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Federal Register / Vol. 76, No. 117 / Friday, June 17, 2011 / Rules and Regulations
FOR FURTHER INFORMATION CONTACT:
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
[Docket No. FDA–1978–N–0018] (Formerly
Docket No. 1978N–0038)
Reynold Tan, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, rm. 5411,
Silver Spring, MD 20993, 301–796–
2090.
SUPPLEMENTARY INFORMATION:
RIN 0910–AF43
Table of Contents
Labeling and Effectiveness Testing;
Sunscreen Drug Products for Over-theCounter Human Use
I. Overview of Document
A. Rulemaking History
B. Scope of This Document
C. Issues Outside the Scope of This
Document
D. Enforcement Policy
E. Summary of Major Revisions to the
Labeling and Testing Requirements
Included in the 2007 Proposed Rule
II. Administrative and Other Issues
III. Principal Display Panel (PDP) Labeling
A. SPF Statement
B. Broad Spectrum Statement
C. Water Resistance Statement
D. UVB and UVA Educational Statement
IV. Drug Facts Labeling
A. Active Ingredients/Purpose
B. Uses
C. Warnings
D. Directions
E. Constitutionality of Labeling Statements
Regarding Skin Cancer and Skin Aging
F. Other Information
G. Reduced Labeling
V. Miscellaneous Labeling Outside Drug
Facts
VI. SPF Test Parameters
A. Solar Simulator
B. Sunscreen Standards
C. Test Subjects
D. Test Sites and Subsites
E. Finger Cot
F. Application Amount
G. Water Resistance
VII. SPF Test Issues (Other Than Test
Parameters)
A. Pass/Fail (Binomial) SPF Test
B. Photostability
C. In Vitro SPF Test
D. Anti-Inflammatory Ingredients
VIII. Broad Spectrum Test
A. In Vivo Test Method: Not Required
B. In Vitro Test Method: Critical
Wavelength
C. Critical Wavelength Test Parameters
IX. Analysis of Impacts
A. Final Regulatory Impact Analysis
B. Small Business Impact (Final Regulatory
Flexibility Analysis)
X. Paperwork Reduction Act of 1995
XI. Environmental Impact
XII. Federalism
XIII. References
Food and Drug Administration
21 CFR Parts 201 and 310
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Final rule.
The Food and Drug
Administration (FDA) is issuing this
document to address labeling and
effectiveness testing for certain over-the
counter (OTC) sunscreen products
containing specified active ingredients
and marketed without approved
applications. This document addresses
labeling and effectiveness testing issues
raised by the nearly 2,900 submissions
that we received in response to the
sunscreen proposed rule of August 27,
2007 (2007 proposed rule). The
document also identifies specific claims
that render a product that is subject to
this rule misbranded or would not be
allowed on any OTC sunscreen product
marketed without an approved
application. The document does not
address issues related to sunscreen
active ingredients or certain other issues
regarding the GRASE determination for
sunscreen products. The document
requires OTC sunscreen products to
comply with the content and format
requirements for OTC drug labeling
contained in the 1999 Drug Facts final
rule (published in the Federal Register
of March 17, 1999, by lifting the delay
of implementation date for that rule that
we published on September 3, 2004).
DATES: Effective Date: This final rule is
effective June 18, 2012. For additional
information concerning this effective
date, see section X in the preamble of
this document. The incorporation by
reference of a certain publication listed
in this rule is approved by the Director
of the Federal Register as of June 18,
2012.
Compliance Date: The compliance
date for all products subject to this final
rule with annual sales less than $25,000
is June 17, 2013. The compliance date
for all other products subject to this
final rule is June 18, 2012.
Implementation date: FDA is lifting
the delay of implementation date for
§ 201.66 as published at 69 FR 53801,
September 3, 2004.
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SUMMARY:
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I. Overview of Document
A. Rulemaking History
This section of the document does not
discuss every regulatory action
associated with OTC sunscreen
products. It highlights the major
regulatory actions that are related to the
regulatory actions being taken in this
document. For a complete list of all
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regulatory actions associated with OTC
sunscreen products, please refer to our
Web site: http://www.fda.gov/Drugs/
DevelopmentApprovalProcess/
DevelopmentResources/Over-theCounterOTCDrugs/StatusofOTC
Rulemakings/ucm072134.htm.
