures that indicate more intense
smoking behavior may be attributed to
compensatory smoking. A concern
raised by some with regard to a nicotine
reduction policy is whether people who
smoke might engage in compensatory
smoking behavior to try to extract more
nicotine from the cigarettes, thus
increasing exposure to tobacco-related
toxicants. Smoking topography study
results are mixed, but the majority of
studies show that individuals who
smoke VLNC cigarettes demonstrate no
statistically significant differences in
smoking topography relative to those
who smoke usual brand or NNC
cigarettes, or they demonstrate changes
in smoking topography measures that
are associated with reductions in
tobacco smoke exposure (e.g., lower
total puff volume) rather than increased
compensatory smoking.
Some studies found no differences in
smoking topography between VLNC and
NNC or usual brand cigarette conditions
(Refs. 389 to 391). However, many other

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studies found that smoking topography
differed between cigarette conditions.
Some of the more reliable findings
replicated across studies were the
effects of VLNC cigarettes on total puff
volume and number of puffs per
cigarette. Under conditions of both brief
(e.g., several hours) and extended (e.g.,
several weeks) exposure, studies found
that total puff volume was lower (Refs.
29, 34, 383, 384, and 392) and number
of puffs per cigarette was lower (Refs.
329, 384, 392, and 393) when
participants smoked VLNC cigarettes,
relative to usual brand or NNC
cigarettes. However, two brief exposure
studies showed higher puff volumes
(Refs. 393 and 394) and puff duration
(Ref. 394) when participants smoked
VLNC cigarettes in short laboratory
sessions. Another brief exposure study
conducted in adolescents showed that
VLNC cigarettes produced higher
numbers of puffs relative to NNC
cigarettes; however, additional measures
were not collected to determine whether
this was a transient or lasting effect (Ref.
395). An extended exposure study
showed initial decreases in puff volume
when participants smoked VLNC
cigarettes relative to NNC cigarettes, but
these differences dissipated over the
course of 7 days (Ref. 383). Finally,
limited evidence suggests that VLNC
cigarettes are smoked faster (Refs. 259
and 396), are smoked with increased
peak velocity (Ref. 384) and may
decrease inter-puff intervals when
compared to NNC cigarettes (Ref. 392).
In all, while smoking topography
study results are mixed, the majority of
studies show that individuals who
smoke VLNC cigarettes demonstrate no
statistically significant differences in
smoking topography relative to those
who smoke usual brand or NNC
cigarettes, or they demonstrate changes
in smoking topography measures that
are associated with reductions in
tobacco smoke exposure (e.g., lower
total puff volume) rather than increased
compensatory smoking.
5. Abuse Potential
Abuse potential refers to the ability of
a product to promote continued use and
the development of dependence. Choice
studies are commonly used to measure
abuse potential, where preference for
one tobacco product over another
indicates greater abuse potential. When
participants are asked to make a real or
hypothetical choice between VLNC
cigarettes and NNC cigarettes in
research studies, they reliably choose
NNC cigarettes (Refs. 391, 397 to 401).
Combined with data showing that VLNC
cigarettes are associated with
significantly lower plasma nicotine

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exposure (Ref. 402) and decreased
positive subjective effects compared to
NNC and usual brand cigarettes (Ref.
391), these data indicate lower abuse
potential of VLNC cigarettes. However,
research has also shown that the choice
between VLNC and NNC cigarettes can
be influenced by factors such as cost or
effort, such that when the effort required
to obtain NNC cigarettes increases, some
people who smoke cigarettes will switch
their preference from NNC cigarettes to
VLNC cigarettes (Ref. 398). For example,
one laboratory study investigating
tobacco product choice when
participants were provided with an
experimental income found that,
although participants rated VLNC
cigarettes as less satisfying than both
LNC and NNC cigarettes, they
purchased statistically significantly
more puffs of the VLNC cigarettes when
LNC and NNC cigarettes were more
expensive (Ref. 403). Thus, if the
proposed product standard is
implemented and the cost, effort, or risk
associated with obtaining NNC
cigarettes increases, individual
preference may shift to VLNC cigarettes
or more readily available tobacco
products rather than attempting to seek
out illicitly marketed NNC products. If
the proposed product standard were to
apply only to cigarettes, these findings
also indicate that people who smoke
cigarettes who do not quit after a final
rule goes into effect would likely be
willing to switch to other NNC
combusted tobacco products rather than
using VLNC cigarettes. If this were the
case, the public health benefit of the
proposed product standard would be
reduced.
Hypothetical choice tasks (e.g.,
cigarette purchase task, multiple choice
questionnaire) are used to characterize
reinforcing efficacy by determining how
changes in the cost of a commodity
affect its consumption. These tasks
typically involve prior experience with
the product or brief laboratory exposure,
followed by a series of questions asking
participants to either (1) report how
many cigarettes they would consume at
a variety of escalating prices; or (2)
choose between cigarettes or money at
a variety of prices. Studies that used
hypothetical choice tasks to assess
VLNC cigarette reinforcement showed
that participants find VLNC cigarettes to
be less reinforcing than NNC cigarettes
(Refs. 265, 343, and 391). In one study,
the reinforcing efficacy of cigarettes
varying in nicotine content following 6
weeks of access to the products was
examined (Ref. 343). Compared to the
NNC cigarette group, those in the VLNC
cigarette group estimated that they

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would smoke fewer cigarettes even if
the cigarettes were free, spend less for
the VLNC cigarettes, and quit smoking
VLNC cigarettes at a lower price point
(i.e., a price point at which participants
would continue to pay for NNC
cigarettes). Responses on the
hypothetical choice task were highly
correlated with the actual number of
cigarettes smoked during week 6 of the
study.
Hypothetical choice tasks can also be
used to investigate the substitutability of
tobacco products. For example, another
study employed a cross-price elasticity
task in which the price of VLNC
cigarettes was held constant while the
price for usual brand cigarettes was
manipulated (Ref. 404). When usual
brand cigarette price increased, demand
for VLNC cigarettes increased and
demand for usual brand cigarettes
decreased, indicating that VLNC
cigarettes are a partial substitute for
usual brand cigarettes (Ref. 404).
Rather than directly assessing choice
between tobacco products, some studies
evaluate how much people who smoke
are willing to work to earn puffs from
cigarettes when the number of responses
required to earn a puff progressively
increases (i.e., a progressive ratio task).
One study that used this method found
that participants assigned to an NNC
cigarette group were willing to work
statistically significantly harder to earn
puffs from their NNC cigarette than
participants assigned to a VLNC
cigarette group, indicating greater abuse
liability (i.e., ability to promote
continued use and the development of
dependence) of the NNC cigarette (Ref.
64).
These studies demonstrate that VLNC
cigarettes are consistently shown to be
of lower abuse potential compared to
NNC cigarettes, as evidenced by
responses to behavioral and
hypothetical choice procedures.
Behavioral and hypothetical choice
research has also shown that the choice
between VLNC and NNC cigarettes can
be influenced such that some people
will switch their preference from NNC
cigarettes to VLNC cigarettes when the
price or effort required to obtain the
products increases. See section VI.B of
this document for further discussion on
the impact of cigarette price on
switching behavior.
6. Biomarkers of Exposure
Research demonstrates that, following
VLNC cigarette use, some biomarkers of
exposure (e.g., CO, measured as breath
CO or carboxyhemoglobin (COHb)) are
typically similar to those observed
following NNC cigarette use, while
other biomarkers (e.g., total nicotine

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equivalents (TNE), which are a
combination of nicotine, cotinine, and
other nicotine metabolites collected
through plasma, saliva, or urine) are
typically lower following VLNC
cigarette use. However, no biomarkers of
exposure are reliably observed to be
higher following VLNC cigarette use
relative to NNC cigarette use, meaning
that study participants are not engaging
in compensatory smoking behaviors.
Some of the most commonly
measured biomarkers of tobacco smoke
exposure are CO, plasma nicotine,
cotinine (collected through plasma,
saliva, or urine), TNE, and other HPHCs
or their metabolites (e.g., NNN, NNAL,
Benzo[a]pyrene (BAP), 3-hydroxypropyl
mercapturic acid (3–HPMA), Sphenylmercapturic acid (S–PMA)).
While nicotine and its metabolites
would be expected to decrease in
individuals who switch from NNC to
VLNC cigarettes, other biomarkers of
exposure would be expected to remain
the same if smoking behavior remained
unchanged. Thus, any changes in
biomarker levels observed between NNC
and VLNC cigarette conditions in
clinical studies may indicate differences
in smoking behavior (e.g., changes in
CPD or smoking topography) between
these two groups. Notably, due to the
short half-lives of some biomarkers (e.g.,
breath CO), decreases in smoking can
produce decreases in these biomarkers
during brief exposure studies. However,
decreases in smoking may not produce
decreases in some biomarkers (e.g.,
NNAL) under such conditions due to
the prolonged half-lives of these
biomarkers.
Most studies have found no
differences in CO exposure between
participants who smoke VLNC cigarettes
and those who smoke usual brand or
NNC cigarettes (Refs. 5, 29, 32, 34, 40,
258, 374, 376, 383, 387, 388, 390, 391,
393, 395, 396, 402, 405 to 417,). This
finding may be somewhat unexpected as
many studies have found that
participants smoke fewer CPD when
they smoke VLNC cigarettes relative to
NNC or usual brand cigarettes.
However, although CO is positively
associated with CPD, research has
shown that the correlation may only be
of moderate strength (Ref. 418).
Furthermore, CO may be impacted by
noncompliance with study cigarettes
(see section VI.B of this document for a
discussion about noncompliance).
Nevertheless, differences were
observed between VLNC and NNC
cigarette conditions in a few studies.
Two brief exposure studies in which
participants were given limited access
to reduced nicotine content cigarettes
over the course of several hours under

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controlled laboratory conditions found
increases in breath CO following VLNC
cigarette use relative to NNC cigarette
use (Refs. 419 and 420). In addition, an
extended exposure study (over the
course of 35 days) showed that CO
levels initially increased when
participants switched from usual brand
cigarettes during baseline to VLNC
cigarettes; however, these effects
dissipated over time as CO levels
eventually returned to baseline levels
(Ref. 384). As discussed in section
VIII.D.7 of this document, these limited
increases in CO exposure may be due to
changes in smoking topography. At least
one extended exposure study found
decreases in CO boost (the difference
between measured CO levels before and
after smoking a cigarette) after VLNC
cigarette use compared to usual brand
cigarettes (Ref. 329). In another study,
one group of participants smoked NNC
cigarettes throughout the study, a
second group smoked study cigarettes
with gradually reduced nicotine
contents, and a third group immediately
switched to VLNC cigarettes (Ref. 421).
This study found that subjects in the
immediate VLNC cigarette group had
statistically significantly lower CO than
did the NNC cigarette or gradual
reduction groups. Breath CO for
participants in the NNC cigarette and
gradual reduction groups did not differ
statistically significantly from each
other (Ref. 421). Moreover, the only
study to date that examined the effects
of VLNC cigarettes on breath CO in
people who smoke who inhabited a
residential research facility found that
when participants only had access to
study cigarettes for 11 days, those who
were assigned VLNC cigarettes had
statistically significantly lower breath
CO than those who were assigned NNC
cigarettes. Furthermore, these
differences increased over the course of
each day such that they were much
larger in the afternoon than in the
morning (Ref. 64).
Notwithstanding the differing CO
studies, studies that examined nicotine,
cotinine, or TNE levels had
overwhelming concurrence regarding
the effects of either brief or extended
exposure to VLNC cigarettes compared
to usual brand or NNC cigarettes. VLNC
cigarette use resulted in substantially
lower levels of nicotine, cotinine, and
TNE than usual brand or NNC cigarettes
(Refs. 5, 29, 32 to 34, 40, 258, 329, 370,
374, 376, 382 to 384, 387, 388, 390, 402,
403, 406, 407, 410, 413, 417, and 419 to
425). One within-subjects laboratory
study compared the nicotine
pharmacokinetic profile of VLNC, LNC,
NNC, and usual brand cigarettes in 12

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participants who smoked cigarettes
daily (Ref. 402). While each of the four
cigarettes produced statistically
significant increases in plasma nicotine
boost (i.e., peak plasma nicotine level
minus baseline level) after smoking, the
VLNC and LNC cigarettes had
statistically significantly lower plasma
nicotine boost and AUC0–120 (i.e.,
plasma nicotine area under the curve
calculated for the first 120 minutes
following product use, indicating extent
of exposure to nicotine and its clearance
rate from the body) compared to the
NNC and usual brand cigarettes. These
data show that although VLNC
cigarettes are associated with
significantly lower nicotine uptake
compared to NNC and usual brand
cigarettes, the cigarettes still deliver a
measurable amount of nicotine.
The effects of VLNC cigarette
exposure on other HPHCs were less
reliable across studies. Nevertheless,
studies consistently found that VLNC
cigarette exposure either reduced or did
not change exposure to NNN, NNAL,
urinary 1-hydroxypyrene, or BAP
relative to NNC or usual brand cigarettes
(Refs. 5, 29, 32, 40, 258, 382, 384, and
329). Two studies also examined 3–
HPMA and S–PMA levels and found
that these biomarkers decreased in
VLNC cigarette conditions compared to
LNC and NNC cigarette conditions (Ref.
32). Another study found that an
immediate switch to VLNC cigarettes
statistically significantly reduced
exposure to acrolein and phenanthrene
tetraol (both are biomarkers of smoke
exposure) throughout a 20-week study
duration compared to a gradual
reduction approach (Ref. 379). The
reductions in biomarkers that were
observed in some of these studies
following VLNC cigarette exposure were
typically correlated with decreases in
CPD or other smoking behaviors. Thus,
as expected, VLNC cigarette use resulted
in fewer CPD, which resulted in overall
reductions in HPHC exposure.
Importantly, none of the studies found
that VLNC cigarette use resulted in
increases in any of these other HPHCs
or their biomarkers. Taken together,
these studies support that VLNC
cigarette use is associated with
biomarker exposure that is similar to or
lower than NNC cigarette use.
7. Physiological Effects
Physiological measures may be proxy
measures for the stimulant effects of
nicotine. Pharmacodynamic effects of
nicotine include central and peripheral
nervous system stimulation, arousal,
and increased heart rate or blood
pressure. Nicotine is a known stimulant,
but physiological effects may occur in

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response to combusted tobacco products
even in the absence of nicotine in those
who regularly use cigarettes and certain
other combusted tobacco products due
to behavioral conditioning or other
psychoactive chemicals in tobacco
smoke. Data show that physiological
effects related to VLNC cigarettes are
similar or less pronounced than those
produced by NNC cigarettes, suggesting
that the nicotine in the VLNC cigarettes
is able to produce physiological effects.
There is slight variability in the data
assessing the physiological effects of
VLNC cigarettes. Some studies show
that, regardless of nicotine content,
acute cigarette smoking is associated
with an increase in baseline heart rate
(Refs. 259, 407, 411, and 419); however,
these increases were either less
pronounced following VLNC cigarette
use compared to NNC cigarette use
(Refs. 259 and 407) or were less
consistent (i.e., observed at some but not
all time points following use) (Ref. 411).
Some research has shown that
escalations in heart rate dissipate after
repeated exposure to VLNC cigarettes
but not usual brand cigarettes (Ref. 407).
In contrast, other studies did not
observe increases in heart rate when
participants smoked VLNC cigarettes
(Refs. 250, 413, 417, and 426), and
several studies showed statistically
significantly reduced escalations in
heart rate compared to acute LNC, NNC,
or usual brand cigarette administration
(Refs. 64, 249, 265, 390, 405, 415, 427,
and 428).
Some studies also investigated the
effects of VLNC cigarettes on blood
pressure. Several studies found no
differences in blood pressure after
smoking a VLNC cigarette compared to
an LNC cigarette (Refs. 249 and 419),
NNC cigarette (Ref. 259), or usual brand
cigarette (Refs. 249, 259, and 419).
However, other studies showed
statistically significantly greater
increases in blood pressure after
smoking NNC or usual brand cigarettes
relative to VLNC cigarettes (Refs. 265
and 390).
A small number of studies examined
the effects of VLNC cigarettes on skin
temperature and skin conductance (a
measure of sympathetic nervous system
activity indicating psychological or
physiological arousal). Although one
study showed that skin temperature
decreased to a greater extent with NNC
cigarettes compared to VLNC cigarettes
(Ref. 259), another study found no
differences in skin temperature as a
function of nicotine content in cigarettes
(Ref. 426). Another study found no
statistically significant differences in
skin conductance between VLNC and
NNC cigarettes (Ref. 429).

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Taken together, findings from these
studies suggest that VLNC cigarettes
produce physiological responses that
are similar to or less pronounced than
those produced by NNC cigarettes.
These data suggest that the nicotine in
the VLNC cigarettes is able to elicit
physiological responses in people who
smoke cigarettes, although a portion of
the response may also be due to
sensorimotor cues, or other stimuli
associated with smoking, that may have
conditioned participants to produce
these physiological effects due to the
historical repeated pairings with
nicotine.
8. Neurological Effects
The main target of nicotine in the
central nervous system is the nicotinic
acetylcholine receptor (nAChR).
Positron emission tomography (PET)
and magnetic resonance imaging (MRI)
data obtained from humans who smoke
using an nAChR-specific radiotracer
indicates that after smoking a VLNC
cigarette, nAChR receptors located in
numerous areas of the brain are
occupied despite the lower nicotine
content of VLNC cigarettes (Ref. 430).
Nicotine also activates the
dopaminergic brain reward system,
which results in dopamine release and
a pleasure response. The release of
dopamine also initiates an adaptive
process in which an individual forms
learned associations between the
subjective state (e.g., pleasure) and the
object or context that led to that state
(e.g., the act of smoking a cigarette) (Ref.
389). Through this process, both
nicotine administration and smoking
stimuli (e.g., a cigarette, a lighter)
contribute to the cycle of nicotine
dependence (Ref. 38). Smoking NNC
cigarettes to satiety results in nearcomplete occupancy of nAChRs in the
brain (Refs. 431 and 432). In contrast,
although studies have shown there is
enough nicotine in VLNC cigarettes to
bind to nAChRs in the brain (Ref. 430)
and to release dopamine (Ref. 389),
results from these studies have also
shown the effects are smaller than those
observed from smoking NNC cigarettes.
These differences in nAChR occupancy
and dopamine release between VLNC
and NNC cigarettes may explain, in part,
why many studies have shown smoking
VLNC cigarettes does not consistently
produce the same magnitude of
subjective craving and withdrawal
responses observed following use of
NNC cigarettes (Refs. 398, 406, 407, 411,
413, 415, 417, 419, 422, 433 to 439).
Taken together, these findings
demonstrate that nicotine from smoking
VLNC cigarettes binds to nAChRs
located in numerous areas of the brain;

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however, nAChR receptor occupancy
and the magnitude of craving and
withdrawal responses observed
following use of VLNC cigarettes are not
as high as those following use of NNC
cigarettes.
9. Dependence
Combusted tobacco product use can
lead to symptoms of nicotine
dependence, which may include
tolerance to the effects of nicotine,
withdrawal upon cessation of use,
craving, and unsuccessful efforts to quit
smoking. Because dependence may take
time to develop or change, it is often
measured under conditions of extended
exposure. Studies typically assess
dependence with questionnaires,
including the Fagerstro¨m Test for
Nicotine Dependence (FTND),
Fagerstro¨m Test for Cigarette
Dependence (FTCD), Nicotine
Dependence Syndrome Scale (NDSS),
and Wisconsin Inventory of Smoking
Dependence Motives (WISDM).
Although some studies found no
evidence of a change in dependence
when the nicotine content of cigarettes
was gradually reduced, most studies
found evidence indicating that
switching to VLNC cigarettes decreases
dependence. Moreover, the evidence
suggests that immediate nicotine
reduction is more likely to lead to
decreases in dependence than gradual
reduction. These findings support the
hypothesis that lowering the nicotine
levels in cigarettes and certain other
combusted tobacco products would
reduce nicotine exposure and, thereby,
nicotine dependence in people who do
not to switch to another nicotinecontaining tobacco product.
In studies that gradually reduced the
nicotine content of cigarettes over the
course of weeks or months, the effects
of VLNC cigarettes on dependence were
somewhat mixed. In a study wherein
nicotine content was gradually reduced
(using NNC, LNC, and VLNC cigarettes)
over the course of 4 weeks, there was a
trend towards statistical significance
(i.e., if more participants had been
tested, the results may have become
statistically significant) in overall
reduction of dependence scores across
conditions (Ref. 329). Another gradual
reduction study found no difference in
dependence when comparing data from
baseline to week 26 in 135 participants
who smoked either gradually reduced
nicotine content cigarettes over the
course of 6 months or their own brand
cigarettes for the same duration (Ref.
258). However, when comparing only
data from week 14 to week 26, while
participants were primarily smoking
VLNC cigarettes, there was a statistically

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significant decrease in dependence in
the group that received gradually
reduced nicotine content cigarettes (Ref.
258). A secondary analysis of data from
51 people who smoke demonstrated that
participants with higher FTND scores at
baseline were more likely to
demonstrate signs of dependence during
the study, regardless of the nicotine
content of their study cigarettes (Ref.
381). In a followup study, participants
assigned to receive gradually reduced
nicotine content cigarettes were given
VLNC cigarettes for an additional 6
months, and no statistically significant
changes in dependence were observed
(Ref. 374).
In studies that immediately reduced
the nicotine content of cigarettes by
switching participants from usual brand
cigarettes to LNC or VLNC cigarettes,
dependence decreased in people who
smoked cigarettes who were not
interested in quitting compared to those
who smoked NNC or usual brand
cigarettes for 6 weeks (Ref. 29), 10
weeks (Ref. 30), or 12 weeks (Ref. 31).
In smoking cessation studies in which
participants endorsed wanting to quit,
VLNC cigarettes were also associated
with reductions in nicotine dependence
over time (Refs. 32 to 35). Conversely,
a trial in which people with serious
mental illness who smoke and were not
seeking smoking cessation treatment
were randomized to use either VLNC or
NNC cigarettes for 6 weeks showed no
statistically significant differences in
FTCD scores across VLNC and NNC
cigarette groups (Ref. 440). However,
these results may be explained by the
high level of noncompliance (i.e.,
ongoing use of NNC cigarettes or other
tobacco products) reported in the VLNC
cigarette condition (Ref. 440) (see
section VI.B of this document for further
discussion of noncompliance).
To date, one study compared the
effects of gradual versus immediate
nicotine reduction on FTND and
WISDM dependence scores (Ref. 379).
In a 20-week double-blind, parallel
design study, adults who smoke
cigarettes (n=1,250) were randomized to
an immediate reduction group that
received VLNC cigarettes, a gradual
reduction group that received cigarettes
containing progressively decreased
nicotine content every 4 weeks (15.5,
11.7, 5.2, 2.4, and 0.4 mg nicotine per
gram of total tobacco, respectively), or a
control group that received NNC
cigarettes. At the conclusion of 20
weeks, the immediate reduction group
showed statistically significantly lower
FTND and WISDM dependence scores
compared with the gradual reduction
group and the NNC cigarette control
group; no statistically significant

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differences in dependence scores were
observed between the gradual reduction
and control groups. These results
suggest that immediate nicotine
reduction is associated with reduced
nicotine dependence compared to
gradual reduction or continued use of
NNC cigarettes (Ref. 379).
The delay to smoking the first
cigarette of the day is a strong predictor
of dependence. In the only study to date
that examined the effects of VLNC
cigarettes on latency (i.e., delay) to
smoke in participants inhabiting a
residential research facility, time to first
cigarette was statistically significantly
longer among people who smoke who
only had access to VLNC cigarettes for
11 days compared to those who only
had access to NNC cigarettes,
supporting the potential for less
dependence over time among those who
switch to VLNC cigarettes (Ref. 64).
Accordingly, despite some mixed
results in studies using a gradual
decrease in nicotine content, most
evidence shows that switching to VLNC
cigarettes decreases dependence among
people who smoke cigarettes. The
evidence also suggests that immediate
nicotine reduction is more likely than
gradual reduction to lead to decreases in
dependence. For more discussion of the
scientific evidence supporting an
immediate nicotine reduction approach,
see section VII.C of this document.
10. Subjective Effects of VLNC
Cigarettes
Self-reported subjective effects (e.g.,
drug ‘‘liking,’’ ‘‘satisfaction’’) are widely
used measures of reinforcing efficacy
and abuse liability of drugs and tobacco
products. Drug ‘‘liking’’ is associated
with drug self-administration and has
been shown to be the most sensitive and
reliable subjective effects measure of
abuse liability (Ref. 441). Many studies
have compared the subjective effects of
VLNC, LNC, NNC, and participants’
usual brand cigarettes using selfreported measures of drug effects (e.g.,
Cigarette Evaluation Scale, Smoking
Effects Questionnaire, Visual Analogue
Scale items). These studies typically
found that VLNC cigarettes are ‘‘liked’’
less than NNC and usual brand
cigarettes and, therefore, subject to
lower abuse potential than NNC
cigarettes.
Under conditions of brief exposure
when participants were given limited
access to cigarettes that varied in
nicotine content, typically over the
course of several hours under controlled
laboratory conditions, studies generally
found that VLNC cigarettes were rated
lower in cigarette ‘‘liking’’ compared to
NNC or usual brand cigarettes (Refs.

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265, 383, 398, 399, 403, 410, 413, 428,
435, 437, 440, 442 to 448). However, a
few studies found no statistically
significant differences in ‘‘liking’’ as a
function of nicotine content in cigarettes
(Refs. 415, 419, 420, and 449). Many
studies also have evaluated other
subjective effects (such as ‘‘good’’ or
‘‘positive’’ effects and ‘‘bad’’ or
‘‘negative’’ effects) and found that they
vary together with drug ‘‘liking.’’ A
number of studies have shown that
VLNC cigarettes were rated lower on
other positive subjective effects items
(e.g., ‘‘satisfaction,’’ ‘‘pleasure,’’ ‘‘taste,’’
‘‘strength,’’ ‘‘stimulation’’) compared to
LNC cigarettes (Refs. 265, 412, 419, and
450), NNC cigarettes (Refs.265, 394, 396,
437, and 451) and usual brand cigarettes
(Refs. 390, 407, 413, and 452). VLNC
cigarettes were also rated lower on
effects such as ‘‘aversiveness,’’
‘‘sickness,’’ and ‘‘dizziness’’ (Refs. 390,
396, 414, 453, and 454), and higher on
items such as ‘‘dislike’’ and
‘‘unpleasant’’ compared to NNC or usual
brand cigarettes (Refs. 265 and 383).
These seemingly contradictory findings
are likely due to the constructs that
these subjective effects measure;
‘‘aversiveness,’’ ‘‘sickness,’’ and
‘‘dizziness’’ are used to measure direct
sensory and physical effects of nicotine,
while ‘‘dislike’’ and ‘‘unpleasant’’ are
used to measure general product liking.
Although often assumed, recent
findings confirm that greater immediate
positive subjective effect ratings (e.g.,
‘‘liking,’’ ‘‘satisfaction’’) predict greater
acute reinforcing effects of cigarettes of
varying nicotine content (Ref. 455).
Several factors have been shown to
influence subjective effects ratings of
VLNC and NNC cigarettes. These factors
include participants’ ability to
discriminate the nicotine content of
cigarettes. For example, NNC cigarettes
have increased ratings of positive
subjective effects when participants are
able to discriminate them from VLNC
cigarettes (Refs. 400 and 401).
Individuals who smoke menthol
cigarettes rated both VLNC and NNC
cigarettes higher in positive subjective
effects compared to people who smoke
nonmenthol cigarettes (Ref. 456). In
addition, positive subjective effects
ratings are higher when participants are
told that they are receiving a nicotinecontaining cigarette, regardless of the
actual nicotine content of the cigarette
(Refs. 428, 435, 444, 445, and 457).
Several studies assessed subjective
effects of VLNC cigarettes following
extended exposure when participants
were given less restricted access to
cigarettes of varying nicotine content in
their natural environments (e.g., homes,
workplaces), typically over the course of

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several weeks. Findings from these
studies were relatively similar to
findings from brief exposure studies. On
average, VLNC cigarettes were rated as
less appealing (e.g., lower ratings of
‘‘liking,’’ ‘‘satisfaction,’’ or ‘‘pleasure’’)
compared to LNC and NNC cigarettes
(Refs. 249 and 384). However, at least
one study found no differences in
subjective effects as a function of
cigarette nicotine content (Ref. 258).
Positive subjective effects ratings for
VLNC cigarettes were shown to remain
constant or decrease over time (Refs.
249 and 373).
In a study where people who smoke
inhabited a residential research facility,
during 11 days of exposure, participants
who received NNC cigarettes rated
positive subjective effects lower and
negative subjective effects higher than
baseline subjective effects of usual
brand cigarettes (indicative of a general
dislike of research cigarettes); however,
subjective ratings of NNC study
cigarettes increased and were similar to
usual brand cigarettes by the end of the
study (Ref. 64). In contrast, participants
assigned to the VLNC cigarette group
rated positive subjective effects of
cigarettes (e.g., ‘‘enjoyable’’) lower and
negative subjective effects (e.g.,
‘‘unpleasant’’) higher than baseline
subjective effects of usual brand
cigarettes throughout the entire study
period (Ref. 64).
Finally, gender may influence
differences in subjective effects. In one
study, women rated all cigarettes as
more flavorful than men, and an
interaction was observed between
gender and nicotine content such that
women demonstrated less sensitivity
than men to the differential subjective
effects of NNC and VLNC cigarettes (Ref.
447). Another study found that women
reported increased satisfaction with
VLNC or LNC cigarettes alone, while
men reported greater satisfaction when
these cigarettes were combined with
NRT (Ref. 458). Finally, one study found
that women reported higher
psychological reward than men across
all nicotine contents tested (Ref. 459).
In sum, subjective effects data
consistently show that VLNC cigarettes
have equal or lower abuse potential
compared to NNC and usual brand
cigarettes under conditions of brief and
extended exposure. FDA is not aware of
any studies that found that VLNC
cigarettes had greater abuse potential
than NNC or usual brand cigarettes.
11. The Effects of VLNC Cigarettes on
Relief From Craving and Withdrawal
Symptoms
Symptoms of nicotine and tobacco
withdrawal may include irritability,

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depression, insomnia, headache, and
increased craving. Although craving is
often characterized as a symptom of
nicotine and tobacco withdrawal, it is
also a symptom of dependence, and it
can occur in the absence of other
withdrawal symptoms. Thus, craving is
usually measured and reported
separately from withdrawal. Studies
typically assess craving and withdrawal
using the Questionnaire of Smoking
Urges (QSU), QSU-Brief, Minnesota
Nicotine Withdrawal Scale (MNWS),
Shiffman-Jarvik Withdrawal Scale, and
Visual Analogue Scale items. Despite
their lower nicotine content, VLNC
cigarettes typically do not produce
greater reports of craving or other
withdrawal symptoms. Although
findings from some brief exposure
studies are mixed, the results of many
studies suggest that brief and extended
exposure to VLNC cigarettes can
suppress craving and withdrawal just as
effectively as NNC and usual brand
cigarettes. The ability of VLNC
cigarettes to suppress craving and
withdrawal in people who smoke
cigarettes is likely at least partially due
to the long history of pairings between
nicotine and the sensorimotor stimuli
associated with smoking. Through
conditioning, these stimuli can suppress
craving and some other withdrawal
symptoms even in the absence of
nicotine (Ref. 38).
In brief exposure studies where
participants were given limited access
to reduced nicotine content cigarettes,
typically over the course of several
hours under controlled laboratory
conditions, VLNC cigarettes suppressed
craving and withdrawal relative to
baseline measures that were typically
assessed following overnight abstinence
(Refs. 452, 460 to 467). Furthermore,
many studies showed that VLNC
cigarettes can reduce craving and
withdrawal as much as usual brand or
NNC cigarettes (Refs. 391, 406, 407, 411,
413, 415, 417, 419, 422, 433 to 439).
However, some studies observed that
suppression of craving and withdrawal
was lower after smoking VLNC
cigarettes compared to usual brand or
NNC cigarettes (Refs. 265, 396, 388, 402,
427, 440, 453, 454, 468, and 469). In
addition, results from a few studies
suggest that VLNC cigarettes influence
craving more than withdrawal. One
study found that VLNC cigarettes
suppressed craving similarly to NNC
cigarettes, but also produced an increase
in other withdrawal symptoms (Ref.
470). Other studies have found no
effects of VLNC cigarettes on
withdrawal symptoms (Refs. 414, 428,
and 448). Notably, some of these brief

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exposure studies reported differences
between genders and generally found
that females who smoke experienced
greater reductions in craving (Refs. 265,
463 and 464) or withdrawal (Refs. 436
and 462) compared to males who smoke
after smoking VLNC cigarettes.
However, another study found that, after
smoking VLNC cigarettes, males who
smoke had greater reductions in craving
compared to females who smoke (Ref.
435).
During extended exposure studies,
when participants smoked VLNC
cigarettes from 4 days to 1 year, ratings
of withdrawal (Refs. 249 and 258) and
craving (Refs. 249 and 383) were
generally similar to ratings observed in
usual brand and NNC cigarette
conditions. In one study, researchers
found that, after switching to VLNC
cigarettes from usual brand cigarettes for
1 week, withdrawal symptoms
increased with no reported change in
craving (Ref. 32). However, these effects
were relatively brief, and, within 6
weeks, withdrawal symptoms returned
to baseline levels, and craving steadily
decreased below baseline levels. Results
from another study showed that VLNC
cigarettes can produce persistent
reductions in craving characterized by
participants as ‘‘moderate’’ or ‘‘a lot’’
after 3 and 6 weeks of exposure;
however, some participants reported
that no relief from craving occurred
during the 6-week study (Ref. 373). In
addition, one study demonstrated that 6
weeks of exposure to LNC and VLNC
cigarettes resulted in less craving and no
difference in other withdrawal
symptoms compared to NNC cigarettes
(Ref. 471). Finally, during week 1 of a
20-week trial, people who smoke and
were randomized to immediately reduce
nicotine with VLNC cigarettes reported
statistically significantly more
withdrawal symptoms compared to
those who gradually reduced nicotine
content every 4 weeks (15.5 (NNC), 11.7
(NNC), 5.2 (LNC), 2.4 (LNC), and 0.4
(VLNC) mg nicotine per gram of total
tobacco, respectively) and compared to
a control group using NNC cigarettes
(Ref. 379). However, at the conclusion of
20 weeks, the immediate reduction
group reported statistically significantly
lower smoking urges compared with the
gradual reduction group and the NNC
cigarette control group. No statistically
significant differences in smoking urges
were observed between the gradual
reduction group and the NNC cigarette
control group, suggesting that gradual
reduction may be less effective than
immediate reduction in reducing urge to
smoke. Similar to findings from brief
exposure studies, female participants

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experienced a reduction in craving after
switching to LNC cigarettes for 1 week,
whereas male participants showed no
change in craving upon switching.
Overall, withdrawal symptoms
increased in both males and females
who smoke cigarettes after 1 week.
However, these differences from
baseline were short-lived. Ratings of
both craving and withdrawal symptoms
were no different than baseline over the
remaining 6 weeks of the study (Ref.
458).
Craving and withdrawal were also
assessed in several smoking cessation
studies wherein participants were
provided VLNC cigarettes along with
pharmacotherapies (e.g., NRT,
varenicline) before a designated quit
date. In these studies, participants who
received VLNC cigarettes plus a nicotine
patch experienced less severe cravings,
with no statistically significant
difference in withdrawal (Ref. 472), a
greater reduction in craving and
withdrawal (Ref. 35), and less frequent
and less intense cravings before and
after the quit date (Ref. 372) compared
to those who received NNC cigarettes
before the quit date. Another study
found that LNC cigarettes plus either
varenicline or NRT resulted in decreases
in craving compared to
pharmacotherapy alone, with no
differences in withdrawal across groups
(Ref. 371).
Accordingly, findings from these
studies suggest that the maximum
nicotine level in this proposed product
standard, consistent with VLNC
cigarette levels, would not result in
substantial increases in craving or other
withdrawal symptoms.
12. VLNC Cigarette Data Applies to
Other Covered Products Under This
Proposed Product Standard
Research regarding the public health
impacts of this proposed maximum
nicotine level applies across the tobacco
products covered under this proposed
product standard. People who smoke
cigarettes who have lower SES have a
greater likelihood of choosing to use
RYO tobacco as a cheaper alternative to
factory-made cigarettes (Ref. 312, Ref.
319). Also, literature shows that tobacco
manufactures reformulate or re-label
pipe tobacco as ‘‘dual purpose’’ and sell
it for RYO use to capitalize on
disparities between tax rates on
different types of tobacco products (Ref.
322). Given that cigarette tobacco, RYO
tobacco, and pipe tobacco can be
effectively used in cigarettes, the VLNC
cigarette research applies to these
products, and any expected benefits that
would accrue as a result of instituting
the proposed product standard for

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cigarettes also would be expected to
accrue for these product categories.
While the current published literature
regarding very low nicotine products
discusses only cigarettes, the many
similarities between cigarettes and most
cigars (in both appearance and use
topography) support the application of
VLNC cigarette research to the coverage
of these cigars. For example, little cigars
are often indistinguishable from
cigarettes given their shape, size, filters,
and packaging, and are perceived as
being healthier than cigarettes (Refs. 297
and 298). Little cigars and certain
cigarillos also ‘‘are packaged and
consumed in a manner similar to
cigarettes’’ (Ref. 473 at p. 584). The
close resemblance of little cigars and
many cigarillos to cigarettes have led
consumers, particularly children and
young adults, to mistake them for
cigarettes (Ref. 474). Because they are
physically similar to cigarettes, little
cigars are generally smoked the same
way as cigarettes, with deeper
inhalation than large cigars (Refs. 53
and 475). Secondhand smoke from
cigars also contains many of the same
toxins and carcinogens as cigarette
smoke, including carbon monoxide,
nicotine, ammonia, benzene,
nitrosamines, and formaldehyde, all of
which are on FDA’s list of HPHCs
(HPHC Established List, 77 FR 20034
(2012)). Moreover, people who smoke
cigarettes who switch to products like
cigars to sustain their addiction tend to
engage in deeper inhalation, making
them even more susceptible to the
dangers associated with tobacco product
use (Ref. 53).
Studies also suggest that people
smoke some cigarillos like cigarettes,
inhaling and smoking them every day
(Refs. 53 and 475). Research has found
that little cigars deliver nicotine levels
similar to, and sometimes higher than,
cigarettes, as well as similar or higher
levels of carcinogens compared to
cigarettes (Refs. 476 and 477). Large
cigars can deliver as much as ten times
the nicotine of a filtered cigarette (Ref.
53). Even if people who smoke cigars do
not breathe or inhale smoke into their
lungs, they are still subject to nicotine’s
addictive effects through buccal
absorption of nicotine or nicotine
absorption through the lips due to cigar
tobacco’s alkalinity (Refs. 54 to 56, 302
and 303). Cigar smoke dissolves in
saliva and makes it possible for people
who smoke cigars to absorb sufficient
amounts of nicotine to create
dependence (Ref. 56). People who
smoke cigars regularly are at increased
risk for many of the same diseases as
people who smoke cigarettes, including
oral, esophageal, laryngeal, and lung

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cancer; cardiovascular diseases; and
COPD (Ref. 163). Accordingly, FDA
believes it is appropriate to bridge these
VLNC cigarette studies to cigars.
C. An Immediate Nicotine Reduction
Approach Is Strongly Supported by
Scientific Evidence
Two approaches have been suggested
for implementing a nicotine product
standard that would limit nicotine yield
by establishing a maximum level of
nicotine content in cigarettes and
certain other combusted tobacco
products. One is a gradual reduction
approach, which decreases the nicotine
content in the tobacco products over
time until it reaches minimally
addictive or nonaddictive levels. The
other is an immediate reduction
approach, or single target approach,
which would immediately reduce the
nicotine content to minimally addictive
or nonaddictive levels. Available
research indicates that both approaches
are associated with noncompliance (i.e.,
use of NNC cigarettes) when
participants reach the VLNC cigarette
phase of the intervention, which
supports findings from other studies
that show people who use VLNC
cigarettes are more likely to use
alternative nicotine-containing products
when such products are concurrently
available. However, the available
scientific evidence suggests that the
gradual approach can lead to
compensatory smoking during the
intermediate steps when people are
smoking products with low to moderate
nicotine content.
Based on scientific evidence, as well
as comments and information submitted
in response to the Nicotine ANPRM,
FDA is proposing an immediate
reduction approach to reach the
maximum nicotine level in this
proposed product standard. We expect
that there would be very little
compensatory smoking with an
immediate reduction approach and that
any compensatory smoking would be
self-limiting and transient (i.e., research
shows that people who smoke would be
unable to obtain their nicotine dose
from VLNC cigarettes no matter how
they smoked them and would quickly
stop trying to do so), which would
increase the benefits of the proposed
product standard. We anticipate most
people who smoke will maintain usual
smoking behavior during these 2 years.
An attempt to taper nicotine intake
could involve switching to VLNC
cigarettes already on the commercial
market (i.e., VLN® cigarettes), reducing
the number of cigarettes smoked per
day, or switching to another tobacco
product. Tapering nicotine intake while

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NNC cigarettes are on the market may
facilitate abstinence in smokers by
increasing motivation to quit and quit
attempts. However, we do not expect
most people who smoke to switch to
VLNC cigarettes while NNC cigarettes
are available. We request comments,
data, and information regarding the
selection of an immediate reduction
approach.
Several studies have investigated the
effects of a gradual approach to reducing
cigarette nicotine content on
compensatory smoking (Refs. 40, 258,
329, and 384). In these studies,
participants were not interested in
quitting and did not receive NRT or
alternative tobacco products. For
example, a pilot study and a clinical
trial examined whether a gradual
reduction in cigarette nicotine content
would increase exposure to tobacco
smoke toxins due to compensatory
smoking (Refs. 40 and 258). Participants
smoked their usual brand cigarettes
during baseline and then were switched
to five types of research cigarettes
containing gradually reduced nicotine
content (i.e., 10.3 (NNC), 6.5 (LNC), 3.9
(LNC), 1.7 (LNC), and 0.5 (VLNC) mg
nicotine per cigarette). In the 10-week
pilot study, participants were switched
weekly, and in the 6-month trial,
participants were switched monthly
(Refs.40 and 258). Little change in
smoking behavior was observed;
however, plasma cotinine concentration
(a biomarker of nicotine exposure)
decreased as a function of cigarette
nicotine content, such that cotinine was
lowest while participants were smoking
VLNC cigarettes. The smaller pilot study
showed little evidence of compensation,
as calculated based on cigarette
consumption, CO, and polycyclic
aromatic hydrocarbon (PAH)
metabolites (Ref. 40); however, the 6month trial showed a slight increase in
compensatory smoking, as measured by
CO and CPD, while participants were in
the intermediate phase of the study.
This increase was no longer evident
once participants reached the VLNC
cigarette phase of the study (Ref. 258).
Another study showed that
compensatory smoking may increase
when participants smoke cigarettes with
intermediate levels of nicotine (e.g.,
LNC cigarettes) compared to usual
brand cigarettes (Ref. 384). Taken
together, these studies demonstrate that
people who smoke cigarettes may
engage in compensatory smoking during
the early stages of a gradual reduction
approach by smoking more intensely in
an attempt to obtain their desired level
of nicotine (Refs. 258, 329, and 369).
Several studies have investigated
whether an immediate reduction

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approach to nicotine reduction would
increase compensatory smoking (Refs.
29 and 31). Like the gradual reduction
studies discussed in this section,
participants in these immediate
reduction studies were not interested in
quitting and did not receive NRT or
alternative tobacco products. In the
most comprehensive immediate
nicotine reduction study to date, 839
participants were randomized to one 6week condition, during which they
smoked their usual brand cigarettes or
immediately switched to research
cigarettes containing either 15.8 (NNC),
5.2 (LNC), 2.4 (LNC), 1.3 (LNC), or 0.4
(VLNC) mg nicotine per gram of total
tobacco (Ref. 29). Participants assigned
to the LNC or VLNC cigarette groups,
who received cigarettes with nicotine
content less than or equal to 2.4 mg
nicotine per gram of total tobacco,
smoked statistically significantly fewer
CPD than participants assigned to the
usual brand and NNC cigarette groups.
Those who received LNC or VLNC
cigarettes containing 5.2 mg nicotine per
gram of total tobacco or less had
statistically significantly lower urinary
TNE than those who received NNC
cigarettes. There were no differences in
breath CO measures, an indicator of
compensatory smoking, between the
cigarette groups. The total puff volume
at week 6 was statistically significantly
lower among participants who smoked
VLNC cigarettes compared to those who
smoked NNC cigarettes. However, much
like the gradual reduction studies, a
secondary analysis showed that
noncompliance (i.e., ongoing use of
NNC cigarettes or other tobacco
products) was high in participants
randomized to the VLNC cigarette
group, suggesting that VLNC cigarettes
have lower appeal and abuse liability
compared to NNC cigarettes and that
people who smoke VLNC cigarettes are
likely to obtain nicotine from other
tobacco product use (Ref. 330).
In another study, 33 participants were
randomized to receive VLNC cigarettes
at no charge or to continue smoking
their usual brand cigarettes for 12 weeks
(Ref. 31). Overall, participants in both
groups smoked a similar total number of
CPD, even though only the participants
in the VLNC cigarette group received
free cigarettes. These data demonstrate
that an immediate reduction in cigarette
nicotine content is unlikely to lead to
significant compensation or increased
toxicant exposure.
A secondary analysis pooled data
from five clinical studies to examine the
relationship between compensatory
smoking and gradual versus immediate
nicotine reduction approaches (Ref.
387). Two of the studies utilized a

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gradual reduction approach, and three
of the studies utilized an immediate
reduction approach. CPD, breath CO,
and cotinine levels were compared
between the immediate reduction group,
the gradual reduction group, and a
control group that received usual brand
cigarettes. Relative to baseline,
statistically significant decreases in CPD
were observed in participants in the
gradual reduction groups (5 percent
decrease in CPD) and immediate
reduction groups (11 percent decrease
in CPD), whereas statistically significant
increases in CPD were observed in
participants in the usual brand groups
(12 percent increase in CPD). Although
statistically significant changes in
breath CO were not observed relative to
baseline in any group, statistically
significant decreases in cotinine were
observed among both gradual and
immediate reduction groups, but not in
the usual brand group.
The largest study designed to directly
investigate gradual versus immediate
nicotine reduction on toxicant exposure
was a 10-site, randomized, double-blind
clinical study in 1,250 adults who
smoke and had no intention to quit (Ref.
379). Participants were randomly
assigned to an immediate reduction
group that received VLNC cigarettes for
20 weeks, a gradual reduction group
that received cigarettes containing
progressively decreased nicotine
content every 4 weeks (15.5, 11.7, 5.2,
2.4, 0.4 mg nicotine per gram of total
tobacco) for 20 weeks, or a control group
that received NNC cigarettes for 20
weeks. Notably, in this study (and
virtually all clinical studies of reduced
nicotine content cigarettes), research
cigarettes were free to participants. Any
changes in biomarker levels observed
between these two groups would
indicate differences in smoking
behavior (e.g., CPD, smoking
topography). Completion rates were
statistically significantly lower for the
immediate reduction group (68 percent)
compared to the gradual reduction
group (81 percent) and control group (86
percent). The immediate reduction
group had statistically significantly
lower levels of three primary biomarker
outcomes (i.e., CO, 3–HPMA, and r-1,t2,3,c-4-tetrahydroxy-1,2,3,4
tetrahydrophenanthrene) compared to
the gradual reduction group, which did
not differ from the control group. In
addition, statistically significantly lower
levels of other biomarkers (i.e., TNE,
NNAL, 2-cyanoethylmercapturic acid, 3hydroxy-1-methylpropylmercapturic
acid, S–PMA) were observed in the
immediate reduction group compared to
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groups. The immediate reduction group
smoked cumulatively fewer CPD over
the course of the 20-week study and had
lower nicotine dependence scores
compared to the gradual reduction
group, with no statistically significant
differences in CPD or dependence in the
gradual reduction versus control groups.
While there was no statistically
significant difference between the
immediate and gradual reduction
groups in the proportion of participants
with any ‘‘cigarette-free days’’ during
the study, the immediate reduction
group had a statistically significantly
higher number of ‘‘cigarette-free days’’
compared to the gradual reduction
group. The immediate reduction group
had statistically significantly higher
withdrawal scores at week 1 compared
to the gradual reduction group;
however, these differences dissipated
after the first week. The immediate
reduction group had higher rates of
noncompliance with non-study cigarette
use and a higher drop-out rate, which
may have impacted the various outcome
measures (e.g., biomarkers of exposure).
Additionally, the immediate reduction
group had an increased number of
adverse events (predominantly related
to withdrawal) compared to the gradual
reduction group. Nevertheless, this
study provides further evidence that
immediate nicotine reduction is
associated with reduced toxicant
exposure and nicotine dependence and
increased smoking abstinence compared
to gradual nicotine reduction. This
suggests that with immediate nicotine
reduction, the potential health benefits
could occur sooner than gradual
nicotine reduction. While the
immediate reduction group had
increased levels of nicotine withdrawal,
this effect was time-limited, dissipating
after 1 week (Ref. 379).
Higher study attrition and
noncompliance with study cigarettes are
common within VLNC cigarette
conditions in clinical studies (Refs. 327,
329, and 330), especially studies such as
the one described above (Ref. 379),
wherein participants are not interested
in quitting smoking, and they are asked
to refrain from using alternative sources
of nicotine. Because of the lower abuse
liability of VLNC cigarettes, participants
in these studies may drop out or use
non-study cigarettes that contain
nicotine. These conditions would not
exist if the proposed product standard is
implemented. People who smoke would
not be able to readily obtain NNC
cigarettes, but they would be able to
obtain alternative noncombusted
products with nicotine content that they

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could switch to or use with VLNC
cigarettes.
In sum, evidence from studies
involving VLNC cigarettes suggests it is
likely that there would be very little or
no compensatory smoking with an
immediate reduction approach to a
maximum nicotine level, which would
increase the public health impact of a
nicotine reduction policy. Additionally,
FDA believes an immediate reduction
approach would have a lesser impact on
manufacturers as compared to a gradual
approach by limiting any changes
necessary for compliance to a single
occasion. Although FDA believes this is
a benefit of the immediate reduction
approach, it is not a determinative factor
given the strength of the scientific
evidence.
D. Scientific Evidence Supports the Use
of an Analytical Test Method To
Determine Nicotine Level
In its considerations regarding the use
of an analytical test method, FDA
determined that any analytical method
to measure compliance must accurately
and reliably detect nicotine at low
concentrations (i.e., below 0.70 mg
nicotine per gram of total nicotine). In
addition, FDA determined that it is
important that the proposed product
standard permit comparison of test
results among finished tobacco products
and testing facilities. FDA also
concluded that it is important that the
test method demonstrate its suitability
and reliability in accurately measuring a
range of nicotine concentrations across
a wide variety of tobacco blends and
products. Accordingly, FDA is
proposing to require manufacturers use
an analytical test method that would
satisfy these preceding factors and
demonstrate that the test method was
validated in an analytical test
laboratory. In lieu of requiring a
specified test method, we are
recommending manufacturers consider
using one of the three following
analytical test methods FDA has
determined satisfy the preceding factors:
FDA’s Tobacco Products Laboratory
method (Ref. 478), Cooperation Centre
for Scientific Research Relative to
Tobacco (CORESTA) Recommended
Method (CRM) No. 62 (Determination of
nicotine in tobacco and tobacco
products by gas chromatographic
analysis; (Ref. 479)), or CRM No. 87
(Determination of nicotine in tobacco
products by gas chromatography-mass
spectrometry (GC–MS); (Ref. 480)).
However, an analytical test method that
meets the requirements of the
regulation, even if it is not one of the
recommended methods, would be
acceptable.