In the Federal Register of May 12,
1993 (58 FR 28194), we published a
proposed rule for OTC sunscreen
products that identified active
ingredients we tentatively considered to
be generally recognized as safe and
effective (GRASE), as well as associated
labeling and sun protection factor (SPF)
testing to be required for these OTC
sunscreen products (the 1993 proposed
rule). The SPF test and corresponding
labeling reflect the level of protection
against sunburn, which is caused
primarily by UVB radiation. The 1993
proposed rule also explained the
importance of protection against UVA
radiation (58 FR 28194 at 28232 and
28233). The proposed rule referenced
published UVA test methods but did not
propose a specific method (58 FR 28194
at 28248 to 28250). Rather, the proposed
rule stated that a sunscreen product
could be labeled as ‘‘broad spectrum,’’
or labeled with a similar statement, if it
protected against UVA radiation as
demonstrated by one of the published
UVA tests or a similar test.
In April 1994, we reopened the
administrative record to allow
additional submissions concerning
UVA-related issues. We also announced
a public meeting to be held in May 1994
to discuss UVA testing procedures (59
FR 16042, April 5, 1994). We held the
public meeting to gather more
information to help us determine the
most appropriate UVA test method and
labeling.
In November 1997, Congress enacted
the Food and Drug Administration
Modernization Act of 1997 (FDAMA),
which addressed OTC sunscreen
products among other FDA issues.
Section 129 of FDAMA stated that ‘‘not
later than 18 months after the date of
enactment of this Act, the Secretary of
Health and Human Services shall issue
regulations for over-the-counter
sunscreen products for the prevention
or treatment of sunburn.’’ We then
determined that the GRASE active
ingredients, SPF testing requirements,
and related labeling were issues that we
could finalize within the timeframe set
by FDAMA. Because we had not
previously proposed specific UVA
testing and labeling requirements, we
did not have sufficient time to finalize
these UVA requirements within the
FDAMA timeframe.
In the Federal Register of May 21,
1999, we published a final rule for OTC
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sunscreen products (64 FR 27666). The
1999 sunscreen final rule added the
sunscreen monograph (regulations) in
part 352 (21 CFR part 352) and included
an effective date of May 2001. The 1999
sunscreen final rule stated that we
would publish a proposed rule outlining
UVA testing and labeling requirements
at a future date. In 2000, we extended
the effective date for the 1999 sunscreen
final rule to December 2002 (65 FR
36319, June 8, 2000).
In December 2001, we stayed the
December 2002 effective date of the
1999 sunscreen final rule indefinitely.
We took this action because we planned
to revise part 352 to add UVA testing
and labeling requirements so that OTC
sunscreen products would be tested and
labeled for both UVB and UVA radiation
protection. We included these revisions
in a proposed rule that published in the
Federal Register of August 27, 2007 (72
FR 49070). The 2007 proposed rule
identified UVA testing and labeling that
we proposed should be required for all
OTC sunscreen products. The proposed
rule also revised SPF testing and
corresponding labeling from the 1999
final rule. The proposed rule did not lift
the existing stay of the effective date for
part 352.
On September 3, 2004 (69 FR 53801),
we delayed until further notice the
implementation date for the Drug Facts
final rule (64 FR 13254, March 17, 1999)
(21 CFR 201.66) for OTC sunscreen
products. The Drug Facts final rule (21
CFR 201.66) establishes general labeling
format and content requirements for all
OTC drugs. We explained that we
postponed the implementation date for
general Drug Facts labeling
requirements for sunscreens because we
did not expect to issue the sunscreen
final rule containing UVA testing and
product-specific labeling requirements
(i.e., this document) by the Drug Facts
implementation date of May 2005.
Therefore, we delayed the
implementation date until further notice
to prevent sunscreen product
manufacturers from having to relabel
their products at two closely related
time intervals, as initially required by
the 1999 Drug Facts final rule and the
1999 sunscreen final rule.
B. Scope of This Document
This final rule establishes the labeling
and testing requirements for OTC
sunscreen products containing specific
ingredients or combinations of
ingredients and marketed without an
approved application under section 505
of the Federal Food, Drug, and Cosmetic
Act (21 U.S.C. 355) (the FD&C Act). The
requirements in this final rule will help
ensure that these currently marketed
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sunscreen products are appropriately
labeled and tested for both UVA and
UVB protection. In addition, the
requirements in this final rule will help
ensure the proper use of these
sunscreens and greater consumer
protection from the damaging effects of
UV radiation. This final rule also
identifies claims that render a product
that is subject to this rule misbranded or
are not allowed on any OTC sunscreen
drug product marketed without an
approved application.