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FDA’s Tobacco Products Laboratory,
located in Atlanta, Georgia, has
developed an analytical test method,
entitled ‘‘Quantitation of Nicotine in
Tobacco Products—Update to LIB No.
4550’’ (LIB #4692), that is capable of
quantifying nicotine levels that include
concentrations well above and below
the proposed nicotine standard level
and also meets formal intralaboratory
validation criteria (Ref. 478). The
method utilizes GC–MS with a run time
of 4.1 minutes. Analysis is conducted
on extracted tobacco or spiked surrogate
matrix samples treated with a base
(sodium hydroxide) to obtain the total
nicotine content for each sample.
Quinoline is used as the internal
standard. Tomato leaves are used as a
surrogate matrix for tobacco to examine
recovery amounts for spiked samples.
Validation was performed using
Moonlight brand VLN Menthol King
ground tobacco and NIST 1573a
(Tomato Leaves) as a blank spiking
matrix. The range of the method was 0.1
to 2.0 mg of nicotine per gram of total
tobacco, meaning nicotine
concentrations in this range can be
accurately measured. Tobacco samples
with nicotine concentrations expected
to be higher than 2.0 mg nicotine per
gram of total tobacco were analyzed
after dilution of the extraction sample
by a factor of ten. The method detection
limit is 0.05 mg nicotine per gram of
total tobacco, which is more than an
order of magnitude below the proposed
maximum nicotine concentration of
0.70 mg per gram of total tobacco. The
limit of quantitation is 0.1 mg nicotine
per gram of total tobacco, which is also
well below the limit of the proposed
product standard. Furthermore, this
method was proven to be applicable to
a wide range of tobacco products.
Tobacco filler and total tobacco from
various marketed tobacco products
including cigarettes, large cigars,
cigarillos, little cigars, RYO cigarettes
and pipe tobacco were analyzed
successfully using FDA’s Tobacco
Products Laboratory method.
CORESTA updated CRM No. 62
(Determination of Nicotine in Tobacco
and Tobacco Products by Gas
Chromatographic Analysis) in December
2021 and CRM No. 87 (Determination of
Nicotine in Tobacco Products by Gas
Chromatography-Mass Spectrometry
(GC–MS)) in April 2020 to extend the
scope of the methods to include VLNC
tobacco by lowering the calibration
range for these analytical test methods
(Refs. 479 and 480). A study determined
that the updated versions of CRM No. 62
and CRM No. 87 are suitable for the
analysis of nicotine content in VLNC

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tobacco and tobacco products (Ref. 481).
These methods can reliably measure
nicotine content as low as 0.117 mg per
gram of total tobacco.
FDA’s Tobacco Products Laboratory
method, entitled ‘‘Quantitation of
Nicotine in Tobacco Products—Update
to LIB No. 4550’’ (LIB #4692), is
publicly available at https://
www.fda.gov/science-research/fieldscience-and-laboratories/laboratoryinformation-bulletins. In addition to the
Tobacco Products Laboratory method,
CRM No.62 (https://www.coresta.org/
determination-nicotine-tobacco-andtobacco-products-gas-chromatographicanalysis-29185.html) and CRM No. 87
(https://www.coresta.org/determinationnicotine-tobacco-products-gc-ms33537.html) are also publicly available
methods that include the proposed
nicotine level in the range of
concentrations that can be accurately
measured. FDA recommends
manufacturers use one of these
analytical test methods to demonstrate
compliance with this proposed product
standard.
It is reasonable to expect some
manufacturers may prefer to use other
test methods. If developed and
validated, such methods may have
different advantages in ease of use,
upper and lower bounds of detection,
equipment, and expertise. We would
evaluate data from analytical test
methods as part of a premarket
submission in accordance with section
910 of the FD&C Act.
FDA requests comments, including
data or other scientific support,
regarding FDA’s Tobacco Products
Laboratory method, CRM No. 62, CRM
No. 87, or other available methods, that
could test the proposed scope of tobacco
products at the proposed maximum
nicotine level.
E. Scientific Evidence Supports the
Technical Achievability of the Proposed
Maximum Nicotine Level Target
While FDA has analyzed various
methods of technical achievability for
this proposed product standard, section
907(b)(1) of the FD&C Act also requires
FDA to consider information submitted
in connection with the proposed
product standard regarding the
technical achievability of compliance.
Therefore, pursuant to section 907(d)(2)
of the FD&C Act, FDA requests
comments by interested parties,
including manufacturers and tobacco
growers, regarding the technical
achievability of compliance with this
proposed product standard, including
information concerning the existence of
patents that may impact the ability to
comply by the proposed 2-year effective

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date of this proposed rule (see section
XI of this document).
The tobacco industry has developed a
range of brands with differing nicotine
levels. Tobacco product manufacturers
have extensive experience blending
tobaccos with different nicotine levels
to ensure that products will have
precise levels of nicotine and using
continuous quality testing throughout
the entire process to ensure that
nicotine levels vary only minimally
within cigarette packs and from pack to
pack (Ref. 482). A cigarette is an
inexpensive and extremely effective
nicotine delivery system that maximizes
the cigarette’s addicting and toxic
effects (Ref. 61).
In fact, the tobacco industry has had
programs in place since the 1960s to
obtain ‘‘any level of nicotine desired’’
(Ref. 2) (see section V.A for a detailed
discussion). Indeed, the tobacco
industry conducted research on
consumer perceptions of RNC cigarettes
to determine the optimal amount of
nicotine in cigarettes to maintain
appeal. Reviews of industry documents
indicate that user experience, such as
poor taste and reduced throat
sensations, impacted the commercial
viability of VLNC cigarettes (Refs. 247,
483, and 484). Internal industry
strategies to mitigate these issues and
maintain VLNC cigarette appeal to
consumers included adding menthol to
enhance the flavor of RNC cigarettes
(Ref. 484) and maintaining or increasing
tar levels to improve taste (Ref. 483).
As discussed in this section, there are
numerous methods for altering the
concentration of nicotine in cigarettes
and certain other combusted tobacco
products, and FDA anticipates that
manufacturers and tobacco farmers may
choose to use a variety of approaches to
meet the proposed maximum nicotine
concentration. Significant reduction of
nicotine in the tobacco products
covered by this proposed product
standard can be achieved principally
through tobacco blending, chemical
extraction, or genetic engineering. Other
practices such as modified growing
conditions (e.g., discontinue the
practice of topping where the flowering
head of the tobacco plant is removed to
produce leaves with a significantly
higher nicotine content, increase plant
density, decrease nitrogen application),
as well as more recent novel techniques,
can also help to reduce nicotine levels.
One or a combination of these processes
can be used to achieve the nicotine
target concentration in this proposed
product standard.

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1. Genetically Engineered Tobacco
Tobacco industry scientists have long
recognized the potential for genetic
engineering to control nicotine content
(Ref. 485). The first practical application
of biotechnology by a major tobacco
manufacturer was the development of
low nicotine content tobacco in the
1980s, which led to the receipt of a
patent for biotechnology for altering
nicotine in tobacco plants (Refs. 483 and
486). Other tobacco researchers and
major manufacturers also recognized the
value of biotechnology for developing
low nicotine content tobacco for
cigarettes, including for use as part of a
smoking cessation program (Ref. 487).
In the 1930s, some Havana and Cuban
cigar tobacco varieties were discovered
to have naturally lower nicotine levels.
Genetic analysis of these low nicotine
containing plants identified a mutation
in the nic1 and nic2 genes that are
responsible for the production of
reduced nicotine in some tobacco
variety leaves (Ref. 488). These varieties
of low nicotine content cigar tobacco
were crossbred with burley tobacco to
produce varieties of cigarette tobacco
with low nicotine content to meet the
health demands of the time (Ref. 489).
Several American and international
tobacco companies genetically
engineered low-nicotine strains in the
1960s and 1970s (Refs. 490 to 493),
including a strain with a nicotine
concentration as low as 0.15 percent
(i.e., 1.5 mg nicotine per gram of total
tobacco), which was much lower than
the 3.15 percent (31.5 mg nicotine per
gram of total tobacco) observed in the
comparator strain (Ref. 492). During that
time period, the Kentucky Tobacco
Research Board worked on genetic
strains of low nicotine content tobacco
(with a nicotine content of 0.2 percent)
to be used for experimental studies on
the role of nicotine in smoking behavior
(Refs. 493 to 497). In addition, Canadian
researchers examined low nicotine
strains of tobacco, particularly in
association with efforts to develop a
strain of flue-cured or air-cured tobacco
that would be suitable as the base
material for reconstituted tobacco (Refs.
493, 498, and 499). Although the early
strains of low-nicotine tobacco that were
developed by these researchers and
companies contained far less nicotine
than strains that were traditionally used
to make cigarettes, the nicotine content
is even lower in strains that have been
developed more recently through
genetic engineering.
Genetic engineering has resulted in
up to a 98 percent reduction in nicotine
levels (Ref. 483). In 2003, Vector
Tobacco began marketing the Quest

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cigarette produced from genetically
modified tobacco containing only trace
amounts of nicotine (this product is no
longer on the market) (Ref. 483). In
2014, the U.S. Patent and Trademark
Office granted a patent for two genes
that may be suppressed to substantially
decrease nicotine in tobacco plants (Ref.
500). Additionally, in 2020, the U.S.
Patent and Trademark Office granted
another patent for methods of
manipulating plant metabolism and
alkaloid levels by controlling
transcription factor NbTF7, which
regulates the nicotinic alkaloid
biosynthetic pathway in the Nicotiana
tabacum plant (Ref. 501). This method
appears to be able to introduce very low
nicotine traits in any variety of
Nicotiana tabacum; therefore, this
method may be applicable to other
combusted tobacco products that use
Nicotiana tabacum (e.g., cigars).
Significant progress has been made in
the genetic modification of nicotine and
other alkaloid production in tobacco.
One powerful gene editing technology,
CRISPR-Cas9, has been used to delete or
silence various genes involved in the
production of nicotine in tobacco plants
resulting in several ultra-low nicotine
CRISPR tobacco lines that have been
grown experimentally (Ref. 502).
However, challenges have presented
themselves in transitioning these ultralow nicotine content tobacco plants to
fields, such as severely stunted plants
and high insect infestation rates (Ref.
503). Studies on the impact of
genetically engineered low-level
nicotine are ongoing and this method
has not been accomplished on a large
scale.
FDA is aware that genetically
engineered tobacco seed has been
created and may be available for
purchase on the market. If this proposed
rule is finalized, licensing agreements
may be needed to support production of
VLNC tobacco, at least initially. FDA
notes that similar agreements with
tobacco manufacturers are common
within the tobacco industry.
2. Chemical Extraction
Another method to achieve lower
nicotine concentrations in tobacco
products is through chemical extraction
technology. By the 1970s, tobacco
manufacturers were regularly practicing
nicotine extraction as a method to
control nicotine delivery (Refs. 493 and
504 to 506). Extraction methods include
water extraction (coupled with steam or
oven drying), solvent extraction, and
extractions of nicotine without usable
leaf (Ref. 493). For example, one
company, Ultratech, Inc., produced
VLNC cigarettes by extracting nicotine

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with an alkaline solution (Ref. 507).
Supercritical fluid extraction (which
extracts chemical compounds using
supercritical carbon dioxide instead of
an organic solvent) also yielded success
in the 1990s, allowing for optimum
extraction times and the elimination of
more time-consuming steps (Ref. 508).
FDA notes that existing patents for
chemical extraction reveal that more
than 96 percent of nicotine can be
successfully extracted from tobacco
while retaining ‘‘a strong characteristic
aroma . . . not different from the
unextracted blend,’’ achieving a product
that ‘‘was subjectively rated as average
in nicotine characteristics’’ (Refs. 509
and 510). A major tobacco manufacturer
also has used a high-pressure carbon
dioxide process similar to the process
used to decaffeinate coffee. In this
process, tobacco leaf is treated with
ammonium salt, and then treated with
carbon dioxide/water vapor, to achieve
a 95 to 98 percent reduction in nicotine
(Refs. 483 and 511).
Water extraction also can be used for
nicotine reduction. Although some
manufacturers believe that some water
extraction practices may have rendered
the tobacco ‘‘unsuitable for use’’ in
cigarettes, other water extraction
projects have yielded suitable smoking
material with sizeable nicotine
reductions (80 to 85 percent reduction
in leaf nicotine) (Refs. 493, 505, 512,
and 513).
3. Tobacco Farming Practices
Different types of farming practices
also can lower nicotine concentrations
in tobacco plants. One example is
alkaloid-minimizing farming practices.
Industry studies have shown that
changes to growing and harvesting
practices affect the development of
tobacco chemistry, including nicotine
content (Ref. 493). Some manufacturers
have revised their agricultural practices
specifically to meet new product
development goals, such as the
production of low nicotine content
tobacco (Ref. 493). For example, one
manufacturer evaluated how various
experimental agricultural practices
including bulk-curing, once-over
harvesting, and high plant density could
affect the tobacco’s chemistry (Refs. 493
and 514). In other cases, chemical
agents were observed to reduce nicotine
content (Refs. 493, 515 to 517).
Modification of tobacco growth
practices can result in reduced levels of
nicotine in tobacco plants. In traditional
tobacco production, plants are topped
and suckered (removing the growth at
the apex and axillary buds) to slow the
ripening rate of the leaves resulting in
increased nicotine content. Therefore,

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discontinuing these practices results in
a significant decrease in nicotine
production (Ref. 518). It has been found
that plant density is conversely
correlated to nicotine production in the
plant as increased plant density creates
a competition for resources, particularly
nitrogen. Therefore, higher plant
densities lead to lower nitrogen
availability and stunted plant growth,
thus resulting in lower nicotine tobacco
(Ref. 519).
Nightshades are a botanical family
that naturally contain alkaloids,
including nicotine. In addition to
tobacco plants, tomatoes, eggplants,
potatoes, and peppers are in the
nightshade category. Nicotine synthesis
begins in the root of the tobacco plant
and researchers have studied whether
replacing tobacco root with other
nightshades via grafting could affect
nicotine biosynthesis (Ref. 519). Studies
have been performed where grafting
tobacco shoots on rootstocks of eggplant
was shown to reduce nicotine
production drastically without
significant changes to the development
of the plants (Ref. 520). Eggplant
grafting results in differential expression
of hundreds of genes involved in the
nicotine biosynthetic pathway (Ref.
520). In these studies, no significant
differences in plant height, leaf length,
leaf width, or stalk circumference were
observed between the tobacco/tobacco
and tobacco/eggplant groups up to 80
days after grafting. However, the grafted
tobacco/eggplant leaves resulted in a 95
percent reduction in nicotine content as
compared to the tobacco/tobacco control
plants (Ref. 520).
4. Tobacco Blending/Crossbreeding
One way to achieve lower nicotine
concentrations in tobacco products is to
selectively blend the tobacco filler. Most
cigarettes sold in the United States are
blended from several different types of
tobacco (Ref. 359). A tobacco industry
executive previously testified that the
main component of a cigarette that
contributes to nicotine delivery is the
tobacco blend, and year-to-year crop
variation does not determine the
nicotine content in a cigarette (Ref. 521).
The term ‘‘leaf blending’’ describes the
selection of tobaccos to be used in a
product by tobacco type (e.g., fluecured, burley, oriental), geographical
origin, year, and tobacco grade (Ref.
493). Blend differences can produce
significant variations in nicotine
concentration in the tobacco rod,
leading to differences in smoke
composition and yield (Ref. 82 at p.
469).
Many tobacco strains are available,
including approximately 1,000 different

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tobacco varieties (Ref. 359). The tobacco
industry has used breeding and
cultivation practices to develop high
nicotine tobacco plants to give
manufacturers greater flexibility in
blending and in controlling the amount
of nicotine to be delivered (Ref. 522 at
41694). These practices could be used to
develop low nicotine content tobacco
plants as well. Tobacco industry
documents show that in the 1960s,
tobacco companies recognized the
increasing demand for low nicotine
content tobacco and began instituting
projects that found low nicotine content
cigarettes can be made by selecting
grades of tobacco with low nicotine
content (Refs. 523 and 524).
Because the nicotine content of
tobacco plants varies, manufacturers
could replace more commonly used
nicotine-rich varieties like Nicotiana
rustica with lower nicotine varieties
(Ref. 525). For example, oriental
Turkish-type cigarettes also deliver
substantially less nicotine than
cigarettes that contain air-cured burley
tobacco (Refs. 82 and 526). Even
without this selective breeding,
manufacturers could use careful tobacco
leaf purchasing plans to control the
nicotine content in their products (Ref.
522 at 41694). By maintaining
awareness of the differences and
monitoring the levels in purchased
tobacco, companies could produce
cigarettes with nicotine deliveries
consistent to one-tenth of 1 percent
(despite annual variations of up to 25
percent in the nicotine content of the
raw material grown in the same area)
(Ref. 522 at 41694).
Grading, which is used to evaluate
and identify differences within tobacco
types, is a function of both plant
position (i.e., higher or lower leaf
position on the stalk) and quality (i.e.,
ripeness), and segregation of grades by
nicotine content has become common
practice (Ref. 493). The position of
leaves on the plant stalk affects nicotine
levels: tobacco leaves located near the
top of the plant can contain higher
concentrations of nicotine, and lower
stalk leaves generally contain lower
nicotine levels (Refs. 493, 525, and 527).
For example, flue-cured tobacco leaves
harvested from the lowest stalk position
may contain from 0.08 to 0.65 percent
nicotine (i.e., 0.8 to 6.5 mg nicotine per
gram of total tobacco), whereas leaves
from the highest positions may contain
from 0.13 to 4.18 percent nicotine (i.e.,
1.3 to 41.8 mg nicotine per gram of total
tobacco) (Refs. 359, 528 and 529).
Therefore, substituting leaves found
lower on the plants (commonly called
‘‘priming’’) could reduce the nicotine
content of tobacco products (Ref. 525).

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Internal tobacco industry documents
describe the use of leaf blending and
tobacco selection to control cigarette
nicotine content (Ref. 493). For
example, one company project
determined that manufacturers could
reduce cigarette nicotine content by
selecting grades of tobacco with
naturally low nicotine content (Ref.
523). Another observed that the demand
for low nicotine content tobacco has
increased worldwide and necessitated a
shift in purchasing standards (Ref. 524).
5. Other Practices
After tobacco is harvested, it is cured
and aged before being used in tobacco
products. The aging process naturally
changes the chemistry of the tobacco,
including some reduction in nicotine
content (Ref. 493). At least one
manufacturer has explored efforts to
speed the tobacco aging process, in part
to alter or limit the changes in chemistry
that naturally occur (Refs. 493 and 530).
Other approaches to curing and
fermenting tobacco have been explored
as methods for altering nicotine content.
For example, in one manufacturer’s
report, researchers observed that the
properties of tobacco, including nicotine
content, could be altered without the
need for nontobacco additives by
modifying curing practices (Ref. 531). In
addition, manufacturers have explored
other approaches to identify microbial
bacteria that actively degrade nicotine
while leaving other components of the
leaf intact (Refs. 532 and 533).
Consumer product testing showed that
the ‘‘product acceptability’’ of that
tobacco was equal to that of untreated
tobacco (Ref. 534).
Researchers also have developed
novel approaches to reducing the
nicotine in tobacco products in recent
years. An example of one such approach
is enzymatic digestion utilizing glucose
oxidase harvested from the salivary
excretion produced by a specific species
of herbivorous caterpillar, helicoverpa
zea (Ref. 535). The extracted enzyme is
applied to the harvested tobacco leaves,
reducing the nicotine in the tobacco leaf
by up to 75 percent, providing an
‘‘effective and economical system for
producing tobacco products which
contain about 0.01 mg nicotine per
cigarette or less . . . while maintaining
the other desirable ingredients for good
taste and flavor’’ (Ref. 535). Another
novel approach is the use of microwaveassisted technology to extract nicotine
from tobacco, including cigar filler (Ref.
536), that also could be effective for
reducing the nicotine content for other
tobacco products such as RYO tobacco
and pipe tobacco.

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By using one or a combination of
methods described above, FDA
concludes there is ample evidence of
the technical feasibility of complying
with this proposed product standard to
reduce the nicotine level in cigarettes
and certain other combusted tobacco
products.
6. Applicability to Other Combusted
Tobacco Products and Smaller
Manufacturers
FDA anticipates that manufacturers of
non-cigarette tobacco products covered
by this proposed product standard may
also choose to use a variety of
approaches to meet the proposed
maximum nicotine level. Given the
similarities between the tobacco used in
cigarettes and in other combusted
tobacco products that FDA proposes to
include within the scope of this product
standard, FDA expects that it is
similarly technically feasible for noncigarette tobacco products to comply
with the proposed maximum nicotine
level. FDA requests comments, data,
and research regarding the feasibility of
using the techniques discussed in this
section, or other nicotine reduction
techniques, for the non-cigarette
products covered under this proposed
product standard.
Although industry documents contain
little information regarding feasibility of
VLNC levels for non-cigarette products,
an early 1962 patent does indicate a
tobacco storage process that
dramatically reduced nicotine levels,
including in shade-grown Connecticut
tobacco used for cigars, from 0.85
percent to 0.075 percent nicotine
content (i.e., from 8.5 to 0.75 mg
nicotine per gram of total tobacco) (Ref.
537). In 1975, a large tobacco
manufacturer also discussed
development of a low nicotine cigar or
cigarillo, including processed low
nicotine content tobaccos such as a
burley filler in the range of 0.34 percent
nicotine (i.e., 3.4 mg nicotine per gram
of total tobacco) and methods for
reducing nicotine in the cigar wrapper
(Ref. 538).
FDA expects that smaller
manufacturers may use a variety of
methods to comply with the proposed
product standard, including purchasing
tobacco blends that are lower in
nicotine or have already undergone
extraction. FDA believes that the supply
chain should be capable of adapting to
the purchasing needs of smaller
manufacturers as well as larger
manufacturers, particularly given the
prevalence of genetically engineered
tobacco, as discussed in this section.
FDA requests comments, including data
and research, regarding the methods and

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options smaller manufacturers may use
to comply with this proposed product
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F. Proposal Does Not Seek To Limit
Nicotine to Zero
Section 907(d)(3) of the FD&C Act
expressly prohibits FDA from requiring
the reduction of the nicotine yield of a
tobacco product to zero, and consistent
with that provision FDA is not seeking
to do so. However, section
907(a)(4)(A)(i) of the FD&C Act
expressly authorizes FDA to establish
product standards with provisions ‘‘for
nicotine yields,’’ which includes the
authority to include a provision, such as
the one in this proposed rule, to require
reduction of nicotine yield to a level
other than zero. The information
provided in this section demonstrates
that the proposed product standard does
not require the level of nicotine to be
zero. The level of nicotine proposed in
this product standard is measurable in
the tobacco filler and in the smoke
yield. Research shows that after use of
VLNC cigarettes, nicotine is measurable
in the body via biomarkers of exposure
and neurological receptor occupancy.
1. Nicotine Biomarkers of Exposure
Studies have shown that levels of
nicotine biomarkers increase in people
who smoke cigarettes containing
nicotine equivalent to FDA’s proposed
nicotine level, thereby demonstrating
exposure to nicotine from smoking
VLNC cigarettes (Refs. 259, 402, and
539). Short-term studies that measure
nicotine exposure in people who smoke
cigarettes who smoke one or two VLNC
cigarettes have generally found
increases in plasma nicotine levels that
follow similar, but less dramatic,
patterns seen following smoking regular
nicotine cigarettes. For example, one
study evaluated plasma nicotine
exposure before and repeatedly after
smoking a single NNC, LNC, VLNC, or
usual brand cigarette (Ref. 402). While
the LNC and VLNC cigarettes were
associated with lower plasma nicotine
levels compared to the NNC and usual
brand cigarettes, all cigarettes were
associated with statistically significant
increases in plasma nicotine compared
to baseline levels (Ref. 402). Similarly,
22nd Century Group, Inc. submitted
modified risk tobacco product
applications to FDA containing data
from two clinical studies showing that
peak plasma nicotine levels following
use of a single VLNC cigarette ranged
from 0.4–0.5 nanograms of nicotine per
milliliter of plasma and total nicotine
levels (i.e., plasma nicotine area under
the curve calculated using the
trapezoidal rule to 180 minutes) ranged

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from 26.2–30.4 nanograms of nicotine
per milliliter of plasma (Ref. 539).
Researchers observed similar effects
among participants who smoked a
single VLNC cigarette made by Philip
Morris for research purposes only (Ref.
259).
Studies with longer exposure to VLNC
cigarettes have also found evidence of
nicotine exposure within study
participants. For example, studies
showed that after several days or weeks
of smoking VLNC cigarettes, biomarkers
of nicotine exposure—such as urinary
cotinine and TNE (i.e., the sum of
nicotine and various nicotine
metabolites)—in people who smoke
cigarettes were drastically reduced but
were still detectable (Refs. 32 and 265).
Notably, if participants in these studies
were noncompliant with study-assigned
cigarettes, then some of the biomarkers
of nicotine exposure could be attributed
to the use of other tobacco products.
However, evidence from studies in
which participants were confined to
hotels or residential research facilities
without access to other tobacco
products also demonstrate that extended
exposure to VLNC cigarettes produces
biomarkers of nicotine exposure and
physiological responses consistent with
nicotine exposure (Refs. 64 and 423).
Taken together, these data consistently
show that levels of nicotine biomarkers
of exposure in people who smoke VLNC
cigarettes are still detectable. For further
discussion of biomarkers of exposure,
see section VII.B.6 of this document.
2. Receptor Occupancy and Cerebral
Response From the Use of VLNC
Cigarettes
Studies have shown that the nicotine
provided by VLNC cigarettes is enough
to occupy sufficient numbers of nicotine
receptors in the brain (i.e., a4b2
nAChRs) to mitigate feelings of
withdrawal and craving. PET and MRI
data obtained from people who smoke
cigarettes indicate that after smoking a
VLNC cigarette, nicotine receptors
located in numerous areas of the brain
are occupied despite the lower nicotine
content of VLNC cigarettes, and these
participants reported a statistically
significant reduction in craving
compared to before smoking the VLNC
cigarette (Ref. 430). In another study
that compared VLNC and NNC
cigarettes, exposure to both types of
cigarettes resulted in the binding of
nicotine to receptors in the brain and
the release of dopamine (Ref. 425).
However, the magnitude of subjective
craving or withdrawal responses
observed following use of VLNC
cigarettes was lower than use of NNC
cigarettes (Refa. 425 and 461). For

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further discussion of receptor
occupancy, see section VII.B.8 of this
document.
3. VLNC Cigarette Nicotine Smoke Yield
Nicotine ‘‘yield’’ refers to the amount
of nicotine in tobacco smoke as
measured through machine-generated
smoking methods (e.g., ISO machine
smoking method, CI smoking method,
FTC smoking method), and is typically
measured and reported in milligrams
per cigarette. The maximum level of
nicotine set by this proposed product
standard would result in nicotine yield
in tobacco smoke that is at detectable
levels above zero. For example,
SPECTRUM NNC cigarettes that contain
15.8–16.6 mg of nicotine per gram
tobacco filler have machine-measured
nicotine yields of 0.7–0.8 mg of nicotine
per cigarette. SPECTRUM VLNC
research cigarettes that contain 0.3–0.4
mg of nicotine per gram tobacco filler
have quantifiable machine-measured
nicotine yields greater than zero,
ranging from 0.03–0.04 mg of nicotine
per cigarette (Ref. 254). Similarly,
Quest® 3 VLNC cigarettes had
quantifiable machine-measured nicotine
yields of approximately 0.03 mg of
nicotine per cigarette (Ref. 540).
In summary, the data indicate that
nicotine is measurable in both the
tobacco filler and the smoke yield of
VLNC cigarettes and therefore does not
equal zero. After using VLNC cigarettes,
nicotine exposure has been shown to
occur as evidenced by studies
measuring biomarkers of nicotine
exposure and neurological receptor
occupancy. Consequently, FDA finds
that the proposed product standard
would not require the reduction of
nicotine yields to zero.
VIII. Determination That the Standard
Is Appropriate for the Protection of the
Public Health
The Tobacco Control Act authorizes
FDA to adopt tobacco product standards
by regulation if it finds that such
tobacco product standards are
appropriate for the protection of the
public health (section 907(a)(3)(A) of the
FD&C Act). The notice of proposed
rulemaking (NPRM) for such a product
standard must set forth this finding with
supporting justification, which FDA is
providing here (section 907(c)(2)(A)) of
the FD&C Act.
In order to make this finding, FDA
must consider scientific evidence
concerning:
• The risks and benefits to the
population as a whole, including users
and nonusers of tobacco products, of the
proposed standard;

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• The increased or decreased
likelihood that existing users of tobacco
products will stop using such products;
and
• The increased or decreased
likelihood that those who do not use
tobacco products will start using such
products.
Section 907(a)(3)(B)(i) of the FD&C Act.
FDA has considered scientific
evidence related to all three factors.
Based on these considerations, as
discussed below, we find that the
proposed standard is appropriate for the
protection of the public health because
it would increase the likelihood that
many people who currently smoke
cigarettes and/or certain other
combusted tobacco products would stop
smoking altogether, yielding significant
health benefits from smoking cessation.
Additionally, we find that the proposed
standard is appropriate for the
protection of the public health because
it would decrease the likelihood that
people who do not smoke cigarettes
and/or use certain other combusted
tobacco products—including youth and
young adults—who experiment with
combusted tobacco products will
become addicted to these products,
thereby decreasing progression to
regular use, resulting in reduced
tobacco-related morbidity and mortality
associated with combusted tobacco
product use. Increased cessation, as well
as decreased initiation, progression to
regular use, and consumption would
lead to lower disease and death in the
U.S. population, due to decreased use of
cigarettes and certain other combusted
tobacco products. Furthermore, the rule
is appropriate for the protection of the
public health because the population as
a whole would likely experience
additional health benefits as a result of
reduced secondhand smoke exposure,
smoking-related fires, and smokingrelated perinatal conditions.
A. Approach To Estimating Impacts to
the Population as a Whole
Current evidence shows that, while
nicotine itself is not the direct cause of
most smoking-related diseases,
addiction to the nicotine in tobacco
products is the proximate driver of
tobacco-related death and disease
because it sustains tobacco use (Refs. 1,
28, 58, and 61). The addiction caused by
nicotine in tobacco products is critical
in the transition of people who smoke
cigarettes from experimentation to
sustained smoking and in the
maintenance of smoking for those who
want to quit (Refs. 1 at p. 113 and 28).
Combusted tobacco products, including
cigarettes, are responsible for the
overwhelming burden of disease and

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death from tobacco product use (Refs. 1
and 28). As a result, FDA expects that
making cigarettes and certain other
combusted tobacco products minimally
addictive or nonaddictive would reduce
tobacco-related harms by promoting
smoking cessation or complete
migration to alternative, potentially less
harmful noncombusted tobacco
products and by reducing initiation. In
this section, we summarize the
approach used to estimate the possible
impact of a potential nicotine tobacco
product standard to the population as a
whole and present the findings of this
analysis.
To assess the potential public health
impacts of a nicotine product standard,
FDA developed a population health
model using inputs derived from
available empirical evidence and expert
opinion to estimate the impact of
changes in tobacco product initiation,
cessation, switching, and dual use on
tobacco use prevalence, morbidity, and
mortality in the United States. Details of
this modeling approach have been
previously published in two peerreviewed publications (Refs. 47 and 48),
which describe the overall model in
terms of the inputs, transition behaviors,
and outputs that it contains, along with
results from simulation studies. In
preparation for this proposed product
standard, FDA updated the model
published previously (Ref. 47), which
describes the impact of a potential
product standard that limits the level of
nicotine in cigarettes, RYO tobacco,
non-premium cigars, and pipe tobacco
so that they are minimally addictive or
nonaddictive.29 The details of this
analysis are presented in an updated
modeling document, entitled
‘‘Methodological Approach to Modeling
the Potential Impact of a Nicotine
Product Standard on Tobacco Use,
Morbidity, and Mortality in the U.S.’’
(Ref. 42). We estimated the potential
impacts of a nicotine product standard
by modeling a baseline scenario of use
of cigarettes and noncombusted tobacco
products including smokeless tobacco,
e-cigarettes, HTPs, and oral nicotine
products. We then compared the
baseline scenario to a product standard
scenario characterized by the
introduction of a potential nicotine
product standard that would apply to
29 The policy scenario presented in Apelberg et al.
2018 (Ref. 47) did not define a specific level of
nicotine as minimally addictive or nonaddictive.
Rather, the policy scenario simulated
implementation of a hypothetical standard in which
cigarettes and certain other combusted tobacco
products were made minimally addictive or
nonaddictive, informed by a formal expert
elicitation process, and used to estimate the impact
of decreasing the addictiveness of cigarettes on
certain tobacco use behaviors.

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cigarettes, RYO tobacco, non-premium
cigars, and pipe tobacco. FDA’s
modeling framework and
methodological approach and the
associated inputs and assumptions have
been peer reviewed by independent
external experts. Taking into
consideration comments from this peer
review (Ref. 49), FDA revised the
modeling document, and the final
modeling document is available in the
docket for this proposed rule (Ref. 42).
FDA’s modeling work informed the
development of this proposed product
standard. FDA requests comments on
the methodology and analysis
(including the overall model in terms of
the inputs, transition behaviors, and
outputs) presented in the scientific
modeling document.
FDA’s population health model
incorporates the following tobacco use
transitions to estimate the impact of the
policy: (1) cigarette smoking cessation;
(2) people who smoke cigarettes
switching to noncombusted tobacco
products rather than quitting tobacco
use entirely; (3) people who continue to
smoke cigarettes beginning dual use of
cigarettes and noncombusted tobacco
products; (4) people who do not smoke
initiating regular cigarette smoking; and
(5) people who do not smoke who have
been dissuaded from smoking cigarettes
and certain other combusted tobacco
products, who instead initiate use of a
noncombusted tobacco product. The
model, based on input parameters
derived from empirical evidence and
expert estimates, projected the impact of
a potential nicotine product standard on
four main outcomes: (1) prevalence of
cigarette smoking and noncombusted
tobacco use; (2) tobacco-attributable
mortality; (3) life years lost due to
tobacco use; and (4) quality-adjusted life
years (QALYs) lost due to cigarette
smoking-attributable morbidity in the
U.S. population over time. The model
explores various baseline scenarios via
sensitivity analyses, including with and
without projections that incorporate
implementations of other future tobacco
product standards (e.g., flavored cigar
and menthol cigarette product
standards).
More detailed information regarding
modeling study methodology, including
descriptions of the model inputs, data
sources, and assumptions used to derive
estimates of the potential impact of a
nicotine product standard on
population health can be found in
FDA’s modeling document (Ref. 42).
Briefly, the simulation began with an
initial population that reflected the sex
and age (based on 2021 U.S. Census
Bureau estimates) and cigarette use
distribution (i.e., never, current, former

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use; estimated from the 2020 NHIS data
and 2020 NYTS data) in the U.S.
population. Next, we incorporated sexspecific rates for smoking initiation and
cessation for year 2021 modeled using
cigarette smoking histories for birth
cohorts reconstructed from NHIS data
by Cancer Intervention and Surveillance
Modeling Network (CISNET) researchers
(Ref. 541). Recent analyses using data
from the Population Assessment of
Tobacco and Health (PATH) Study (Ref.
542) provide data on initiation of ENDS
from Wave 4 (2016–2017) to Wave 5
(2018–2019); however, those estimates
are related to transitions from never use
to ever use of a specific product at the
current wave, rather than transitions to
established use, as defined in the
population model. In the absence of upto-date estimates of exclusive
noncombusted product initiation rates
from the published scientific literature,
data regarding exclusive initiation of
noncombusted tobacco products and
dual use were derived by scaling the
sex- and age-specific smoking initiation
rates from CISNET using youth (ages 9–
17) prevalence estimates from the 2017–
2020 NYTS, and young adult (ages 18–
24) prevalence estimates from the 2020
NHIS (Ref. 542). NYTS prevalence
estimates for noncombusted product use
correspond to frequent use, defined as
use at least 20 days in the past 30
days.30 Additional details regarding the
estimation of scaling factors to compute
noncombusted product initiation rates
can be found in FDA’s modeling
document (Ref. 42). CISNET sex- and
age-specific cigarette smoking cessation
rates derived from NHIS data were
utilized as cessation rates for all product
categories, including noncombusted
tobacco use. Age-specific rates of
switching from cigarettes to
noncombusted tobacco products were
derived from prior research (Ref. 543).
Overall U.S. death rates from 2019 vital
statistics data were used to reflect the
death rates at baseline for individuals
under age 35 who never smoked, since
smoking-related mortality is minimal
before this age (Ref. 544). For ages 35
and older at baseline, FDA estimated
annual death rates from 2019 NHIS–
LMF data among participants who have
never smoked in NHIS from 1997
through 2018 who were followed for
30 While past 30-day use is the conventional
definition of current use of a tobacco product in the
NYTS, we utilized the corresponding definition of
frequent use (20 or more days of use in past 30
days) to correspond with initiation of regular use
that is more closely associated with longer-term
health outcomes. In this context, we have scaled the
initiation rates to reflect the initiation of regular,
longer-term use. This approach is consistent with
that for adult initiation to regular use and long-term
cessation as defined by CISNET.

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mortality through linkage with the
National Death Index from 2002 through
2019 (Ref. 545). NHIS–LMF never-user
death rates are adjusted for low
mortality in the NHIS’s civilian
noninstitutionalized population, due to
the survey’s exclusion of people in
institutionalized settings such as longterm care institutions (e.g., nursing
homes, hospitals for the chronically ill
or physically or intellectually disabled,
wards for abused or neglected children),
persons in correctional facilities (e.g.,
prisons or jails, juvenile detention
centers, halfway houses), and U.S.
nationals living in foreign countries.
The adjustment was done by using the
ratio of U.S. death rates from the 2019
vital statistics data to NHIS–LMF death
rates by sex and age (Ref. 546). Death
rates for people who have never smoked
cigarettes are projected for the period
from 2022 through 2100 using mortality
scaling factors obtained from the LeeCarter mortality forecasting method
(Refs. 547 to 549). To estimate mortality
for e-cigarettes and other noncombusted
tobacco products, we apply the same
risks that are used for smokeless
tobacco. Our assumptions about allcause mortality risk among people who
use smokeless tobacco in the United
States were informed by the first
NHANES, Cancer Prevention Study I
(CPS–I), and Cancer Prevention Study II
(CPS–II). Mortality probabilities for
people who currently use and formerly
used tobacco are obtained by
multiplying never-user probabilities of
dying by relative risk according to
tobacco use status.
Quantitative inputs for tobacco use
transitions following implementation of
the proposed product standard were
obtained through a formal expert
elicitation process that was first
conducted in 2015 and then repeated in
2018. FDA is conducting another expert
elicitation to obtain updated
quantitative inputs for tobacco use
transitions and intends to publish the
results for public review and comment.
For the 2015 and 2018 expert
elicitations, the methodology used to
identify experts, develop the protocol,
conduct the elicitation, and summarize
the findings can be found in a previous
peer-reviewed publication (Ref. 47) and
in FDA’s modeling document (Ref. 42).
Briefly, the initial elicitation process
centered around three online
conferencing sessions held during
January and February 2015, following a
written protocol designed to elicit
opinions using a structured,
standardized approach. Briefing books
with key papers on the topics of interest
as well as background data on tobacco

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use and policy were provided to a panel
of eight experts prior to the conference
sessions. Experts were asked to identify
any other relevant information to share
with the panel. Detailed written
questionnaires were completed by each
expert as independent take-home
exercises. To maintain the
independence of the experts and
encourage open discussion,
involvement of FDA staff was limited.
This general process was repeated in
2018 to ensure that estimates reflected
the experts’ current assessment of the
research literature and potential effects
of a hypothetical product standard.
Seven of the original eight experts
agreed to participate in the second
elicitation. Participants received
updated briefing materials, and an
online workshop was held in April
2018. The experts, once again,
subsequently completed a detailed
questionnaire.
To explore the possible impact of a
hypothetical policy reducing nicotine
levels, the experts were asked to assume
that combusted tobacco products that
could be viewed as highly likely to
serve as substitutes for traditional
cigarettes (i.e., RYO tobacco, pipe
tobacco, non-premium cigars) would be
included in the policy, while other
tobacco products (i.e., premium cigars,
waterpipe/hookah, e-cigarettes,
smokeless tobacco) would be excluded.
While the policy scenario presented in
FDA’s modeling document (Ref. 42) is
based on a reduction of the nicotine
level in cigarettes, cigarette tobacco,
RYO tobacco, certain cigars and pipe
tobacco, the estimated population
impact in the main analysis is solely
based on reductions in cigarette
smoking. Cigarettes are the only one of
these combusted products to be
incorporated directly in the model,
given that cigarette smoking is
responsible for the bulk of morbidity
and mortality caused by combusted
tobacco product use. Estimates of
mortality benefits due to reductions in
non-premium cigar and pipe tobacco
use are derived from model outputs, as
explained below, although these
estimates would not include other
population health benefits such as
reduced morbidity.
The experts were asked to predict and
quantify the anticipated impact of the
policy on the following model
parameters: (1) cigarette smoking
cessation rates; (2) switching from
cigarette smoking to other tobacco
products excluded from the
hypothetical policy scenario (i.e.,
premium cigars, waterpipe/hookah
tobacco, smokeless tobacco, e-cigarettes
or other ENDS); (3) dual use rates; (4)

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cigarette smoking initiation rates; and
(5) initiation rates for other tobacco
products excluded from the
hypothetical policy scenario. Each of
the experts was asked to provide his or
her best estimate of the parameters’ true
value, estimates of the minimum and
maximum plausible values, and
estimates of the 5th, 25th, 75th, and
95th percentile values. Experts were
asked first about impacts in the first
year immediately following the
potential product standard’s
implementation and then about impacts
in the years following the first full year
of implementation. Experts had the
option of providing separate estimates
of impacts for males and females for the
initial and subsequent years. For each
question, experts were asked to provide
the factors they considered pertinent to
answering the question, including the
studies and research findings most
influential to informing their views, and
to rate their familiarity with the relevant
literature. The elicitation process
provided the experts with opportunities
to interact and discuss divergent views,
from which each expert generated their
initial and final estimates. In the
updated elicitation, experts were also
asked to assess the potential effects of
an alternative product standard that
would only apply to cigarettes, cigarette
tobacco, and RYO tobacco, although
they were not required to provide
quantitative estimates of the effects of
such a standard.
While parameter estimates and their
probability distributions varied
somewhat among participants, most
experts had the view that making
cigarettes and certain other combusted
tobacco products minimally addictive
would lead to substantial initial and
long-term increases in smoking
cessation among people who smoke
cigarettes and decreased initiation
among people who do not smoke
cigarettes. The experts’ parameter
estimates fell within a broad range,
although the updated estimates were
often somewhat more consistent and
found greater effects from the potential
policy than in the original elicitation. In
general, estimates of the effects of a
nicotine product standard on use
behaviors such as smoking cessation,
product switching, and smoking
initiation were greater in magnitude in
the 2018 expert elicitation than in the
previous 2015 elicitation. For example,
the median estimates of smoking
cessation were 36 percent in the first
year following implementation of a
nicotine product standard and 34
percent in subsequent years in the 2018
elicitation, compared to 25 and 22

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percent, respectively, in 2015. For
product switching (from cigarettes to
noncovered tobacco products), the
median estimates were 56 and 58
percent in the first and subsequent years
following implementation in the 2018
expert elicitation and 41 and 40 percent
in 2015. Median estimates of reductions
in smoking initiation were 63 and 65
percent in the first and subsequent years
in the 2018 elicitation, and 46 and 49
percent in 2015. Overall, the experts’
estimates indicate that the proposed
product standard would introduce
substantial changes in tobacco use
behaviors which would result in
substantial public health benefits. Given
the inherent uncertainty associated with
projecting the long-term impact of a
future regulatory action, FDA conducted
a range of analyses to examine the
impact of uncertainty around key model
inputs and assumptions on tobacco use
prevalence and premature mortality.
First, in the main analysis, we examined
uncertainty in the behavioral responses
to a potential nicotine product standard
by conducting a Monte Carlo simulation
(Ref. 550). For the product standard
scenario, a Latin hypercube sampling
design with 1,000 simulations was
conducted for each set of expert-defined
distributions, resulting in a total of
7,000 simulations (Ref. 551 at p. 524).
The resulting outputs were aggregated to
create an overall set of output
distributions, and distribution
percentiles were calculated across all
7,000 simulations. For each simulation,
the policy scenario was compared to the
baseline scenario to estimate changes in
the outcomes. Key distribution
responses in FDA’s modeling document
highlight the positive impacts to the
public health of the proposed product
standard (Ref. 42). More information on
this topic can be found throughout this
document.
In addition, we conducted sensitivity
analyses to assess the impact of specific
data input assumptions, including those
related to baseline trends in
noncombusted product use,
noncombusted product mortality risk,
dual product use mortality risk, and
switching to non-covered combusted
products. Specifically, we conducted
sensitivity analyses to examine the
impact of increased initiation of
noncombusted tobacco product use
among those who would otherwise not
have used tobacco; the impact of an
increase in switching from cigarettes to
noncombusted tobacco product use; the
impact of a varying mortality risk
associated with dual use of cigarettes
and noncombusted tobacco products;
the impact of lower and higher

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noncombusted tobacco product risk;
and the effects of a nicotine product
standard, accounting for the emergence
of an illicit market for normal nicotine
content cigarettes. Additional detailed
information concerning these sensitivity
analyses can be found in FDA’s
modeling document (Ref. 42). Overall,
the results from FDA’s population
health modeling, even accounting for
the impacts of the factors utilized in
FDA’s sensitivity analyses, clearly
demonstrate the public health benefit of
the proposed product standard.
In 2022, FDA issued proposed
product standards to prohibit menthol
as a characterizing flavor in cigarettes
(87 FR 26454, May 4, 2022) and to
prohibit all characterizing flavors (other
than tobacco) in cigars (87 FR 26396,
May 4, 2022). If finalized, these rules are
anticipated to reduce overall youth
initiation and increase cessation among
individuals who smoke cigarettes and
non-premium cigars. In sections VIII.E
and VIII.F of this document, we describe
how we adjusted our model by utilizing
estimates of the likely population health
impact of these rules, quantified in peerreviewed publications and discussed in
the proposed rules, to adjust the
baseline inputs for initiation of
combusted and noncombusted products,
as well as cessation of combusted
products and likelihood of switching to
incorporate the impact of the rules in
this proposed nicotine product
standard.
B. The Likelihood That Nonusers Would
Start Using Cigarettes or Other
Combusted Tobacco Products
Nicotine is an addictive chemical and
the primary constituent in cigarettes and
other tobacco products that causes and
maintains addiction. It is a significant
contributor to youth and young adult
initiation of smoking cigarettes and
other combusted tobacco products. In
section IV.A of this document, we
summarize evidence from multiple
study designs, incorporating findings
from experimental and laboratory-based
studies, clinical trials, and pre-clinical
research that illustrate the role that
nicotine plays in facilitating initiation of
and addiction to cigarettes and other
combusted tobacco products. As
discussed in section IV.B of this
document, scientific research
demonstrates that adolescence is a
period of development when
individuals who experiment with
tobacco products are more susceptible
to developing nicotine dependence and
progressing to regular use of such
products. Indeed, almost 90 percent of
adults who currently and regularly
smoke initiated smoking by age 18, and

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98 percent initiated smoking by age 26,
which is notable given that 25 is the
approximate age at which the brain has
completed development (Refs. 1 and 17
to 19). The developing brain is more
vulnerable to developing nicotine
dependence than the adult brain is, and
the earlier an individual begins smoking
the less likely they are to quit (Ref. 20).
Compounding this are the findings
described in section IV.C of this
document that demonstrate that many
youth and adults who smoke want to
quit smoking but have difficulty doing
so. Further, the scientific literature on
relapse in those who try to quit confirms
the powerful addictive properties of
nicotine in tobacco products, a principal
factor limiting a person who smokes’
ability to quit, and further underscores
the public health importance of
decreasing the addictiveness of these
products, particularly to reduce
susceptibility to addiction for youth and
young adults who experiment with
smoking. In this section, we discuss
how, given this scientific evidence, as
well as the findings from our population
health model, FDA expects the
proposed nicotine product standard for
cigarettes and certain other combusted
tobacco products would decrease
experimentation and progression to
regular use of these products among
people who currently do not use these
products.
Data from the 2023 NSDUH found
that, in the United States, approximately
452,000 youth (ages 12–17) smoked
their first cigarette and approximately
245,000 youth tried a cigar for the first
time during 2023 (Ref. 86 Table A.13A).
The 2023 NSDUH also found that
approximately 945,000 young adults
(ages 18 to 25) initiated with cigarettes
and 1,065,000 young adults initiated
with cigars in 2021 (Ref. 552 see Table
4.7B). Additionally, nearly 90 percent of
U.S. adults who currently smoke
cigarettes daily report having smoked
their first cigarette by age 18 (Ref. 1).
Given that nicotine is highly addictive
and present in all cigarettes and cigars,
as people who experiment with
cigarettes and cigars continue to use
these products, there is a substantial
risk of the development of nicotine

dependence and progression to regular
use.
Nicotine is a highly addictive
substance, and multiple studies have
shown that symptoms of nicotine
dependence can arise early after youth
start smoking cigarettes, even among
people who infrequently use the
products (Refs. 24, 93, and 553).
Although the majority of adolescents
who smoke daily meet the criteria for
nicotine dependence, one study found
that the most susceptible youth lose
autonomy (i.e., independence in their
actions) regarding tobacco within 1 or 2
days of first inhaling from a cigarette
(Ref. 93). Another study found that 19.4
percent of adolescents (initially aged
12–13 years and followed over 6 years)
who smoked weekly were dependent on
nicotine (Ref. 95). In a study regarding
nicotine dependence among adolescents
who recently initiated smoking (9th and
10th grade students), adolescents who
smoked cigarettes at the lowest levels
(i.e., smoking on only 1 to 3 days of the
past 30 days) experienced nicotine
dependence symptoms such as loss of
control over smoking (42 percent) and
irritability after not smoking for a while
(23 percent) (Ref. 96). Researchers in a
4-year study of 6th grade students also
found that ‘‘[e]ach of the nicotine
withdrawal symptoms appeared in some
subjects prior to daily smoking’’ (Ref.
93) (emphasis added). Ten percent of
the study participants showed signs of
tobacco dependence within 1 or 2 days
of first inhaling from a cigarette, and
half had done so by the time they were
smoking seven cigarettes per month
(Ref. 93). Moreover, nicotine can disrupt
brain development and have long-term
consequences for executive cognitive
functioning (e.g., decreased attention
and working memory and increased
impulsivity) and increases the risk of
developing a substance use disorder and
various mental health problems—
particularly affective disorders such as
anxiety and depression—as an adult
(Refs. 554 to 556). Therefore,
progressing to regular use during
adolescence can have lasting
consequences and signs of nicotine
dependence are evident in youth who
smoke cigarettes. Taken together, this

research suggests that even infrequent
experimentation can lead to early signs
of dependence, which underscores the
public health importance of decreasing
the likelihood of cigarette
experimentation among youth and
young adults in the United States.
If this proposed rule is finalized,
cigarettes and the other combusted
tobacco products covered would be
rendered minimally addictive or
nonaddictive, thereby breaking the link
between experimentation, nicotine
dependence, and progression to regular
use. As a result, FDA expects a
significant reduction in youth initiation
and progression to regular cigarette
smoking and use of other combusted
tobacco products, which would
ultimately protect youth from a lifetime
of addiction, disease, and premature
death attributable to combusted tobacco
use. To the extent that youth and young
adults in the United States who would
have initiated use of cigarettes and other
combusted tobacco products covered by
the scope of this proposed rule do not
initiate with such tobacco products, the
proposed standard would prevent future
cigarette- and combusted tobacco
product-related disease and death.
Findings from FDA’s population
health model, previously described in
section VIII.A of this document and in
the docket (Ref. 42), estimate the
likelihood that youth and young adults
who do not smoke would initiate
regular cigarette smoking use under the
proposed standard. Table 2 provides an
estimated projection of the cumulative
number of youth and young adults who
would not initiate regular cigarette use
as a result of implementation of this
proposed product standard over time
(Ref. 42 Appendix J for annual
estimates). Since a sustained decrease in
smoking initiation rates is expected, the
cumulative number of people dissuaded
from initiating smoking would continue
to increase over time. By 2100, we
estimate that, as a result of this
proposed nicotine product standard,
over 47 million youth and young adults
who would have otherwise initiated
smoking would not start smoking.

TABLE 2—PROJECTED CUMULATIVE NUMBER OF YOUTH AND YOUNG ADULTS WHO WOULD NOT INITIATE SMOKING AS A
RESULT OF A NICOTINE PRODUCT STANDARD IMPLEMENTED IN 2027
[Millions]
Year
2028
2030
2040
2050
2060

Median

.........................................................................................................................................................
.........................................................................................................................................................
.........................................................................................................................................................
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2.6
8.6
14.8
21.1

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(5th, 95th percentiles)
(0.4, 1.7)
(0.7, 3.4)
(2.3, 11.5)
(4.0, 19.8)
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TABLE 2—PROJECTED CUMULATIVE NUMBER OF YOUTH AND YOUNG ADULTS WHO WOULD NOT INITIATE SMOKING AS A
RESULT OF A NICOTINE PRODUCT STANDARD IMPLEMENTED IN 2027—Continued
[Millions]
Year
2070
2080
2090
2100

.........................................................................................................................................................
.........................................................................................................................................................
.........................................................................................................................................................
.........................................................................................................................................................

For these reasons, FDA expects that
establishing a maximum limit of the
nicotine content in cigarettes and
certain other combusted tobacco
products, as described in this proposed
rule, would reduce the likelihood that
youth and young adults would initiate
with and progress to regular cigarette
smoking and use of other combusted
tobacco products, thereby protecting
many youth and young adults from a
lifetime of addiction and disease, and
premature death, attributable to the use
of combusted tobacco (see section VIII.D
of this document for a discussion of life
years gained and other public health
benefits as a result of decreased
initiation). Thus, from the expected
impact on people who would not
initiate smoking cigarettes, especially
youth and young adults, this proposed
product standard is appropriate for the
protection of public health.
C. The Likelihood That Existing Users
Would Reduce Cigarette and Other
Combusted Tobacco Product
Consumption or Stop Smoking

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Median

In addition to the long-term public
health benefits that would accrue from
the prevention of cigarette smoking and
other combusted tobacco use among
youth and young adults, FDA
anticipates that the proposed standard
also would increase the likelihood that
many people who currently smoke
cigarettes and certain other combusted
tobacco products would stop smoking
altogether, yielding health benefits from
smoking cessation. FDA expects that the
proposed standard would result in
substantial changes in tobacco use
patterns among people who currently
use tobacco. Given that tobacco
products are addictive primarily due to
the presence of nicotine, FDA expects
that the proposed standard would lead
many people who currently smoke
cigarettes and certain other combusted
tobacco products to: (1) quit using these
tobacco products altogether, (2)
transition to dual use of cigarettes or
other combusted tobacco products with
other potentially less harmful tobacco
products, or (3) transition completely to

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use of other potentially less harmful
tobacco products.
As discussed in section IV of this
document, the scientific evidence is
clear that nicotine is an addictive
chemical and is the primary constituent
that causes and maintains addiction to
cigarettes and other combusted tobacco
products. The U.S. Surgeon General has
concluded that there is a causal
relationship between smoking and
addiction to nicotine (Ref. 1), and the
earlier that individuals begin smoking,
the less likely they are to successfully
quit (Ref. 27). FDA expects that, if this
proposed rule is finalized, many people
who smoke cigarettes will either quit
smoking entirely, switch to a
noncombusted tobacco product entirely,
or transition to dual use. As discussed
previously, those who switch
completely to a noncombusted product
may sustain their nicotine dependence
but would significantly reduce their risk
of tobacco-related death and disease to
the extent that the products they switch
to result in less harm. That is, while
dependence on any tobacco product
remains a health concern, the vast
majority of tobacco-related cancer, lung
disease, and heart disease is due to
exposure to constituents of tobacco
smoke (Ref. 323). Switching completely
to a noncombusted tobacco product
would reduce exposure to the chemical
constituents created through
combustion (Ref. 8).
There are multiple sources of
evidence to inform FDA’s analysis of
how the proposed standard would affect
the likelihood that people who smoke
would reduce cigarette and combusted
tobacco product consumption or stop
smoking altogether. Findings from
clinical studies offer insight into
tobacco product switching, as well as
cigarette smoking cessation behaviors
occurring following the implementation
of the proposed product standard. As
described previously in section VI.B of
this document, a clinical trial intended
to assess the use of noncombusted and
non-cigarette combusted tobacco
products among participants
randomized to receive LNC and NNC
cigarettes found that participants who

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27.5
34.1
40.8
47.6

(5th, 95th percentiles)
(7.3,
(9.1,
(10.8,
(12.6,

37.0)
45.9)
54.9)
64.1)

received LNC cigarettes used alternative
combusted and noncombusted tobacco
products on a statistically significantly
higher percentage of days compared to
those who received NNC cigarettes (Ref.
5). Another analysis of switching
behavior in the context of a clinical
study examined the influence of LNC
cigarette use on alternative tobacco
product use in participants who did not
smoke cigarettes daily. Among
participants who did not use e-cigarettes
at baseline, new use of e-cigarettes was
statistically significantly more prevalent
in the LNC cigarette group compared to
the NNC cigarette group (Ref. 377). Both
findings suggest that people who smoke
cigarettes, and do not quit tobacco use
altogether, are likely to seek alternative
sources of nicotine once a nicotine
product standard for combusted tobacco
products is in place.
As discussed in section VII.B.2 of this
document, numerous studies have
investigated the effects of VLNC or LNC
cigarettes—alone or in combination
with NRT products—on smoking
cessation among people who smoke
cigarettes and are interested in quitting
(Refs. 32, 35, 41, 369 to 373), as well as
among samples of people who smoke
cigarettes and are not interested in
quitting (Refs. 31, 40, 258, and 374).
Taken together, results from these
studies demonstrate that people who
smoke cigarettes and are interested in
quitting who are given VLNC cigarettes
are more likely to achieve initial
smoking abstinence compared to those
who continue to smoke their usual
brand or NNC cigarettes. In addition,
provision of NRT and/or behavioral
intervention with VLNC cigarettes can
further increase smoking cessation
among individuals interested in quitting
(Ref. 19).
Estimates from FDA’s population
health model—described in section
VIII.A of this document—indicate that
in the first year following the
implementation of the proposed
standard in 2027, smoking prevalence
would decline from 9.1 percent in the
baseline scenario to a median of 4.5
percent in the product standard
scenario, due to the large increase in

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smoking cessation in the first year after
implementation. In subsequent years,
the difference in smoking prevalence
between the scenarios would continue
to grow due to sustained increases in
cessation and decreases in initiation
relative to baseline. The projected
smoking prevalence drops to 0.2 percent
under the product standard scenario by
2050, compared to 5.3 percent under
baseline. By 2100, smoking prevalence
is estimated at 0.2 percent in the
product standard scenario, compared to
4.6 percent under baseline. Estimates of
the projected cumulative number of
people who quit smoking are depicted
in table 3. Within the first year of the
proposed standard implementation, 12.9
million additional people who smoke

cigarettes are estimated to either quit
tobacco altogether or switch from
cigarette smoking to using
noncombusted tobacco products,
signifying a considerable gain over the
estimated 1.6 million people who smoke
that would have quit under the baseline
scenario. The mortality risk of switching
is greater than quitting all tobacco
products, therefore the public health
model assumes the risk for people who
switch to noncombusted products as 8
percent higher than the risk for those
who quit tobacco use entirely based on
evidence in the literature (Ref. 557), see
section VIII.D of this document for a
more detailed discussion. The number
of additional people who quit smoking
would increase to approximately 19.5

million within 5 years after the
implementation of the proposed
standard, representing a gain of more
than the 7.3 million people who quit
smoking than would be anticipated
under the baseline scenario. The median
estimates grow closer to the 95th
percentile estimates than to the 5th
percentile estimates over time. A closer
analysis of this pattern indicates that the
5th percentile estimates are affected by
lower estimates given by two experts in
the expert elicitation. Those estimates
indicate that a lower percentage of
people who currently use cigarettes will
quit smoking cigarettes, following a
nicotine product standard’s
implementation.

TABLE 3—CUMULATIVE NET PEOPLE WHO QUIT SMOKING 1 (MILLIONS) AS A RESULT OF A NICOTINE PRODUCT STANDARD
IMPLEMENTED IN 2027
Period
Within
Within
Within
Within
Within

Median

1st year (2027) .............................................................................................................................
2 years (2027–2028) ....................................................................................................................
3 years (2027–2029) ....................................................................................................................
4 years (2027–2030) ....................................................................................................................
5 years (2027–2031) ....................................................................................................................

12.9
17.5
19.3
19.8
2 19.5

(5th, 95th percentiles)
(0.8,
(1.2,
(1.6,
(1.8,
(2.0,

24.8)
24.1)
23.2)
22.3)
21.4)

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1 Net people who quit smoking cigarettes (including those who switch to noncombusted tobacco products), defined as people who quit smoking
cigarettes in addition to baseline, is computed as: (number of people who quit smoking cigarettes under the nicotine product standard scenario)
¥ (number of people who quit smoking cigarettes under baseline scenario).
2 Cumulative net people who quit smoking declines slightly in year 5 of the simulation because there are more people who quit smoking cigarettes in the baseline scenario compared with the product standard scenario. Since there are millions of fewer people smoking cigarettes in the
product standard scenario as the years continue, eventually there are fewer people available to quit smoking cigarettes compared to baseline.

We also examined the potential for an
illicit market for NNC cigarettes to
develop in response to the proposed
product standard (see section IX.D of
this document for a discussion on illicit
trade). In order to examine the potential
impact of such an illicit market,
sensitivity analyses were conducted for
the effects of diversion from cessation to
illicit trade, and initiation into illicit
products, on the estimated benefits of a
nicotine product standard. These

analyses demonstrate that increasing the
assumed proportion of people who
smoke who may divert to the use of
illicit NNC cigarettes (for purposes of
illustration, we use a low-end estimate
(3.8 percent), a midpoint estimate (5.9
percent), and a high-end estimate (21.0
percent)),31 and allowing youth and
young adults (who would have
otherwise initiated NNC cigarette use) to
initiate into illicit NNC cigarette use (0
percent, 2.6 percent, and 10 percent) 32

under the proposed nicotine standard,
resulted in reductions in the projected
cumulative net people who quit
smoking following the implementation
of the nicotine product standard policy
(table 4). However, even in the case of
significant diversion to illicit NNC
cigarettes, the number of people
projected to quit smoking remains
substantial.

31 We use 3.8 percent as a low-end estimate based
on 2017 estimates of illicit trade volume in
cigarettes from (Ref. 558). This estimate excludes
interstate smuggling for purposes of tax avoidance.
For a midpoint estimate, using findings from the
International Tobacco Control United States Survey
(Ref. 559), we estimate that 5.9 percent of U.S.
people who use cigarettes last purchased cigarettes
from low-tax locations. We use these figures as
proxies for the proportions of people who use
cigarettes who may actively seek out illicit NNC
cigarettes under a nicotine product standard,
although we note that the product standard would
be implemented nationwide, avoiding disparate
pricing/availability between states. We use 21.0

percent as a high-end estimate based on the
difference in non-compliance rates between
reduced nicotine intervention groups (78 percent)
and control groups assigned to NNC cigarettes (57
percent) in clinical trial data from (Ref. 29, Ref.
330). This estimate of 21.0 percent also represents
the high-end of the range estimated in (Ref. 560),
which reflected the methodology of the pack return
survey by (Ref. 561). While FDA uses this 21.0
percent high-end estimate for the purpose of
analyzing potential impacts, we note that it
represents a highly unlikely upper bound, because
for such a substantial percentage of people who use
cigarettes to acquire NNC cigarettes, convenient and
consistent access to an illicit market would be

needed, which is highly unlikely. We also note that
basing a high-end estimate on non-compliance rates
found in studies (where NNC cigarettes are legally
available outside the confines of the study
environment) is not equivalent to real-world
conditions where NNC cigarettes would not be
legally available in the U.S. marketplace.
32 We use findings from an expert elicitation
developed to gauge the impact of a menthol
cigarette and cigar prohibition in the United States
(Ref. 562), which indicates that among people ages
12–24 who would have otherwise initiated menthol
cigarette use, 2.6 percent would initiate illicit
menthol cigarette use (estimate ranged from 0
percent to 10 percent).

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TABLE 4—CUMULATIVE NET PEOPLE WHO QUIT SMOKING COMBUSTED CIGARETTES (MILLIONS) AS A RESULT OF A NICOTINE PRODUCT STANDARD IMPLEMENTED IN 2027 UNDER ILLICIT TRADE SCENARIOS. MEDIAN (5TH, 95TH PERCENTILES) ESTIMATES
Illicit trade impact scenarios
Period

Main scenario
(no impact)

Within 1st year (2027) .............................................................
Within 5th year (2027–2031) ...................................................

12.9 (0.8, 24.8)
19.5 (2.0, 21.4)

Low Impact 1
12.4 (0.7, 24.6)
19.3 (1.7, 21.3)

Medium Impact 2
12.1 (0.7, 24.4)
19.2 (1.5, 21.4)

High Impact 3
9.9 (0.3, 22.6)
18.1 (0.3, 21.4)

1 Low Impact: 3.8 percent people who smoke would divert to use illicit NNC cigarettes, and 0 percent youth and young adults would initiate illicit NNC cigarettes.
2 Medium Impact: 5.9 percent people who smoke would divert to use illicit NNC cigarettes, and 2.6 percent youth and young adults would initiate illicit NNC cigarettes.
3 High Impact: 21.0 percent people who smoke would divert to use illicit NNC cigarettes, and 10.0 percent youth and young adults would initiate illicit NNC cigarettes.

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The sum of the available evidence—
including the current use of cigarettes
by millions of Americans, findings from
studies assessing the effects of VLNC or
LNC cigarettes on smoking cessation,
and findings from FDA’s population
health model—supports FDA’s finding
that the proposed product standard
would increase the likelihood that many
people who smoke cigarettes and/or
other combusted tobacco products
would stop smoking altogether, yielding
significant health benefits from smoking
cessation. Additionally, we find that the
proposed standard is appropriate for the
protection of the public health because
it would decrease the likelihood that
people who do not smoke cigarettes
and/or use certain other combusted
tobacco products—particularly youth
and young adults—who experiment
with combusted tobacco products will
become addicted to these products,
thereby decreasing progression to
regular use, resulting in reduced
tobacco-related morbidity and mortality
associated with combusted tobacco
product use. As of 2021, more than 48
million people in the United States ages
12 and older used tobacco products
within the past 30 days (Refs. 25 and
274). Further, in 2021, 35.6 million U.S.
adults (14.5 percent) and nearly 1
million middle and high school
students (3.2 percent) used any
combustible tobacco product (Ref. 274).
Thus, even small changes in initiation
and cessation would result in a
significant reduction in the burden of
death and disease caused by smoking.
D. Benefits and Risks to the Population
as a Whole
We expect that the proposed nicotine
product standard, if finalized, would
reduce tobacco-related harms. As
discussed in section IV of this
document, nicotine is the primary
constituent in cigarettes and other
tobacco products that causes and
maintains addiction. By enacting a

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product standard that would seek to
limit the nicotine content in cigarettes
and certain other combusted tobacco
products to minimally addictive or
nonaddictive levels, FDA anticipates
that reductions in population harm
would be realized through long-term
health benefits resulting from
prevention of cigarette uptake and
progression to regular cigarette smoking
among young people, as well as shorterterm health benefits resulting from
increased cessation of cigarette smoking
among people who currently smoke.
Each of these impacts alone would
result in significant health benefits to
the U.S. population. In totality, they
provide overwhelming evidence that the
proposed standard would result in
substantial health benefits over both the
short- and long-term. In this section, we
summarize the health benefits of never
progressing to regular cigarette smoking
and combusted tobacco product use, the
health benefits of quitting smoking, the
population health benefits of switching
from cigarettes to potentially less
harmful tobacco products, and the
health benefits of not being exposed to
secondhand smoke. We also describe
additional public health benefits of the
proposed standard not addressed in
FDA’s population health model. Finally,
we describe potential risks or limiting
effects of the product standard,
including risks of compensatory
smoking. Based on the available
evidence, FDA concludes that any such
potential risks or limiting effects would
be significantly outweighed by the
anticipated substantial benefits of this
proposed nicotine product standard.
1. Given the Harmful Effects of Cigarette
Smoking and Combusted Tobacco Use,
Never Progressing to Regular Smoking
Prevents Death and Disease and
Improves Quality of Life
Never progressing to regular cigarette
smoking prevents death and disease
caused by smoking. Any effects of a

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nicotine product standard in cigarettes
and certain other combusted tobacco
products on preventing youth, young
adult, and even adults who have never
smoked from initiating/experimenting
and progressing to regular cigarette
smoking will have a population health
benefit. Youth and young adults would
experience the greatest benefits from a
nicotine product standard, because it is
likely that most of them would not
progress beyond experimentation or
occasional use and, therefore, may not
experience the dangerous and deadly
tobacco-related health effects associated
with combusted tobacco product use.
Fetuses and children also would benefit
if their parents quit smoking or using
most combusted tobacco products, given
the negative health consequences to the
fetus of a smoking mother and the
dangers of secondhand smoke (Ref. 19).
Children of parents who smoke, when
compared with children whose parents
do not smoke, have an increased
frequency of respiratory infections like
pneumonia and bronchitis (Ref. 563).
Smoking cessation reduces the rates of
these respiratory symptoms and of
respiratory infections among children
(Ref. 63 at p. 467). Children exposed to
tobacco smoke in the home also are
more likely to develop acute otitis
media (middle ear infections) and
persistent middle ear effusions (thick or
sticky fluid behind the eardrum) (Ref.
563). If parents were more readily able
to quit because these products were
minimally addictive or nonaddictive,
the incidence of these health problems
among youth would be expected to
decline. Additionally, such health
problems would not occur in future
years, as fewer individuals would
initiate and progress to regular smoking.
According to the 2014 Surgeon
General’s Report, which summarizes
thousands of peer-reviewed scientific
studies and is itself peer-reviewed,
smoking remains the leading
preventable cause of disease and death

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in the United States, and cigarettes have
been shown to cause an ever-expanding
number of diseases and health
conditions (Ref. 1). As stated in the
report, ‘‘cigarette smoking has been
causally linked to disease of nearly all
organs of the body, to diminished health
status, and to harm to the fetus’’ and
‘‘[t]he burden of death and disease from
tobacco use in the United States is
overwhelmingly caused by cigarettes
and other combusted tobacco products’’
(Ref. 1). The 2014 Surgeon General’s
Report estimates that 16 million people
live with diseases caused by smoking
cigarettes (Ref. 1). Additionally, the
burden of tobacco-related addiction and
disease disproportionately impacts
certain populations, such as individuals
experiencing poverty, those of lower
educational attainment, in historically
marginalized racial and ethnic groups,
in the LGBTQI+ community, people
living with a mental health condition, in
the military, and in certain geographic
areas (Ref. 120). In particular, Black
individuals experience the highest rates
of incidence and mortality from
tobacco-related cancers compared to
people from other racial and ethnic
groups (Refs. 102 and 103).
Additionally, mortality related to other
tobacco-related diseases such as heart
disease, stroke, and hypertension is
higher among Black individuals than

other racial and ethnic groups (Refs.
105, 106, 108 to 110, and 123).
Moreover, when comparing mortality
to morbidity, for every person who dies
from smoking, 30 more are living with
a smoking-attributable disease (Ref. 1).
Smoking is causally associated with a
number of diseases affecting nearly all
organs in the body, such as numerous
types of cancer, heart disease, stroke,
lung diseases such as COPD, and
diabetes, in addition to putting
individuals at increased risk for
tuberculosis, certain eye diseases, and
immune system issues (Ref. 1). One
study estimated that individuals in the
United States have had 14.0 million
major smoking-attributable medical
conditions, including more than 7.4
million cases of COPD, nearly 2.3
million heart attacks, 1.8 million cases
of diabetes, nearly 1.2 million stroke
events, more than 300,000 cases of lung
cancer, and nearly 1 million cases of
other smoking-attributable cancers
(bladder, cervix, colon/rectum, kidney,
larynx, mouth, tongue, lip, throat,
pharynx, stomach) (Ref. 564). Therefore,
increased smoking cessation, reduced
cigarette consumption, and lower
progression to regular use would reduce
not only the mortality from smoking,
but also the enormous burden of
cigarette-attributable disease in the
United States.
In addition to the years of life gained
due to reduced premature mortality

from tobacco, the substantial reductions
in smoking initiation and increases in
smoking cessation will result in
improvements in quality of life for those
who quit or do not initiate smoking
because of the product standard. To
estimate the potential impact of the
proposed standard on morbidity and
mortality, we used estimates from FDA’s
population health model, which is
described in section VIII.A of this
document. Table 5 presents cumulative
estimates of mortality and morbidity
avoided as a result of the proposed
nicotine product standard, for certain
years in the simulation period (Ref. 42
at Appendix J). By 2060, we estimate
that approximately 1.8 million deaths
due to tobacco would be avoided, rising
to 4.3 million by the end of the century.
The reduction in premature deaths
attributable to the proposed product
standard would result in 19.6 million
life years gained by 2060 and 76.4
million life years gained by 2100. Based
on previously reported quality of life
scores derived for people who do and
do not smoke, stratified by age group
(Ref. 565), we estimate that the
proposed nicotine product standard
would result in 24.0 million QALYs
gained by 2060 due to reduced smoking
morbidity. By 2100, this estimate is
projected to increase to 53.1 million
QALYs gained due to reduced smoking
morbidity (Ref. 42 at Section 2.3).

TABLE 5—PROJECTED NUMBER OF TOBACCO-ATTRIBUTABLE DEATHS AVOIDED, LIFE YEARS GAINED, AND QALYS GAINED
DUE TO REDUCED SMOKING AS A RESULT OF A NICOTINE PRODUCT STANDARD IMPLEMENTED IN 2027

Year

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2040
2060
2080
2100

Scenario

.........................................................................................
.........................................................................................
.........................................................................................
.........................................................................................

In addition to the main analyses
concerning projected death and
disability, we examined the sensitivity
of modeled results to underlying
assumptions related to baseline product
use projections and mortality risk
estimates. Sensitivity analyses
accounted for the following: an increase
in noncombusted product initiation;
different assumptions of people who
smoke switching to noncombusted
products per year; decrease in smoking
initiation; lower and higher
noncombusted product mortality risk
compared to baseline; different
assumptions for dual product use
mortality risk; changes in baseline

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Median
Median
Median
Median

(5th,
(5th,
(5th,
(5th,

95th)
95th)
95th)
95th)

Cumulative tobacco-attributable
deaths avoided
(millions)
0.4
1.8
3.1
4.3

(0.1,
(0.4,
(1.0,
(1.6,

mortality rate projections; and the
potential impact of a substantial illicit
market for NNC cigarettes. Changes to
baseline inputs of noncombusted
product use trajectories and health risks
had minimal impact on smoking
prevalence and attributable morbidity
and mortality, and the nicotine product
standard still resulted in substantial
public health benefits. Assuming
increasing initiation rates for
noncombusted product use until year
2030 implies that the number of people
who use tobacco will be higher under
the baseline and nicotine product
standard scenarios, with a higher

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0.5)
2.0)
3.4)
4.6)

Cumulative life
years gained
(millions)
2.0 (0.2, 2.7)
19.6 (3.6, 22.7)
47.4 (12.5, 52.5)
76.4 (26.5, 82.5)

Cumulative
QALYs gained
due to reduced
smoking morbidity
(millions)
9.6 (2.7,
24.0 (10.1,
38.2 (18.5,
53.1 (27.5,

10.0)
24.7)
39.2)
54.4)

proportion being people who use
noncombusted tobacco products.
In terms of mortality risk, we applied
a relative risk of 1.18 for people who use
noncombusted tobacco products as
compared with people who have never
smoked (i.e., the risk of death associated
with noncombusted tobacco use is
assumed to be 1.18 times greater than
the risk of death associated with never
smoking). For combusted cigarette
smoking, the relative mortality risk
varies with age, but is generally around
2.5, as compared to people who have
never smoked (i.e., the risk of death
associated with smoking is estimated to
be 2.5 times greater than the risk of

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death associated with never smoking).
Mortality risk for people who have
never used tobacco is 1, so the excess
mortality risk of using a product beyond
that of those who have never used
tobacco, and therefore related to the

product used, can be calculated by
subtracting 1 from the mortality risk
(i.e., excess mortality risk for
noncombusted tobacco use is 1.18¥1 =
0.18, and for combusted cigarette use it
is 2.5¥1=1.5). Thus, in our main

5085

modeling projections, we apply an
excess risk of using noncombusted
tobacco products that is 12 percent that
of the excess risk associated with
cigarette smoking (i.e., 100 × (0.18/1.5)
= 12 percent).

TABLE 6—IMPACT OF VARYING BASELINE ASSUMPTIONS ON PROJECTED SMOKING PREVALENCE AND AVOIDED MORTALITY
AND MORBIDITY BY 2100. MEDIAN (5TH, 95TH PERCENTILES) ESTIMATES
Projections through year 2100
Scenario

Cigarette smoking
prevalence
(%)

Main scenario ..........................................................................

Cumulative
tobacco-attributable mortality
avoided
(millions)

0.2 (0.1, 1.9)

4.3 (1.6, 4.6)

Cumulative
life years gained
(millions)

Cumulative
QALYs gained
from reduced
smoking morbidity
(millions)

76.4 (26.5, 82.5)

53.1 (27.5, 54.4)

76.5 (26.7, 82.5)
74.9 (28.6, 80.7)
73.6 (30.3, 79.0)

53.1 (27.5, 54.4)
51.9 (29.0, 52.9)
50.8 (30.2, 51.6)

4.1 (1.5, 4.4)

72.9 (24.3, 79.0)

45.2 (22.9, 46.4)

4.0 (1.5, 4.3)

70.9 (24.9, 76.4)

50.1 (26.3, 51.2)

4.3 (1.6, 4.6)
4.4 (1.6, 4.7)

75.0 (26.0, 81.4)
77.2 (26.9, 83.2)

53.1 (27.5, 54.4)
53.1 (27.5, 54.4)

0.2 (0.1, 1.9)

4.3 (1.6, 4.6)

75.9 (25.0, 82.4)

53.1 (27.5, 54.4)

0.2 (0.1, 1.9)
0.2 (0.1, 1.9)

4.3 (1.6, 4.6)
4.3 (1.6, 4.6)

77.0 (28.6, 82.6)
77.6 (30.7, 82.7)

53.1 (27.5, 54.4)
53.1 (27.5, 54.4)

77.9 (28.2, 83.9)

53.0 (27.4, 54.2)

Baseline noncombusted tobacco product trajectory
Increased noncombusted initiation ..........................................
50% increased complete switching .........................................
100% increased complete switching .......................................

0.2 (0.1, 1.9)
0.13 (0.06, 1.7)
0.12 (0.06, 1.5)

4.3 (1.6, 4.6)
4.2 (1.7, 4.5)
4.2 (1.8, 4.4)

Baseline smoking initiation trajectory
25% decrease in smoking initiation during the period 2021–
2030 .....................................................................................

0.13 (0.1, 1.6)

Baseline smoking cessation
10% increase in smoking cessation ........................................

0.15 (0.1, 1.8)

Baseline noncombusted mortality relative risk (RR)
Higher RR than main scenario (RR = 1.3) ..............................
Lower RR than main scenario (RR = 1.1) ...............................

0.2 (0.1, 1.9)
0.2 (0.1, 1.9)

Baseline dual use RR
Dual use RR is 18% greater than for cigarette smoking ........
Dual use RR is the average of cigarette and noncombusted
use RR .................................................................................
Dual use RR is equal to the noncombusted use RR ..............

Baseline mortality rate projections

ddrumheller on DSK120RN23PROD with PROPOSALS3

Keep mortality rates constant starting at 2060 .......................

As shown in table 6, varying baseline
input parameter values had very small
effects on estimates of the potential
population health effects of a nicotine
product standard. Assuming a 25
percent decrease in cigarette smoking
initiation during the period from 2021
to 2030 resulted in modest decreases in
smoking prevalence and health benefits,
in particular reductions in morbidity
due to smoking, by 2100 in the policy
scenario compared to the main analysis.
Increases in baseline complete
switching to noncombusted tobacco
product use resulted in similar small
decreases in smoking prevalence and
health benefits in terms of life years
gained and reduced smoking morbidity
by 2100 compared to the main analysis.
Different assumptions about baseline
relative risks also produced modest

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0.2 (0.1, 2.0)

4.7 (1.9, 5.1)

changes in differences in life years
gained. Additional details regarding the
sensitivity analyses can be found in
FDA’s modeling document (Ref. 42).
Sensitivity analyses were also
conducted examining assumptions
about the potential effect of the nicotine
product standard on smoking cessation.
In addition to the modeling results
obtained through expert-derived inputs,
we also generated projections based on
results from clinical studies of VLNC
cigarette use and cessation. Based on
these studies, we applied a two-fold
increase in cessation (estimates ranged
from 6.4 percent to 19.8 percent), as
compared to the baseline cessation rate
(estimates ranged from 3.2 percent to 9.9
percent), as an alternative estimate of
the long-term impact of the proposed
product standard on cessation, while

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maintaining the median of the expertderived values for the other parameters
(Ref. 42 at Section 2.3). Given the wide
variation in the expert-derived cessation
rates, the projected health impacts
assuming a two-fold increase in
cessation fell within the range of results
obtained from expert-derived inputs
(see table 6).
Additionally, increasing the assumed
proportion of people who smoke who
may divert to the use of illicit NNC
cigarettes (3.8 percent, 5.9 percent, and
21.0 percent),33 and allowing youth and
33 We use 3.8 percent as a low-end estimate based
on 2017 estimates of illicit trade volume in
cigarettes from Euromonitor International (Ref.
558). This estimate excludes interstate smuggling
for purposes of tax avoidance. Using findings from
the International Tobacco Control United States
Survey, we estimate that 5.9 percent of U.S. people

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Federal Register / Vol. 90, No. 10 / Thursday, January 16, 2025 / Proposed Rules

young adults (who would have
otherwise initiated NNC cigarette use) to
initiate into illicit NNC cigarette use (0
percent, 2.6 percent, and 10 percent) 34
under the proposed nicotine standard
resulted in reductions in the projected

cumulative attributable morbidity and
mortality outcomes following the
implementation of the policy (table 7).
It is noteworthy that significant benefits
in terms of reduced morbidity and
mortality are realized as a result of this

product standard, even in a scenario in
which greater proportions of the
population who smoke are assumed to
divert to use of illicit NNC cigarettes.

TABLE 7—PROJECTED HEALTH BENEFITS AS A RESULT OF A NICOTINE PRODUCT STANDARD IMPLEMENTED IN 2027
UNDER ILLICIT TRADE SCENARIOS
[Median (5th, 95th percentiles) estimates]
Illicit trade impact scenarios
Year

Main scenario
(no impact)

Low impact 1

Medium impact 2

High impact 3

0.4 (0.04,
1.8 (0.3,
3.1 (0.8,
4.3 (1.4,

0.4 (0.01,
1.7 (0.1,
3.0 (0.4,
4.2 (0.9,

Tobacco-Attributable Deaths Avoided (Millions)
2040
2060
2080
2100

.........................................................................................
.........................................................................................
.........................................................................................
.........................................................................................

0.4
1.8
3.1
4.3

(0.1,
(0.4,
(1.0,
(1.6,

0.5)
2.0)
3.4)
4.6)

0.4 (0.04,
1.8 (0.4,
3.1 (0.8,
4.3 (1.5,

0.5)
2.0)
3.4)
4.6)

0.5)
2.0)
3.4)
4.6)

0.5)
2.0)
3.3)
4.5)

Cumulative Life Years Gained (Millions)
2040
2060
2080
2100

.........................................................................................
.........................................................................................
.........................................................................................
.........................................................................................