As described in the previous section
of this document, we issued the 2007
proposed rule as a proposed amendment
to the sunscreen monograph
requirements in 21 CFR part 352
primarily to establish UVA testing and
labeling requirements so that all OTC
sunscreen products marketed under the
sunscreen monograph would be tested
and labeled for both UVB and UVA
radiation protection. Sunscreen active
ingredients, UVB testing, UVB labeling,
and other conditions under which
sunscreens would be considered GRASE
and not misbranded had been addressed
in the 1999 (stayed) final rule. In
response to the 2007 proposed rule,
however, we received submissions from
the public concerning all aspects of the
sunscreen monograph (i.e., the
conditions specified in the 1999 final
rule and the 2007 proposed rule). As
discussed further in this section, some
of the issues regarding the monograph
conditions raised in the public
submissions will require further
evaluation by us. Therefore, we are not
issuing a final monograph with GRASE
conditions for sunscreens in this
document. Instead, we are publishing
this final rule establishing labeling and
the effectiveness testing upon which it
relies, which applies to the same
sunscreens that were the subject of the
2007 proposed rule to amend the
monograph, because it is in the best
interest of public health to publish this
final rule while we work on remaining
issues that need to be addressed in order
to publish a final monograph. This
labeling will help ensure that these
products are not misbranded by
providing specific indications,
directions, warnings, and other
important information to help
consumers select and use them
appropriately.
In this final rule, then, we are
codifying in 21 CFR part 201
requirements for OTC sunscreen
products containing specified active
ingredients and marketed without
approved applications under section
505 of the FD&C Act (21 U.S.C. 355)
(hereafter referred to as ‘‘covered’’
products). With respect to these covered
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products, this new section 21 CFR
201.327 includes requirements for
labeling and the effectiveness testing
upon which it relies. Because we have
not yet resolved all of the issues
regarding conditions under which
sunscreens are GRASE and not
misbranded, the stay of 21 CFR part 352
remains in effect. Although we are not
yet codifying these labeling and related
effectiveness testing provisions in the
monograph regulation, they do embody
the agency’s current determination on
appropriate regulation of these aspects
of sunscreens that were previously
identified as falling within the
monograph in part 352, and supersede
the prior approach embodied in the
never-effective provisions of 21 CFR
part 352 subparts C and D. While this
rule does not lift the stay of part 352, we
are lifting the delay of implementation
date for the Drug Facts labeling
requirements of 21 CFR 201.66. In
addition, this rule codifies certain
specific claims that render a covered
product misbranded or are not allowed
on any OTC sunscreen drug product
marketed in the United States without
an approved application.
We note that all provisions of new 21
CFR 201.327 and the amendments to
310.545 included in this rule apply only
to the aforementioned covered products,
and references in this document to
‘‘covered’’ products recognize this
limitation. Manufacturers of sunscreen
products that are already being
marketed pursuant to an approved
application can contact FDA’s Center for
Drug Evaluation and Research to discuss
supplemental submissions that would
enable them to include labeling on their
products like that specified in this final
rule.
C. Issues Outside the Scope of This
Document
There are a number of issues that
were raised in public submissions
responding to the 2007 proposed rule
that are outside the scope of this
document. The issues fall into two
categories:
• GRASE determination for sunscreen
products and active ingredients
• Issues affecting multiple OTC drug
monographs
As explained below, in this document,
we are not addressing these issues
related to determining the GRASE status
of sunscreen products or sunscreen
active ingredients and are not
addressing the issues described below
affecting multiple OTC drug
monographs.
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1. Issues Regarding GRASE
Determination for Sunscreen Products
and Active Ingredients
A large number of submissions on the
2007 proposed rule raised issues related
to the conditions that define what
constitutes a GRASE finished OTC
sunscreen product, irrespective of its
active ingredients. These included over
1000 submissions requesting that we
limit the monograph to sunscreens that
offer broad spectrum protection and
have SPF values of 15 or higher.
Because this final rule is a labeling rule,
and not a monograph, we do not address
these issues here but plan to address
them in future rulemakings regarding
the monograph and conditions for
general recognition of safety and
effectiveness.
This rule also does not address issues
related to the GRASE status of
sunscreen active ingredients that are
included in the 2007 proposed rule
(proposed 21 CFR 352.10 and 352.20).