2.0 (0.2, 2.7)
19.6 (3.6, 22.7)
47.4 (12.5, 52.5)
76.4 (26.5, 82.5)

2.0 (0.1, 2.7)
19.4 (3.2, 22.6)
47.1 (11.4, 52.4)
76.0 (24.6, 82.3)

2.0 (0.1, 2.7)
19.3 (3.0, 22.6)
46.9 (10.7, 52.3)
75.8 (23.4, 82.2)

1.8 (0.01, 2.6)
18.4 (1.2, 22.0)
45.3 (5.3, 51.5)
73.9 (13.7, 81.3)

Cumulative QALYs Gained from Reduced Smoking Morbidity (Millions)
2040
2060
2080
2100

.........................................................................................
.........................................................................................
.........................................................................................
.........................................................................................

9.6 (2.7,
24.0 (10.1,
38.2 (18.5,
53.1 (27.5,

10.0)
24.7)
39.2)
54.4)

9.6 (2.5,
24.0 (9.6,
38.2 (17.7,
53.0 (26.6,

10.0)
24.7)
39.2)
54.4)

9.5 (2.4,
23.9 (9.2,
38.0 (17.0,
52.8 (25.5,

10.0)
24.7)
39.2)
54.3)

9.2 (1.5, 9.9)
23.4 (6.5, 24.6)
37.3 (12.6, 39.0)
51.9 (19.3, 54.1)

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1 Low Impact: 3.8 percent people who smoke would divert to use illicit NNC cigarettes, and 0 percent youth and young adults would initiate illicit NNC cigarettes.
2 Medium Impact: 5.9 percent people who smoke would divert to use illicit NNC cigarettes, and 2.6 percent youth and young adults would initiate illicit NNC cigarettes.
3 High Impact: 21.0 percent people who smoke would divert to use illicit NNC cigarettes, and 10.0 percent youth and young adults would initiate illicit NNC cigarettes.

As previously discussed, nicotine is
the primary driver of addiction in
tobacco products and facilitates
progression to regular cigarette smoking
and other regular combusted tobacco
product use. FDA anticipates that
establishing a maximum level of
nicotine in cigarettes and certain other
combusted tobacco products will
prevent a substantial number of youth
and young adults who experiment with
combusted tobacco products from
developing an addiction to these
products, thereby decreasing
progression to regular use, resulting in
reduced tobacco-related morbidity and
mortality associated with combusted
tobacco product use.

2. Given the Harmful Effects of Cigarette
Smoking and Other Combusted Tobacco
Product Use, Quitting Smoking Reduces
Death and Disease
Although the health benefits are
greater for people who stop smoking at
earlier ages (Refs. 63 and 563),
researchers estimate that people who
regularly smoke can gain years of
additional life expectancy no matter
when they quit (Ref. 566). Quitting
cigarette smoking and use of other
combusted tobacco products
substantially reduces the likelihood of
tobacco-related death and disease. As
stated in the 2004 Surgeon General’s
Report, ‘‘[q]uitting smoking has
immediate as well as long-term benefits,
reducing risks for diseases caused by

smoking and improving health in
general’’ (Ref. 63). The 2020 Surgeon
General’s Report also concluded that
‘‘[s]moking cessation is beneficial at any
age. Smoking cessation improves health
status and enhances quality of life.’’
(Ref. 19). As previously noted, FDA
expects that, if this proposed rule is
finalized, there will be a significant
increase in smoking cessation in the
U.S. population (see section VIII.C of
this document).
The benefits associated with smoking
cessation happen quickly (Ref. 63).
Within 2 to 12 weeks of quitting
smoking, an individual’s lung function
and blood circulation improve (Ref. 63).
During the first 1 to 9 months following
cessation, coughing and shortness of
breath decrease (Ref. 63). Within several

who use cigarettes last purchased cigarettes from
low-tax locations (Ref. 559). We use these figures
as proxies for the proportions of people who use
cigarettes who may actively seek out illicit NNC
cigarettes under a nicotine product standard,
although we note that the product standard would
be implemented nationwide, avoiding disparate
pricing/availability between states. We use 21
percent as a high-end estimate based on the

difference in non-compliance rates between
reduced nicotine intervention groups (78 percent)
and control groups assigned to NNC cigarettes (57
percent) in clinical trial data (Refs. 29 and 330).
This estimate of 21 percent also represents the highend of the range estimated by the National Research
Council, which reflected the methodology of the
pack return survey by Fix, et al. (Refs. 560 and 561).

34 We use findings from an expert elicitation
developed to gauge the impact of a menthol
cigarette and cigar prohibition in the United States,
which indicates that among people ages 12–24 who
would have otherwise initiated menthol cigarette
use, 2.6 percent would initiate illicit menthol
cigarette use (estimate ranged from 0 percent to 10
percent) (Ref. 562).

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Federal Register / Vol. 90, No. 10 / Thursday, January 16, 2025 / Proposed Rules
months of quitting smoking, individuals
can expect further improvement in lung
function (Ref. 63). Additionally, the
benefits of cessation continue for those
who remain smoke-free. Smoking
cessation reduces the risk of cancers and
other diseases (Ref. 19). For example,
the risk of fatal lung cancer in adults
over age 55 is about 25 times higher
among people who smoke cigarettes
relative to people who have never
smoked (Ref. 567). After 10–15 years of
abstinence from smoking, the risk of
lung cancer is about 50 percent of the
risk for individuals who continue to
smoke (Ref. 19). The risk of cancer of
the mouth, throat, esophagus, stomach,
bladder, cervix, pancreas, liver, kidney,
colon, and rectum, and the risk of acute
myeloid leukemia also decreases (Refs.
19 and 568). The evidence is also
sufficient to infer that the risk of stroke
decreases after smoking cessation and
approaches that of people who have
never smoked cigarettes over time (Ref.
569). Furthermore, the evidence is
sufficient to infer that the relative risk
of coronary heart disease among people
who formerly smoked cigarettes falls
rapidly after cessation and then declines
more slowly (Ref. 19).
In addition, smoking cessation
substantially reduces the risk of other
dangerous diseases that can lead to
death or disability and cause a financial
strain on healthcare resources. For
example, quitting smoking substantially
reduces the risk of peripheral artery
occlusive disease (which can cause
complications that lead to loss of limbs)
(Ref. 563). It also reduces the relative
risk of coronary heart disease and stroke
morbidity and mortality among people
who formerly smoked compared with
people who have never smoked (Ref.
19). People who formerly smoked
cigarettes also have half the excess risk
of experiencing an abdominal aortic
aneurysm compared to people who
currently smoke cigarettes (Ref. 563).
Furthermore, cigarette smoking
complicates many diseases (e.g., people
who smoke and have diabetes have
higher risk of complications, including
heart and kidney disease, poor blood
flow in the legs and feet, retinopathy,
and peripheral neuropathy), and
smoking cessation can alleviate those
complications as well (Ref. 28).
Even people who smoke and quit
smoking after the onset of a lifethreatening disease experience
significant health benefits from
cessation. Quitting smoking after a
diagnosis reduces the chance of
recurrences and future health problems.
For example, people who quit smoking
after having a heart attack can reduce
their chances of having a second heart

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attack by 50 percent (Ref. 568). For
those persons who have already
developed cancer, quitting smoking
reduces the risk of developing a second
cancer (Refs 563, 570 to 572).
Additionally, quitting smoking after a
diagnosis of lung cancer reduces the risk
of cancer progression and mortality (Ref.
573). Researchers also estimate that for
people who currently smoke and have
been diagnosed with coronary heart
disease, quitting smoking reduces the
risk of death overall and reduces the
risk of recurrent heart attacks and
cardiovascular death by 30 to 40 percent
(Refs. 19 and 563). The 2020 Surgeon
General’s Report concluded that quitting
smoking reduces the risk of fatal and
non-fatal stroke, and earlier reports have
also stated that it is reasonable to
assume that quitting smoking would
reduce the risk of recurrent strokes
(Refs.19 and 563). Quitting smoking
helps the body tolerate the surgery and
treatments, such as chemotherapy and
radiation, associated with certain
smoking-related diseases, and quitting
also improves the likelihood of
responding to those treatments (Refs. 63,
563, 570, and 574) and reduces the risk
of respiratory infections compared to
continued smoking (Refs. 563 and 575).
Given the reduction in risk of
smoking-related death and disease
associated with cessation, those who
successfully quit smoking also increase
their life expectancy. Using data from
the CPS–II—an ongoing study of 1.2
million adults—scientists have found
that, among men who smoke cigarettes,
men who smoked at age 35 and
continued to smoke until death had a
life expectancy of 69.3 years, compared
with a life expectancy of 76.2 years for
those who stopped smoking at age 35
(Ref. 576). After adjusting for the
subsequent quit rate among people who
currently smoke cigarettes at baseline
(to account for the possibility that some
people who currently smoke at baseline
quit smoking or some people who
formerly smoked relapsed during
followup and, thus, were incorrectly
classified as people who continue to
smoke in the unadjusted analysis), the
life expectancy for males who formerly
smoked increased to 77.8 years (a life
extension of 8.5 years) (Ref. 576).
Women who smoked at age 35 and
continued to smoke until death had a
life expectancy of 73.8 years, compared
with a life expectancy of 79.7 years for
those who stopped smoking at age 35
(Ref. 576). After adjustment for the
subsequent quit rate among people who
currently smoke at baseline, the life
expectancy for females who formerly
smoked increased to 81 years (a life

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5087

extension of 7.7 years) (Ref. 576).
Furthermore, a man aged 60–64 years
who smokes 20 cigarettes (one pack) or
more per day and then quits smoking
reduces his risk of dying during the next
15 years by 10 percent (Ref. 563).
While cessation is beneficial for
people of all ages, the health benefits are
greatest for people who stop smoking at
earlier ages (Refs. 63 and 563). Scientists
in the United Kingdom found that
people who quit smoking at age 30
reduce their risk of dying prematurely
(i.e., dying before their expected average
life expectancy) from smoking-related
diseases by more than 90 percent (Refs.
544 and 577). Those who quit at age 50
reduce their risk of dying prematurely
by 50 percent compared to those who
continue to smoke (Ref. 544). Using
NHIS data, researchers also estimated
that life expectancy in the United States
would increase by 4 years among people
who smoke who quit at ages 55–64, and
10 years among people who smoke who
quit at ages 25–34 (Ref. 566). Scientists
using the CPS–II data (while accounting
for the possibility that some people who
currently smoke at baseline quit
smoking and some people who formerly
smoked relapsed during followup)
found that even people who smoke who
quit at age 65 had an expected life
increase of 2 years for men and 3.7 years
for women (Ref. 576).
The benefits continue for those who
remain smoke-free. At year one, an
individual’s risk of coronary heart
disease becomes half that of a person
who smokes cigarettes (Refs. 219 and
578). Beginning 2 and 5 years after
cessation, an individual’s stroke risk is
reduced to that of a person who does
not smoke cigarettes (Refs. 19 and 578).
In addition, the risk of cancers of the
mouth, throat, esophagus, and bladder
for a person who formerly smoked is
halved within 5 years (Ref. 578). By 10
years post-cessation, an individual’s risk
of cancers of the kidney and pancreas
decreases (Ref. 578). The risk of
coronary heart disease becomes that of
a person who does not smoke after 15
years of abstinence (Ref. 578). FDA
anticipates that limiting nicotine yield
by setting a maximum level of nicotine
in cigarettes and certain other
combusted tobacco products would
improve smoking cessation outcomes in
adults who smoke and result in longer
life expectancies for more individuals.
Additionally, FDA anticipates that this
proposed product standard will benefit
populations that use tobacco products at
disproportionately high levels by
reducing tobacco-related morbidity and
mortality by improving quitting and
cessation among these populations.

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ddrumheller on DSK120RN23PROD with PROPOSALS3

Research has shown that people from
specific population groups who smoke
cigarettes bear a disproportionate
burden of tobacco-related morbidity and
mortality. Black individuals, and in
particular Black men, experience the
highest rates of incidence and mortality
from tobacco-related cancers compared
to people from other racial and ethnic
groups (Refs. 102 and 103).
Additionally, mortality due to tobaccorelated disease such as heart disease,
stroke, and hypertension is higher
among Black individuals compared to
other racial and ethnic groups (Refs.
105, 106, 108 to 110, 123, and 579).
Furthermore, individuals with
symptoms of mental health disorders
and persons who have substance use
disorders smoke cigarettes in
disproportionately large numbers (Refs.
128, 580 to 585), resulting in increased
risk for tobacco-related morbidity and
mortality (Ref. 585). Based on these
collective findings, FDA anticipates that
the proposed product standard will
improve smoking cessation outcomes
across the U.S. population, including
among populations at increased risk for
tobacco-related morbidity and mortality,
leading to a reduction in adverse
tobacco-related health effects.
3. Given the Harmful Effects of Cigarette
Smoking, Switching to a Potentially
Less Harmful Nicotine Delivery Product
May Reduce Death and Disease
Some people who smoke and who
want to quit use NRT products, or other
smoking cessation products that do not
contain nicotine, that FDA has approved
as safe and effective for smoking
cessation. These products have been
shown to significantly increase the
success of smoking cessation (Ref. 586).
FDA continues to be committed to
enabling the development of safe and
effective drug product innovations that
help smokers quit combustible
cigarettes and improve their health.
FDA also recognizes, however, that
other people may seek to switch from
cigarette smoking to using other
noncombusted tobacco products that
deliver nicotine. People who smoke and
switch completely to a potentially less
harmful noncombusted tobacco product
to maintain their nicotine dependence
also could, to the extent that use of
those products result in less harm,
significantly reduce their risk of
tobacco-related death and disease (Ref.
8).
As described in section VI.B of this
document, studies have reported on the
ways in which people who use tobacco
have predicted how their patterns of
tobacco use would change in response
to the implementation of a nicotine

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product standard. While most people
who use tobacco in these studies
indicated that they would continue to
smoke cigarettes—or other combusted
products—or simply quit tobacco use,
some participants reported that they
would switch to using or increase use of
a noncombusted product (Refs. 262,
264, and 587).
One clinical trial compared use of
NRT and alternative tobacco products
(i.e., smokeless tobacco, e-cigarettes,
cigars, cigarillos) among people who
smoke cigarettes and were randomized
to one of three groups (Ref. 5). One
group received LNC cigarettes along
with access to NRT, noncombusted
tobacco products (i.e., smokeless
tobacco, e-cigarettes), and combusted
non-cigarette products (i.e., cigars,
cigarillos); a second group received LNC
cigarettes, and NRT, and noncombusted
tobacco products only; and a third
group received NNC cigarettes along
with NRT, noncombusted tobacco
products, and combusted tobacco
products. Overall, those who received
the LNC cigarettes used more alternative
combusted and noncombusted tobacco
products as well as NRT. These
participants also smoked fewer total
combusted tobacco products and had a
greater number of quit attempts.
Tobacco toxicant levels in participants
who received LNC cigarettes and only
NRT and noncombusted products were
statistically significantly lower than
those of participants who received NNC
cigarettes, while toxicant levels in those
who received LNC cigarettes and had
access to NRT, combusted, and
noncombusted products did not differ
from the NNC cigarette group (Ref. 5).
Findings demonstrate that when people
who smoke cigarettes are switched to
LNC cigarettes and are provided with
alternative sources of nicotine, they will
readily use the alternative sources of
nicotine. Moreover, the LNC cigarette
group that had access to NRT and
noncombusted nicotine sources only
had statistically significantly reduced
biomarker levels of certain harmful
constituents (NNN and NNAL)
compared to those who continued to
smoke NNC cigarettes (Ref. 5). The LNC
cigarette group with access to NRT and
both combusted and noncombusted
tobacco products resembled the NNC
cigarette group (Ref. 5).
Moreover, in general, the high levels
of noncompliance with study-issued
VLNC cigarettes in the context of
clinical trials, and continued use of nonstudy provided tobacco products
(particularly NNC cigarettes), suggest
that VLNC cigarettes have lower appeal
and abuse potential compared to NNC
cigarettes (Refs. 327 to 331). As a result,

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these findings suggest that people who
smoke VLNC cigarettes are likely to use
alternative nicotine-containing
products, if such products are
concurrently available, once a nicotine
product standard for combusted tobacco
products is in place.
Under FDA’s population health
model’s product standard scenario, an
increase in noncombusted product use
would occur concurrently with a
dramatic reduction in cigarette smoking.
Although the model assumes that
noncombusted product initiation would
remain constant until the end of the
projection period (i.e., 2100), the
product standard scenario shows that
noncombusted use continues to climb
due to higher switching rates from
combusted products as compared to the
baseline scenario. This is because the
number of people who start using
noncombusted tobacco products would
be much higher compared to the
number of people who quit using
noncombusted products. That is, there
would be more people who currently
use noncombusted tobacco products
every year than people who quit using
noncombusted products, which would
cause an increase in noncombusted
tobacco use prevalence throughout the
projection period. According to the
model, adult noncombusted tobacco use
would increase from 7.7 percent in the
baseline scenario to 12.8 percent in the
product standard scenario within 1 year
after policy implementation, due to the
increase in switching from cigarette
smoking and dual use as a result of a
nicotine product standard. The
prevalence of noncombusted tobacco
use would remain higher in the product
standard scenario over time due both to
increased uptake among people who
smoke and increased initiation due to
some dissuaded initiation of cigarette
use, compared to those individuals
taking up noncombusted products
instead.
Under the product standard scenario
in the model, dual use of cigarettes and
noncombusted tobacco products also
would increase immediately, since a
greater proportion of people who
continue to smoke cigarettes would take
up noncombusted products than in the
baseline scenario, but this pattern
would not continue over time with dual
use prevalence reaching levels below
0.1 percent by the year 2035. Although
the increase in noncombusted tobacco
product use trend changes over time
(i.e., results showed a spike increase in
noncombusted use prevalence within
the first 3 years after implementation of
a nicotine product standard), the
decrease in smoking prevalence
becomes greater than the increase in

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Federal Register / Vol. 90, No. 10 / Thursday, January 16, 2025 / Proposed Rules
noncombusted use following the
implementation of a nicotine product
standard. Consequently, overall tobacco
use under the product standard scenario
would remain lower than in the baseline
scenario.
As described in section VIII.A of this
document, in addition to the
aforementioned main analyses, FDA
conducted a series of sensitivity
analyses to examine the impact of key
modeling assumptions on the main
outcome metrics of interest. In these
analyses, we examined the sensitivity of
modeled results to underlying
assumptions related to baseline product
use projections and mortality risk
estimates. Sensitivity analyses included
examining the impact of increased
initiation of noncombusted tobacco
product use among those who would
otherwise not have used tobacco, the
impact of an increase in switching from
cigarettes to noncombusted tobacco
product use, the impact of a varying
mortality risk associated with dual use
of cigarettes and noncombusted tobacco
products, the impact of lower and

higher noncombusted tobacco product
risk, and the emergence of an illicit
market for full nicotine content
cigarettes.
In general, changes to baseline inputs
of noncombusted product use
trajectories and health risks had
minimal impact on smoking prevalence
and attributable morbidity and mortality
and the nicotine product standard
policy scenario still resulted in
substantial public health benefits. In the
main modeling analysis, we account for
people who would have initiated on
smoking cigarettes initiating on
noncombusted tobacco products instead
because of the product standard. It is
also possible that there could be
increased initiation of noncombusted
tobacco use among those who would
otherwise not have used tobacco under
the product standard scenario; for
example, due to increased marketing of
noncombusted products because of the
policy or changes in public perceptions
of the harms of noncombusted products.
In a sensitivity analysis, starting at 2027
(year of the proposed standard

5089

implementation), we assumed a 20
percent increase in the initiation of
noncombusted tobacco products among
those who would otherwise have not
used tobacco. Table 8 provides the
projected impacts on tobacco-related
mortality and morbidity through the
year 2100. Compared with the main
results, a 20 percent increase in
initiation of noncombusted tobacco use
had minimal impact in mortality
outcomes given the substantial
reduction in adverse health effects
projected under a potential nicotine
product standard. For example, by year
2100, cumulative life years gained
decreased by less than 1 percent
compared with the main results, while
cumulative tobacco-attributable deaths
avoided remained almost the same. It is
important to note that, because we only
have data on the effect of cigarette
smoking (and not noncombusted
product use) on quality of life, the
projected changes in QALYs gained
from reduced smoking morbidity are not
affected by increasing noncombusted
product use initiation.

TABLE 8—IMPACT OF INCREASED INITIATION OF NONCOMBUSTED TOBACCO PRODUCTS AS A RESULT OF THE PROPOSED
NICOTINE PRODUCT STANDARD IMPLEMENTED IN 2027 ON PROJECTED SMOKING PREVALENCE AND TOBACCO-RELATED MORTALITY AND MORBIDITY BY 2100
[Median (5th, 95th percentiles) estimates]
Projections through year 2100
Noncombusted
tobacco use
prevalence
(%)

Scenario

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Main scenario ..........................................................................
20% increased initiation of noncombusted products ...............

Taken together, findings from prior
research, as well as FDA’s population
health model, suggest that if the
proposed product standard reduces the
nicotine yield by setting a maximum
level of nicotine in cigarettes only, but
people who smoke cigarettes still have
access to other NNC combusted tobacco
products, they likely would substitute
with the NNC combusted tobacco
products and negate a significant
proportion of the public health impact
of the product standard. If other
combusted tobacco products also are
covered by this proposed product
standard, however, data suggest that
people who smoke may switch from
combusted tobacco product use to
potentially less harmful tobacco
products. Moreover, findings indicate
that switching from combusted cigarette
use to noncombusted tobacco product
use has the potential to impart

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14.1 (12.7, 14.9)
15.4 (14.0, 16.1)

Cumulative
tobaccoattributable
mortality avoided
(millions)
4.3 (1.6, 4.6)
4.3 (1.6, 4.6)

significant health-related benefits on a
population level. The population health
model estimates that on average
approximately 50 percent of people who
smoke cigarettes will switch to
noncombusted tobacco products use per
year, and although we estimate that
such switching carries an 8 percent
higher risk than quitting tobacco use
entirely (based on findings from Henley
et al. 2007 (Ref. 557)), this is still a
significant health-related benefit
compared to continuing to use
combusted tobacco products.
4. Having Fewer People Smoke
Cigarettes and Other Combusted
Tobacco Products Will Reduce Death
and Disease Associated With
Secondhand Smoke Exposure
Cigarettes and other combusted
tobacco products also have deadly
effects on people who do not smoke

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Cumulative life
years gained
(millions)
76.4 (26.5, 82.5)
75.9 (26.1, 82.1)

Cumulative
QALYs gained
from reduced
smoking morbidity
(millions)
53.1 (27.5, 54.4)
53.1 (27.5, 54.4)

because they produce secondhand
smoke. It is well-established that
secondhand tobacco smoke causes
premature death and disease in children
and in adults who do not smoke (Ref.
15 at p.11). Secondhand smoke
exposure is currently estimated to be
responsible for over 41,000 deaths
annually in the United States (Ref. 1).
For example, an estimated 7,300 lung
cancer deaths and nearly 34,000
coronary heart disease deaths annually
can be attributed to secondhand smoke
(Ref. 1). Additionally, productivity
losses due to secondhand smokeattributable deaths are estimated to cost
the United States $5.6 billion each year
(Ref. 1).
Children are one group
disproportionately exposed to and
impacted by secondhand smoke. The
2014 Surgeon General’s Report
estimated that secondhand smoke is

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associated with 150,000 to 300,000
lower respiratory tract infections in
infants and children under age 18
months, 790,000 doctor’s office visits
related to ear infections per year, and
202,000 asthma cases each year (Refs. 1
and 137). In 2014, the U.S. Surgeon
General reported that 400 sudden infant
death syndrome (SIDS) deaths annually
are related to perinatal smoking or
exposure to secondhand smoke; the
‘‘Reproductive Outcomes’’ section
describes the impact of perinatal
smoking (Ref. 1). Children of parents
who smoke, when compared with
children of parents who do not smoke,
have an increased frequency of
respiratory infections like pneumonia
and bronchitis (Ref. 563). Children
exposed to tobacco smoke in the home
are also more likely to develop acute
otitis media (middle ear infections) and
persistent middle ear effusions (fluid
behind the eardrum) (Ref. 563). More
recent data from the 2013–2014
NHANES estimates that approximately
58 million Americans who do not
smoke (1 in 4) were exposed to
secondhand smoke, including 14
million children (Ref. 588).
Approximately half of all U.S. children
ages 3–18 are exposed to cigarette
smoke regularly at home or other
locations that still permit smoking (Ref.
1). In 2019, approximately one-quarter
of middle and high school students
reported breathing in secondhand
smoke in their homes or in a vehicle
(Ref. 145).
The burden of secondhand smoke
exposure is experienced
disproportionately among members of
some racial and ethnic groups and lower
income groups. Among people who do
not smoke and were ages 3 and older,
findings from 2011 to 2018 NHANES
data indicate that non-Hispanic Black
persons and those living below the
poverty level had the highest levels of
secondhand smoke exposure compared
to people of other races and those living
above the poverty level, respectively;
these disparities persisted across all
years of the study analysis from 2011 to
2018 (Ref. 139). From 1999 to 2012, the

percentage of people who do not smoke
and were age 3 and older exposed to
secondhand smoke (defined in the study
as levels 0.05–10 nanogram per
milliliter) declined across all racial and
ethnic groups (Ref. 141). However, a
significantly higher proportion of nonHispanic Black persons who do not
smoke continued to have detectable
serum cotinine levels compared to
Mexican American and non-Hispanic
White persons who do not smoke. For
example, in 2011–2012, nearly 50
percent of non-Hispanic Black people
who do not smoke had detectable serum
cotinine levels, compared with 22
percent of non-Hispanic White and 24
percent of Mexican American people
who do not smoke (Ref. 141).
Additionally, disparities in secondhand
smoke exposure are found across
various environmental settings,
including homes, vehicles, workplaces,
and public places. These disparities
speak to the interrelated influences of
individual factors (e.g., age, race and
ethnicity, income) and existing
inequities in places where members of
communities impacted by tobaccorelated health disparities are likely to
reside, spend time, and work (Ref. 174).
The proposed product standard is
anticipated to reduce smoking-related
morbidity and mortality for specific
population groups that do not smoke
that are disproportionately exposed to
secondhand smoke, especially youth.
Moreover, there is also some scientific
evidence supporting disparities in
secondhand smoke exposure by sexual
orientation. An analysis of NHANES
data from 2003–2010 found that
secondhand smoke exposure (defined as
a serum continine 17 levels ≥0.05
nanogram per milliliter) differed by
sexual orientation among women 20–59
years of age (Ref. 143). This study found
that among women 20–59 years of age,
secondhand smoke exposure was higher
among non-smoking women who
identified as lesbian (56.2 percent) or
who reported a lifetime experience with
a same-gender partner (47.7 percent)
than those women who identified as
exclusively heterosexual (33.0 percent;

p<0.001) (Ref. 143). However, among
men 20–59 years of age, exposure to
secondhand smoke did not significantly
differ by sexual orientation.
FDA anticipates that the overall
public health benefits of this proposed
nicotine product standard would be far
greater than those described above once
we account for the impacts of reduced
cigarette smoking on secondhand smoke
exposure. As evidenced by evaluations
of smoke-free policies, decreasing
exposure to secondhand smoke will
decrease smoking-related death and
disease among people who do not
smoke (Refs. 589 and 590).
To estimate the potential impact of
the proposed standard on morbidity and
mortality, FDA evaluated the existing
scientific literature as well as findings
from our population health model,
which is described in section VIII.A of
this document. Estimation of the
mortality benefits of a nicotine product
standard for secondhand smoke
exposure used a similar approach. This
approach relied on scaling the estimate
of 437,400 deaths annually attributable
to direct cigarette smoking from 2005–
2009 (Ref. 1), to the number of deaths
attributed to secondhand smoke
exposure. That ratio was then applied to
the model-derived projected changes in
avoided cigarette-attributable deaths
under the main product standard
scenario to project the number of
avoided deaths over time from
secondhand smoke exposure. In the
population health model, the impacts of
a nicotine product standard on mortality
from secondhand smoke exposure were
estimated by first calculating the ratio of
secondhand smoke (41,280 deaths; (Ref.
1)) to primary smoking-attributable
deaths. That value, 9.4 percent, was
then applied to the projections of
cigarette-attributable deaths avoided
yielding an estimate of approximately
169,000 cumulative deaths from
secondhand smoke exposure avoided by
2060, rising to approximately 415,600
cumulative deaths avoided by the end of
the century (see table 9).

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TABLE 9—PROJECTED NUMBER OF TOBACCO-ATTRIBUTABLE DEATHS AVOIDED FOR SECONDHAND SMOKE AS A RESULT
OF A NICOTINE PRODUCT STANDARD IMPLEMENTED IN 2027
Year
2040
2060
2080
2100

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Cumulative secondhand
smoking-attributable
deaths avoided

Scenario

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Median
Median
Median

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(5th,
(5th,
(5th,
(5th,

95th)
95th)
95th)
95th)

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39,800 (4,900, 49,200)
169,000 (38,500, 189,000)
297,000 (91,200, 323,200)
415,600 (159,700, 444,400)

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5. Estimated Mortality Impact of
Reduced Smoking-Related Fires,
Smoking-Related Perinatal Conditions,
and Use of Non-Premium Cigars and
Pipe Tobacco as a Result of
Implementation of the Proposed
Standard
FDA anticipates that the overall
public health benefits of this proposed
nicotine product standard would be
greater than those described above once
we account for the impacts of reduced
cigarette smoking on smoking-related
fires and perinatal conditions, in
addition to the impacts of reduced use
of other combusted tobacco products.
To estimate the potential impact of the
proposed standard on mortality, FDA
evaluated the existing scientific
literature, as well as findings from the
population health model—which is
described in section VIII.A. of this
document. Similar to the approach
taken to estimate the mortality benefits
of a nicotine product standard for
secondhand smoke exposure, estimation
of the mortality benefits of a nicotine
product standard for smoking-related
fires, smoking-related perinatal
conditions, and use of non-premium
cigars and pipe tobacco used a
consistent approach. This approach
relied on scaling the estimate of 437,400
deaths annually attributable to direct
cigarette smoking from 2005–2009 (Ref.
1), to the number of deaths attributed to
each of the following causes: smokingrelated fires, smoking-related perinatal
conditions, and use of non-premium
cigars and pipe tobacco. That ratio was
then applied to the model-derived
projected changes in avoided cigaretteattributable deaths under the main
product standard scenario to project the
number of avoided deaths over time
from each of these causes (i.e., smokingrelated fires, smoking-related perinatal
conditions, and use of non-premium
cigars and pipe tobacco) (see table 10).
During 2012–2016, an estimated
annual average of 18,100 reported home
structure fires in the United States were
caused by smoking materials, which
killed an average of 590 people annually
(Ref. 591). Moreover, smoking materials
remain a leading cause of fatal home
fires in the United States, and people
who smoke are not the only victims
(Ref. 592). By one estimate, one out of
every four fatal victims of smokingmaterial fires is not the person whose
cigarette initiated the fire (Ref. 593). A
lower prevalence of cigarette smoking
and reduced cigarette consumption is
likely to decrease the occurrence of fires
caused by smoking materials, including
cigarettes and other combusted tobacco
products. To estimate the impact of a

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nicotine product standard on the
number of deaths caused by smokingrelated fires, we applied the average of
590 deaths annually from 2012–2016
from home structure fires started by
smoking materials (Ref. 591). We
calculated the ratio of smoking-related
fire deaths to cigarette-attributable
deaths to be approximately 0.1 percent
and applied that value to the projections
of avoided cigarette-attributable deaths,
yielding an estimate of approximately
cumulative 2,400 deaths due to
smoking-related fires avoided by 2060,
rising to approximately cumulative
5,900 deaths avoided by the end of the
century (table 10).
Cigarette smoking is responsible for
approximately 1,000 deaths from
perinatal conditions annually, including
over 600 deaths from prenatal
conditions and 400 deaths from SIDS
(Ref. 1). Exposure to secondhand smoke
can also cause adverse health effects in
infants and children. Currently,
approximately half of all U.S. children
and adolescents ages 3–18 years are
exposed to cigarette smoke regularly at
home or other locations that still permit
smoking (Ref. 1). Exposure to cigarette
smoke among children and adolescents
can trigger asthma attacks and lead to
more frequent respiratory infections
compared to those not exposed to smoke
(Ref. 1). Prenatal tobacco exposure and
postnatal secondhand smoke exposure
increase the risks of fetal deaths, fetal
growth restriction/low birth weight,
respiratory conditions, and SIDS (Ref.
15, Ref. 1). In addition, thirdhand
smoke—the chemical residue from
combusted tobacco smoke that can
become embedded in the environment
(e.g., carpet, dust)—results in exposure
to harmful constituents, such as tobacco
specific nitrosamines (Ref. 138).
Exposure to thirdhand smoke is
especially concerning for young
children, given their size and behaviors,
like crawling on the ground and
frequently putting their hands in their
mouths.
FDA estimated the impacts of a
potential nicotine product standard on
perinatal mortality by first calculating
the ratio of perinatal deaths (1,013
deaths; (Ref. 1)) to primary smokingattributable deaths. That value, 0.2
percent, was then applied to the
projections of cigarette-attributable
deaths avoided yielding an estimate of
approximately 4,100 cumulative
perinatal deaths avoided by 2060, rising
to approximately 10,200 cumulative
deaths avoided by the end of the
century (table 10). Since decreases in
cigarette smoking prevalence under the
proposed product standard would have
immediate, rather than lagged, impacts

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on fetal health and the health of
newborn children, we expect avoided
smoking-attributable perinatal deaths to
accrue more rapidly than the estimates
presented here.
The smoke of other combusted
tobacco products, particularly those that
could be alternatives to cigarettes, such
as cigars and pipes, contains many of
the same toxic constituents as cigarette
smoke, sometimes at even greater
concentrations, and consequently
carries significant health risks (Refs. 53
and 594). In fact, NNAL concentrations
measured in people who smoke cigars
daily were found to be as high as those
measured in people who smoke
cigarettes daily (Ref. 160). Cigar and/or
pipe smoking cause cancers of the lung
and upper aerodigestive tract, including
the oral cavity, oropharynx,
hypopharynx, larynx and esophagus
(Ref. 158). Additional evidence suggests
that cigar and/or pipe smoking is
causally associated with cancers of the
pancreas, stomach, and bladder (Ref.
165). People who smoke cigars also have
increased risks for coronary heart
disease and COPD compared with
people who have never used tobacco
(Ref. 166). In a 2014 publication,
researchers estimated that regular cigar
smoking was the cause of approximately
9,000 premature deaths in the year
2010, and more than 140,000 years of
potential life lost in the United States in
2010 (Ref. 134). The total number of
cigar-attributable deaths may be even
larger for several reasons. For example,
the analysis included only causes of
death found to be statistically
significantly higher in two cohorts that
studied people who smoke cigars,
although there may be additional causes
of death that are attributable to cigar
smoking. In addition, there may be
increases in cigar smoking relative risks
over time, due to greater variety of cigar
products and differences in inhalation
patterns (Ref. 134). Therefore, cessation
and reduced initiation of combusted
tobacco products other than cigarettes as
a result of the proposed product
standard could yield even greater public
health impacts than those presented.
To estimate the impacts of a potential
nicotine product standard on avoided
deaths attributable to covered cigar
products, we used estimates of
premature deaths attributable to regular
cigar smoking from a prior publication
(Ref. 134). Given that the prior analysis
included all cigar types in its estimate
of 9,246 premature deaths for the year
2010 and that we did not include
premium cigars in our current analysis,
we estimated the fraction of deaths
attributed to cigar products other than
premium cigars. We estimate that

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among people who ever smoked cigars
fairly regularly and now smoke every
day or some days in Wave 4 of the
PATH Study, 80 percent reported
smoking non-premium cigars and 20
percent reported smoking premium
cigars, using a classification
methodology described previously (Ref.
290) and subsequently updated (Ref.
595). On that basis, 7,397 (i.e., 9,246 ×
0.8) deaths annually are attributed to
using non-premium cigar products. By
considering a relatively stable trend in
adult cigar use 35 and assuming that
adult cigar use is the main driver of
cigar-attributable deaths in the close
future, we assumed that non-premium
cigar-attributable mortality would
remain constant at 7,397 cigarattributable deaths per year through
2065 (or roughly the time at which
people who use cigars aged 26 and older
in 2021 would all have reached age 70
and older). However, as youth and
young adult cigar smoking has declined
in recent years, we adopt a different
trend in baseline cigar-attributable
mortality in the further future (after
2065). To obtain baseline non-premium
cigar-attributable mortality from 2066
through the end of the modeling period
(2100), we assume non-premium cigarattributable mortality will eventually
follow the observed relative decline in
cigar use among young adults as they
reach older ages. Specifically, we
assume that non-premium cigar

smoking-attributable deaths among
youth who initiate cigar smoking will
decrease on average by 37.5 percent 36
over 40 years (from 2078 to 2117).37
That is, the cigar smoking-attributable
deaths will decrease on average to 4,600
(≈ 7,397 × (1¥0.375)) deaths per year
over the period from 2078 to 2117.
Assuming a linear decrease in cigar
smoking-attributable mortality from
2065 to 2117, and an average of
approximately 4,600 deaths per year
over the period from 2078 to 2117,
implies non-premium cigar smokingattributable mortality will decline
linearly from 7,397 in 2065 to
approximately 4,390 deaths in 2100. We
assume a linear decrease for simplicity
and because trends for cigar use
considered in this post-processing
strategy come from a short interval
(PATH Study data, Waves 1 to 5, and
Waves 3 to 5). We then calculate the
ratio of non-premium cigar to cigaretteattributable deaths for each year in the
projection period and apply those
values to the projections of avoided
cigarette-attributable deaths to estimate
non-premium cigar-attributable deaths
under the nicotine policy scenario.
Using this approach, by 2060, we
estimate approximately 54,800
cumulative deaths due to non-premium
cigar products would be avoided, rising
to approximately 214,700 cumulative
deaths avoided by 2100 (see table 10).
Similar methods were used to calculate

estimates accounting for the mortality
effects of a product standard prohibiting
characterizing flavors other than tobacco
in cigars. These estimates reduced
baseline non-premium cigar-attributable
deaths in a phased-in manner reaching
a constant reduction of 780 deaths
averted per year after 30 years (Ref.
597). These estimates and results are
presented in detail in sections VIII.E
and VIII.F of this document.
To estimate the impacts of a nicotine
product standard on avoided deaths
attributable to pipe tobacco smoking, we
used the estimate of 1,095 premature
deaths per year provided by a prior
analysis (Ref. 598). We calculated the
ratio of pipe tobacco to cigaretteattributable deaths to be 0.3 percent and
applied that value to the projections of
avoided cigarette-attributable deaths,
yielding an estimate of approximately
4,500 cumulative deaths due to pipe
tobacco smoking avoided by 2060, rising
to approximately 11,000 cumulative
deaths avoided by the end of the
century (see table 10).
Based on these collective findings and
estimates, FDA anticipates that the
proposed product standard will further
improve public health due to the
impacts of reduced cigarette smoking on
smoking-related fires and perinatal
conditions, in addition to the impacts of
reduced use of other, non-cigarette
combusted tobacco products covered by
this proposed rule.

TABLE 10—PROJECTED NUMBER OF TOBACCO-ATTRIBUTABLE DEATHS AVOIDED FOR SMOKING RELATED FIRES, SMOKING
RELATED PERINATAL CONDITIONS, NON-PREMIUM CIGAR AND PIPE TOBACCO USE AS A RESULT OF A NICOTINE
PRODUCT STANDARD IMPLEMENTED IN 2027
Year
2040
2060
2080
2100

.........
.........
.........
.........

Scenario
Median
Median
Median
Median

(5th,
(5th,
(5th,
(5th,

95th)
95th)
95th)
95th)

.....
.....
.....
.....

Cumulative
smoking-related
fire deaths avoided

Cumulative perinatal
deaths avoided

Cumulative non-premium
cigar-attributable
deaths avoided

Cumulative pipe
tobacco-attributable
deaths avoided

600 (100, 700)
2,400 (600, 2,700)
4,200 (1,300, 4,600)
5,900 (2,300, 6,400)

1,000 (100, 1,200)
4,100 (900, 4,600)
7,300 (2,200, 7,900)
10,200 (3,900, 10,900)

8,900 (1,000, 11,000)
54,800 (13,200, 60,500)
134,700 (46,000, 144,100)
214,700 (91,600, 225,800)

1,100 (130, 1,300)
4,500 (1,000, 5,000)
7,900 (2,400, 8,600)
11,000 (4,200, 11,800)

While FDA’s population health
model’s estimates of the potential
impact from a nicotine product standard

suggest a significant public health
benefit to the United States resulting
from substantial reductions in smoking
prevalence, these analyses do not
address other additional benefits. The
overall public health benefits of this

proposed product standard are likely to
be even greater than those quantified,
since our analysis does not account for
the full range of impacts that smoking
has on public health in the United
States.

35 Adult cigar smoking has historically remained
stable. Data from the NHIS over 2000–2015 has
shown that prevalence of current cigar smoking has
remained generally stable at around 2.3 percent
among U.S. adults aged 18 years and older (Ref.
596). Adult (ages 26 or older) cigar use also
remained relatively stable in NSDUH data for 2011
and 2019 and did not significantly change (4.2
percent in 2011 to 4.0 percent in 2019 for cigars)
(Ref. 286).
36 According to data from the PATH Study, young
adult (ages 18–24) past 30-day cigar use declined

from 15.7 percent during Wave 1 (2013–2014) to 11
percent during Wave 5 (2018–2019), representing a
30 percent relative decline in prevalence.
Additionally, data from the PATH Study Waves 3
(2015–2016) and 5 (2018–2019) indicate that cigar
use among 18-year-olds declined from 7.2 percent
to 3.9 percent, implying a steeper decline of
approximately 45 percent in more recent years
within this smaller age cohort. We use these two
data points to estimate the decrease in cigar
smoking among young people because both provide
relevant information from a national survey that is

specific to tobacco use and average them to produce
an estimate of 37.5 percent (i.e., (30 + 45)/2).
37 For youth, we assume that initiation occurs by
the age of 18, followed by a cigar smokingattributable death 52 years later. We then assume
cigar use initiation occurs during years 2025 to
2064 (40-year period), and cigar smokingattributable deaths begin to occur a year after the
period from 2077 (i.e., 2025 + 52) through 2116 (i.e.,
2064 + 52); that is, over the period from 2078 to
2117.

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Proposed Standard Not Addressed in
FDA’s Population Health Model

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First, although we estimated the
impact of self-reported quality of life,
this may not capture the full breadth
and depth of smoking-attributable
morbidity. Tobacco smoke exposure can
cause immediate and long-term adverse
health effects (Ref. 1). Cigarette smoking
‘‘has been causally linked to diseases of
nearly all organs of the body, to
diminished health status, and to harm to
the fetus’’ (Ref. 1). Each year, an
estimated 480,000 people in the United
States die from smoking; the U.S.
Surgeon General has reported that for
every person that dies from smoking,
about 30 individuals will suffer from at
least one smoking-related disease (Ref.
1). One study estimated that individuals
in the United States have had 14.0
million major smoking-attributable
conditions, including more than 7.4
million cases of COPD, nearly 2.3
million heart attacks, 1.8 million cases
of diabetes, nearly 1.2 million stroke
events, more than 300,000 cases of lung
cancer, and nearly 1 million cases of
other smoking-attributable cancers (i.e.,
bladder, cervix, colon/rectum, kidney,
larynx, mouth, tongue, lip, throat,
pharynx, stomach) (Ref. 564). Cigarette
smoking, in addition to causing disease,
can diminish overall health status
leading to higher risks for surgical
complications, including wound healing
and respiratory complications,
increased absenteeism from work, and
greater use of healthcare services (Ref.
1). In terms of a monetary measure of
the impact of cigarette smoking on the
public health, in 2018, cigarette
smoking cost the United States more
than $600 billion, including more than
$240 billion in healthcare spending
(Ref. 10), nearly $185 billion in lost
productivity from smoking-related
illnesses and health conditions (Ref. 10),
nearly $180 billion in lost productivity
from smoking-related premature death
(Refs. 1 and 10), and $7 billion in lost
productivity from premature death from
secondhand smoke exposure (Refs. 1
and 11). Increased smoking cessation,
reduced cigarette consumption, and
lower progression to regular use will
reduce both mortality from smoking and
the enormous burden of cigaretteattributable diseases in the United
States.
Second, the estimated impacts to
public health do not include the
reductions in morbidity associated with
reduced exposure to secondhand smoke
among infants and children. A report of
the U.S. Surgeon General (Ref. 1) found
that approximately half of all children
and adolescents ages 3–18 in the United
States are exposed to cigarette smoke
regularly at home or other locations that

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still permit smoking. Also, a recent
study using NYTS data reported that, in
2019, 25.3 percent and 23.3 percent of
students were exposed to home and
vehicle secondhand smoke, respectively
(Ref. 145). Exposure to cigarette smoke
among children and adolescents can
trigger asthma attacks and lead to more
frequent respiratory infections
compared to those not exposed to smoke
(Ref. 1).
Third, a lower prevalence of cigarette
smoking and reduced cigarette
consumption will decrease the
occurrence of fire-related injuries and
damages caused by smoking materials,
including cigarettes and other
combusted tobacco products. From 2012
to 2016, an estimated average of 18,100
home structure fires in the United States
annually were caused by smoking
materials (Ref. 591). Reductions in
smoking as a result of the proposed
nicotine product standard are likely to
lead to not only fewer fatalities (as
described previously) but also
reductions in the annual average of
1,130 injuries (Ref. 591).
Fourth, these projections did not
include the potential health benefits
associated with people who smoke
cutting down on the number of
cigarettes smoked as a result of the
proposed nicotine product standard.
Quitting cigarette smoking entirely
clearly leads to the greatest reductions
in disease risk, and duration of smoking
has been shown to be a greater driver of
disease risk than frequency of use (Ref.
28). Although some studies have not
found evidence of lower disease risk
after cutting down on cigarettes (Refs.
28, 266, 599 to 601), others have shown
that substantial reductions in cigarette
consumption can lead to some
reductions in disease risk, especially for
lung cancer, for those who would have
otherwise continued to smoke (Ref.
602). Such studies have found
decreased risk of lung cancer deaths
(Ref. 603) and decreased risk of lung
cancer among people who smoke who
reduce cigarette consumption (Refs. 604
and 605). As described above, studies of
VLNC cigarettes have shown that their
use results in reductions in cigarettes
smoked per day and exposure to toxic
constituents among individuals who
continue to smoke, which may reduce
smoking-related disease risks.
Consequently, additional public health
benefits may be observed among those
who continue to smoke cigarettes (but
substantially fewer CPD) after a nicotine
product standard is in place.

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7. Potential Risks to the Population as
a Whole of the Proposed Nicotine
Product Standard Versus the Potential
Benefits of the Proposed Product
Standard
There are possible countervailing
effects that could occur from the
proposed product standard, if finalized,
and potential factors that could limit its
population health effect. Potential risks
to the population, however, would
generally only occur among individuals
currently smoking cigarettes and other
combusted tobacco products covered by
the scope of this proposed rule, as FDA
concludes there are little to no risks to
those who do not use tobacco. These
potential risks do not offset the
anticipated benefits of the rule. The
countervailing or limiting effects on
people who currently use tobacco
products could include compensatory
smoking. As part of this rulemaking,
FDA is required by the Tobacco Control
Act to consider information submitted
on such possible countervailing effects,
including among populations that are
disproportionately impacted by tobaccorelated morbidity and mortality, such as
adolescents who use tobacco and other
populations.
With a lower level of nicotine in
cigarettes, some people who use
cigarettes and certain other combusted
tobacco products could alter their
smoking behavior in the form of
compensatory smoking (i.e., a change in
normal smoking behavior that would
increase exposure to cigarette smoke to
compensate for reduced nicotine intake)
when switching from usual brand or
NNC cigarettes to VLNC cigarettes. This
concern is echoed in qualitative
research of people who currently use
tobacco who report fears that a potential
reduction in nicotine will cause them to
engage in compensatory smoking (Refs.
264, 606 to 608). Compensatory
smoking—or compensation—occurs
when people who smoke seek to obtain
the amount of nicotine needed to
sustain their addiction by smoking more
CPD, taking more and deeper puffs, or
puffing with a faster draw rate. In both
brief and extended exposure studies
with VLNC cigarettes, compensation
was measured using CPD, puff
topography measures, and biomarkers of
CO exposure, such as breath CO or
COHb. Some transient compensatory
smoking may occur following initial
VLNC cigarette exposure. However, after
continued use of VLNC cigarettes,
people who smoke stop attempting to
compensate for the reduced nicotine
content, because they are unable to
obtain adequate amounts of nicotine
through these behaviors. The following

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paragraphs discuss data demonstrating
this outcome. See also section VII.B of
this document discussing compensatory
smoking with an immediate nicotine
reduction approach versus a gradual
reduction approach.
When exposure to VLNC cigarettes is
brief (e.g., the first few uses of VLNC
cigarettes), transient compensatory
smoking may occur. In brief exposure
studies, changes in smoking topography
(Refs. 393 to 395) and increases in CO
(Refs. 393, 411, and 420) have been
observed. For example, one study
demonstrated the transient nature of
compensatory smoking by showing
increases in smoking topography and
CO exposure during the first and second
exposures to VLNC cigarettes, followed
by the subsequent dissipation of these
effects by the third and fourth exposures
((Ref. 394). Similarly, another study
found that during a 5-day study where
participants checked into a hotel and
were restricted to only study-issued
cigarettes, mouth-level nicotine
exposure indicated that participants
initially puffed VLNC cigarettes with
greater intensity than NNC cigarettes,
although this effect diminished across
sessions (Ref. 609). However, results
from the majority of studies show no
compensatory smoking as a result of
switching from usual brand or NNC
cigarettes to VLNC cigarettes. Although
not all studies examined every measure
of compensatory smoking, most studies
found no differences between control
and VLNC cigarette conditions
regarding CPD (Refs. 5, 32, 34, 40, 41,
265, 331, 374, 387, 386, 390, 396, and
415), CO exposure (Refs. 5, 32, 34, 40,
41, 265, 374, 381, 390, 391, 396, 402,
409, 410, 412 to 414, 467, and 610),
smoking topography (Refs. 381, 391,
403, 411, 415, and 611), or all three
measures (Refs. 329, 382 to 384).
Notably, compensatory smoking has
been observed with some reduced
nicotine content cigarettes containing
intermediate levels of nicotine (e.g.,
LNC cigarettes). For example, in a study
of 165 people who use cigarettes
assigned to switch to LNC cigarettes or
VLNC cigarettes, researchers found
small but statistically significant
differences in CPD between the LNC
and VLNC cigarette conditions, such
that LNC CPD increased over the course
of the 6-week intervention, while VLNC
CPD decreased (Ref. 32). However, one
of the largest studies involving reduced
nicotine content cigarettes found no
compensatory smoking behavior for
cigarettes containing intermediate levels
of nicotine (Ref. 29). Therefore, FDA
concludes the nicotine level proposed
for this standard would result in
limited, if any, compensatory smoking

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that would likely dissipate over time.
These data also support FDA’s proposed
immediate nicotine reduction approach
(see section VII.C of this document).
Studies consistently report that
consumers have misperceptions about
the harms of nicotine and VLNC
cigarettes (see sections IV.F and V.B of
this document). A majority of U.S.
consumers incorrectly believe that
nicotine is the primary cause of cancer
and health harms from cigarettes (Refs.
227 to 229, 232, 233, 235 to 245, 264,
and 612 to 618), and a proportion of
consumers with this misperception also
believe that RNC cigarettes are less
harmful than NNC cigarettes (Refs. 260
to 262). Additionally, while a majority
of consumers understand that nicotine
is addictive (Refs. 227 to 229, 232, 233,
and 619), they do not necessarily
believe that RNC cigarettes would be
less addictive than NNC cigarettes (Refs.
260 and 261). There is also evidence
from qualitative studies showing that
some consumers do not understand the
technical feasibility of reducing nicotine
in cigarettes to minimally addictive or
nonaddictive levels, which may impact
consumers’ ability to comprehend and
accept messages communicating the
policy (Refs. 270 and 229). FDA
recognizes the importance of addressing
consumer misperceptions of the harm
and addictiveness of nicotine and VLNC
cigarettes to minimize the unintended
effects of a proposed product standard
that limits the level of nicotine in
cigarettes and certain other combusted
tobacco products to make those
products minimally addictive or
nonaddictive. FDA will continue to
conduct research on consumer
perceptions of tobacco product harms,
use communication tools (e.g.,
consumer outreach, public education
initiatives, engagement with interested
parties), and consider further regulatory
options within our authorities (e.g.,
potential future labeling and advertising
regulations) to ensure that all consumers
are informed of the risks of using
tobacco products that contain nicotine,
including VLNC cigarettes.
Prior work also has explored whether
the proposed product standard may
have a differential impact on specific
populations. Studies that have
investigated the effects of VLNC
cigarettes in adolescents who smoke
cigarettes have done so under
conditions of brief exposure (e.g., single
exposure to a VLNC cigarette in a
laboratory setting). A study comparing
VLNC and LNC cigarette smoking
topography in adolescents who smoke
cigarettes found that participants took
statistically significantly more puffs
from the VLNC cigarette compared to

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the LNC cigarette, and a non-significant
trend emerged such that increases in
breath CO were higher after smoking the
VLNC cigarette compared to the LNC
cigarette (Refs. 395 and 416). However,
the LNC cigarette was rated as
statistically significantly more pleasant
than the VLNC cigarette (Ref. 395).
Similar to studies in adults who
smoke cigarettes, studies in youth and
young adults who smoke cigarettes have
shown that positive subjective effects
ratings (e.g., ‘‘satisfaction,’’ ‘‘pleasure,’’
‘‘taste,’’ ‘‘strength,’’ and ‘‘stimulation’’)
are lower for VLNC cigarettes compared
to LNC and NNC cigarettes. A laboratory
study of people ages 15–19 who smoke
found no effect of nicotine content on
withdrawal, negative affect, or CO boost;
however, NNC cigarettes were
associated with greater reductions in
craving and increased smoking
satisfaction relative to VLNC cigarettes
(Ref. 442). A similar laboratory study in
young adults (age 18–25) found no
influence of nicotine content on total
nicotine withdrawal score, affect, or
smoking topography; however, NNC
cigarettes were associated with
increased subjective effects ratings
compared to LNC and VLNC cigarettes
(Ref. 620). Notably, a secondary analysis
of data from a clinical trial (Ref. 29)
found that, at the end of the 6-week
trial, there was no influence of age on
subjective effects, TNE levels, or puff
volume in participants who smoked
LNC or VLNC cigarettes (Ref. 621).
Several studies have examined the
effects of nicotine content in cigarettes
on adolescents and young adults who
smoke. One laboratory study that
assessed the effects of nicotine content
and menthol preference among
adolescents (ages 15–19) who smoke
found that VLNC cigarettes were rated
statistically significantly lower than
NNC cigarettes, and menthol preference
did not affect subjective effects ratings
of VLNC cigarettes (Ref. 408). One study
also found that young adults (ages 18–
24) who smoke exhibited lower demand
for LNC and VLNC cigarettes than
adults, but there were no other
differences between the two age groups
in smoking topography, breath CO,
cigarette puffs, craving, withdrawal, or
smoking urge measures (Ref. 622).
Another study investigating how
nicotine exposure contributes to relief of
craving and negative affect among
young adults (ages 18–25) who smoke
found that smoking reduced craving and
negative affect regardless of nicotine
content, and smoking topography did
not vary as a function of nicotine
content (Ref. 611). Finally, a study of
youth and young adults who smoke
found that two-thirds of participants

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believed that study cigarettes had lower
health risks than usual brand cigarettes,
that they were largely concerned with
compensatory smoking following a
nicotine reduction policy, and that half
stated an intention to quit smoking after
the policy is put in place while the
other half would continue to smoke or
switch to another tobacco product (Ref.
606).
One study assessed longer duration
effects (i.e., 3 weeks) of VLNC cigarettes
in adolescent daily smokers (ages 15–
19) not currently intending to quit.
Participants assigned to smoke VLNC
cigarettes smoked significantly fewer
total CPD than those in the NNC
cigarette group. VLNC cigarettes were
associated with lower levels of craving
reduction than NNC cigarettes; however,
there were no differences nicotine
dependence or TNE levels among VLNC
and NNC cigarette groups at the end of
the study (Ref. 623). A secondary
analysis of this study showed that
participants assigned to smoke VLNC
cigarettes had significantly lower
demand for study cigarettes than those
assigned to smoke NNC cigarettes,
suggesting that a nicotine reduction
policy may reduce the reinforcing value
of combusted cigarettes in adolescents
(Ref. 624).
In summary, while existing data
suggest that adolescents prefer LNC
cigarettes over VLNC cigarettes, and that
they may display compensatory
smoking behaviors in response to VLNC
cigarettes, these data are limited. As
discussed in section VII.B of this
document, compensation typically
dissipates after repeated exposure.
Thus, in the absence of extended
exposure studies, it is difficult to draw
conclusions regarding the effects of
VLNC cigarette use on compensatory
smoking in adolescents and young
adults.
Individuals with symptoms of mental
health disorders smoke cigarettes in
disproportionately large numbers.
People with symptoms of mental health
disorders who smoke cigarettes have
increased nicotine withdrawal
symptoms (Refs. 625 and 626) and are
more likely to smoke to ameliorate
negative mood (Ref. 627). As a result,
this population has increased risk of
tobacco-related mortality (Ref. 130).
Researchers have investigated the
effects of VLNC cigarettes in people who
use cigarettes with symptoms of mental
health disorders to determine whether
VLNC cigarettes are associated with
differential effects on craving,
withdrawal, smoking topography, or use
behavior among this group compared to
the general population. In this group, as
in the general population, NNC

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cigarettes were associated with greater
reductions in craving and withdrawal
symptoms compared to VLNC cigarettes.
In this group, VLNC cigarettes were not
associated with increased markers of
compensatory smoking (e.g., smoking
topography, CO) compared to the
general population. Researchers also
assessed psychiatric symptomatology as
a function of VLNC cigarette use and
found that VLNC cigarettes were
associated with improvements in mood
symptoms, likely due to the anxietyincreasing properties of nicotine.
Several studies investigated the
effects of LNC and VLNC cigarettes on
mood following mood induction (i.e., an
experimental method for inducing a
specific mood state) in people who use
cigarettes with symptoms of mental
health disorders (Refs. 434, 450, and
628). These studies found that,
following positive mood induction, LNC
cigarettes compared to VLNC cigarettes
were associated with an enhancement of
positive mood among people who
smoke and are prone to depression, but
not control participants (Refs. 450 and
628). In addition, LNC cigarettes, but
not VLNC cigarettes, were associated
with a worsening of negative mood in
response to negative mood induction
among people who smoke, regardless of
baseline mental health status (Ref. 628).
Similarly, following an anxiety-eliciting
mood induction, participants with posttraumatic stress disorder self-reported
greater relief of anxiety after smoking
LNC cigarettes compared to VLNC
cigarettes; however, LNC cigarettes
increased physical autonomic
symptoms of anxiety (e.g., skin becomes
a better conductor of electricity, heart
rate) relative to VLNC cigarettes (Ref.
434).
A secondary analysis of an extended
exposure study assessed the effects of
cigarettes varying in nicotine content on
changes in psychiatric symptomatology
among those with and without elevated
depression symptoms (Ref. 629). Among
participants with elevated depression
symptoms, those assigned to smoke LNC
or VLNC cigarettes for 6 weeks had
lower depressive symptoms at the end
of the study compared to those assigned
to smoke NNC cigarettes. Another study
that assigned participants with serious
mental illness to receive either NNC or
VLNC cigarettes saw no change in
participants’ psychiatric symptoms at
the end of 6 weeks (Ref. 440).
Several studies assessed the effects of
VLNC cigarettes on smoking rates,
nicotine craving, dependence,
withdrawal, and subjective effects
among those with symptoms of mental
health disorders (Refs. 391, 409, 434,
467, 468, 629, and 630). While some

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studies found no statistically significant
differences in craving or withdrawal as
a function of nicotine content following
brief smoking abstinence in those with
symptoms of mental health disorders
(Refs. 391, 434, and 467), others showed
that use of usual brand cigarettes was
associated with larger decreases in
craving and withdrawal compared to
VLNC cigarettes (Ref. 468). An extended
exposure study found that, relative to
NNC cigarettes, use of LNC and VLNC
cigarettes reduced smoking rates,
nicotine dependence, and cigarette
craving, and these effects were not
moderated by baseline depressive
symptoms (Ref. 629). In addition,
similar to the general population,
people who smoke with poor mental
health rate NNC cigarettes as more
rewarding (e.g., taste, satisfaction) and
reinforcing compared to VLNC
cigarettes (Refs. 391, 450, 467, and 628).
Additionally, a 33-week study that
randomized participants to either NNC
cigarettes or a gradual nicotine
reduction to VLNC levels found that the
gradual reduction group exhibited
significantly lower cotinine levels, CPD,
and exhaled CO compared to the NNC
cigarette group. Mental health effects
and adverse events did not significantly
differ between the two groups, and
significantly more participants in the
gradual nicotine reduction group were
abstinent at the end of the treatment
compared to the NNC cigarette group
(Ref. 631).
A study that compared the effects of
VLNC, LNC, and NNC cigarettes on
smoking behavior in people with opioid
use disorder who smoke cigarettes,
women of childbearing age with a high
school education or less who smoke
cigarettes, or individuals with affective
disorders who smoke cigarettes found
no statistically significant differences in
smoking topography or breath CO as a
function of nicotine content (Ref. 391).
Subsequent analyses of this study also
found that cannabis use status, presence
of chronic health conditions, and sex
did not correlate with differences in
smoking topography or the reinforcing
effects of nicotine among people who
smoke (Refs. 459 and 632). A larger 12week RCT among these same three
populations found statistically
significantly lower CPD and nicotine
dependence levels across study weeks
among those assigned to received VLNC
or LNC cigarettes compared to those
assigned to receive NNC cigarettes (Ref.
633). A secondary analysis of this study
found no statistically significant effects
of nicotine dose or population on tests
of cognitive performance, suggesting
that cognitive performance was not

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significantly impaired with prolonged
exposure to VLNC cigarettes among
vulnerable populations (Ref. 634). A
study among participants with
schizophrenia found that both people
with schizophrenia who smoke and
control participants smoked fewer puffs
and had lower total puff volumes,
shorter inter-puff intervals, longer puff
durations, and marginally higher
individual puff volumes when smoking
VLNC cigarettes compared to usual
brand cigarettes (Ref. 467). However, a
subsequent analysis using data from this
same study showed that these
differences were not associated with
increases in breath CO boost (Ref. 392).
A 33-week randomized clinical study
evaluated the effects of gradually
reducing the nicotine content in
cigarettes to VLNC cigarette levels on
ratings of dependence, biomarkers, and
cessation in 245 adults of low
socioeconomic status. CPD, plasma
cotinine, CO, and NNAL levels were
significantly lower for the gradual
reduction group compared to the NNC
cigarette group; however, there were no
significant differences in dependence or
withdrawal as a function of group.
Those who received VLNC cigarettes
were statistically significantly more
likely to make a quit attempt during the
study compared to those in the NNC
cigarette group; however, there was no
statistically significant difference in quit
rates as a function of group among those
who chose to make a quit attempt (Ref.
635). A secondary analysis of this study
showed that outcomes did not differ as
a function of menthol status, except that
those participants who smoked menthol
cigarettes had less of a cotinine
reduction (Ref. 636).
Several studies used laboratory
paradigms to assess the effects of
alcohol on specific components of
smoking behavior for nicotine versus
non-nicotine factors in people who
consume alcohol heavily. One study
found that alcohol increased smoking
urge and subjective ratings of smoking
for both NNC and VLNC cigarettes (Ref.
637), while another study found that
NNC cigarettes were associated with
increases in subjective effects and a
greater reduction in cigarette craving
than VLNC cigarettes, and these effects
were enhanced by ethanol selfadministration (Ref. 448). In addition, in
a sample of people who smoked who
also regularly consumed alcohol, NNC
cigarettes reduced craving and increased
cognitive performance compared to
VLNC cigarettes (Ref. 448). Furthermore,
several secondary analyses of clinical
studies found no evidence that alcohol
or marijuana use moderates the effects
of VLNC cigarettes, and VLNC cigarette

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use does not increase compensatory
alcohol, marijuana, or other illicit drug
use (Refs. 386, 632, and 638). However,
one secondary analysis found that
although 20-weeks of VLNC cigarette
use reduced CPD compared to NNC
cigarette use, co-users of marijuana and
cigarettes showed increased marijuana
use when assigned to VLNC cigarettes
(Ref. 639).
In summary, research has shown that
VLNC cigarettes reduce the number of
cigarettes smoked per day among
populations that use tobacco at
disproportionately high levels,
including those of low socioeconomic
status, and those with mental or
behavioral health conditions.
Importantly, there has been little to no
evidence that VLNC cigarettes increase
risk of adverse effects (e.g.,
exacerbations of psychiatric
symptomatology, drug use) in these
populations. The proposed nicotine
product standard is not anticipated to be
detrimental to these populations; rather,
it is anticipated to benefit these groups,
as well as the general population as a
whole.
FDA recognizes that actors
participating in illicit markets are
unlikely to conform their products and
sales to Federal, State, and local laws.
As discussed elsewhere in this
document, the available evidence
suggests that the health impacts of
counterfeit products should be minimal.
As the National Research Council (NRC)
and the Institute of Medicine (IOM)
(NRC/IOM) Report notes, ‘‘Research on
counterfeit cigarettes to date has shown
some differences in levels of tar and
selected toxicants in comparison with
conventional cigarettes . . . but these
elevated levels have not been shown to
affect overall toxicity and, based on
current evidence, are unlikely to
significantly increase the health risk of
an already dangerous product’’ (Ref.
560). Even in studies (Ref. 640) that
suggest that counterfeit cigarettes can
contain higher levels of harmful
substances, the studies cannot make
conclusions about the individual or
population-wide health risks from such
substances, in part because of the
variations between them, inconsistent
distribution of the products among the
population, and inconsistent use among
consumers. FDA will continue to
monitor the best available science to
determine if this changes in the future.
Based on the available evidence, FDA
finds that, while there may be potential
risks that could diminish the expected
population health benefits of the
proposed standard, such effects would
be significantly outweighed by the
potential benefits of the proposed

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nicotine product standard. FDA requests
additional information concerning the
potential risks discussed in this section,
as well as any other negative effects that
could result from this rule, and how
they could be minimized.
E. Approach Concerning Adjustments to
Inputs to the Model Accounting for
Other Tobacco Product Standards
In 2022, FDA issued proposed tobacco
product standards to prohibit menthol
as a characterizing flavor in cigarettes
and to prohibit all characterizing flavors
(other than tobacco) in cigars (87 FR
26454, May 4, 2022). If finalized, these
rules are anticipated to reduce overall
youth initiation and increase cessation
among individuals who smoke
cigarettes and cigars. In this adjusted
model, we utilized estimates of the
likely population health impact of these
rules, quantified in peer-reviewed
publications and discussed in the rules,
to adjust the baseline inputs for
initiation of combusted and
noncombusted products, as well as
cessation of combusted products and
likelihood of switching to incorporate
the impact of the final rules in this
proposed nicotine product standard.
We quantified the potential impact of
a menthol cigarette product standard on
the U.S. population (87 FR 26454),
assuming that the implementation of a
rule prohibiting menthol affects baseline
model input parameters associated with
smoking initiation, smoking cessation,
noncombusted initiation, and switching
from cigarettes to noncombusted
products. To avoid confusion with the
main analysis baseline scenario, we
called this new scenario a ‘‘menthol
product standard baseline scenario.’’
First, we assumed that a menthol
product standard is implemented in
2025, 2 years before the implementation
of a potential nicotine product standard
in 2027. Changes in tobacco use
behaviors due to the implementation of
a menthol product standard (primarily
for people who would initiate future
menthol cigarette use and people who
currently use menthol cigarettes) were
derived from an expert elicitation that
was developed to assess the impact of
a menthol product standard on smoking
initiation and cessation, and on
noncombusted use (Ref. 562).
Specifically, 11 experts were asked to
estimate anticipated behaviors under a
menthol product standard, including
transitioning to illicit menthol
combusted products, switching to nonmenthol combusted products, switching
to ENDS products or HTPs, or quitting
use of all tobacco products. We used the
results of the expert elicitation
(finalized in September 2020) to

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compute factors that can be used to
scale smoking initiation and cessation
rates, as well as switching and
noncombusted initiation, accounting for
a potential reduction/increase in rates.
People who currently smoke nonmenthol cigarettes were assumed to be
unaffected by a menthol product
standard. We used the average impact
scenario from Levy et al. 2023 (Ref. 562)
to be consistent with the approach taken
in the proposed menthol product
standard rule. Details regarding the
calculation of scaling factors,
considering the expert elicitation data,
can be found in Appendix K of FDA’s
modeling document (Ref. 42).
In the menthol product standard
baseline scenario, baseline smoking
initiation and noncombusted initiation
rates were adjusted starting in 2025 (i.e.,
year of a potential menthol prohibition
implementation) until the end of the
simulation period. Also, baseline
smoking cessation and complete
switching (from cigarettes to
noncombusted products) were adjusted
only at the first year of such a potential
menthol product standard
implementation. After the first year,
when a sudden increase in smoking
cessation and complete switching was
incorporated, the remaining people who
smoke initiated use of non-menthol or
illicit menthol cigarettes, subject to the
cessation and complete switching rates
for people who smoke non-menthol
cigarettes (Ref. 641). We conducted the
analysis considering a mean decrease in
cigarette smoking initiation (based on
estimates from an expert elicitation), a
mean increase in noncombusted
product initiation, and a mean increase
in smoking cessation and switching, as
presented in Levy et al. 2023 (Ref. 562).
It is important to note that the mentholadjusted population health model does
not directly estimate the public health
impacts of a prohibition on menthol as
characterizing flavor in cigarettes. In
other words, the difference between the
unadjusted baseline scenario and
menthol-adjusted baseline scenario of
the model should not be expected to
approximate the impact of a potential
menthol product standard. FDA’s
determination of the estimated public
health impact of the menthol product
standard is discussed in detail in the
preamble to the proposed menthol
product standard. In the nicotine
population health model, FDA utilizes
results from an expert elicitation (Ref.
562) developed to estimate changes in

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tobacco use behaviors resulting from a
menthol product standard (such as
changes in smoking initiation or
cessation) to adjust for the effect of a
menthol rule over time. One important
assumption of the FDA model is that the
nicotine product standard would be
implemented in 2027, whereas a
menthol rule would be implemented in
2025. This is important to keep in mind
as public health benefits attributable to
a menthol rule (such as mortality and
morbidity health impacts) will be
accruing for 2 years before
implementation of the nicotine product
standard (and, therefore, not captured in
this model).
A more comprehensive analysis of the
public heath impact of the menthol
cigarette product standard can therefore
be found in the proposed menthol
product standard. There are also other
important differences between the
menthol-adjusted FDA model and the
Levy et al. modeling approach that can
impact comparability, such as input
model parameters, modeling
frameworks, assumptions, and source
data. For these reasons, it is not
appropriate to expect that the difference
between public health impact estimates
of the nicotine product standard with
and without the menthol adjustment
would directly approximate the
potential public health benefits of the
menthol product standard as presented
in the proposed menthol product
standard.
In 2022, FDA also issued a proposed
product standard to prohibit
characterizing flavors (other than
tobacco) in cigars (87 FR 26396, May 4,
2022). It is estimated that such a
standard would prevent 780 deaths due
to cigar smoking in the United States
each year (Ref. 134). A post-processing
analysis of cumulative non-premium
cigar-attributable deaths avoided was
conducted to account for the effects of
such a product standard, considering
the adjustments due to the menthol
cigarette product standard. For this
analysis, we assumed both rules—the
menthol cigarette and flavored cigar
product standards—to be implemented
in 2025. Specifically, we assumed that
the avoided cigar-attributable deaths
expected to result from the flavored
cigar rule begin to occur 2 years after the
rule’s effective date (2027) and would
increase in a phased-in manner over a
30-year period. We then assumed a full
annual mortality benefit of 780 avoided
deaths would continue after 30 years

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(from 2026 to 2055), with a constant
benefit of 780 deaths avoided until year
2064. We also assumed avoided cigarattributable deaths will increase from
780 in 2064 to 1,120 in 2100.
Details regarding the calculation of
avoided cigar-attributable deaths
because of the flavored cigar rule can be
found in Appendix L of FDA’s modeling
document (Ref. 42). The estimated
deaths averted by a flavored cigar
product standard were subtracted from
baseline non-premium cigar deaths in
the United States each year to produce
yearly estimates for non-premium cigar
deaths with a flavored cigar standard.
We used these estimates to calculate a
ratio of non-premium cigar to cigaretteattributable deaths for each year in the
projection period and applied those
values to the projections of avoided
cigarette-attributable deaths to estimate
non-premium cigar-attributable deaths
under the nicotine product standard
scenario.
F. Benefits and Risks to the Population
as a Whole Accounting for Other
Tobacco Product Standards
Table 11 presents the impact results
of the nicotine product standard using
baseline assumptions adjusted for the
effect of a menthol cigarette product
standard for years 2040, 2060, 2080, and
2100. In general, changes to baseline
inputs of initiation and cessation of
combusted products as well as
switching to noncombusted products as
a result of implementation of a menthol
cigarette product standard slightly
reduced projected smoking prevalence
and avoided mortality and morbidity,
compared to the main analysis results.
Specifically, we estimate that by 2060,
the proposed nicotine product standard
would avert approximately 1.6 million
deaths due to tobacco, rising to
approximately 3.4 million by 2100.
These estimates are approximately 11
percent and 21 percent less than the
corresponding estimates that do not
account for the potential impact of a
menthol product standard. The
reduction in premature deaths as a
result of the nicotine product standard,
when accounting for a menthol product
standard, would result in 17.9 million
life years gained by 2060, raising to 60.6
million life years gained by 2100. These
estimates represent a 9 percent and 21
percent reduction compared with the
corresponding estimates under the main
analysis.

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TABLE 11—IMPACT OF PROPOSED NICOTINE PRODUCT STANDARD IMPLEMENTED IN 2027 ON PROJECTED SMOKING PREVALENCE AND AVOIDED MORTALITY AND MORBIDITY FROM THE MAIN ANALYSIS (UNADJUSTED BASELINE SCENARIO)
AND WITH ADJUSTMENT FOR A MENTHOL CIGARETTE PRODUCT STANDARD IMPLEMENTED IN 2025
[Median (5th, 95th percentiles) estimates]
Estimates from
main analysis

Year/period

Estimates with
adjustment for a
menthol cigarette
standard

Cigarette Smoking Prevalence (%)
2040
2060
2080
2100

.............................................................................................................................................................
.............................................................................................................................................................
.............................................................................................................................................................
.............................................................................................................................................................

0.2
0.2
0.2
0.2

(0.07,
(0.07,
(0.06,
(0.06,

4.0)
2.2)
2.0)
1.9)

0.1
0.1
0.1
0.1

(0.06,
(0.05,
(0.05,
(0.05,

2.8)
1.4)
1.3)
1.2)

Cumulative Tobacco-Attributable Deaths Avoided (Millions)
2040
2060
2080
2100

.............................................................................................................................................................
.............................................................................................................................................................
.............................................................................................................................................................
.............................................................................................................................................................

0.4
1.8
3.1
4.3

(0.1,
(0.4,
(1.0,
(1.6,

0.5)
2.0)
3.4)
4.6)

0.4
1.6
2.6
3.4

(0.1,
(0.4,
(0.7,
(1.1,

0.5)
1.7)
2.8)
3.6)

Cumulative Life Years Gained (Millions)
2040
2060
2080
2100

.............................................................................................................................................................
.............................................................................................................................................................
.............................................................................................................................................................
.............................................................................................................................................................

2.0 (0.2, 2.7)
19.6 (3.6, 22.7)
47.4 (12.5, 52.5)
76.4 (26.5, 82.5)

2.0 (0.2, 2.6)
17.9 (3.4, 20.4)
40.6 (10.3, 44.5)
60.6 (19.2, 65.3)

Cumulative QALYs Gained from Reduced Smoking Morbidity (Millions)
2040
2060
2080
2100

.............................................................................................................................................................
.............................................................................................................................................................
.............................................................................................................................................................
.............................................................................................................................................................

by 2060, in the United States,
approximately 45,600 deaths due to
non-premium cigar use will be averted,
rising to approximately 164,000 deaths
avoided by 2100 (table 12). In general,
these estimates are approximately 17

Table 12 presents the impact results
of the nicotine product standard
implemented in 2027, using baseline
assumptions adjusted for the effect of a
flavored cigar product standard
implemented in 2024. We estimate that

9.6 (2.7,
24.0 (10.1,
38.2 (18.5,
53.1 (27.5,

10.0)
24.7)
39.2)
54.4)

7.8 (2.1, 8.1)
17.5 (7.0, 17.9)
26.1 (11.9, 26.6)
34.9 (17.0, 35.7)

and 30 percent less than the
corresponding estimates without the
potential impact of a product standard
for flavored cigars.

TABLE 12—PROJECTED NUMBER OF TOBACCO-ATTRIBUTABLE DEATHS FROM NON-PREMIUM CIGAR USE AVOIDED FOR AS
A RESULT OF A NICOTINE PRODUCT STANDARD IMPLEMENTED IN 2027 FROM THE MAIN ANALYSIS AND WITH ADJUSTMENT FOR FLAVORED CIGAR AND MENTHOL CIGARETTE PRODUCT STANDARDS IMPLEMENTED IN 2025
Year

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2040
2060
2080
2100

..............................
..............................
..............................
..............................

Median
Median
Median
Median

(5th,
(5th,
(5th,
(5th,

95th)
95th)
95th)
95th)

G. Conclusion
FDA has considered scientific
evidence related to the likely impact of
the proposed rule establishing a
maximum nicotine level in cigarettes
and certain other combusted tobacco
products on people who currently do
not use these products, people who
currently use these products, and the
U.S. population as a whole. The impact
of the proposed standard was

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Cumulative non-premium
cigar-attributable deaths
avoided from main analysis

Percentiles

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..............................................
..............................................
..............................................
..............................................

8,900 (1,000, 11,000)
54,800 (13,200, 60,500)
134,7000 (46,000, 144,100)
214,700 (91,600, 225,800)

considered alone, as well as adjusted for
the inclusion of other tobacco product
standards: prohibition of menthol as a
characterizing flavor in cigarettes and
prohibition of all characterizing flavors
(other than tobacco) in cigars. Based on
these considerations, we find that the
proposed tobacco product standard is
appropriate for the protection of the
public health because it would increase
the likelihood that many people who

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Cumulative non-premium
cigar-attributable deaths
avoided with flavored cigar
and menthol cigarette standards
8,000 (1,000, 9,500)
45,600 (11,100, 49,700)
107,700 (35,000, 114,500)
164,000 (65,000, 172,100)

currently smoke cigarettes and/or
certain other combusted tobacco
products would stop smoking
altogether, yielding significant health
benefits from smoking cessation.
Additionally, we find that the proposed
standard is appropriate for the
protection of the public health because
it would decrease the likelihood that
people who do not smoke cigarettes
and/or use certain other combusted

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tobacco products—particularly youth
and young adults—who experiment
with combusted tobacco products will
become addicted to these products,
thereby decreasing progression to
regular use, resulting in reduced
tobacco-related morbidity and mortality
associated with combusted tobacco
product use. The proposed standard
would also yield benefits in terms of
reduced mortality as a result of reduced
secondhand smoke exposure, smokingrelated fires, smoking-related perinatal
conditions, and use of alternative
tobacco products.
Tobacco use is the leading
preventable cause of disease and death
in the United States. Cigarettes are
responsible for 480,000 premature
deaths every year from many diseases,
put a substantial burden on the U.S.
healthcare system, and cause massive
economic losses to society (Ref. 1 at p.
659–666). Even modest reductions in
the percentage of people initiating and
modest increases in the percentage of
people quitting smoking would lead to
substantial reductions in the annual
smoking-attributable deaths and fewer
cases of disease attributed to
combustible tobacco products in the
United States.
In the United States, approximately
362,000 youth (ages 12–17) smoked
their first cigarette in 2021 (Ref. 552).
Additionally, nearly 90 percent of
adults who currently smoke cigarettes
daily in the United States report having
smoked their first cigarette by the age of
18 (Ref. 1). Nicotine is a highly
addictive substance, and multiple
studies have shown that symptoms of
nicotine dependence can arise early
after youth start smoking cigarettes,
even among those who smoke cigarettes
infrequently (Refs. 24, 65, and 93).
Reducing the addictive potential of
combusted cigarettes and certain other
tobacco products via establishing a
maximum level of nicotine in these
products would help to decrease the
likelihood that people who do not
smoke cigarettes and/or use certain
other combusted tobacco products—
particularly youth and young adults—
who experiment with them will develop
addiction to nicotine and progress to
regular use, thereby greatly reducing the
chances of suffering from tobaccorelated disease and death. FDA
anticipates that the proposed standard
would produce substantial health
benefits. Even small changes in
initiation and cessation would result in
a significant reduction in the burden of
death and disease in the United States
caused by smoking, including
reductions in smoking-related morbidity
and mortality, diminished exposure to

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secondhand smoke among people who
do not smoke cigarettes, decreased
potential years of life lost, decreased
disability, and improved quality of life
for current and future generations to
come.
While preventing initiation to regular
cigarette smoking and combusted
tobacco product use by even modest
amounts carries the greatest potential
from this proposed standard to improve
population health in the long term, FDA
anticipates that the proposed standard
would produce substantial short- and
long-term health benefits resulting from
decreased consumption and increased
cessation among people who currently
smoke cigarettes or other combusted
tobacco products and wish to decrease
use or quit. In the United States, there
are currently approximately 39 million
people ages 12 and older who smoke
combusted tobacco products (Refs. 275
and 281). As previously described, the
health benefits of smoking cessation are
substantial. FDA’s population health
model estimates that approximately 1.8
million deaths in the United States due
to tobacco would be avoided by the year
2060, rising to 4.3 million by the end of
the century. The reduction in premature
deaths attributable to the product
standard would result in 19.6 million
life years gained by 2060 and 76.4
million life years gained by 2100.
Beyond averted deaths, societal benefits
would include reduced smoking-related
morbidity and health disparities,
diminished exposure to secondhand
smoke among people who do not smoke
cigarettes, decreased potential years of
life lost, decreased disability, and
improved quality of life among people
who formerly smoked cigarettes.
FDA’s finding that the proposed
product standard would be appropriate
for the protection of the public health is
reasonable and well-supported by
scientific evidence. Cigarettes are the
most toxic consumer product when
used as intended, and nicotine is the
primary constituent in cigarettes and
other tobacco products that causes and
maintains addiction. Given the existing
scientific evidence described in sections
VIII.B and VIII.C of this document, FDA
finds that the proposed product
standard is appropriate for the
protection of the public health because
it would increase the likelihood that
many people who currently smoke
cigarettes and/or certain other
combusted tobacco products who wish
to stop smoking altogether, would be
able to do so, yielding significant health
benefits from smoking cessation.
Additionally, we find that the proposed
standard is appropriate for the
protection of the public health because

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it would decrease the likelihood that
people who do not smoke cigarettes
and/or certain other combusted tobacco
products—particularly youth and young
adults—who experiment with them and
initiate use, develop an addiction to
nicotine, and progress to regular use as
result of that addiction, thereby greatly
reducing the chances of suffering from
tobacco-related disease or death. Across
the population, these changes in
cigarette smoking behavior and
combusted tobacco product use would
lead to lower disease and death in the
United States in both the short-term and
in the future, due to diminished
exposure to tobacco smoke among both
people who smoke cigarettes and people
who do not smoke cigarettes.
In addition to the determination that
the proposed product is appropriate for
the public health, FDA anticipates the
proposed product standard also will
improve health outcomes among
populations that are disproportionately
impacted by tobacco use and tobaccorelated morbidity and mortality, such as
adolescents as well as those with mental
health and substance use disorders. As
previously described, adolescence is a
period of significant vulnerability
regarding the onset and progression of
tobacco use. Additionally, cigarette
smoking is disproportionately prevalent
among persons with symptoms of
mental health disorders and substance
use disorders, resulting in increased risk
of tobacco-related morbidity and
mortality in these groups. Accordingly,
the proposed product standard is
anticipated to promote better public
health outcomes across these population
groups.
IX. Additional Considerations and
Requests for Comment
A. Section 907 of the FD&C Act
FDA is required by section 907 of the
FD&C Act to consider the following
information submitted in connection
with a proposed product standard:
• For a proposed product standard to
require the reduction or elimination of
an additive, constituent (including
smoke constituent), or other component
of a tobacco product because FDA has
found that the additive, constituent
(including a smoke constituent), or
other component is or may be harmful,
scientific evidence submitted by any
party objecting to the proposed standard
demonstrating that the proposed
standard will not reduce or eliminate
the risk of illness or injury (section
907(a)(3)(B)(ii) of the FD&C Act).
• Information submitted regarding the
technical achievability of compliance
with the standard, including with regard

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to any differences related to the
technical achievability of compliance
with such standard for products in the
same class containing nicotine not made
or derived from tobacco and products
containing nicotine made or derived
from tobacco (section 907(b)(1) of the
FD&C Act).
• All other information submitted,
including information concerning the
countervailing effects of the tobacco
product standard on the health of
adolescent tobacco users, adult tobacco
users, or nontobacco users, such as the
creation of a significant demand for
contraband or other tobacco products
that do not meet the requirements of
chapter IX of the FD&C Act and the
significance of such demand (section
907(b)(2) of the FD&C Act).
As required by section 907(c)(2) of the
FD&C Act, FDA invites interested
persons to submit a draft or proposed
tobacco product standard for the
Agency’s consideration (section
907(c)(2)(B)) and comments on and
information regarding structuring the
standard so as not to advantage foreigngrown tobacco over domestically grown
tobacco (section 907(c)(2)(C)) of the
FD&C Act. In addition, FDA invites the
Secretary of Agriculture to provide any
information or analysis that the
Secretary of Agriculture believes is
relevant to the proposed tobacco
product standard (section 907(c)(2)(D) of
the FD&C Act).
With this proposed rule, FDA is
requesting all relevant documents and
information described in this section.
Such documents and information may
be submitted in accordance with the
‘‘Instructions’’ included in the
preliminary information section of this
document.
Section 907(d)(5) of the FD&C Act
allows FDA to refer a proposed
regulation for the establishment of a
tobacco product standard to the Tobacco
Products Scientific Advisory Committee
(TPSAC) at the Agency’s own initiative
or in response to a request that
demonstrates good cause for a referral
and is made before the expiration of the
comment period. Sections 917(c)(2) and
(c)(3) (21 U.S.C. 387q(c)(2) and (c)(3))
also provide that TPSAC shall provide
advice, information, and
recommendations on the effects of the
alteration of the nicotine yields from
tobacco products and regarding whether
there is a threshold level below which
nicotine yields do not produce
dependence on the tobacco product
involved, respectively.

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B. Pathways to Market
To legally market a new tobacco
product 38 in the United States, a
tobacco product must receive
authorization from FDA permitting the
marketing of the new tobacco product
under one of three premarket review
pathways: (1) the applicant obtains an
order under section 910(c)(1)(A)(i) of the
FD&C Act (order after review of a
premarket tobacco product application
under section 910(b)); (2) the applicant
obtains an order finding the new
tobacco product to be substantially
equivalent to a predicate tobacco
product and in compliance with the
requirements of the FD&C Act under
section 910(a)(2)(A)(i) (order after
review of a Substantial Equivalence (SE)
Report submitted under section 905(j) of
the FD&C Act (21 U.S.C. 387e(j))); or (3)
the applicant makes a request under 21
CFR 1107.1 and obtains an exemption
from the requirements related to SE
(section 905(j)(3)(A)), and at least 90
days before commercially marketing the
product, submits a report under section
905(j) including the information
required in section 905(j)(1)(A)(ii) and
(B) of the FD&C Act.
Applicants may be able to use the SE
pathway for products seeking to comply
with this proposed product standard (if
finalized) by making modifications to
their products in a manner that FDA
finds does not cause the new tobacco
product to raise different questions of
public health. Applicants may be able to
submit a streamlined SE Report
containing information sufficient to
demonstrate that the changes to the
subject of that SE Report do not cause
the new tobacco product to raise
different questions of public health and
to certify that no other changes were
made to the new tobacco product as
compared with the predicate product
and that all other characteristics are
identical (see relevant provisions of the
SE final rule codified at 21 CFR
1107.18(l)(2)). FDA has received
numerous successful applications where
the manufacturer described all
modification(s) between the new and
predicate tobacco product and provided
a certification statement that all other
characteristics are identical. For
example, for products modified to
comply with this product standard, the
applicant could demonstrate how the
modification was made to the tobacco
filler, provide test data to show that the
38 Products that were commercially marketed in
the United States as of February 15, 2007 (referred
to as ‘‘pre-existing tobacco products,’’ previously
referred to as ‘‘grandfathered products’’), are not
considered new tobacco products and do not
require prior authorization to be legally marketed
(section 910(a) of the FD&C Act).

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modification reduced the nicotine
content to meet the standard and did
not cause the new product to raise any
different questions of public health, and
provide a certification that no other
modifications were made to the new
tobacco product other than those made
to reduce the level of nicotine.
An applicant may also be able to use
the SE Exemption pathway under
section 905(j)(3)(A) of the FD&C Act to
the extent the applicant is modifying a
legally marketed tobacco product by
adding or deleting a tobacco additive, or
increasing or decreasing the quantity of
an existing tobacco additive if such
modification would be a minor
modification. While the SE Exemption
pathway may be a viable option in
limited circumstances, FDA notes that
the statutory definition of ‘‘additive’’
excludes tobacco or a pesticide
chemical residue in or on raw tobacco
or a pesticide chemical (section 900(1)
of the FD&C Act). Therefore, to the
extent modifications to a tobacco
product involve changes to the tobacco
(e.g., changes to the nicotine content of
the tobacco used in a tobacco product),
such changes would render section
905(j)(3) of the FD&C Act inapplicable.
If a currently legally marketed tobacco
product is already in compliance with
this proposed product standard, a
premarket authorization application
would not be needed.
FDA requests comments regarding
changes manufacturers may make to
their tobacco products to comply with
this proposed product standard and
what information and evidence they
might provide to satisfy the premarket
review requirements of the Tobacco
Control Act.
C. Considerations and Request for
Comments on Scope of Products
As indicated throughout this
document, FDA has determined that the
proposed standard, which would apply
to cigarettes and certain other
combusted finished tobacco products, is
appropriate for the protection of the
public health. It would cover the
products that are responsible for the
greatest amount of tobacco-related
morbidity and mortality. The proposed
scope of this rule—applying to
cigarettes (other than noncombusted
cigarettes, such as HTPs that meet the
definition of a cigarette), cigarette
tobacco, RYO tobacco, cigars (other than
premium cigars), and pipe tobacco—is
appropriate to protect the public health
and is justified by existing evidence. We
request comments, data, and research
regarding the proposed scope of this
rule.

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FDA is not proposing to include
noncombusted cigarettes, such as HTPs
that meet the definition of a cigarette in
section 900(3) of the FD&C Act
(proposed § 1160.3 includes a definition
of cigarette), within the scope of this
proposed product standard. While
noncombusted cigarettes (such as HTPs)
that meet the definition of cigarette in
the FD&C Act must adhere to existing
restrictions for cigarettes under FDA
regulations, some of these products may
deliver fewer or lower levels of some
toxicants than combusted cigarettes
(Ref. 642). FDA recognizes that tobacco
products exist on a continuum of risk,
with combusted cigarettes being the
deadliest, and that certain specific
products meeting the definition of a
cigarette (e.g., some that are not
combusted) may pose less risk to
individuals who use these products or
to population health than other
products meeting the definition of a
cigarette.
In general, as discussed in this
document, nicotine is the primary
addictive constituent in tobacco
products, and it is the nicotine in such
products that both creates and sustains
addiction, playing a significant role in
creating and perpetuating tobaccorelated negative health consequences.
While these effects raise concerns in the
context of any tobacco product—none of
which is without risk—FDA recognizes
that certain products that meet the
definition of cigarette in the FD&C Act
may present different considerations
with respect to this proposed product
standard. Accordingly, FDA requests
comments, data, and research regarding
the proposal to exclude noncombusted
cigarettes (such as HTPs that are
cigarettes) from the scope of this
proposed rule, including any data that
could justify otherwise.
FDA considered including waterpipe
tobacco products within the scope of
this proposed product standard;
however, the Agency has determined
that waterpipe tobacco involves
profoundly different use behaviors than
combusted cigarettes, which makes it an
unlikely substitute for cigarettes. We
therefore do not propose including
waterpipe tobacco products within the
scope of this proposed rule.
Data on frequency of use differentiates
waterpipe tobacco from cigarettes. For
instance, according to the 2024 NYTS,
0.7 percent of middle and high school
students (or approximately 190,000
students) reported using waterpipe
tobacco within the previous 30 days,
compared with estimates for previous
30-day cigarette use (1.4 percent;
380,000 students) and cigar use (1.2
percent; 330000 students) (Ref. 3).

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However, waterpipe tobacco is
significantly less likely to be smoked
daily. In fact, given the relative
infrequency of waterpipe use, it is often
reported in terms of monthly versus less
than monthly use, rather than daily
versus non-daily. Data from Waves 1
(2013–2014) and 2 (2014–2015) of the
PATH Study indicated that, among
adults who used waterpipes in the past
year, 77.1 percent reported less than
monthly use at Wave 1; by Wave 2, 44.9
percent of these adults continued using
waterpipe less than monthly, while 6.4
percent progressed to monthly or more
frequent use (Ref. 643). For comparison,
59.1 percent of adults in the 2018 NHIS
who smoke cigarettes report daily use
(Ref. 644). Wave 3 (2015–2016) PATH
Study data also indicate the infrequency
of daily waterpipe use: 0.1 percent of
youth, 0.3 percent of young adults, and
0 percent of adults 25 and older
reported daily waterpipe use (Ref. 645).
Comparatively, analysis from Wave 3 of
the PATH study found that 0.6 percent
of youth, 11.4 percent of young adults,
and 15.3 percent of adults older than 25
reported daily cigarette smoking (Ref.
646).
FDA acknowledges that the health
consequences of waterpipe usage are far
from innocuous. People who use
waterpipes are exposed to many of the
same toxicants as people who smoke
cigarettes, and due to the extended
duration of each waterpipe session (i.e.,
approximately 1 hour), waterpipe use
may lead to higher toxicant exposure
per session than toxicant exposure from
one cigarette (Refs. 647 and 648). Thus,
people who use waterpipes are likely
subject to many of the same severe
negative health effects as people who
smoke cigarettes (Ref. 649).
However, FDA does not anticipate
significant migration to waterpipe usage
under the proposed product standard.
Waterpipes as currently marketed are
generally large and require timeconsuming preparation, leading to an
approximate waterpipe smoking session
of 1 hour (Ref. 650). The limited
accessibility and mobility of waterpipes
as generally currently used contribute to
their predominant intermittent usage
patterns (Ref. 650). FDA assesses that
these aspects of waterpipe design would
similarly substantially limit their utility
as a substitute for cigarettes and other
combusted tobacco products that would
be subject the proposed product
standard, especially as compared to the
portability and ease of use of many HTP,
ENDS, and other noncombusted tobacco
products that are currently legally
marketed and not subject to the
proposed product standard.

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FDA requests information and data
regarding the proposal to exclude
waterpipe tobacco from the scope of this
proposed rule.
FDA is not including noncombusted
tobacco products, such as ENDS (which
include e-cigarettes) and smokeless
tobacco products, in the scope of this
proposed product standard. FDA’s
approach in proposing this product
standard for cigarettes and certain other
combusted tobacco products seeks to
protect public health by reducing
combusted tobacco product use (and
therefore reducing exposure to harmful
toxicants created through combustion)
while potentially less harmful,
noncombusted tobacco products remain
available for people who do not quit all
tobacco-product use. As such, at this
time, FDA is focusing this proposed rule
on nicotine levels in cigarettes and
certain other combusted products
because combusted tobacco products are
responsible for the majority of death and
disease due to tobacco use. Importantly,
this action would also help to prevent
people who experiment with cigarettes
and cigars (mainly youth) from moving
beyond experimentation, developing an
addiction to nicotine, and progressing to
regular use of combusted tobacco
products as a result of that addiction.
We request comments, data, and
research regarding the proposed scope
of this rule.
D. Considerations and Request for
Comments on the Potential for Illicit
Trade
The implementation of a maximum
nicotine level in cigarettes and certain
other combusted tobacco products could
result in some people seeking NNC
combusted tobacco products through
illicit trade markets. FDA is also
considering whether illicit trade could
occur as a result of a nicotine product
standard and whether such activity
could significantly undermine the
public health benefits of the product
standard.
Since the enactment of the Tobacco
Control Act, FDA has been committed to
studying and understanding the
potential effects of a product standard
on the illicit tobacco market. As part of
FDA’s consideration of possible
regulations, the Agency asked the NRC
and IOM of the National Academy of
Sciences (now the National Academies)
to assess the international illicit tobacco
market, including variations by country;
the effects of various policy mechanisms
on the market; and the applicability of
international experiences to the United
States (Ref. 560). In 2015, the NRC/IOM
issued its final report entitled
‘‘Understanding the U.S. Illicit Tobacco

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Market: Characteristics, Policy Context,
and Lessons from International
Experiences,’’ finding that, although
there is insufficient evidence to draw
firm conclusions regarding how the U.S.
illicit tobacco market would respond to
regulations requiring a reduction in the
nicotine content of these products,
demand for illicit cigarettes would be
limited because some people who
smoke would quit, and others would
use modified products (e.g., VLNC
cigarettes) or seek legal alternatives (Ref.
560 2015 at p. 9). In addition, in March
2018, FDA issued a draft concept paper,
entitled ‘‘Illicit Trade in Tobacco
Products after Implementation of a Food
and Drug Administration Product
Standard,’’ as an initial step in assessing
the possible health effects of a tobacco
product standard in the form of demand
for contraband or nonconforming
tobacco products (83 FR 11754). Among
other issues, the draft concept paper
examined the factors that might support
or hinder the establishment of a
persistent illicit trade market related to
a product standard (Ref. 44).
Additionally, in the Nicotine ANPRM,
FDA expressed interest in data
regarding possible increases in illicit
trade and its effect on the marketplace
in the event that a nicotine tobacco
product standard is finalized.
Comments were submitted by members
of the tobacco industry, public health
organizations, academic researchers,
and the public. Comments varied in
their conclusions as to how significant
illicit trade might be after
implementation of an FDA product
standard, but no information was
submitted in response to the Nicotine
ANPRM that caused FDA to revise its
overall assessment about the difficulties
in establishing sustained, significant
illicit trade markets that are able to
evade enforcement authorities.
Establishing and maintaining illicit
markets in relevant tobacco products
will be challenging, and to the extent
that they emerge, it is unlikely they will
be significant enough to outweigh the
benefits of the product standard.
Although some people who smoke may
seek to purchase illicit products if
available and accessible, the NRC/IOM
report stated that this ‘‘would require
established distribution networks and
new sources of product (which would
either have to be smuggled from other
countries or produced illegally) to create
a supply of cigarettes with prohibited
features’’ (Ref. 560 at p. 9). The current
illicit cigarette trade in the United States
is predominantly based on tax evasion
and is facilitated by ease of access to
tobacco products close to where the

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sales to consumers take place (e.g.,
across State lines). Enforcement against
such illicit trade is outside the scope of
FDA’s authority (as FDA does not
enforce tax laws) and is complicated by
the inability to distinguish tax-paid
from tax-evading cigarette packs in most
instances. However, due to the
reduction of nicotine in combusted
tobacco products nationwide, a lack of
supply would likely limit illicit trade of
NNC cigarettes and certain other
combusted tobacco products once a
product standard is in place. Illicit
manufacturing of NNC cigarettes at a
scale large enough to diminish the
public health benefits of this proposed
product standard would be difficult to
disguise from Federal, State, and local
enforcement authorities. Moreover,
importation across international borders
is substantially more difficult than
across State borders, particularly for the
volume necessary to sustain nicotine
addiction in people who smoke.
Additionally, while it would remain
legal for domestic cigarette
manufacturers to produce NNC
cigarettes and certain other combusted
tobacco products for export (as
previously described in section III.C of
this document), it is unclear the extent
to which there would be diversion of
legally manufactured products for
export that are subsequently sold
illegally domestically. As noted in
multiple FDA reports to Congress
regarding U.S. tobacco product exports,
after the product standard prohibiting
characterizing flavors (other than
tobacco or menthol) in cigarettes was
implemented, the U.S. Census Bureau
surveyed the vast majority of domestic
manufacturers and found no evidence
that any continued to manufacture
flavored cigarettes or their components
or parts (Ref. 651). Importantly, and
relevant to any continued domestic
manufacture for export, section 920(d)
of the FD&C Act (21 U.S.C. 387t(d))
requires that manufacturers and
distributors notify the Attorney General
and the Secretary of the Treasury of
illicit trade activities (such as import,
export, distribution, or diversion),
increasing the overall vigilance on the
matter. Finally, as the NRC/IOM Report
explains, comprehensive interventions
by several countries show it is possible
to reduce the size of the illicit tobacco
market through enforcement
mechanisms and collaborations across
jurisdictions (Ref. 560).
Research also has shown that the
choice between VLNC and NNC
cigarettes can be influenced by factors
such as cost (see section VI.B of this
document for further discussion). It is

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well-established that people who smoke
are price-sensitive, and there is a direct
correlation with the increased price of
cigarettes and reductions in
consumption (Ref. 652), showing for
every ten percent increase in price,
there is an overall reduction in
consumption of 3–5 percent, and youth
smoking decreases by 6–7 percent. This
price sensitivity also contributes to the
willingness of people who smoke
cigarettes to shift consumption toward
non-cigarette tobacco products in times
of economic or product constraint (Refs.
345, 346, and 349). Additionally, there
is an ‘‘inconvenience cost’’ to the
purchase of illicit tobacco products that
rises and falls depending upon the
location of illegal sales, reliability of
supply, fear of embarrassment and legal
penalties, and more (Ref. 560 at p. 67).
Although illicit NNC cigarettes and
certain other combusted tobacco
products will not be subject to taxes,
participants in any illicit market will
demand profits sufficient to cover both
their costs as well as compensate for the
risks of enforcement, limiting how low
they can price the illicit tobacco
products. As a result, when the cost or
effort required to obtain illicit products
increases, people who smoke may
switch their preference from NNC
combusted tobacco products to VLNC
versions (Ref. 391), to other legal
tobacco products, and/or renew their
cessation efforts. Each of these
alternatives reduces the number of
potential buyers of illicit products,
lowering the incentives to try, create,
and sustain such markets.
Related to concerns about
enforcement against individual
consumers for possessing or using
nonconforming tobacco products
acquired through an illicit market,
FDA’s enforcement will only address
manufacturers, distributors,
wholesalers, importers, and retailers.
This regulation does not include a
prohibition on individual consumer
possession or use of nonconforming
product acquired through an illicit
market, and FDA cannot and will not
enforce against individual consumers
for possession or use of NNC cigarettes
or other combusted tobacco products
covered by this proposed product
standard. In addition, State and local
law enforcement agencies do not
enforce the FD&C Act. These entities do
not and cannot take enforcement actions
against any violation of chapter IX of the
Act or this regulation on FDA’s behalf.
FDA recognizes concern about how
State and local law enforcement
agencies enforce their own laws in a
manner that may impact equity and

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community safety and seeks comments
on how FDA can best make clear the
respective roles of FDA and State and
local law enforcement.
FDA is not proposing to ban any
category of tobacco products with this
proposed product standard, and
authorized products that are not subject
to the proposed product standard will
remain legally available. Therefore, this
proposed product standard is not
expected to lead to a surge in illicit
tobacco product use. In reaching this
conclusion, FDA has considered several
factors that are likely to affect the
potential for illicit trade. For example,
FDA anticipates that a nationwide
standard that prohibits the manufacture
(other than for export as previously
described in section III.C of this
document) and sale of cigarettes and
certain other combusted tobacco
products that exceed the maximum
nicotine level set by this proposed
product standard, coupled with FDA’s
authority to take enforcement actions
and other steps regarding the sale and
distribution of illicit tobacco products,
would limit the manufacture and
distribution of these products. FDA also
expects that a nationwide product
standard would eliminate the use of
online retailers to purchase illicit
tobacco products as well as any
incentive to travel within the United
States in search of jurisdictions without
a nicotine product standard because no
such jurisdictions would exist. FDA
thus anticipates that the rule would
result in much less illicit trade than
observed in the case of a State or local
requirement and that any such trade
would be significantly outweighed by
the benefits of the rule. Even if some
amount of illicit trade develops (Refs. 42
and 653 discuss projected impacts of
various rates of potential illicit trade), it
would have to be of significantly greater
magnitude than any previously seen
illicit markets in order to outweigh the
significant public health benefits of this
proposed standard, and it would have to
continue to exist at those levels despite
the various enforcement agencies and
tools involved.
FDA requests comments, including
supporting data and research, regarding
whether and to what extent this
proposed rule would result in an
increase in illicit trade in NNC
cigarettes and certain other combusted
tobacco products covered by the
proposed nicotine product standard and
how any such increase could impact
public health. Data or other reliable
information that do not rely on
estimates of current, interstate taxevading illicit trade would be
particularly relevant. If an illicit market

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develops after this proposed product
standard is finalized, FDA has the
authority to take enforcement actions
and other steps regarding the sale and
distribution of illicit tobacco products,
including those imported or purchased
online. FDA conducts routine
surveillance of sales, distribution,
marketing, and advertising related to
tobacco products and takes appropriate
actions when violations occur. If this
product standard is finalized as
proposed and goes into effect, it would
be illegal to import cigarettes and
certain other combusted tobacco
products that exceed 0.70 mg nicotine
per gram of total tobacco, and such
products would be subject to import
examination and refusal of admission
under the FD&C Act. Similarly, it would
be illegal to sell or distribute cigarettes
and certain other combusted tobacco
products that do not comply with this
product standard, including those sold
online, and doing so may result in FDA
initiating enforcement or regulatory
actions. We note that the Prevent All
Cigarette Trafficking Act of 2009
establishes restrictions that make
cigarettes generally nonmailable
through the U.S. Postal Service, subject
to certain exceptions (18 U.S.C. 1716E).
Outside of these exceptions, the U.S.
Postal Service cannot accept or transmit
any package that it knows, or has
reasonable cause to believe, contains
nonmailable cigarettes, smokeless
tobacco, or ENDS.39
X. Description of Proposed Regulation
This proposed rule would establish a
new part 1160 that would set a
maximum level of nicotine in finished
cigarettes and certain other finished
combusted tobacco products. Part 1160
would describe the scope of the
proposed regulation, applicable
definitions, the establishment of a
maximum nicotine level in products
covered by this proposed rule, product
testing and related requirements, and
recordkeeping requirements.
A. General Provisions (Proposed
Subpart A)
1. Scope (Proposed § 1160.1)
Proposed § 1160.1(a) would provide
that this part sets out a tobacco product
standard under the FD&C Act to limit
nicotine yield by setting a maximum
nicotine content level for certain
finished tobacco products. We are
proposing that this product standard
would cover the following finished
tobacco products: cigarettes (other than
39 These restrictions were updated to include
similar prohibitions on the shipment of ENDS in
2021 (86 FR 58399, October 21, 2021).

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noncombusted cigarettes, such as HTPs
that meet the definition of a cigarette),
cigarette tobacco, RYO tobacco, cigars
(other than premium cigars), and pipe
tobacco (other than waterpipe tobacco).
These products are defined in proposed
§ 1160.3. As stated throughout this
preamble, this proposed product
standard focuses on cigarettes and
certain other combusted tobacco
products given their addictiveness,
availability as migration and dual use
candidates with cigarettes, and the
extent of tobacco-related death and
disease associated with such products.
As stated in section IX.C of this
document, FDA requests comment
regarding the scope of products covered
by this proposed rule.
Proposed § 1160.1(b) would prohibit
the distribution, sale, or offering for
distribution or sale within the United
States finished tobacco products within
the scope of the rule that are not in
compliance with the tobacco product
standard. For example, FDA would
consider such finished tobacco products
to be noncompliant if they contain a
nicotine level that exceeds the proposed
maximum nicotine level set forth in
proposed § 1160.10. Additionally,
manufacturers and importers would not
be allowed to enter or introduce into
domestic commerce any finished
tobacco product (i.e., cigarettes,
cigarette tobacco, RYO tobacco, cigars,
and pipe tobacco) that does not comply
with the requirements of the final rule,
irrespective of the date of manufacture.
Proposed § 1160.1(c) would prohibit
the manufacture within the United
States of finished tobacco products
within the scope of the rule that are not
in compliance with the tobacco product
standard unless such tobacco products
are intended for export and are eligible
for export under section 801(e)(1) of the
FD&C Act (21 U.S.C. 381(e)(1)). A
tobacco product intended for export
shall not be deemed to be in violation
of section 907 of the FD&C Act or this
product standard if it meets the criteria
enumerated in section 801(e)(1),
including not being sold or offered for
sale in domestic commerce.
2. Definitions (Proposed § 1160.3)
Proposed § 1160.3 provides the
definitions for the terms used in the
proposed product standard. Several of
these definitions are included in the
FD&C Act or have been used in other
regulatory documents.
• Accessory: Consistent with 21 CFR
1140.3 and the Consolidated
Appropriations Act, 2022 (Pub. L. 117–
103), FDA proposes to define
‘‘accessory’’ as any product that is
intended or reasonably expected to be

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used with or for the human
consumption of a tobacco product; does
not contain tobacco or nicotine from any
source and is not made or derived from
tobacco; and meets either of the
following: (1) is not intended or
reasonably expected to affect or alter the
performance, composition, constituents,
or characteristics of a tobacco product;
or (2) is intended or reasonably
expected to affect or maintain the
performance, composition, constituents,
or characteristics of a tobacco product;
but (i) solely controls moisture and/or
temperature of a stored product; or (ii)
solely provides an external heat source
to initiate but not maintain combustion
of a tobacco product. Accessories of
cigarettes, cigarette tobacco, and RYO
tobacco, as three of the originallyregulated products under the FD&C Act,
are considered ‘‘tobacco products’’ and,
therefore, would be subject to this
proposed product standard (if finalized).
However, accessories of other tobacco
products (e.g., cigars) are not regulated
as ‘‘tobacco products’’ pursuant to
FDA’s final deeming rule (81 FR 28974
at 29015–29016, May 10, 2016) and,
therefore, would not be subject to this
proposed product standard. Examples of
such accessories would be ashtrays,
cigar clips, and pipe pouches, because
they do not contain tobacco or nicotine
from any source, are not made or
derived from tobacco, and do not affect
or alter the performance, composition,
constituents, or characteristics of a
tobacco product. However, if such a
product was intended or reasonably
expected to affect the performance of a
tobacco product (e.g., nicotine
impregnated ash tray), it would no
longer be considered an accessory and
would be subject to the proposed
product standard.
• Batch: FDA proposes to define
‘‘batch’’ as a specific identified amount
of a finished tobacco product produced
in a unit of time or quantity and that is
intended to have the same
specifications. FDA proposes to give
tobacco product manufacturers
flexibility to determine what unit of
time or quantity is appropriate for their
product, and how batches would be
designated. For example, manufacturers
likely would have, as part of existing
manufacturing processes, defined a
‘‘batch’’ for cigarette production, which
is almost continuous, differently than a
batch for smokeless tobacco, which
likely would be defined based on the
amount processed in a vat through the
fermentation process. Currently, there is
no definition of ‘‘batch’’ for tobacco
products. However, the proposed
regulation Requirements for Tobacco

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Product Manufacturing Practice (TPMP)
(see https://www.federalregister.gov/
documents/2023/03/10/2023-04591/
requirements-for-tobacco-productmanufacturing-practice) includes a
proposed definition of ‘‘batch,’’ and this
rulemaking’s provision is modeled on
the proposed TPMP provision. Pursuant
to proposed § 1160.12, manufacturers
would be required to conduct batch
testing and maintain those records.
• Cigar: FDA proposes to define a
‘‘cigar’’ as a tobacco product that: (1) is
not a cigarette and (2) is a roll of tobacco
wrapped in leaf tobacco or any
substance containing tobacco. This
definition was used in the seven
consent orders that the FTC entered into
with the largest mass marketers of cigars
(see, e.g., In re Swisher International,
Inc., Docket No. C–3964 (FTC August
18, 2000)) and also is codified at 21 CFR
1143.1. The cigar wrapper would be
considered a ‘‘component or part’’ of a
cigar (see definition herein) and,
therefore, would be covered by this
proposed product standard. As
discussed elsewhere in this document
and in proposed § 1160.1, premium
cigars are excluded from the scope of
this proposed rule.
• Cigarette: As defined in section
900(3) of the FD&C Act, the term
‘‘cigarette’’: (1) means a product that: (i)
is a tobacco product; and (ii) meets the
definition of the term ‘‘cigarette’’ in
section 3(1) of the Federal Cigarette
Labeling and Advertising Act (15 U.S.C.
1332(1)); and (2) includes tobacco, in
any form, that is functional in the
product, which, because of its
appearance, the type of tobacco used in
the filler, or its packaging and labeling,
is likely to be offered to, or purchased
by, consumers as a cigarette or as RYO
tobacco.
• Cigarette tobacco: As defined in
section 900(4) of the FD&C Act, the term
‘‘cigarette tobacco’’ means any product
that consists of loose tobacco that is
intended for use by consumers in a
cigarette. Unless otherwise stated, the
requirements applicable to cigarettes
under this chapter also apply to
cigarette tobacco.
• Commercial distribution: Consistent
with 21 CFR 1107.12, FDA proposes to
define ‘‘commercial distribution’’ as any
distribution of a finished tobacco
product, whether domestic or imported,
to consumers or to any person, but does
not include interplant transfers of a
tobacco product between establishments
within the same parent, subsidiary, and/
or affiliate company, nor does it include
providing a tobacco product for product
testing where such product is not made
available for consumption or resale.
‘‘Commercial distribution’’ does not

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include the handing or transfer of a
tobacco product from one consumer to
another for personal consumption.
• Component or part: Consistent with
21 CFR 1140.3, FDA proposes to define
‘‘component or part’’ as any software or
assembly of materials intended or
reasonably expected: (1) to alter or affect
the tobacco product’s performance,
composition, constituents, or
characteristics or (2) to be used with or
for the human consumption of a tobacco
product. The term excludes anything
that is an accessory of a tobacco
product. Components or parts of
cigarettes, cigarette tobacco, and RYO
tobacco, as three of the originally
regulated products under the FD&C Act,
are considered ‘‘tobacco products’’ and,
therefore, would be subject to this
proposed product standard (if finalized).
Examples of cigarette components or
parts that would be subject to this
proposed product standard include
cigarette paper and filters. In addition,
components or parts of other tobacco
products (e.g., cigars) are regulated as
‘‘tobacco products’’ pursuant to FDA’s
final deeming rule (81 FR 28974 at
29015–29016) and, therefore, would be
subject to this proposed product
standard (if finalized). Some examples
of such components or parts include
cigar blunt wraps, removable tips,
mouthpieces, and filters. These
examples generally are intended or
reasonably expected to alter or affect the
performance, composition, constituents,
or characteristics of a tobacco product.
If a liquid nicotine product or other
tobacco product is intended or
reasonably expected to alter the nicotine
content of any tobacco product covered
by this proposed rule, such liquid
nicotine or other tobacco product would
be considered a component or part of a
finished tobacco product covered under
the rule’s scope and, therefore, would be
in violation of the rule if the amount of
nicotine in the finished tobacco product
exceeds 0.70 mg of nicotine per gram of
total tobacco. With respect to these
definitions, FDA notes that
‘‘component’’ and ‘‘part’’ are separate
and distinct terms within chapter IX of
the FD&C Act. However, for purposes of
this rule, FDA is using the terms
‘‘component’’ and ‘‘part’’
interchangeably and without
emphasizing a distinction between the
terms. FDA may clarify the distinctions
between ‘‘component’’ and ‘‘part’’ in the
future.
• Finished tobacco product:
Consistent with 21 CFR 1107.12, FDA
proposes to define a ‘‘finished tobacco
product’’ to mean a tobacco product,
including all components and parts,
sealed in final packaging (e.g., filters or

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filter tubes sold to consumers separately
or as part of kits) or in the final form in
which it is intended to be sold to
consumers (e.g., tobacconists selling
cigars individually from a box or pipe
tobacco filler by weight). Examples of
finished tobacco products include a
pack of cigarettes or a bag of RYO or
pipe tobacco.
• Manufacturing code: FDA proposes
to define ‘‘manufacturing code’’ as any
distinctive sequence or combination of
letters, numbers, or symbols that begins
with the manufacturing date, followed
by the batch number, and concludes
with ‘‘-NS.’’ This information would
help determine the product’s history
(e.g., batch testing records) and assist
manufacturers and FDA in the event of
a nonconforming tobacco product
investigation and any corrective actions
that stem from such investigation.
• Manufacturing date: FDA proposes
to define ‘‘manufacturing date’’ as the
month, day, and year in 2-digit
numerical values in the format
(MMDDYY) that a finished tobacco
product is packaged for distribution.
The manufacturing date is included in
the manufacturing code, which can be
used by the manufacturer and FDA to
help determine the product’s history
(e.g., batch testing history) in the event
of a nonconforming tobacco product
investigation. As stated in section X.C of
this document, FDA requests comment
regarding the manufacturing code
requirements in this proposed rule.
• Nicotine: FDA proposes to define
‘‘nicotine’’ as the chemical substance
named 3–1(1-methyl-2-pyrrolidinyl)
pyridine or C[10]H[14]N[2], including
any salt or complex of nicotine, derived
from any source.
• Nonconforming tobacco product:
FDA proposes to define
‘‘nonconforming tobacco product’’ as
any tobacco product that does not meet
the requirements of § 1160.10 (nicotine
level specifications) or § 1160.30
(manufacturing code).
• Package or packaging: As defined
in section 900(13) of the FD&C Act, the
term ‘‘package’’ means a pack, box,
carton, or container of any kind or, if no
other container, any wrapping
(including cellophane) in which a
tobacco product is offered for sale, sold,
or otherwise distributed to consumers.
• Person: As defined in section 201(e)
of the FD&C Act (21 U.S.C. 321(e)), the
term ‘‘person’’ includes an individual,
partnership, corporation, or association.
• Pipe tobacco: FDA proposes to
define the term ‘‘pipe tobacco’’ as any
tobacco that, because of its appearance,
type, packaging, or labeling, is suitable
for use and likely to be offered to, or
purchased by, consumers as tobacco to

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be smoked in a pipe. However, this
definition specifically excludes tobacco
labeled and sold exclusively for use in
a waterpipe (i.e., hookah tobacco). As
discussed in section IX.C of this
document, FDA is not proposing to
include waterpipe tobacco within the
scope of this product standard.
• Rework: FDA proposes to define
‘‘rework’’ as action taken on a
nonconforming tobacco product to
ensure that the product meets the
specifications and other requirements of
this part before it is released for
commercial distribution.
• Roll-your-own tobacco: As modeled
after section 900(15) of the FD&C Act,
FDA proposes to define the term ‘‘rollyour-own tobacco’’ (or RYO) as any
tobacco product which, because of its
appearance, type, packaging, or labeling,
is suitable for use and likely to be
offered to, or purchased by, consumers
as tobacco for making cigarettes or
cigars. This product is frequently used
interchangeably with cigarette tobacco
and pipe tobacco (as defined in this
section).
• Specification: We propose to define
‘‘specification’’ as any requirement with
which a product, process, service, or
other activity must conform. A tobacco
product specification is a requirement
established by the manufacturer,
including a requirement established to
ensure that the tobacco product meets
any applicable product standard under
section 907 of the FD&C Act.
• Tobacco filler: FDA proposes to
define ‘‘tobacco filler’’ as cut, ground,
powdered, or leaf tobacco or other
nicotine-containing substances in a
finished tobacco product. For portioned
tobacco products, the material enclosing
any tobacco or nicotine-containing
substances (e.g., cigarette paper) is not
considered tobacco filler.
• Tobacco product: As defined in
section 201(rr) of the FD&C Act, the
term ‘‘tobacco product’’ means any
product made or derived from tobacco,
or containing nicotine from any source,
that is intended for human
consumption, including any
component, part, or accessory of a
tobacco product (except for raw
materials other than tobacco used in
manufacturing a component, part, or
accessory of a tobacco product). The
term ‘‘tobacco product’’ does not mean
an article that is: a drug under section
201(g)(1); a device under section 201(h);
a combination product described in
section 503(g) (21 U.S.C. 353(g)); or a
food under section 201(f) of the FD&C
Act if such article contains no nicotine,
or no more than trace amounts of
naturally occurring nicotine.

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• Tobacco product manufacturer: As
defined in section 900(20) of the FD&C
Act, the term ‘‘tobacco product
manufacturer’’ means any person,
including a repacker or relabeler, who:
(1) manufactures, fabricates, assembles,
processes, or labels a tobacco product or
(2) imports a finished tobacco product
for sale or distribution in the United
States.
• Total tobacco: FDA proposes to
define the term ‘‘total tobacco’’ as the
tobacco filler (defined in proposed
§ 1160.3) and any other tobacco or
tobacco-derived material used as part of
a tobacco product. For cigars (i.e., those
cigars that are covered by this proposed
product standard, as defined in
proposed § 1160.3), the tobacco
included in the wrapper and binder
would be part of the ‘‘total tobacco.’’
The nicotine content in the total tobacco
of the finished tobacco product must not
exceed the proposed maximum nicotine
level.
• United States: As defined in section
900(22) of the FD&C Act, the term
‘‘United States’’ means the 50 States of
the United States of America and the
District of Columbia, the
Commonwealth of Puerto Rico, Guam,
the Virgin Islands, American Samoa,
Wake Island, Midway Islands, Kingman
Reef, Johnston Atoll, the Northern
Mariana Islands, and any other trust
territory or possession of the United
States.
B. Product Requirements (Proposed
Subpart B)
1. Maximum Nicotine Level (Proposed
§ 1160.10)
FDA is proposing to regulate nicotine
yield by requiring that a finished
tobacco product contain no more than
0.70 mg of nicotine per gram of total
tobacco. As stated in proposed § 1160.3,
the term ‘‘total tobacco’’ means both the
tobacco filler and any other tobacco or
tobacco-derived material used as part of
a tobacco product. This level would be
based on the nicotine content of the
tobacco product, as the means to
regulate nicotine yield in the tobacco
smoke or emissions. If a liquid nicotine
product or other tobacco product
(including a tobacco product containing
nicotine from any source) is intended or
reasonably expected to alter the nicotine
content of any tobacco product covered
by this proposed rule, such liquid
nicotine or other tobacco product would
be considered a component or part of a
tobacco product covered under the
rule’s scope and, therefore, would be in
violation of the rule if the total amount
of nicotine in the finished tobacco

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product exceeds 0.70 mg of nicotine per
gram of total tobacco.
As stated previously, the term
‘‘finished tobacco product’’ refers to
those products subject to this regulation,
including any components, parts, or
accessories that are regulated as tobacco
products and sealed in a final package,
except for components, parts, or
accessories not made or derived from
tobacco. For cigarettes, cigarette
tobacco, and RYO tobacco, all of which
were covered under Congress’s original
grant of authority (section 901(b) of the
FD&C Act), all components, parts, and
accessories of such products would be
covered under this proposed product
standard and subject to the proposed
maximum nicotine level. Accessories of
deemed tobacco products (i.e.,
accessories for cigars, pipe tobacco)
would not be covered. FDA intends to
use its premarket review authority
under sections 905 and 910 of the FD&C
Act to ensure that manufacturers do not
reengineer their products in a way that
would circumvent the proposed
maximum nicotine level.
2. Product Testing (Proposed § 1160.12)
Proposed § 1160.12 contains
provisions for the testing of finished
tobacco products that would be subject
to this proposed rule. Specifically,
proposed § 1160.12(a) would require
that tobacco product manufacturers
conduct testing on each batch of
finished tobacco products to ensure that
the batch conforms with proposed
§ 1160.10. Under this provision, the
manufacturer of the finished tobacco
product would be required to use an
analytical test method that meets the
requirements set forth in proposed
§ 1160.14. FDA recommends
manufacturers use one of three
analytical test methods described in
section VII.D of this document (i.e.,
FDA’s Tobacco Products Laboratory
method, CRM No. 62, or CRM No. 87).
This section also states that samples for
such testing would need to be selected
in accordance with proposed § 1160.16.
Proposed § 1160.12(b) would require
that a full report of the source data and
results of all batch testing be maintained
by the tobacco product manufacturer in
accordance with proposed § 1160.32.
These reports would be generated for
test samples from each batch and would
not be required for each individual
finished tobacco product. This report
would have to include the following
information:
(1) Full identification of the finished
tobacco product that is the subject of the
report, including, if applicable, the
submission tracking number (STN)
associated with marketing authorization

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(including the static product ID (PD), if
applicable), product name(s) (including
brand and subbrand and the original
name described in the premarket
application, if different), product
category, subcategory, package type,
package quantity, and nicotine source;
(2) Nicotine level of each sample
tested from the batch and standard
deviation;
(3) The batch manufacturing date and
location, including facility name and
address, for each sample;
(4) The testing date and location,
including the facility name and address;
(5) The manufacturing code of each
sample tested (in accordance with
proposed § 1160.30(c));
(6) The test method and sampling
procedure used;
(7) Names and qualifications of the
person(s) conducting the testing and any
laboratory accreditation;
(8) The manufacturing and testing
equipment used (including
documentation to show that the
equipment is appropriate for its
intended purpose and has been
calibrated to ensure accurate and
reliable results); and
(9) The criteria used to make a
decision to accept or reject each batch
and the decision made with respect to
each batch (e.g., accept, reject) based on
the results of the product testing. This
information would constitute the
documentation of the source data and
actual results of the product testing
conducted on each batch.
The main purpose of this report
would be to verify that products subject
to this proposed product standard do
not exceed the maximum nicotine level
and to document the company’s
decision for each batch with respect to
acceptance, rejection, and reworking of
the products. FDA expects that
information collected pursuant to
proposed § 1160.16(b) would be
integrated into the proposed
§ 1160.12(b) records (i.e., proposed
§ 1160.16(b) records would be the basis
for documenting background
information about the product being
tested, including, for example, the
product category and subcategory, brand
and subbrand, packaging information,
nicotine source, manufacturing date,
and the manufacturing code). These
proposed § 1160.12(b) records also
would document the ultimate
disposition of the batch based on the
testing of the representative samples.
Section III.C of this document describes
FDA’s rulemaking and inspection
authorities related to these records.
While the proposed batch testing and
sampling requirements would provide
FDA with critical information, the

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Agency also recognizes concerns that it
could be costly for certain
manufacturers to test each batch.
Therefore, FDA requests comment,
including supporting data, regarding
potential alternatives to batch testing
and sampling to ensure finished tobacco
product compliance with proposed
§ 1160.10 that would reduce costs for
manufacturers.
3. Analytical Test Method (Proposed
§ 1160.14)
Proposed § 1160.14 would require
that tobacco product manufacturers use
an analytical test method and
demonstrate that the test method was
validated in an analytical test
laboratory.
Validation means a process of
demonstrating or confirming that the
analytical test method is suitable and
reliable for its intended purpose.
Validation of an analytical method
applies to a specific laboratory, for a
specific product, and equipment
performing the analytical test method
for an intended use over a reasonable
period. Although there are various
approaches to demonstrate that an
analytical test method is validated (e.g.,
ICH Guideline Validation of Analytical
Procedures: Text and Methodology Q2),
FDA intends to use the approach
outlined in the draft guidance entitled
‘‘Validation and Verification of
Analytical Testing Methods Used for
Tobacco Products’’ to determine if a
submitted test method is fit-for-purpose.
In March 2024, FDA published a final
guidance for industry entitled ‘‘Q2(R2)
Validation of Analytical Procedures’’
and although it is not specific to tobacco
products, FDA’s approach under that
guidance to determine if a method is fitfor-purpose is applicable for use under
this tobacco product standard.40
As described in section VII.D of this
document, FDA recommends
manufacturers use one of three publicly
available analytical test methods—
FDA’s Tobacco Products Laboratory
method, CRM No. 62, or CRM No. 87—
to demonstrate compliance with this
proposed product standard. Each of
these analytical test methods includes
the proposed nicotine level in the range
of levels that can be accurately
measured.
40 FDA has announced the availability of a draft
guidance for industry entitled ‘‘Validation and
Verification of Analytical Testing Methods Used for
Tobacco Products’’ (86 FR 72603, December 22,
2021; see https://www.fda.gov/media/155033/
download). The draft guidance, when finalized,
would represent FDA’s current thinking on method
validation for tobacco products. FDA final guidance
‘‘Q2(R2) Validation of Analytical Procedures’’ is
available at https://www.fda.gov/media/161201/
download.

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It is reasonable to expect some
manufacturers may prefer to use other
test methods. If they are developed and
validated, such methods may have
different advantages in ease of use,
upper and lower bounds of detection,
equipment, and expertise. Thus, under
this proposal we would evaluate
analytical test methods and data as part
of a manufacturer’s premarket
submission in accordance with section
910 of the FD&C Act.
4. Sampling Plans and Procedures
(Proposed § 1160.16)
Proposed § 1160.16 would require
each tobacco product manufacturer to
design and implement a sampling plan
that covers each finished tobacco
product that it manufactures. This
sampling plan must be based on a valid
statistical rationale to ensure that the
finished tobacco product complies with
proposed § 1160.10. This sampling plan
would be used in conjunction with the
analytical test method in proposed
§ 1160.14 and would provide
procedures for the manufacturer to
select samples to demonstrate
conformance to the proposed maximum
nicotine level requirement.
The required procedures are intended
to help ensure that tobacco products
containing more than the maximum
nicotine level are not sold or distributed
to consumers. Manufacturers would be
required to ensure that all finished
tobacco products comply with the
requirements of this proposed product
standard. Products that do not conform
to this standard would be deemed
adulterated under section 902(5) of the
FD&C Act and subject to enforcement
action.
Proposed § 1160.16(a) provides the
general requirements for sampling
plans. The proposed provision would
require manufacturers to design and
implement a sampling plan or plans for
each finished tobacco product based on
a valid scientific rationale to ensure that
the product consistently conforms to the
requirements set forth in § 1160.10. This
provision also explains that the
sampling plan must ensure that samples
taken are representative of an entire
batch (i.e., randomized or systematically
selected across the entire batch) and
collected from each batch for testing. To
account for the variability of nicotine in
finished tobacco products, the following
factors must be based on adequate
statistical criteria: the confidence
intervals, the level of necessary
precision, and the number of finished
products sampled. The sampling plan
must take into account the
manufacturing quality history of the
manufacturer (e.g., batch testing records,

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nonconforming tobacco product
investigations). For example, a
manufacturer that has a high number of
nonconforming tobacco product
investigations or a high number of batch
rejections may decide to create a more
robust sampling plan because of its
history of producing nonconforming
tobacco products.
The basic principles of an adequate
sampling plan include the following:
the samples are representative of the
batch or quantity being sampled; the
number of samples is based on a valid
scientific rationale; and the number of
samples is sufficient for the intended
purpose. ‘‘Valid scientific rationale’’
refers to scientific techniques or
methods used to establish the number of
representative samples and should take
into account tolerance for variability,
confidence levels, and the degree of
precision required (Refs. 654 to 656).
FDA believes that requiring the number
of samples to be based on a ‘‘valid
scientific rationale’’ would provide
manufacturers with the flexibility to
determine the appropriate number of
representative samples for any sampling
plan. While FDA is proposing this
flexibility, this provision would require
that manufacturers have support for the
scientific technique or methods used to
establish the number of representative
samples used and to show that the
sampling size is representative of the
material being sampled. FDA requests
comment, including supporting data,
regarding whether a final rule should
provide a more detailed definition of or
criteria for what constitutes ‘‘valid
scientific rationale’’ (such as
representative sampling) with regard to
an adequate sampling plan.
Proposed § 1160.16(a) also would
require that the sampling plan describe
the sampling methodology (including
scientific rationale), incorporate all
sources of variability (including
variability of the analytic method and
nicotine levels), and describe the
sample size needed (including a full
description of how the sample size is
calculated) consistent with the sampling
plan to achieve the sampling objective.
The sampling plan must also describe
the criteria the manufacturer would use
to make a decision to accept or reject
each batch. FDA proposes to give
tobacco product manufacturers
flexibility to determine what unit of
time or quantity is appropriate for their
product and how batches would be
designated. For example, manufacturers
likely would define a batch for cigarette
production, which is almost continuous,
differently than a batch for machine or
hand-rolled cigars.

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With regard to the variability of the
tobacco product, confidence intervals,
level of necessary precision, and
number of finished tobacco products
sampled must be based on adequate
statistical criteria. This provides
manufacturers flexibility to determine
the appropriate number of
representative samples for any sampling
plan. While FDA is proposing this
flexibility, this provision would require
that manufacturers have the support for
the scientific technique or methods used
to establish the representative samples
used and to show that the sampling size
is representative of the material being
sampled. The manufacturer must
maintain a nicotine content level no
greater than 0.70 mg nicotine per gram
of total tobacco for any products within
the batch.
Proposed § 1160.16(b) would require
that test samples from each batch be
collected and examined in accordance
with certain procedures. These
procedures are consistent with ISO
8243, an international standard that
specifies two methods of providing
representative samples of a population
of cigarettes manufactured for sale.
Under proposed § 1160.16(b)(1), test
samples would have to consist of the
finished tobacco product as it is
intended to be sold or distributed to
consumers and not of a separate
production sample.
Proposed § 1160.16(b)(2) would
require that all test samples be stored
according to the intended storage
conditions for the finished tobacco
product. In addition, the manufacturer
would have to include all of its
factories, stock rooms, warehouses, and
other locations containing finished
tobacco products among the population
to be sampled. Because a batch may
include product that is in the warehouse
and product that is in the factory, or in
a place between the warehouse and
factory, this requirement would ensure
that the sample is representative of the
entire population (batch) of finished
tobacco products packaged for
consumer use. This practice is
consistent with the ISO 8243 standard
(for sampling nicotine) and ensures that
the samples are representative of the
population of finished tobacco products
packaged for consumer use.
Under proposed § 1160.16(b)(3), the
manufacturer would have to take test
samples from each batch within 30
calendar days of the date the product is
manufactured. Based on FDA’s
experience, any protracted time between
manufacturing and testing will add
uncertainty in the accuracy of reported
results. Thus, we are proposing a 30
calendar day timeframe from the

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manufacture date for the manufacturer
to take test samples from each batch.
The amount of material acquired during
sampling must be sufficient to complete
all testing required by proposed
§ 1160.14, including any repeat testing
that may be necessary. The sample
materials would have to be selected
from each batch in accordance with the
applicable sampling plan. This would
ensure that there has not been any
degradation or change in part of the
samples.
Proposed § 1160.16(b)(4) would
require that sampling be performed by
persons who have sufficient education,
training, and experience to accomplish
their assigned functions.
Under proposed § 1160.16(b)(5), each
test sample would need to be identified
so that the following information can be
determined:
• Full identification of the finished
tobacco product sampled, including, if
applicable, the STN associated with
marketing authorization (including the
PD, if applicable), product name(s)
(including brand and subbrand and the
original name described in the
premarket application, if different),
product category, subcategory, package
type, package quantity, and nicotine
source;
• The manufacturing code;
• The date on which the sample was
taken;
• The sampling location (including
the address of the facility and specific
location within the facility where the
sample was taken);
• The name of the person(s) who
collected the sample; and
• The location where the sample will
be tested (including the facility name
and address).
This information would be generated
at the time the samples are pulled for
testing and for each sample pulled,
rather than reflecting aggregate
information for all the samples in a
particular batch. The purpose of this
information is to fully identify each
sample, including what the product is,
when and where it was taken, and the
batch from which it was taken. These
records would serve dual purposes.
First, they could be used to verify that
a company is following its sampling
plan and the required procedures in the
codified including number of samples
pulled, when they are pulled, and
locations from where they are pulled.
Second, these records would be used to
generate some of the information for the
records required under proposed
§ 1160.16(b)(8). They also would
document the start of the chain of
custody for the samples.

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Proposed § 1160.16(b)(6) provides
packaging requirements for when
samples are sent for testing. Test
samples would have to be packed
securely with adequate protection
against damage that might occur,
including mechanical damage or
adverse changes in humidity or
temperature. The manufacturer also
would have to send, under separate
cover, a list of the samples included in
each shipment to the testing facility.
These samples should be identified by
the relevant information required by
proposed § 1160.16(b)(5).
Proposed § 1160.16(b)(7) would
require that all samples from a single
batch be tested at the same testing
facility. This requirement is designed to
ensure consistency in the procedures
used and to protect against sample
degradation.
Proposed § 1160.16(b)(8) provides
sampling requirements for the testing
facility. If samples will be transported to
a different facility from the
manufacturing facility for testing, once
test samples arrive at the testing facility,
samples must be inspected, accounted
for, and properly stored under the
finished tobacco product’s intended
storage conditions. The facility also
would be responsible for generating a
report for the batch test, maintained by
the manufacturer in accordance with
§ 1160.32, which includes the
information in proposed
§ 1160.16(b)(8)(i) through (vi):
• Full identification of the finished
tobacco product sampled, including, if
applicable, the STN associated with
marketing authorization (including the
PD, if applicable), product name(s)
(including brand and subbrand and the
original name described in the
premarket application, if different),
product category, subcategory, package
type, package quantity; and nicotine
source;
• The manufacturing code;
• The date on which the samples
were taken, if available;
• The sampling location (including
the address and specific locations
within any facilities where the samples
were taken);
• The number of test samples drawn
from the batch; and
• Complete records of the samples
received and tested, including the date
of receipt, the identifier of all persons
who tested the samples, and the test
results.
This information would be generated
once the test samples arrive at the
testing facility. Unlike the information
required under proposed
§ 1160.16(b)(5), this report would be an
aggregate report for all the samples

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taken from a batch. The primary
purpose of this information, along with
the information required by proposed
§ 1160.16(b)(5), would be to establish
the chain of custody for the samples
from the time they were taken through
their transfer to the testing facility
where they will be tested. FDA expects
that this information would be
integrated into the records required by
proposed § 1160.12(b) to provide
information across the batch.
Proposed § 1160.16(b)(9) explains that
each batch must be withheld from
commercial distribution until it has
been sampled and tested, and a decision
has been made by the tobacco product
manufacturer that the batch conforms to
the requirements of this part and may be
released for commercial distribution. As
discussed in proposed § 1160.18, the
manufacturer would be required to
reject any nonconforming tobacco
products unless a disposition decision
and justification to release the batch is
made after an investigation determines
that the batch meets the requirements of
this part.
As noted in the discussion of
proposed §§ 1160.12 and 1160.16, the
reporting requirements in proposed
§§ 1160.12(b), 1160.16(b)(5), and
1160.16(b)(8) are interrelated but
intended for different purposes.
Because this tobacco product standard
defines the amount of nicotine relative
to the amount of total tobacco,
manufacturers may be able to base
sampling plans on batch sizes based on
the tobacco filler. For example,
cigarettes of two different lengths made
from the same tobacco filler blend may
be able to be considered a single batch
for the purposes of calculating the
sampling plan under proposed
§ 1160.16. Testing for nonconforming
tobacco product under proposed
§ 1160.16 would require the
manufacturer to adequately sample from
the entire batch in proportion to
production. For example, if two-thirds
of the batch is produced as cigarette
length A and one-third as cigarette
length B, then two-thirds of the samples
for testing for conformance would have
to be sampled from cigarette length A
and one-third from cigarette length B.
Manufacturers that purchase bulk
tobacco filler can utilize results of filler
testing by the seller in designing and
implementing their sampling plan.
Reliance on the seller’s filler testing
would not relieve the manufacturer of
the finished tobacco product from its
responsibility to test finished tobacco
products or from responsibility for
complying with this proposed product
standard.

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5. Nonconforming Tobacco Product
(Proposed § 1160.18)
Proposed § 1160.18 would require
finished tobacco product manufacturers
to establish procedures for the control
and disposition of nonconforming
tobacco products. A ‘‘nonconforming
tobacco product’’ is proposed to be
defined as any tobacco product that
does not meet the requirements of
§ 1160.10 (nicotine level specifications)
or § 1160.30 (manufacturing code).
These procedures are necessary to help
prevent the distribution of
nonconforming tobacco products by
ensuring that all potential
nonconforming products are identified,
investigated, and segregated, and that
appropriate disposition and followup
are taken for products determined to be
nonconforming. These provisions are
also intended to help manufacturers
determine the extent of any
nonconformity and, in cases in which
nonconforming product has already
been released for distribution,
determine where it was distributed.
Proposed § 1160.18 would require
tobacco product manufacturers to
establish and maintain procedures to
identify, investigate, segregate, and
make disposition decisions (i.e.,
acceptance, rejection, rework) about
nonconforming tobacco products to
prevent their release for commercial
distribution. ‘‘Establish and maintain’’
for purposes of proposed § 1160.18
means define, document (in writing or
electronically), implement, follow, and,
when necessary, update. This section
allows manufacturers the flexibility to
determine how they would perform
these activities.
Proposed § 1160.18(a) would require
tobacco product manufacturers to
identify and segregate potential
nonconforming tobacco product to
prevent the commercial distribution of
such products prior to investigation and
disposition. Identification of potential
nonconforming product can be
accomplished in many ways (e.g.,
applying a label with the relevant
information directly to the product
container; if an electronic system is
utilized, associating the nonconforming
product information with the relevant
barcode). Identification is a critical first
step to preventing further processing,
production, or distribution of potential
nonconforming tobacco products.
Proposed § 1160.18(a) also would
require potential nonconforming
tobacco product to remain segregated
pending an investigation until it is
determined to be conforming. If a
potential nonconforming product is
determined to be nonconforming, it

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would need to remain segregated
throughout investigation and
disposition, including any rework. For
purposes of proposed part 1160,
‘‘segregation’’ means setting the
identified potential nonconforming
product apart from other product (i.e.,
placing it away from conforming
finished product). This segregation
could be accomplished by placing it in
a quarantined or specifically marked-off
area. Manufacturers should use
prudence and segregate potential
nonconforming tobacco product in a
manner that is appropriate, given the
nature of the potential nonconformity.
The requirements to identify and
segregate would be triggered upon
discovery of a potential nonconforming
product. For example, if a tobacco
product manufacturer tests samples of
finished tobacco product and
determines that the representative
samples from that batch do not conform
to the requirement set forth in proposed
§ 1160.10, the manufacturer would
determine that the batch and related
products must be identified and
segregated as they may be
nonconforming products.
Proposed § 1160.18(b) would require
tobacco product manufacturers to
investigate all potential nonconforming
tobacco products. This may include, for
example if:
• The nicotine level of a test sample
from any batch of finished tobacco
products is determined to be out of
conformance with the requirements of
proposed § 1160.10;
• FDA notifies the manufacturer that
a finished tobacco product in
commercial distribution does not
conform to the requirements of part
1160; or
• The manufacturer has come to
know through any other means that a
product is nonconforming.
In this context, a test sample would
consist of a number of individual test
units that are drawn based on a valid
scientific rationale (such as
representative sampling) and intended
to ensure that the sample accurately
reflects the material being sampled. The
purpose of a nonconforming product
investigation would be to determine the
extent and the cause, if possible, of the
nonconformity so that additional
nonconforming products are not
produced or released for commercial
distribution. In addition, it would help
to prevent recurrence of the
nonconformity.
Under proposed § 1160.18(b), the
manufacturer would be required to
conduct an investigation to determine
the extent of the nonconformity upon
identification of a nonconforming

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5109

product and, as applicable, the locations
where the nonconforming products have
been distributed. We expect the
manufacturer would be able to
determine the locations of initial
consignees (e.g., wholesalers,
distributors, retailers) where the affected
products were shipped in the event a
corrective action needs to be taken. The
investigation would have to include an
examination of all relevant processes
and controls, laboratory testing,
complaints, and any other relevant
records and sources of information
concerning the nonconforming product.
For example, a manufacturer could
determine the extent of the
nonconformity by examining records
and in-process control records for any
batches, or portions of batches, that
have been rejected during either inprocess or finished inspection for failing
to meet any or all of the product’s
specifications. Furthermore, in the event
that a similar nonconforming product is
identified in a different batch, a
manufacturer’s investigation could
include any applicable information and
records from the previous
nonconforming product investigation
that are relevant to determining the
extent of the nonconformity of the
affected batch.
Proposed § 1160.18(b) would also
require that, for products determined to
be nonconforming, the investigation
must also determine the scope and
cause of nonconformance. Examination
of relevant production processes and
controls and any other relevant records
and sources of information could help a
manufacturer determine if any other
batches are affected or if nonconforming
product has been distributed. For
example, if a manufacturer’s sampling
plan and subsequent repeat testing
under proposed § 1160.18 determines
that a batch of finished cigarettes fail to
meet the established nicotine level
specification and acceptance criteria,
the manufacturer will have to
investigate the scope and cause of the
nonconformance under this proposed
section. If the investigation determines
that the cause of the nonconformance is
attributed to cut filler received from its
supplier that contain nicotine levels that
exceed the maximum nicotine level
established by the proposed product
standard, the manufacturer must also
determine the scope of the
nonconformance, such as all batches of
finished cigarettes that used the affected
cut filler.
The manufacturer would have to
document any investigation, including
any material review, name of the
person(s) making the disposition
decisions, justification for the

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disposition decisions, results of
retesting, decisions with respect to
reworking, and followup results from
the investigation (e.g., corrective
actions). FDA may inspect these records
to verify that the manufacturer has
performed an adequate investigation.
For example, if a manufacturer uses a
laboratory to perform product testing
under proposed § 1160.12, and there is
an out-of-specification (OOS) laboratory
test result, the manufacturer would need
to investigate the OOS test result under
proposed § 1160.18(b) to determine
whether the product is nonconforming
or the OOS result is due to another
cause, such as laboratory error. Under
proposed § 1160.18(b), the investigation
would be required to include an
examination of relevant processes,
operations, and any other relevant
sources of information such as the
laboratory method and review of initial
testing and calibration of the laboratory
equipment. Such an investigation could
determine that the OOS test results
came from an aberration of the
measurement process (e.g., laboratory
error, defective testing equipment,
deviation from an established laboratory
test method) and that the potential
nonconforming tobacco product is not
nonconforming. Alternatively, an
investigation could conclude that the
OOS test result was valid, and that the
product was nonconforming as a result
of, for example, the manufacturing
process. If the manufacturer’s
nonconforming product investigation
determines that the OOS result is due to
a legitimate reason such as a testing
aberration, e.g., instrument malfunction,
and the re-test or rework establishes that
the finished tobacco product conforms
to the nicotine level of the product
standard, such product could be
released for commercial distribution.
Proposed § 1160.18(c) would require
tobacco product manufacturers to reject
a batch of a finished tobacco product if
the nicotine level of the test sample
does not meet the requirements of
§ 1160.10, unless a disposition decision
and justification to release the batch is
made after an investigation shows the
batch meets the requirements of part
1160. This might occur in the event of
a laboratory or sampling error.
Manufacturers would not be able to
simply resample a batch until the batch
conforms with the proposed maximum
nicotine level in § 1160.10 if previous
test samples did not the meet the
requirements of part 1160. If the initial
test samples of the batch were not in
conformance, the manufacturer must
conduct a nonconforming tobacco
product investigation. If the
manufacturer, for instance, determines

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that the nicotine levels were
erroneously high due to a malfunction
of the testing equipment, the
manufacturer could determine that the
batch is acceptable for release for
commercial distribution.
Proposed § 1160.18(d) would require
manufacturers to determine the
disposition of all nonconforming
tobacco products and any necessary
followup. Under proposed § 1160.18(d),
nonconforming product cannot be
released for distribution without rework
or an adequate justification (developed
and maintained in accordance with
§ 1160.32). Thus, nonconforming
product could be reworked, distributed
with an adequate justification, or
discarded. Additionally, nonconforming
product could be exported if it meets
the requirements of section 801(e)(1) of
the FD&C Act. Proposed § 1160.18(d)
also would require the manufacturer to
develop an adequate written
justification before releasing such
product for commercial distribution. An
adequate written justification would be
required to address how the
nonconforming product meets all
requirements under this part.
Nonconforming product cannot be
released for commercial distribution
without rework or an adequate written
justification supporting its release. An
example of reworking a nonconforming
product would be a manufacturer
reblending the cut filler and retesting to
ensure that it conforms to the
established product standard.
Proposed § 1160.18(e) would require
each tobacco product manufacturer to
maintain records of all activities
required under § 1160.18. Records must
include the date and time of the activity,
the individual performing the activity,
the type of activity performed, any
information that demonstrates the
requirement was met, and any data or
calculations necessary to reconstruct the
results.
C. Manufacturing Code and
Recordkeeping Requirements (Proposed
Subpart C)
1. Manufacturing Code Requirements
(Proposed § 1160.30)
Proposed § 1160.30 would require
that the packaging of all finished
tobacco products include a
manufacturing code. The manufacturing
code would allow manufacturers and
FDA to identify the production batch of
a particular finished product that has
been released for distribution. This
information is intended to help
determine the product’s history (e.g.,
batch production records) and assist
manufacturers and FDA in the event of

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a nonconforming tobacco product
investigation and any corrective actions
to be taken by a manufacturer as a result
of the investigation. The ‘‘-NS’’
designation will enable retailers to
readily identify that a finished tobacco
product conforms with this standard.
Finished tobacco products that do not
have this designation do not conform to
this standard. The manufacturing code
information also would aid FDA in
ensuring compliance with this proposed
product standard by clearly identifying
those products that conform to the
standard and linking those products to
records that substantiate their
conformance.
As stated in proposed § 1160.30(a),
the manufacturing code would be
required to be permanently affixed to
the packaging or label of all finished
tobacco products. The manufacturing
code must be affixed in a manner that
ensures it will remain on the packaging
or label through the expected duration
of use of the product by the consumer.
In addition, proposed § 1160.30(b)
would require that the manufacturing
code be permanently affixed, legible,
conspicuous, prominent, and appear in
the English language.
As stated in proposed § 1160.30(c),
the manufacturing code must contain
the following information listed in the
following order:
• The manufacturing date in 2-digit
numerical values in the month-day-year
format (MMDDYY);
• The finished tobacco product batch
number; and
• The designation ‘‘-NS’’ at the end 41
(to signify that the product was
manufactured in accordance with this
nicotine product standard).
FDA requests comment on the
manufacturing code requirements in
this proposed rule.
2. Recordkeeping Requirements
(Proposed § 1160.32)
Proposed § 1160.32 contains
recordkeeping requirements. This
information is necessary for FDA to
ascertain and confirm that finished
tobacco products are in compliance
with the proposed product standard.
First, proposed § 1160.32(a) would
require that each facility that
manufactures tobacco products subject
to this part (i.e., cigarettes and certain
other finished tobacco products)
establish and maintain records related
to compliance with this part, including
the following:
41 The ‘‘-NS’’ designation will enable retailers to
readily identify that a finished tobacco product
conforms with this standard. Finished tobacco
products that do not have this designation do not
conform to this standard.

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Federal Register / Vol. 90, No. 10 / Thursday, January 16, 2025 / Proposed Rules
(1) The source data and results of
analyses conducted to determine
conformance with § 1160.10, including
all information identified in
§ 1160.12(b);
(2) All source data used to validate an
analytical test method;
(3) All sampling plans and sampling
reports under § 1160.16;
(4) Documentation that the persons
performing sampling under § 1160.16
have sufficient education, training, and
experience to accomplish the assigned
functions; and
(5) All nonconforming tobacco
product identification, segregation,
investigation, rework, and disposition
decision procedures, including
justifications under § 1160.18.
This information is necessary for FDA
to ascertain and confirm that the
products are in compliance with the
proposed product standard.
Second, proposed § 1160.32(b)
provides certain specifications for these
records. All records required under this
part, regardless of storage medium,
would need to be attributable (i.e.,
traceable to its source), legible (i.e., in a
readable format), contemporaneously
recorded (i.e., recorded at the time of
performance), original (i.e., first capture
of the data), and accurate (i.e., correct,
truthful, complete, valid, and reliable).
In addition, these records would be
required to be written in English;
alternatively, an accurate English
translation must be made available upon
request. Documents that have been
translated from a foreign language into
English would have to be accompanied
by the foreign language version of the
document and a certification by the
manufacturer’s authorized
representative (which could be a U.S.
agent for the manufacturer) that the
English language translation is complete
and accurate, and a brief statement of
the qualifications of the person who
made the translation (e.g., education,
experience). These records would need
to be maintained at the manufacturing
establishment or another location that is
readily accessible to responsible
officials of the manufacturer and to
FDA. These records, including those not
stored at the establishment, would need
to be readily accessible to FDA during
the retention period (as discussed in
§ 1160.32(c)) for inspection and
photocopying or other means of
reproduction. Original or true copies of
these records that can be immediately
retrieved from another location,
including by computer or other
electronic means, would satisfy the
requirements of this section.
FDA expects that requested records
that are maintained offsite would be

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made available within 24 hours or, if
that is not feasible, as soon as possible
before the close of the inspection. While
the Agency expects that most records
can be made available to FDA within 24
hours, FDA recognizes that, in some
cases, additional time may be needed to
retrieve records from a third party or
archival storage. Records that can be
immediately retrieved from another
location, including by computer or other
electronic means, would meet the
requirement that the records be readily
available.
Proposed § 1160.32(c) would require
that the records kept under this part be
retained for at least 4 years from the
date of commercial distribution of the
finished tobacco product that is the
subject of the record. FDA has selected
4 years to help ensure that the records
would be available for at least one
biennial FDA inspection under sections
704 and 905(g) of the FD&C Act.
FDA believes that detailed
recordkeeping requirements are
necessary to confirm that finished
tobacco products are in compliance
with the proposed product standard. For
example, requiring manufacturers to
document their test results would
enable FDA to confirm that the
manufacturer’s analytical test method is
adequate to meet the requirements of
part 1160. In addition, requiring
nonconforming tobacco product records
would help the manufacturer and FDA
determine the extent of the
nonconformity with the product
standard and, as applicable, the
locations where the nonconforming
products have been distributed, for
example, in the event of a recall.
XI. Proposed Effective Date
In accordance with section 907(d)(2)
of the FD&C Act,42 FDA proposes that
any final rule that may issue based on
this proposal become effective 2 years
after the date of publication of the final
rule. Therefore, after the effective date,
no manufacturer or importer would be
allowed to distribute, sell, or offer for
distribution or sale within the United
States any finished tobacco product that
does not comply with proposed part
1160. After the effective date of the final
rule, manufacturers and importers
would not be allowed to enter or
introduce into domestic commerce any
finished tobacco product (i.e., cigarettes,
42 Section 907(d)(2) of the FD&C Act states that
a regulation establishing a tobacco product standard
shall set forth the date or dates upon which the
standard shall take effect, but no such regulation
may take effect before 1 year after the date of its
publication unless the Secretary determines that an
earlier effective date is necessary for the protection
of the public health.

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cigarette tobacco, RYO tobacco, cigars,
and pipe tobacco) that does not comply
with the requirements of the final rule,
irrespective of the date of manufacture.
Prior to the effective date of any final
rule that may issue based on this
proposed rule, wholesalers, retailers,
and related entities would be able to sell
available stock of finished tobacco
products that are not in compliance
with part 1160 while transitioning
inventory in anticipation of the effective
date of the final rule; however, they
would not be permitted to sell off such
stock after the effective date. FDA notes
that keeping products subject to this
proposed rule with higher nicotine
levels on the market for an extended
period of time is not in the interest of
public health.
The Nicotine ANPRM requested
comment on a proposed effective date
for a nicotine tobacco product standard.
Several comments recommended that
FDA establish a 1-year timeframe for
implementation. Other comments urged
FDA to set a 2-year timeframe for
implementation, which they stated
would be the minimum required by
section 907 of the FD&C Act due to the
impact on farmers. A few comments
argued that an implementation period
should be required for all
manufacturers, regardless of the number
of employees and/or annual revenues,
because the long time to develop the
regulation plus the implementation
period would be sufficient warning for
all companies. However, many
comments argued that the
implementation period should be
significantly longer than a 1- or 2-year
period to allow farmers, tobacco
intermediaries, and manufacturers to
develop and implement the methods of
reduction.
The comments differed as to whether
FDA should allow manufacturers any
time to sell off nonconforming tobacco
product. Several comments urged FDA
to allow manufacturer sell-off of existing
nonconforming inventory, with some
stating that a 6-month or 12-month
selloff period should be sufficient for
nonconforming product to move
through the supply chain. Nevertheless,
several comments opposed provisions
that would allow sell-off of existing
inventory, arguing that the extensive
period of the development of the
standard combined with a 2-year phasein period would give the companies
more than enough time to sell-off or
recall existing inventory. Some
comments stated that a 60-day selloff
period would be a sufficient selloff
period while still maintaining the
public health goals of the standard. FDA
requests comments, including

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supportive data and research, regarding
a selloff period (e.g., 60 days after the
effective date of the final rule) for
retailers to sell through their current
inventory of nonconforming product.
FDA considered many factors in
determining an appropriate proposed
effective date. Pursuant to section
907(d)(2) of the FD&C Act, FDA
considered the technical achievability of
compliance with the proposed product
standard and the existence of patents
that would make it impossible to
comply in the proposed 2-year
timeframe. For example, for
manufacturers that may not want to use
chemical extraction, FDA considered
how long it would likely take for a
tobacco product manufacturer to acquire
sufficient VLNC tobacco to meet the
proposed product standard. Industry
documents indicate that the timing of
availability of leaf once commercial
seed is provided is one growing season
(Ref. 657). Seed production and
germination testing can be conducted in
multiple seasons within a single year
with small-scale trial to commercial
availability taking place over the course
of 1 year (Ref. 658). For example,
industry documents indicate that a
request for purchase of low alkaloid
nicotine in March 1990 would be
expected to result in leaf delivery
during August and September (Ref.
657).
Once purchased, FDA considered
how long tobacco must be stored prior
to use in cigarettes and other combusted
tobacco products. Industry documents
suggest a minimum storage age
(particularly for burley and flue-cured
tobaccos) of around 12 months (Refs.
659 to 663). Other tobacco
manufacturers suggest that tobaccos
should be stored for 22 months,
although other studies suggest that aging
beyond 12 months has minimal effects
(Refs. 662 and 664). Industry documents
also indicate that processed tobaccos do
not appear to require long-term
inventory or aging in the same manner
as whole-leaf tobaccos (Ref. 659). FDA
requests comments, including
supportive data and research, on the
technical achievability of compliance
with the proposed product standard and
the existence of patents that would
make it impossible to comply in the
proposed 2-year timeframe.
FDA also finds that a 2-year effective
date will ‘‘minimize, consistent with the
public health, economic loss to, and
disruption or dislocation of, domestic
and international trade’’ pursuant to
section 907(d)(2) of the FD&C Act. As
discussed extensively throughout this
document, tobacco use is the leading
cause of preventable disease and death

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in the United States, and nearly all of
the adverse health effects are ultimately
the result of addiction to the nicotine in
cigarettes and certain other combusted
tobacco products, which leads to
repeated exposure to toxicants from
these products. Given the tremendous
public health risks presented—
particularly to youth who experiment
with these products, develop an
addiction to nicotine, and progress to
regular use—by combusted tobacco
products, FDA finds that any balancing
of impacts to domestic and international
trade is far outweighed by the
significant public health benefits of this
proposed product standard for all age
groups. FDA also believes that a 2-year
effective date would allow adequate
time for implementing any necessary
changes in technology to achieve the
proposed nicotine level, for making any
changes to tobacco purchasing choices
and curing methods, and for preparation
or changes needed in facilities, which
can be accomplished simultaneously. In
addition, this timeframe should provide
adequate time for manufacturers to seek
and obtain marketing authorization from
FDA for their new tobacco products.
FDA believes that this 2-year period
would provide sufficient time for a
tobacco product manufacturer to
submit, and FDA to review, applications
for new tobacco products that comply
with this provision. This is particularly
true given our expectation that most
manufacturers that reduce the nicotine
levels of their products to comply with
the proposed standard would be
submitting SE Reports, which may
decrease the amount of data required for
authorization. See section IX.B of this
document regarding pathways to market
tobacco products that have been
modified to meet the proposed standard.
FDA requests comments, including
supportive data and research, on the
timeframe for manufacturers to prepare
applications and obtain marketing
authorization from FDA for their new
tobacco products.
FDA finds this proposed effective date
to be appropriate for the protection of
the public health, given that current
nicotine levels in the finished tobacco
products cause addiction and repeated
exposure to toxicants, which ultimately
result in the majority of tobacco-related
disease and death in the United States.
Additional delay, past 2 years, would
only increase the number of youth and
young adults who transition to regular
use of cigarettes and certain other
combusted tobacco products and would
delay switching to potentially less
harmful tobacco products or cessation

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by people who currently smoke
cigarettes.
Pursuant to section 907(d)(2), FDA
requests comments by interested parties,
including manufacturers and tobacco
growers, regarding the technical
achievability of compliance with this
proposed product standard, including
information concerning the existence of
patents that make it impossible to
comply in the proposed 2-year
timeframe. FDA also requests comment
on the timeframe for manufacturers to
prepare applications and obtain
marketing authorization from FDA for
their new tobacco products. Further,
FDA requests comments and data
regarding whether 2 years is sufficient
to comply with this standard or whether
this effective date should be later to
provide additional time for
manufacturers to develop any necessary
changes in technology, facilities,
farming methods, or other factors or
business practices affecting compliance.
FDA also requests comments and
supporting data as to whether a shorter
effective date would be necessary for the
protection of the public health.
XII. Preliminary Economic Analysis of
Impacts
A. Introduction
We have examined the impacts of the
proposed rule under Executive Order
12866, Executive Order 13563,
Executive Order 14094, the Regulatory
Flexibility Act (5 U.S.C. 601–612), and
the Unfunded Mandates Reform Act of
1995 (Pub. L. 104–4).
Executive Orders 12866, 13563, and
14094 direct us to assess all benefits,
costs, and transfers of available
regulatory alternatives and, when
regulation is necessary, to select
regulatory approaches that maximize
net benefits (including potential
economic, environmental, public health
and safety, and other advantages;
distributive impacts; and equity). Rules
are ‘‘significant’’ under Executive Order
12866 Section 3(f)(1) (as amended by
Executive Order 14094) if they ‘‘have an
annual effect on the economy of $200
million or more (adjusted every 3 years
by the Administrator of [the Office of
Information and Regulatory Affairs
(OIRA)] for changes in gross domestic
product); or adversely affect in a
material way the economy, a sector of
the economy, productivity, competition,
jobs, the environment, public health or
safety, or State, local, territorial, or tribal
governments or communities.’’ OIRA
has determined that this proposed rule
is a significant regulatory action under
Executive Order 12866 Section 3(f)(1).

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The Regulatory Flexibility Act
requires us to analyze regulatory options
that would minimize any significant
impact of a rule on small entities.
Because businesses, including small
businesses, would incur costs to comply
with the proposed product standard, we
find that the proposed rule will have a
significant economic impact on a
substantial number of small entities.
The Unfunded Mandates Reform Act
of 1995 (section 202(a)) requires us to
prepare a written statement, which
includes an assessment of anticipated
costs and benefits, before proposing
‘‘any rule that includes any Federal
mandate that may result in the
expenditure by State, local, and tribal
governments, in the aggregate, or by the
private sector, of $100,000,000 or more
(adjusted annually for inflation) in any
one year.’’ The 2023 threshold after
adjustment for inflation is $183 million,
using the 2023 Implicit Price Deflator
for the Gross Domestic Product. This
proposed rule would result in an
expenditure in at least 1 year that meets
or exceeds this amount.
B. Summary of Costs and Benefits
We have developed a comprehensive
Preliminary Economic Analysis of
Impacts that assesses the impacts of the
proposed rule. The full preliminary
analysis of economic impacts is
available in the docket for this proposed
rule (Ref. 653) and at https://
www.fda.gov/about-fda/economicsstaff/regulatory-impact-analyses-ria.
The summary of costs, benefits, and
transfers is presented in table 13.
Benefits occur because the proposed
rule would discourage people who do
not use tobacco products from initiating
combusted tobacco products and
progressing to regular use and increase
cessation or switching to potentially
lower risk tobacco products among
people who currently use covered
combusted tobacco products and wish
to quit. Lower prevalence of combusted
tobacco product use would lead to
reduced health consequences for people
who formerly used combusted tobacco
products and those who were
previously exposed to secondhand
smoke. The main quantified benefits
come from averted mortality and
morbidity as a result of reduced
prevalence for people who currently use
combusted tobacco products, and
reduced mortality from reduced
exposure to secondhand smoke among
people. As described in section VIII.A
above, to assess the potential public
health impacts of a nicotine product
standard, FDA developed a population
health model using inputs derived from
available empirical evidence and expert

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opinion to estimate the impact of
changes in tobacco product initiation,
cessation, switching, and dual use on
tobacco use prevalence, morbidity, and
mortality in the United States. We use
output from this population health
model to estimate averted mortality and
preliminarily apply the value of a
statistical life while requesting feedback
about how to follow HHS guidance (see
PRIA Section II.M.6). The morbidity
estimates come from population health
model output that evaluates the health
difference for being in the state of
smoking verse not smoking.
Unquantified benefits include medical
cost savings, productivity loss savings,
reduced exposure to thirdhand smoke,
and environmental impacts. We
estimate that the present value of the
quantified benefits over a 40-year time
horizon ranges between $7.6 trillion and
$33.2 trillion with a primary estimate of
$30.6 trillion at a 2 percent discount
rate. The primary annualized
quantifiable benefits equal $1.1 trillion
at a 2 percent discount rate.
As most of the benefits from avoided
initiation among youth and young
adults due to this proposed product
standard are expected to fall outside of
the 40-year time horizon of the main
analysis, we present an extended
analysis over a period beyond the 40year time horizon to capture the impact
on youth and young adults. The present
value of quantified benefits, mostly
attributable to youth and young adults,
over this extended period range between
$8.4 trillion and $19.7 trillion with a
primary estimate of $19.1 trillion at a 2
percent discount rate. Additionally, we
present the incidence of benefits for
specific populations in the
Distributional Effects section.
We expect this proposed rule, if
finalized, to impose costs on industry to
follow the product standard, on the
broader economy to repurpose land,
labor, and capital, on consumers
impacted by the product standard, and
on FDA to enforce this product
standard. The tobacco market faces a
one-time primary cost with a present
value of $374 million at a 2 percent
discount rate (low-impact scenario
estimate of $112 million to a highimpact scenario estimate of $700
million) to read and understand the
rule.43 We also use population health
43 For the purposes of our analysis, we use the
population health model described in section VIII.A
of this document to estimate impacts for a range of
averted mortality and tobacco prevalence. The
‘‘high impact scenario’’, generally referred to as the
upper bound, corresponds to the scenario where the
policy has 95th percentile averted mortality
projected by the population health model, which
also corresponds with the lowest (5th percentile)

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model output on prevalence to estimate
the baseline and policy market size.
These estimates feed into cost estimates,
such as lost producer surplus. Producers
of combusted tobacco products incur a
primary annualized producer surplus
loss of $1.7 billion (low-impact scenario
of $0.2 billion and a high-impact
scenario of $2 billion) at a 2 percent
discount rate. We expect that some
manufacturers would reformulate their
products to comply with this standard.
We estimate a one-time reformulation
cost with present value of $0.6 billion
(low-impact scenario estimate of $8.8
billion to a high-impact scenario
estimate of $0.04 billion). Manufacturers
that reformulate would collectively
incur a one-time cost to submit their
new tobacco product for FDA review,
estimated at a present value $1 million
at a 2 percent discount rate (low-impact
scenario estimate of $15 million to a
high-impact scenario estimate of $0.1
million). In addition, these
manufacturers would also incur
recurring costs to test the nicotine level
of their products with a primary
annualized estimate of $0.3 million
(low-impact scenario estimate of $1.9
million to a high-impact scenario
estimate of $0.1 million) at a 2 percent
discount rate. We estimate a one-time
cost for FDA to review submissions for
new tobacco products at a present value
of $1.0 million at a 2 percent discount
rate (low-impact scenario estimate of
$15.3 million to a high-impact scenario
estimate of $0.1 million). The economy
faces a one-time economic transition
cost with a present value of $7.2 billion
at a 2 percent discount rate (low-impact
scenario estimate of $4.3 billion to a
high-impact scenario estimate of $9.1
billion) to reallocate productive
resources (such as labor and capital)
currently devoted to the manufacture of
NNC covered combusted tobacco
products to other tobacco products or to
non-tobacco products. We estimate
transition cost based on average
industry capital expenditures and
literature on the cost of labor transition.
Consumers of NNC covered combusted
tobacco products would face a one-time
search cost with a present value of $1.4
billion at a 2 percent discount rate (lowimpact scenario estimate of $0.46 billion
to a high-impact scenario estimate of
$2.8 billion) to find other tobacco
products or NRT as a replacement for
the prohibited NNC products. We
estimate one-time withdrawal costs for
post-policy combusted tobacco prevalence. For
some costs (product reformulation, premarket
submission, and review, and testing costs), the
‘‘upper bound’’ corresponds to the scenario with
the fewest products and, thus, would reflect the
lowest estimate of costs.

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billion to a high-impact scenario of
$76.2 billion) at a 2 percent discount
rate. The primary estimates for the
annualized costs are $2.1 billion at a 2
percent discount rate.
In addition to benefits and costs, this
rule would cause transfers from the
Federal Government, State governments,
and firms to consumers, who in turn
would spend this money in other
sectors of the economy (including
savings), in the form of reduced revenue
and tax revenue. We also estimate
transfers between or within firms to
cover shifts in user fee obligation. The
primary estimate for the annualized
transfers from the Federal Government,
in the form of reduced excise tax, ranges
from $1.4 billion to $4.3 billion, with a
primary estimate of $4.1 billion at a 2

consumers who quit tobacco products,
with a primary estimate of $1.4 billion
at a 2 percent discount rate (low-impact
scenario estimate of $0.02 billion to a
high-impact scenario estimate of $8.99
billion), at a 2 percent discount rate. We
estimate additional costs associated
with FDA enforcement of the product
standard to range from an annualized
value of $3.3 million to $7 million at a
2 percent discount rate. Unquantified
costs may include changes in consumer
surplus for some people who smoke
NNC products, including potential
utility changes for consumers who
switch from NNC to VLNC combusted
tobacco products. The present value of
the costs over a 40-year time horizon
has a primary estimate of $58 billion
(low-impact scenario estimate of $19.3

percent discount rate. The primary
estimate for the annualized transfers
from State governments, in the form of
reduced excise tax, ranges from $2.8
billion to $8.9 billion, with a primary
estimate of $8.4 billion at a 2 percent
discount rate. The primary estimate for
the annualized transfers from the firms,
in the form of reduced revenue, is $20.0
billion at a 2 percent discount rate (lowimpact scenario of $6.2 billion; highimpact scenario of $17.6 billion). The
primary estimate for the annualized user
fee obligation shifted from combusted
tobacco products to noncombusted
tobacco products has a range from $26.3
million to $461.1 million with a primary
estimate of $332.6 million at a 2 percent
discount rate. Transfers are summarized
in table 13.

TABLE 13—SUMMARY OF BENEFITS, COSTS, AND DISTRIBUTIONAL EFFECTS OF THE PROPOSED RULE
[Millions of 2023 dollars over a 40-year time horizon]
Primary
estimate

Category

Low
estimate

High
estimate

Dollar
year

Discount
rate
(%)

2023
....................

2
................

Time horizon

Notes

Benefits
$273,521
....................

$1,190,582
....................

See footnote.44

Annualized monetized benefits ...................
Annualized quantified, but non-monetized,
benefits.

$1,097,053
....................

2025–2064 (40 years)

Unquantified benefits ..................................

Medical cost savings, productivity loss savings, reductions in smoking-related fires (excluding mortality), reduced litter,
and other associated harms to the environment
Costs

Annualized monetized costs .......................
Annualized quantified, but non-monetized,
costs.

2,077
....................

690
....................

2,729
....................

2023
....................

2
................

2025–2064 (40 years).

Unquantified costs .......................................

Changes in consumer surplus for some people who smoke normal nicotine content combusted tobacco products,
including potential utility changes for consumers who switch from NNC to VLNC combusted tobacco products.
Transfers

Annualized monetized Federal budgetary
transfers.
Bearers of transfer gain and loss? .............

4,092

8,414

2

I

2025–2064 (40 years).

I

I

8,877

I

2023

I

2

I

2025–2064 (40 years).

I

I

Transfers of Excise Tax Revenues from State Governments to Consumers
19,964

I

6,235

I

17,603

2023

I

I

2

I 2025–2064 (40 years). I

2

I 2025–2064 (40 years). I

Transfers of Revenues from Tobacco Firms to Consumers

Other annualized monetized transfers ........
Bearers of transfer gain and loss? .............

2023

I

2,848

I

Other annualized monetized transfers ........
Bearers of transfer gain and loss? .............

4,313

I

Transfers of Excise Tax Revenues from Federal Governments to Consumers

Annualized monetized State budgetary
transfers.
Bearers of transfer gain and loss? .............

1,386

I

333

I

26

461

I

2023

I

I

Transfers from User Fees Owed by Combusted Tobacco Firms to s Owed by Noncombusted Tobacco Firms
Net benefits

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Annualized monetized net benefits .............

1,094,976

I

272,831

I

1,187,853

Category

2023

I

I

2

I 2025–2064 (40 years).

Effects

Notes

Effects on State, local, or Tribal governments.

Significant transfer of tax revenues for State governments. Potential transfer of tax revenue for
local and Tribal governments.

Effects on small businesses .......................

Significant revenue reductions and compliance costs for small, combusted tobacco product
manufacturers. We expect most small, combusted manufacturers would shut down or switch
industries.

Effects on wages .........................................

No significant wage impacts.

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TABLE 13—SUMMARY OF BENEFITS, COSTS, AND DISTRIBUTIONAL EFFECTS OF THE PROPOSED RULE—Continued
[Millions of 2023 dollars over a 40-year time horizon]
Primary
estimate

Category

I

Low
estimate

I

High
estimate

Category

XIII. Analysis of Environmental Impact
The Agency has carefully considered
the potential environmental effects of
this action. FDA has concluded that the
action will not have a significant impact
on the human environment, and that an
environmental impact statement is not
required. The Agency’s finding of no
significant impact and the evidence
supporting that finding is available in
the docket for this proposed rule (Refs.
665 and 666) and may be seen in
Dockets Management Staff (see
ADDRESSES) between 9 a.m. and 4 p.m.,
Monday through Friday; it is also
available electronically at https://
www.regulations.gov. Under FDA’s
regulations implementing the National
Environmental Policy Act (21 CFR part
25), an action of this type would require
an environmental assessment under 21
CFR 25.20.
XIV. Paperwork Reduction Act of 1995
This proposed rule contains
information collection provisions that
are subject to review by the Office of
Management and Budget (OMB) under
the Paperwork Reduction Act of 1995
(44 U.S.C. 3501–3521). A description of
these provisions is given in the
Description section of this document

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I

Time horizon

Notes
Notes

Anticipated growth in the noncombusted tobacco sector.

We request comment on our estimates
of benefits, costs, and transfers of this
proposed rule.

44 FDA notes that these results hinge on an expert
elicitation in which the experts were provided peer
reviewed literature on VLNC and NNC cigarette use
in experiments. The expert elicitation and much of
the literature specifically referenced the nicotine
level of 0.4 mg nicotine per gram total tobacco.
However, in 22nd Century Group, Inc.’s modified
risk tobacco product applications, the company
reported that after 9 years of sampling by the
company, the average nicotine content of its
genetically engineered VLNC tobacco is 0.6 mg
nicotine per gram of total tobacco, with a range of
0.4 to 0.7 mg nicotine per gram of total tobacco. It
is likely that the Quest and SPECTRUM Nicotine
Research Cigarettes, used throughout the scientific
literature, also contained between 0.4 to 0.7 mg
nicotine per gram of total tobacco (Ref. 257). This
suggests the literature the experts reviewed studied
cigarettes in the range of 0.4–0.7 mg nicotine per
gram total tobacco as opposed to only 0.4 mg
nicotine per gram total tobacco. Therefore, the
results of the expert elicitation are still applicable
to a nicotine level of 0.7 mg nicotine per gram total
tobacco. For reference, nicotine content in the top
100 cigarette brands (2017) is 17.2 mg nicotine per
gram total tobacco (Ref. 9).

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Discount
rate
(%)

Effects

Effects on growth ........................................

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year

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with an estimate of the annual
reporting, recordkeeping, and thirdparty disclosure burden. Included in the
estimate is the time for reviewing
instructions, searching existing data
sources, gathering and maintaining the
data needed, and completing and
reviewing each collection of
information. If finalized, this proposed
rule will seek approval of a new
information collection.
FDA invites comments on these
topics: (1) whether the proposed
collection of information is necessary
for the proper performance of FDA’s
functions, including whether the
information will have practical utility;
(2) the accuracy of FDA’s estimate of the
burden of the proposed collection of
information, including the validity of
the methodology and assumptions used;
(3) ways to enhance the quality, utility,
and clarity of the information to be
collected; (4) ways to minimize the
burden of the collection of information
on respondents, including through the
use of automated collection techniques,
when appropriate, and other forms of
information technology; and (5) the
standard and customary business
practices of tobacco manufacturers as it
relates to capital, operating, and
maintenance costs associated with this
collection of information.
Title: Tobacco Product Standard for
Nicotine Yield of Cigarettes and Certain
Other Combusted Tobacco Products
(0910–NEW).
Description: The FD&C Act authorizes
FDA to adopt tobacco product
standards, including product standards
that include provisions for nicotine
yields and for the reduction or
elimination of other constituents
(including smoke constituents) or
harmful components (section
907(a)(3)(A) and (4) of the FD&C Act).
FDA is proposing to limit nicotine yield
by setting a maximum nicotine content
level for finished cigarettes and certain
other finished combusted tobacco
products not to exceed 0.70 mg of
nicotine per gram of total tobacco.
Subpart A contains the general
provisions of this proposed product
standard including scope, prohibited
activities, and definitions.

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Subpart B contains the proposed
product standard requirements
pertaining to finished tobacco products
that cover product testing (§ 1160.12),
sampling plans (§ 1160.16), analytical
test methods (§ 1160.14),
nonconforming tobacco products
(§ 1160.18), package label requirements
(§ 1160.30) and recordkeeping
requirements (§ 1160.32).
Subpart C contains manufacturing
code (§ 1160.14) and recordkeeping
(§ 1160.32) requirements.
Proposed § 1160.12 contains
provisions for the testing of finished
tobacco products that would be subject
to this proposed rule. Specifically,
proposed § 1160.12(a) would require
that tobacco product manufacturers
conduct testing on each batch of
finished tobacco products.
Proposed § 1160.12(b) would require
that a full report of the source data and
results of all batch testing be maintained
by the tobacco product manufacturer.
Based on FDA subject matter expertise
and experience from tobacco
inspections, we expect that
manufacturers would discuss in these
reports how their product is batched.
These reports would be generated for
test samples from each batch and would
not be required for each individual
finished tobacco product. This report
would have to include the following
information:
(1) Full identification of the finished
tobacco product that is the subject of the
report, including the product category,
subcategory, product name (brand and
subbrand), package type, package
quantity, and nicotine source;
(2) Nicotine level of each sample
tested from the batch and standard
deviation;
(3) The batch manufacturing date and
location, including facility name and
address, for each sample;
(4) The testing date and location,
including the facility name and address;
(5) The manufacturing code of each
sample tested (in accordance with
proposed § 1160.30(c));
(6) The test method and sampling
procedure used;
(7) Names and qualifications of the
person(s) conducting the testing and any
laboratory accreditation;

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(8) The equipment used (including
documentation to show that the
equipment is appropriate for its
intended purpose and has been
calibrated to ensure accurate and
reliable results); and
(9) The criteria used to make a
decision to accept or reject each batch
and the decision made with respect to
each batch (e.g., accept, reject) based on
the results of the product testing. This
information would constitute the
documentation of the source data and
actual results of the product testing
conducted on each batch.
The main purpose of this report
would be to verify that products subject
to this proposed product standard do
not exceed the maximum nicotine level
and to document the company’s
decision for each batch with respect to
acceptance, rejection, and reworking of
the products. FDA expects that
information collected pursuant to
proposed § 1160.12(b) would be
integrated with the proposed
§ 1160.18(b) records (i.e., proposed
§ 1160.12(b) records regarding the
product being tested, including, for
example, the product category and
subcategory, brand and subbrand,
packaging information, nicotine source,
manufacturing date, and the
manufacturing code would inform the
1160.18(b) investigation). These
proposed § 1160.12(b) records also
would document the ultimate
disposition of the batch based on the
testing of the representative samples.
Proposed § 1160.14 would require
that manufacturers analyze the nicotine
levels of cigarettes and certain other
finished combusted tobacco products
covered by the rule using a validated
analytical test method. Manufacturers
would be required to demonstrate that
the test method used was validated in
an analytical test laboratory. Proposed
§ 1160.16 would require each tobacco
product manufacturer to design and
implement a sampling plan that covers
each finished tobacco product that it
manufactures. This sampling plan
would provide procedures for the
manufacturer to select samples to
demonstrate conformance to the
proposed maximum nicotine level
requirement. The required procedures
would help ensure that products that
exceed the maximum level of nicotine
are not sold or distributed to consumers.
This provision also explains that the
sampling plan must ensure samples
taken are representative of an entire
batch and are randomly selected and
collected from each batch for testing.
This section would also require test
samples from each batch be collected
and examined in accordance with

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certain procedures (proposed
§ 1160.16(b)). Each test sample would
need to be identified so that the
following information can be
determined:
• Full identification of the finished
tobacco product sampled, including
product category, subcategory, product
name (brand and subbrand), package
type, package quantity, and nicotine
source;
• The manufacturing code;
• The date on which the sample was
taken;
• The sampling location (including
the address of the facility and specific
location within the facility where the
sample was taken);
• The name of the person(s) who
collected the sample; and
• The location where the sample will
be tested (including the facility name
and address).
Proposed § 1160.18 would require
finished tobacco product manufacturers
to establish procedures for the control
and disposition of nonconforming
tobacco products. The proposed
procedures would require tobacco
product manufacturers to establish and
maintain procedures to identify,
investigate, segregate, and make
disposition decisions (i.e., acceptance,
rejection, rework) about nonconforming
finished tobacco products to prevent
their release for commercial
distribution. FDA interprets ‘‘establish
and maintain’’ for purposes of proposed
§ 1160.18 to mean define, document (in
writing or electronically), implement,
follow, and, when necessary, update.
Identification of potential
nonconforming product (i.e., a tobacco
product that does not conform to the
proposed maximum nicotine level
requirement) can be accomplished in
many ways (e.g., applying a label with
the relevant information directly to the
product container; if an electronic
system is utilized, associating the
nonconforming product information
with the relevant barcode). If a potential
nonconforming product is determined
to be nonconforming, it would need to
remain segregated throughout
investigation and disposition, including
any rework. For purposes of proposed
part 1160, ‘‘segregation’’ means setting
the identified potential nonconforming
product apart from other product (i.e.,
placing it away from conforming
finished product). This segregation
could be accomplished by placing it in
a quarantined or specifically marked-off
area.
The manufacturer would be required
to conduct an investigation to determine
the extent of the nonconformity upon
identification of a nonconforming

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product and, as applicable, the locations
where the nonconforming products have
been distributed. We expect the
manufacturer would be able to
determine the locations of initial
consignees (e.g., wholesalers,
distributors, retailers) where the affected
products were shipped in the event a
corrective action needs to be taken. The
investigation would have to include an
examination of all relevant processes
and controls, laboratory testing,
complaints, and any other relevant
records and sources of information
concerning the nonconforming product.
Tobacco product manufacturers would
be required to reject a batch of a
finished tobacco product if the nicotine
level of the test sample does not meet
the requirements unless a disposition
decision and justification to release the
batch is made after an investigation
shows the batch meets the requirements.
Tobacco product manufacturers
would be required to determine the
disposition of all nonconforming
tobacco products and any necessary
followup. Nonconforming product
cannot be released for commercial
distribution without rework or an
adequate justification (developed and
maintained in accordance with
§ 1160.32). Thus, nonconforming
product could be reworked, distributed
with an adequate justification, or
discarded. An adequate written
justification would be required to
address how the nonconforming
product meets all requirements under
this part.
Proposed § 1160.18(e) would require
each tobacco product manufacturer to
maintain records of all activities
required under § 1160.18. Records must
include the date and time of the activity,
the individual performing the activity,
the type of activity performed, any
information that demonstrates the
requirement was met, and any data or
calculations necessary to reconstruct the
results.
FDA expects that information
collected pursuant to proposed
§ 1160.12(b) would be integrated with
the proposed § 1160.18(b) records (i.e.,
proposed § 1160.12(b) records regarding
the product being tested, including, for
example, the product category and
subcategory, brand and subbrand,
packaging information, nicotine source,
manufacturing date, and the
manufacturing code would inform the
1160.18(b) investigation). These
proposed § 1160.12(b) records also
would document the ultimate
disposition of the batch based on the
testing of the representative samples.
Proposed § 1160.30 would require the
use of a manufacturing code to serve as

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a common identifier for production and
distribution records. The purpose of the
manufacturing code is to allow
manufacturers and FDA to identify the
production batch of a particular finished
product that has been released for
distribution. This information is
intended to help determine the
product’s history (e.g., batch production
records) and assist manufacturers and
FDA in the event of a nonconforming
product investigation and any corrective
actions to be taken as a result of the
investigation.
The manufacturing code would be
required to be permanently affixed to
the packaging or labeling of all finished
tobacco products. The manufacturing
code must be affixed in a manner that
ensures it will remain on the packaging
or label through the expected duration
of use of the product by the consumer.
In addition, proposed § 1160.30(b)
would require that the manufacturing
code be permanently affixed, legible,
conspicuous, prominent, and appear in
the English language.
As stated in proposed § 1160.30(c),
the manufacturing code must contain
the following information listed in the
following order:
• The manufacturing date in 2-digit
numerical values in the month-day-year
format (MMDDYY);
• The finished tobacco product batch
number; and
• The designation ‘‘-NS’’ at the end.
The manufacturing code would allow
manufacturers and FDA to identify the
production batch of a particular finished
product that has been released for
distribution. This information is
intended to help determine the
product’s history (e.g., batch production
records) and assist manufacturers and
FDA in the event of a nonconforming
product investigation and any corrective
actions to be taken as a result of the
investigation.
Proposed § 1160.32 contains
recordkeeping requirements that are
necessary for FDA to ascertain and
confirm that finished tobacco products
are in compliance with the proposed
product standard. The proposed product
standard would require that
manufacturers establish and maintain
records regarding the results of testing
conducted on each batch to determine
conformance with the proposed
standard. In addition, this proposed
product standard would require that
manufacturers maintain records of batch
testing, source data for analytical test
method validation, sampling plans and
sampling procedures, and
nonconforming tobacco products.
First, proposed § 1160.32(a) would
require that each facility that

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manufactures tobacco products subject
to this part (i.e., finished tobacco
products) establish and maintain
records related to compliance with this
part, including the following:
(1) The source data and results of
analyses conducted to determine
conformance with § 1160.10, including
all information identified in
§ 1160.12(b);
(2) All source data used for analytical
test method validation;
(3) All sampling plans and sampling
reports under § 1160.16;
(4) Documentation that the persons
performing sampling under § 1160.16
have sufficient education, training, and
experience to accomplish the assigned
functions; and
(5) All nonconforming tobacco
product identification, segregation,
investigation, rework, and disposition
decision procedures, including
justifications, under § 1160.18. This
information is necessary for FDA to
ascertain and confirm that the products
are in compliance with the proposed
product standard.
Second, proposed § 1160.32(b)
provides certain specifications for these
records. All records required under this
part, regardless of storage medium,
would need to be attributable, legible,
contemporaneously recorded, original,
and accurate. In addition, these records
would be required to be written in
English; alternatively, an accurate
English translation must be made
available upon request. Documents that
have been translated from a foreign
language into English would have to be
accompanied by the foreign language
version of the document and a
certification by the manufacturer’s
authorized representative (which could
be a U.S. agent for the manufacturer)
that the English language translation is
complete and accurate, and a brief
statement of the qualifications of the
person who made the translation (e.g.,
education, experience). These records
would need to be maintained at the
manufacturing establishment or another
location that is readily accessible to
responsible officials of the manufacturer
and to FDA.
Proposed § 1160.32(c) would require
that the records kept under this part be
retained for at least 4 years from the
date of commercial distribution of the
finished tobacco product that is the
subject of the record. FDA has selected
4 years as a means to help ensure that
the records would be available for at
least one biennial FDA inspection under
sections 704 and 905(g) of the FD&C
Act.
FDA believes that detailed
recordkeeping requirements are

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5117

necessary to confirm that finished
tobacco products are in compliance
with the proposed product standard. For
example, requiring manufacturers to
document their test results would
enable FDA to confirm the
manufacturer’s test method is adequate
to meet the requirements of part 1160.
In addition, requiring nonconforming
product records would help the
manufacturer and FDA determine the
extent of the nonconformity with the
product standard and, as applicable, the
locations where the nonconforming
products have been distributed; for
example, in the event of a recall.
Description of Respondents: The
information collection requirements in
the proposed standard would apply to
tobacco product manufacturers, which
means any person, including a repacker
or relabeler, who (1) manufactures,
fabricates, assembles, processes, or
labels a tobacco product; or (2) imports
a finished tobacco product for sale or
distribution in the United States.
Specifically, the information collection
would apply to manufacturers of
cigarettes (other than noncombusted
cigarettes, such as heated tobacco
products that meet the definition of a
cigarette), cigarette tobacco, roll-yourown (RYO) tobacco, cigars (including
little cigars, cigarillos, and large cigars,
but excluding ‘‘premium cigars’’), and
pipe tobacco (other than waterpipe
tobacco). FDA recognizes that many of
the proposed provisions of the proposed
rule are in accordance with the quality
control and manufacturing practices
that manufacturers have already
adopted on a voluntary basis.
Application requirements are set by the
final Substantial Equivalence (0910–
0673) and Premarket Tobacco Product
Application (0910–0879) rules. For
products covered by this proposed
standard, we expect most manufacturers
will seek authorization using the
substantial equivalence premarket
pathway, which may decrease the
amount of data required for
authorization. See section IX.B of this
document regarding pathways to market
tobacco products that have been
modified to meet the proposed standard.
Based on FDA’s subject matter expertise
and industry data, we recognize that
between 85 and 90 percent of all
cigarette production is conducted by
large manufacturers. We also find that
the other tobacco product categories,
such as non-premium cigars, pipe, and
RYO tobacco, have similar levels of
market concentration. We assume that
large tobacco product manufacturers
represent the bulk of tobacco product

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production capacity and so represent
the majority of recordkeeping burden.
The proposed provision § 1160.12
(batch testing), is part of standard and
customary business practices of tobacco
manufacturers. As such, there are no
capital costs or operating and
maintenance costs associated with this
collection of information. Batch testing
is conducted either by the manufacturer
in-house or by a 3rd-party accredited
laboratory. If sent to a 3rd-party
laboratory, we do not expect any capital,
operating, or maintenance costs
associated with batch testing to be
incurred by the manufacturer. We
expect a manufacturer would only test
their products in-house if they already
possess an in-house laboratory
accredited to conduct scientific tests.
We would not anticipate capital,
operating, or maintenance costs for
these in-house laboratories as capital
and maintenance are components of
maintaining accreditation. We do not
expect any manufacturers currently
without an in-house laboratory to newly
establish an in-house accredited
laboratory as a result of this product
standard.
The proposed provision § 1160.14
(analytical test method), is also part of
standard and customary business
practices of tobacco manufacturers. As
such, there are no capital costs or
operating and maintenance costs
associated with this collection of

information. Manufacturers are already
required to submit test results of
analytical testing for nicotine and other
relevant harmful and potentially
harmful constituents (HPHCs) as part of
premarket submissions. As the
establishment and use of analytical
testing is already generally required for
premarket submissions, we do not
anticipate capital, operating, or
maintenance cost from these provisions.
The proposed provision § 1160.16
(sampling plans), is part of standard and
customary business practices of tobacco
manufacturers. As such, there are no
capital costs or operating and
maintenance costs associated with this
collection of information. Manufacturers
already routinely conduct analytical
testing to check for consistency in their
finished products. To conduct such
testing, manufacturers would have
needed to establish a sampling plan to
generate a representative sample of their
product for testing. As such, we do not
anticipate capital, operating, or
maintenance cost from these provisions.
The proposed provision § 1160.18
(nonconforming tobacco products), is
part of standard and customary business
practices of tobacco manufacturers. As
such, there are no capital costs or
operating and maintenance costs
associated with this collection of
information. Based on FDA subject
matter expertise and inspections, we
find that almost all manufacturers

already check for consistency and
conformance of their products and
rework product as necessary to supply
information for internal quality checks
and distribution purposes, we do not
anticipate capital, operating, or
maintenance cost from these provisions.
The proposed provision § 1160.30
(manufacturing code labeling), is part of
standard and customary business
practices of tobacco manufacturers. As
such, there are no capital costs or
operating and maintenance costs
associated with this collection of
information. Based on FDA subject
matter expertise and industry
information, we find that almost all
manufacturers already apply a
manufacturing code to their products.
Because a manufacturing code also
supplies information that the
manufacturer needs for internal quality
and distribution purposes (standard and
customary practices), we do not
anticipate additional capital, operating,
or maintenance cost from these
provisions.
FDA specifically invites comments on
our discussion of the standard and
customary business practices of tobacco
manufacturers as it relates to capital,
operating, and maintenance costs
associated with this collection of
information.
FDA estimates the burden of this
collection of information as follows:

TABLE 14—ESTIMATED ANNUAL RECORDKEEPING BURDEN 45
Number of
recordkeepers

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21 CFR section or activity
§ 1160.12 Product Testing .........................................
§ 1160.14 Analytical Test Method ..............................
§ 1160.16 Sampling Plan ...........................................
§ 1160.18 Procedures for Nonconforming Tobacco
Products and Related Investigations; Procedures
for Control and Disposition of Nonconforming Tobacco Products .......................................................
§ 1160.30 Package Label Requirements (Manufacturing Code) ............................................................
§ 1160.32 Recordkeeping Requirements (Batch
Testing Records) ....................................................
Total Annual Burden ...........................................

Table 14 displays the recordkeeping
burden associated with this proposed
rule. Included in this estimate is the
recordkeeping burden for establishing
and maintaining records regarding the
results of testing conducted on each
batch to determine conformance with
the proposed standard, sampling plans
45 There are no capital costs or operating and
maintenance costs associated with this collection of
information.

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Number of
records per
recordkeeper

Total annual
records

Total hours

143
143
143

50.84
4
4

7,270
572
572

9
1
1

65,430
572
572

143

1

143

14

2,002

143

4

572

7

4,004

143

50.84

7,270

6

43,620

..........................

..........................

..........................

..........................

116,200

and sampling procedures, and records
related to manufacturing controls.
FDA’s burden estimates are based on
CTP’s Tobacco Registration and Listing
Module Next Generation (TRLM NG)
data and Dun & Bradstreet firm data
(D&B). The requirements in the Tobacco
Product Standard for Nicotine Yield of
Cigarettes and Certain Other Combusted
Tobacco Products proposed rule would
apply to both domestic and foreign

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burden per
recordkeeping

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manufacturers of finished tobacco
products that are distributed or sold in
the United States. We estimate the
number of affected entities, by tobacco
product category and size of operation
group. We estimate that there are a total
of 143 entities potentially affected by
the proposed rule (domestic
manufacturers and importers of
impacted tobacco products, including
133 manufacturers and importers of

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cigarettes, cigars, pipe tobacco, and RYO
tobacco and 10 dual operation facilities
that manufacture both combusted and
noncombusted products). For purposes
of the PRA estimates, FDA used the
entities affected and a weighted average
of the median hours to calculate the
respondents and total burden hours.
We estimate a total of 7,270 batches
per year are required to be tested under
§ 1160.12 (product testing). Based on
information from inspections and other
FDA subject matter expertise, including
typical batch sizes and projected
combusted tobacco production by year,
FDA estimates that there will be 50.84
records per recordkeeper with 9 hours
of average burden per recordkeeping.
FDA assumes respondents will establish
a total of 7,270 annual records for a total
of annual 65,430 hours.
Based on information from
inspections and other FDA subject
matter expertise, we expect that core
blends are the products that
manufacturers will choose to
reformulate to meet the product
standard. Manufacturers would incur a
burden to establish an analytical test
method and sampling plan for each
reformulated core blend. FDA experts
assume that each manufacturer, on
average, utilizes four different core
blends per tobacco category that they
manufacture. Under § 1160.14
(analytical test method), respondents

would determine an analytical test
method to use for complying with the
product standard. During validation of
the analytical test method within the
laboratory to be used, the respondent
would record and collect the data
generated and maintain these records.
FDA estimates there will be 4 records
per recordkeeper with 1 hour of average
burden per recordkeeping and
respondents will establish a total of 572
annual records for a total of annual 572
hours. Under § 1160.16 (sampling plan),
FDA estimates there will be 4 records
per recordkeeper with 1 hour of average
burden per recordkeeping. FDA assumes
respondents will establish a total of 572
annual records for a total of annual
records for a total of annual 572 hours.
Under § 1160.18 (procedures for
nonconforming products), FDA assumes
there will be 1 record per recordkeeper
with 14 hours of average burden per
recordkeeping for a total of 143 annual
records and a total of annual 2,002
hours. This estimate is based on
information from tobacco inspections
and FDA experience in developing good
manufacturing practices in non-tobacco
industries. Further, as stated above,
based on FDA subject matter expertise
and inspections, we find that almost all
manufacturers already check for
consistency and conformance of their
products and rework product as
necessary to supply information for

5119

internal quality checks and distribution
purposes.
Proposed § 1160.30 would require
manufacturers to apply a manufacturing
code to the packaging and label of
tobacco products. Based on FDA subject
matter expertise and market tracking
information, we find that almost all
manufacturers already apply a
manufacturing code to their products.
FDA assumes 4 records per
recordkeeper with 7 hours of average
burden per recordkeeping, and a total of
572 annual records for a total of annual
4,004 hours.
Under § 1160.32 (batch testing
records), FDA assumes 50.84 records
per recordkeeper with 6 hours of
average burden per recordkeeping. This
estimate is based on establishing the
format and maintaining batch test
records for detailed recordkeeping
requirements, including English
translation and accessibility, that are
necessary to confirm that finished
tobacco products are in compliance
with the proposed product standard.
FDA assumes that respondents will
maintain a total of 7,270 annual records
for a total of annual 43,620 hours.
FDA expects the additional one-time
(i.e., occurring only in the first year)
reporting burden for the information
collection that will result from this rule,
to be as follows:

TABLE 15—ESTIMATED ONE-TIME REPORTING BURDEN
Number of
respondents

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Activity

Number of
responses per
respondent

Average
burden per
response

Total annual
responses

Total hours

Review and familiarization with the rule ....................

1,465

1

1,465

10

14,650

Total One-Time Burden ......................................

..........................

..........................

..........................

..........................

14,650

Based on FDA subject matter
expertise, we assume that all entities
affected by this proposed rule would
spend time to read and understand the
rule, resulting in a one-time reporting
burden. FDA estimates that there will be
293 entities and 5 individuals at each
entity that will read the final rule. It is
estimated that each respondent will
spend up to 10 hours reading and
understanding the rule for a total of
14,650 one-time burden hours. Per the
requirements of this proposed rule, FDA
estimates the total burden will be
130,850 hours (116,200 + 14,650).
FDA invites comments on the
estimates in this section and specifically
any burden specific to small
manufacturers to whom this proposed
standard would apply. To ensure that
comments on information collection are

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received, OMB recommends that written
comments be submitted through
reginfo.gov (see ADDRESSES). All
comments should be identified with the
title of the information collection.
In compliance with the Paperwork
Reduction Act of 1995 (44 U.S.C.
3407(d)), we have submitted the
information collection provisions of this
proposed rule to OMB for review. These
information collection requirements
will not be effective until FDA
publishes a final rule, OMB approves
the information collection requirements,
and the rule goes into effect. FDA will
announce OMB approval of these
requirements in the Federal Register.
XV. Federalism
We have analyzed this proposed rule
in accordance with the principles set

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forth in Executive Order 13132. Section
4(a) of the Executive order requires
Agencies to ‘‘construe . . . a Federal
statute to preempt State law only where
the statute contains an express
preemption provision or there is some
other clear evidence that the Congress
intended preemption of State law, or
where the exercise of State authority
conflicts with the exercise of Federal
authority under the Federal statute.’’ We
have determined that the proposed rule,
if finalized, would not contain policies
that have substantial direct effects on
the States, on the relationship between
the National Government and the States,
or on the distribution of power and
responsibilities among the various
levels of government. Accordingly, the
Agency tentatively concludes that the
rule does not contain policies that have

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Federal Register / Vol. 90, No. 10 / Thursday, January 16, 2025 / Proposed Rules

federalism implications as defined in
the Executive order and, consequently,
a federalism summary impact statement
is not required.
This rule is being issued under
section 907 of the FD&C Act, which
enables FDA to prescribe regulations
relating to tobacco product standards,
and the sale and distribution restriction
in this rule is also being issued under
section 906(d) of the FD&C Act, which
enables FDA to prescribe regulations
restricting the sale and distribution of a
tobacco product. If this proposed rule is
made final, the final rule would create
requirements whose preemptive effect
would be governed by section 916 of the
FD&C Act (21 U.S.C. 387p) entitled
‘‘Preservation of State and local
authority.’’
Section 916 of the FD&C Act broadly
preserves the authority of States and
localities to protect the public against
the harms of tobacco use. Specifically,
section 916(a)(1) of the FD&C Act
establishes a general presumption that
FDA requirements do not preempt or
otherwise limit the authority of States,
localities, or tribes to, among other
things, enact and enforce laws regarding
tobacco products that relate to certain
activities (e.g., sale, distribution) and
that are in addition to or more stringent
than requirements established under
chapter IX of the FD&C Act.
Section 916(a)(2)(A) of the FD&C Act
is an express preemption provision that
establishes an exception to the
preservation of State and local
governmental authority over tobacco
products established in section
916(a)(1). Specifically, section
916(a)(2)(A) of the FD&C Act provides
that ‘‘[n]o State or political subdivision
of a State may establish or continue in
effect with respect to a tobacco product
any requirement which is different
from, or in addition to, any requirement
under the provisions of this chapter
relating to tobacco product standards
. . . .’’
However, section 916(a)(2)(B) limits
the applicability of section 916(a)(2)(A)
of the FD&C Act, narrowing the scope of
State and local requirements that are
subject to express preemption.
Paragraph (a)(2)(B) provides that
preemption under paragraph (a)(2)(A)
does not apply to State or local
‘‘requirements relating to the sale,
distribution, possession, information
reporting to the State, exposure to,
access to, the advertising and promotion
of, or use of, tobacco products by
individuals of any age, or relating to fire
safety standards for tobacco products.’’
If this proposed rule is finalized as
proposed, the final rule would create
requirements that fall within the scope

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of section 916(a)(2)(A) of the FD&C Act
because they are ‘‘requirements under
the provisions of the chapter relating to
tobacco product standards.’’
Accordingly, the preemptive effect of
those requirements on any State or local
requirement would be determined by
the nature of the State or local
requirement at issue—specifically,
whether the State or local requirement
is preserved under section 916(a)(1) of
the FD&C Act, and/or excepted under
section 916(a)(2)(B) of the FD&C Act
(such as if it relates to the ‘‘sale,
distribution, possession, information
reporting to the State, exposure to,
access to, the advertising and promotion
of, or use of, tobacco products’’). State
and local prohibitions on the sale and
distribution of tobacco products would
not be preempted by this rule, if
finalized, because such prohibitions
would be preserved by section 916(a)(1)
of the FD&C Act or, as applicable,
excepted from express preemption by
section 916(a)(2)(B) of the FD&C Act.
FDA invites comments on how State or
local laws may be implicated if this
proposed rule is finalized.
XVI. Severability
In accordance with section 5 of the
Tobacco Control Act, which provides
for the severability of, inter alia, all
‘‘regulations promulgated under’’ the
authorities provided by that Act, FDA
would consider the various
requirements and prohibitions
established by this rule, if finalized, to
be severable. It is FDA’s interpretation
and position that the invalidity of any
provision of a final rule would not affect
the validity of any other part of the rule.
In the event any court or other lawful
authority were to temporarily or
permanently invalidate, restrain, enjoin,
or suspend any provision of a final rule,
FDA intends for the remaining parts to
continue to be valid. Additionally, as
further stated in section 5 of the
Tobacco Control Act, if certain
applications of a final rule to persons or
circumstances (discussed in the
preamble or otherwise) are held to be
invalid, application of such provisions
to any other person or circumstance will
not be affected and will continue to be
enforced to the fullest extent possible.
Each provision of the rule is
independently supported by data and
analysis as described or referenced in
this preamble and, if issued separately,
would remain a proper exercise of FDA
authority.
XVII. Consultation and Coordination
With Indian Tribal Governments
We have analyzed this proposed rule
in accordance with the principles set

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forth in Executive Order 13175. We
have tentatively determined that the
rule contains policies that may have a
substantial direct effect on one or more
Indian Tribes, on the relationship
between the Federal Government and
Indian Tribes, or on the distribution of
power and responsibilities between the
Federal Government and Indian Tribes.
We expect some tribal governments to
be impacted given that some are
manufacturers and retailers of cigarettes.
The Agency solicits comments from
tribal officials on any potential impact
on Indian Tribes from this proposed
action.
XVIII. References
The following references marked with
an asterisk (*) are on display at the
Dockets Management Staff (see
ADDRESSES) and are available for
viewing by interested persons between
9 a.m. and 4 p.m., Monday through
Friday; they also are available
electronically at https://
www.regulations.gov. References
without asterisks are not on public
display at https://www.regulations.gov
because they have copyright restriction.
Some may be available at the website
address, if listed. References without
asterisks are available for viewing only
at the Dockets Management Staff.
Although FDA verified the website
addresses in this document, please note
that websites are subject to change over
time.
* 1. HHS. The Health Consequences of
Smoking—50 Years of Progress. A Report
of the Surgeon General. Atlanta, GA:
HHS, CDC, National Center for Chronic
Disease Prevention and Health
Promotion, Office on Smoking and
Health. 2014. Available at https://
www.ncbi.nlm.nih.gov/books/
NBK179276/pdf/Bookshelf_
NBK179276.pdf.
* 2. Brown & Williamson Tobacco
Corporation, and R.B. Griffith. Letter
from RB Griffith to John Kirwan
Regarding Neil Gilliam’s Presentation at
Chelwood. British American Tobacco
Records; Master Settlement Agreement,
1963. Available at https://
www.industrydocuments.ucsf.edu/docs/
jglw0200.
* 3. Jamal, A., E. Park-Lee, J. Birdsey, et al.
‘‘Tobacco Product Use among Middle
and High School Students—National
Youth Tobacco Survey, United States,
2024.’’ MMWR Morbidity and Mortality
Weekly Report, 73(41):917–924, 2024.
Available at 10.15585/mmwr.mm7341a2.
* 4. VanFrank, B., A. Malarcher, M.E.
Cornelius, et al. ‘‘Adult Smoking
Cessation—United States, 2022.’’ MMWR
Morbidity and Mortality Weekly Report,
73(29):633–641, 2024. Available at
10.15585/mmwr.mm7329a1.
* 5. Hatsukami, D.K., X. Luo, L. Dick, et al.
‘‘Reduced Nicotine Content Cigarettes

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and Use of Alternative Nicotine
Products: Exploratory Trial.’’ Addiction,
112(1):156–167, 2017. Available at
10.1111/add.13603.
* 6. FDA. ‘‘Cigarettes.’’ FDA.gov. Accessed
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ucsf.edu/docs/mhfb0085.
* 662. Crellin, R.A., and R.L. Prowse. A
Review of Tobacco Aging. British
American Tobacco Records; Master
Settlement Agreement, 1988. Available
at https://www.industrydocuments.
ucsf.edu/docs/rfxd0213.
* 663. Rhoades, C.M., Jr. Procedure Note. Uti
Specification Review/Update. RJ
Reynolds Records; Master Settlement
Agreement, 1994. Available at https://
www.industrydocuments.ucsf.edu/docs/
rqwx0084.
* 664. British American Tobacco. PM Leaf
Technology. British American Tobacco
Records; Master Settlement Agreement.
Available at https://
www.industrydocuments.ucsf.edu/docs/
khkj0192.
* 665. FDA. Environmental Assessment of
the Tobacco Product Standard for
Nicotine Yield of Certain Tobacco
Products. Silver Spring, MD: HHS, FDA,
Center for Tobacco Products. 2025.
* 666. FDA. Finding of No Significant
Impact: Tobacco Product Standard for
Nicotine Yield of Certain Tobacco
Products. Silver Spring, MD: HHS, FDA,
Center for Tobacco Products. 2025.

Authority: 21 U.S.C. 331, 371(a), 374,
381(e), 381(p)(2), 387b, 387c, 387f(d), 387f(e),
387g, 387i, 387j.

Subpart A—General Provisions
§ 1160.1

Administrative practice and
procedure, Labeling, Smoke, Smoking,
Tobacco, Tobacco products.
Therefore, under the Federal Food,
Drug, and Cosmetic Act, and under
authority delegated to the Commissioner
of Food and Drugs, it is proposed that
chapter I of title 21 of the Code of
Federal Regulations be amended by
adding part 1160 to subchapter K to
read as follows:

■

PART 1160—TOBACCO PRODUCT
STANDARD FOR NICOTINE YIELD OF
CIGARETTES AND CERTAIN OTHER
COMBUSTED TOBACCO PRODUCTS
Subpart A—General Provisions
Sec.
1160.1
1160.3

Scope.
Definitions.

Subpart B—Product Requirements
1160.10
1160.12
1160.14
1160.16
1160.18

Nicotine level.
Product testing.
Analytical test method.
Sampling plans and procedures.
Nonconforming tobacco product.

Subpart C—Manufacturing Code and
Recordkeeping Requirements
1160.30
1160.32

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Scope.

(a) This part sets forth the product
standard to limit nicotine yield by
setting a maximum nicotine content
level for certain finished tobacco
products. The provisions of this part are
applicable to cigarettes (other than
noncombusted cigarettes, such as heated
tobacco products that meet the
definition of a cigarette), cigarette
tobacco, roll-your-own tobacco, cigars
(other than premium cigars), and pipe
tobacco (other than waterpipe tobacco).
(b) No person may distribute, sell, or
offer for sale or distribution within the
United States finished tobacco products,
as described in paragraph (a) of this
section, that are not in compliance with
this part.
(c) No person may manufacture
within the United States finished
tobacco products, as described in
paragraph (a) of this section, that are not
in compliance with this part, unless
such tobacco products are intended for
export and are eligible for export under
section 801(e)(1) of the Federal Food,
Drug, and Cosmetic Act.
§ 1160.3

List of Subjects in 21 CFR Part 1160

5141

Definitions.

For purposes of this part:
Accessory means any product that is
intended or reasonably expected to be
used with or for the human
consumption of a tobacco product; does
not contain tobacco or nicotine from any
source and is not made or derived from
tobacco; and meets either of the
following:
(1) Is not intended or reasonably
expected to affect or alter the
performance, composition, constituents,
or characteristics of a tobacco product;
or
(2) Is intended or reasonably expected
to affect or maintain the performance,
composition, constituents, or
characteristics of a tobacco product; but
(i) Solely controls moisture and/or
temperature of a stored tobacco product;
or
(ii) Solely provides an external heat
source to initiate but not maintain
combustion of a tobacco product.
Batch means a specific identified
amount of a finished tobacco product
produced in a unit of time or quantity
and that is intended to have the same
specifications.
Cigar means a tobacco product that:
(1) Is not a cigarette; and
(2) Is a roll of tobacco wrapped in leaf
tobacco or any substance containing
tobacco.

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Cigarette, as used in this part:
(1) Means a product that:
(i) Is a tobacco product; and
(ii) Meets the definition of the term
‘‘cigarette’’ in section 3(1) of the Federal
Cigarette Labeling and Advertising Act;
and
(2) Includes tobacco, in any form, that
is functional in the product, which,
because of its appearance, the type of
tobacco used in the filler, or its
packaging and labeling, is likely to be
offered to, or purchased by, consumers
as a cigarette or as roll-your-own
tobacco.
Cigarette tobacco means any tobacco
product that consists of loose tobacco
that is intended for use by consumers in
a cigarette. Unless otherwise stated, the
requirements applicable to cigarettes
under this chapter also apply to
cigarette tobacco.
Commercial distribution means any
distribution of a finished tobacco
product, whether domestic or imported,
to consumers or to any person, but does
not include interplant transfers of a
tobacco product between establishments
within the same parent, subsidiary, and/
or affiliate company, nor does it include
providing a tobacco product for product
testing where such product is not made
available for personal consumption or
resale. ‘‘Commercial distribution’’ does
not include the handing or transfer of a
tobacco product from one consumer to
another for personal consumption.
Component or part means any
software or assembly of materials
intended or reasonably expected:
(1) To alter or affect the tobacco
product’s performance, composition,
constituents, or characteristics; or
(2) To be used with or for the human
consumption of a tobacco product. The
term excludes anything that is an
accessory of a tobacco product.
Finished tobacco product means a
tobacco product, including all
components and parts, sealed in final
packaging (e.g., filters or filter tubes sold
to consumers separately or as part of
kits) or in the final form in which it is
intended to be sold to consumers.
Manufacturing code means any
distinctive sequence or combination of
letters, numbers, or symbols that begins
with the manufacturing date, followed
by the batch number, and concludes
with ‘‘-NS.’’
Manufacturing date means the month,
day, and year in 2-digit numerical
values in the format (MMDDYY) that a
finished tobacco product is packaged for
distribution.
Nicotine means the chemical
substance named 3-(1-methyl-2pyrrolidinyl) pyridine or
C[10]H[14]N[2], including any salt or

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complex of nicotine, derived from any
source.
Nonconforming tobacco product
means any tobacco product that does
not meet the requirements of § 1160.10
or § 1160.30.
Package or packaging means a pack,
box, carton, or container of any kind or,
if no other container, any wrapping
(including cellophane) in which a
tobacco product is offered for sale, sold,
or otherwise distributed to consumers.
Person includes an individual,
partnership, corporation, or association.
Pipe tobacco means any tobacco
product that, because of its appearance,
type, packaging, or labeling, is suitable
for use and likely to be offered to, or
purchased by, consumers as tobacco to
be smoked in a pipe.
Rework means action taken on a
nonconforming tobacco product to
ensure the product meets the
specifications and other requirements of
this part before it is released for
commercial distribution.
Roll-your-own tobacco means any
tobacco product which, because of its
appearance, type, packaging, or labeling,
is suitable for use and likely to be
offered to, or purchased by, consumers
as tobacco for making cigarettes or
cigars.
Specification means any requirement
with which a product, process, service,
or other activity must conform.
Tobacco filler means cut, ground,
powdered, or leaf tobacco or other
nicotine-containing substances in a
finished tobacco product.
Tobacco product means any product
made or derived from tobacco, or
containing nicotine from any source,
that is intended for human
consumption, including any
component, part, or accessory of a
tobacco product (except for raw
materials other than tobacco used in
manufacturing a component, part, or
accessory of a tobacco product). The
term ‘‘tobacco product’’ does not mean
an article that under the Federal Food,
Drug, and Cosmetic Act is: a drug
(section 201(g)(1)); a device (section
201(h)); a combination product (section
503(g)); or a food under section 201(f) if
such article contains no nicotine, or no
more than trace amounts of naturally
occurring nicotine.
Tobacco product manufacturer means
any person, including a repacker or
relabeler, who:
(1) Manufactures, fabricates,
assembles, processes, or labels a tobacco
product; or
(2) Imports a finished tobacco product
for sale or distribution in the United
States.

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Total tobacco means tobacco filler
and any other tobacco or tobaccoderived material used as part of a
tobacco product.
United States means the 50 States of
the United States of America and the
District of Columbia, the
Commonwealth of Puerto Rico, Guam,
the Virgin Islands, American Samoa,
Wake Island, Midway Islands, Kingman
Reef, Johnston Atoll, the Northern
Mariana Islands, and any other trust
territory or possession of the United
States.
Subpart B—Product Requirements
§ 1160.10

Nicotine level.

A finished tobacco product must not
exceed a nicotine content of 0.70
milligrams of nicotine per gram of total
tobacco.
§ 1160.12

Product testing.

(a) Batch testing. Tobacco product
manufacturers must conduct testing on
finished tobacco products to ensure that
the batch conforms with § 1160.10. The
manufacturer must use an analytical test
method that meets the requirements set
forth in § 1160.14. Samples for testing
each batch to determine if it conforms
with § 1160.10 must be selected in
accordance with the requirements set
forth in § 1160.16.
(b) Documentation of test results. A
full report of the source data and results
of all batch testing must be maintained
by the tobacco product manufacturer in
accordance with § 1160.32, including
the following:
(1) Full identification of the finished
tobacco product that is the subject of the
report, including, if applicable, the
submission tracking number (STN)
associated with marketing authorization
(including the static product ID (PD), if
applicable), product name(s) (including
brand and subbrand and the original
name described in the premarket
application, if different), product
category, subcategory, package type,
package quantity, and nicotine source;
(2) Nicotine level of each sample
tested and standard deviation;
(3) The batch manufacturing date and
location, including facility name and
address, for each sample;
(4) The testing date and location,
including the facility name and address;
(5) The manufacturing code of each
sample tested;
(6) The test method and sampling
procedure used;
(7) The names and qualifications of
the person(s) conducting the testing and
any laboratory accreditation;
(8) The equipment used (including
documentation to show that the

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equipment is appropriate for its
intended purpose and has been
calibrated to ensure accurate and
reliable results); and
(9) The criteria used to make a
decision to accept or reject each batch
and the decision made with respect to
each batch (e.g., accept, reject) based on
the results of the product testing.
§ 1160.14

Analytical test method.

Tobacco product manufacturers must
use an analytical test method and must
demonstrate that the test method used
was validated in an analytical test
laboratory.

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§ 1160.16

Sampling plans and procedures.

(a) Sampling plans. Each tobacco
product manufacturer must design and
implement a sampling plan or plans that
cover each finished tobacco product
based on a valid scientific rationale to
ensure that the product consistently
conforms to the requirement set forth in
§ 1160.10. The sampling plan must
ensure that samples taken are
representative of an entire batch (i.e.,
randomized or systematically selected
across the entire batch) and collected
from each batch for testing. To account
for the variability of nicotine in finished
tobacco products, the following factors
must be based on adequate statistical
criteria: the confidence intervals, the
level of necessary precision, and the
number of finished products sampled.
The sampling plan must take into
account the manufacturing quality
history of the manufacturer (e.g., batch
testing records, nonconforming tobacco
product investigations). Each sampling
plan must describe the sampling
methodology, with scientific rationale,
incorporate all sources of variability
(including variability of the analytic
method and nicotine levels), and
describe the sample size needed
(including a full description of how the
sample size is calculated) consistent
with the sampling plan to achieve the
sampling objective. The sampling plan
must also describe the criteria the
tobacco product manufacturer will use
to make a decision to accept or reject
each batch.
(b) Sampling procedures. Test
samples must be collected from each
batch and examined in accordance with
the following procedures:
(1) Test samples are to consist of the
finished tobacco product as it is
intended to be sold or distributed to
consumers and not of a separate
production sample.
(2) All test samples must be stored
according to the intended storage
conditions for the finished tobacco
product. A tobacco product

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manufacturer must include all of its
factories, stock rooms, warehouses, and
other locations containing finished
tobacco products in the population to be
sampled.
(3) Test samples must be taken from
each batch and tested within 30
calendar days of the manufacturing
date. The amount of material acquired
during sampling must be sufficient for
all testing required by § 1160.14,
including any repeat testing that may be
necessary. Samples must be selected
from each batch in accordance with the
applicable sampling plan.
(4) Sampling must be performed by
persons who have sufficient education,
training, and experience to accomplish
the assigned functions.
(5) Each test sample must be
identified so that the following
information can be determined:
(i) Full identification of the finished
tobacco product sampled, including, if
applicable, the STN associated with
marketing authorization (including the
PD, if applicable), product name(s)
(including brand and subbrand and the
original name described in the
premarket application, if different),
product category, subcategory, package
type, package quantity, and nicotine
source;
(ii) The manufacturing code;
(iii) The date on which the sample
was taken;
(iv) The sampling location (including
the address of the facility and specific
location within the facility where the
sample was taken);
(v) The name of the person(s) who
collected the sample; and
(vi) The location where the sample
will be tested (including the facility
name and address).
(6) Samples sent for testing must be
packed securely with adequate
protection against damage (e.g.,
mechanical damage, adverse changes in
humidity or temperature). A list of the
samples in each shipment must be sent
to the testing facility under separate
cover.
(7) All samples for a batch test must
be tested at the same facility.
(8) If samples will be transported to a
different facility from the manufacturing
facility for testing, once test samples
arrive at the testing facility, they must
be inspected, accounted for, and
properly stored under the finished
tobacco product’s intended storage
conditions, and a report that includes
the following information must be
generated for the batch test and be
maintained by the tobacco product
manufacturer in accordance with
§ 1160.32:

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5143

(i) Full identification of the finished
tobacco product sampled, including, if
applicable, the STN associated with
marketing authorization (including the
PD, if applicable), product name(s)
(including brand and subbrand and the
original name described in the
premarket application, if different),
product category, subcategory, package
type, package quantity, and nicotine
source;
(ii) The manufacturing code;
(iii) The date on which samples were
taken, if available;
(iv) The sampling location (including
the address and specific locations
within any facilities where samples
were taken);
(v) The number of test samples drawn;
and
(vi) Complete records of the samples
received and tested, including the date
of receipt, the identifier of all persons
who tested the samples, and the test
results.
(9) Each batch must be withheld from
commercial distribution until it has
been sampled and tested and a decision
has been made by the tobacco product
manufacturer that it conforms to the
requirements of this part and may be
released for commercial distribution.
§ 1160.18
product.

Nonconforming tobacco

Each tobacco product manufacturer
must establish and maintain procedures
for the control and disposition of
nonconforming tobacco product. The
procedures must include the following
requirements:
(a) Identification and segregation.
Each tobacco product manufacturer
must identify and segregate potential
nonconforming product in a manner
that prevents commercial distribution of
potential nonconforming product prior
to investigation and disposition.
(b) Investigation. Each tobacco
product manufacturer must investigate
all potential nonconforming tobacco
products to determine if the product is
nonconforming. The investigation must
include an examination of relevant
production processes and controls,
laboratory testing, complaints, and any
other relevant records and sources of
information. For products determined to
be nonconforming, the investigation
must also determine the scope and
cause of nonconformance.
(c) Rejection of nonconforming
product. Tobacco product
manufacturers must reject a batch of a
finished tobacco product if the nicotine
level of a test sample from the batch
does not conform to the requirements of
this part unless a disposition decision
and justification to release the batch is

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made after an investigation determines
that the batch meets the requirements of
this part.
(d) Disposition and followup. Each
tobacco product manufacturer must
determine the disposition of all
nonconforming tobacco products and
any necessary followup. If the
disposition decision is that the tobacco
product can be released for distribution
without rework, an adequate written
justification must be developed and
maintained in accordance with
§ 1160.32. An adequate written
justification must address why releasing
the nonconforming product would not
result in the tobacco product being
adulterated or misbranded.
Nonconforming product cannot be
released for distribution without rework
or an adequate justification.
(e) Records. Each tobacco product
manufacturer must maintain records of
all activities required under this section.
Records must include the date and time
of the activity, the individual
performing the activity, the type of
activity performed, any information that
demonstrates that the requirement was
met, and any data or calculations
necessary to reconstruct the results.
Subpart C—Manufacturing Code and
Recordkeeping Requirements
§ 1160.30 Manufacturing code
requirements.

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(a) Each tobacco product
manufacturer must permanently affix a
manufacturing code to the packaging or
labeling of all finished tobacco
products. For a finished tobacco
product, the manufacturing code must
be affixed in a manner that assures it

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will remain on the packaging or labeling
through the expected duration of use of
the tobacco product by the consumer.
(b) The manufacturing code for each
finished tobacco product must be
permanently affixed, legible,
conspicuous, prominent, and appear in
the English language.
(c) The manufacturing code must
contain the following information listed
in the following order:
(1) The manufacturing date in 2-digit
numerical values in the month-day-year
format (MMDDYY);
(2) The finished tobacco product
batch number; and
(3) The designation ‘‘–NS’’ at the end.
§ 1160.32

Recordkeeping requirements.

(a) Each facility that manufactures
tobacco products subject to this part
must establish and maintain records
related to compliance with this part,
including the following:
(1) The source data and results of
batch testing conducted to determine
conformance with § 1160.10, including
all information specified in § 1160.12(b);
(2) All source data for analytical test
method validation;
(3) All sampling plans and reports
under § 1160.16;
(4) Documentation that the persons
performing sampling under § 1160.16
have sufficient education, training, and
experience to accomplish the assigned
functions; and
(5) All nonconforming tobacco
product identification, segregation,
investigation, rework, and disposition
decision procedures, including
justifications, under § 1160.18.
(b) All records required under this
part, regardless of storage medium, must

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be attributable, legible,
contemporaneously recorded, original,
and accurate. These records must be
written in English, or an accurate
English translation must be made
available upon request. Documents that
have been translated from another
language into English must be
accompanied by the original language
version of the document, a signed
statement by the authorized
representative of the manufacturer
certifying that the English language
translation is complete and accurate,
and a brief statement of the
qualifications of the person that made
the translation. These records must be
maintained at the manufacturing
establishment or another location that is
readily accessible to responsible
officials of the tobacco product
manufacturer and to FDA. These
records, including those not stored at
the establishment, must be made readily
accessible to FDA during the retention
period for inspection and photocopying
or other means of reproduction. Original
or true copies of these records that can
be immediately retrieved from another
location, including by computer or other
electronic means, meet the requirements
of this paragraph.
(c) All records required under this
part must be retained for a period of at
least 4 years from the date of
commercial distribution of the finished
tobacco product that is the subject of the
record.
Dated: January 6, 2025.
Robert M. Califf,
Commissioner of Food and Drugs.
[FR Doc. 2025–00397 Filed 1–15–25; 8:45 am]
BILLING CODE 4164–01–P

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