We received 20 submissions raising
questions about the safety of ingredients
in sunscreens (Ref. 1). Ten of the
submissions specifically asked that we
ensure that none of the ingredients are
carcinogenic. Others asked that we
ensure that all ingredients in sunscreens
are safe without citing a specific
concern. We intend to address
carcinogenicity and other safety
considerations related to sunscreen
active ingredients in a future
rulemaking.
We also received submissions
requesting that we increase the GRASE
concentration of avobenzone from 3
percent to 5 percent (Ref. 1). Another
submission points out that there are two
USP 1 monographs for zinc oxide:
• Zinc oxide (Ref. 2)
• Zinc oxide neutral (Ref. 3)
The submission would like us to clarify
that zinc oxide in OTC sunscreen
products can meet the specifications of
either USP monograph (Ref. 1). We
intend to address all of these issues
regarding GRASE determination for
sunscreen active ingredients in future
rulemakings.
In addition, we received two
submissions requesting that we classify
three new ingredients not previously
marketed in the United States as
GRASE: bemotrizinol, bisoctrizole, and
octyl triazone (Ref. 1). We found these
active ingredients eligible for review
under the OTC drug monograph system
in 2003 (octyl triazone) and 2005
(bemotrizinol and bisoctrizole) (68 FR
41386, July 11, 2003, and 70 FR 72449,
December 5, 2005). We are currently
1 United
States Pharmacopeia.
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reviewing the safety and effectiveness
data submitted for these and other
sunscreen active ingredients found
eligible for potential addition to the
monograph. When we complete our
review, we will issue proposed rules
stating our tentative conclusions on the
safety and effectiveness of all of these
ingredients.
2. Issues Affecting Multiple OTC Drug
Monographs
This final rule also does not address
three issues raised in response to the
2007 sunscreen proposed rule that are
not specific to sunscreen products.
Because these issues apply more
generally to multiple categories of OTC
drug products, we are not addressing
these issues in this final rule, which is
limited to OTC sunscreen products.
The first issue concerns the inclusion
of expiration dates on sunscreen labels.
We received 12 submissions requesting
that we require OTC sunscreen products
to be labeled with an expiration date
(Ref. 1). Currently, regulations in 21
CFR 211.137(h) do not require that an
expiration date be included in labeling
if an OTC drug product does not have
any dosage limitations and is stable for
at least 3 years. This regulation applies
to many OTC drug products, including
sunscreen products. Any modification
of the existing regulations would require
publication of a proposed rule
addressing all OTC drug products
affected by the expiration date
regulations.
The second issue concerns the term
‘‘final monograph.’’ One submission
argued that we should not use this term
because it is inaccurate (Ref. 1). As the
submission states, ‘‘FDA is to
continually evaluate products, so
nothing is ever finalized.’’ This issue
applies to monographs representing all
categories of OTC drug products.
Therefore, we are not addressing the
issue in this document.
The third issue concerns the country
of origin listing for all ingredients (i.e.,
both active and inactive ingredients) on
a sunscreen drug product. We received
a submission requesting that we provide
the country of origin for each ingredient.
The submission also requested that
manufacturers be required to provide
specific details about what each
ingredient does in the product. This
issue applies to all OTC drug products
and, therefore, we are not addressing it
in this document.
D. Enforcement Policy
As noted, no final monograph is
currently in effect for OTC sunscreen
drug products, and in its absence,
questions may arise regarding FDA’s
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enforcement policy for OTC sunscreen
products marketed without approved
applications. To clarify expectations for
industry, elsewhere in this issue of the
Federal Register, we are announcing the
availability of a draft guidance
document, explaining the agency’s
intended enforcement policy for these
products until a final sunscreen
monograph becomes effective.
E. Summary of Major Revisions to the
Labeling and Effectiveness Testing
Included in the 2007 Proposed Rule
In response to the 2007 proposed rule,
we received almost 2,900 submissions
from the public. Of these submissions,
over 2,500 expressed general support for
the proposed rule and urged us to
finalize and implement the new rule
quickly. Three hundred twenty-five of
the submissions raised approximately
90 specific issues related to the
proposed rule. We have addressed the
issues specifically relating to labeling
and effectiveness testing in this final
rule. Based on the submissions received,
and the information and data included
in those submissions or otherwise
available to us, we have re-evaluated
our position on several issues in the
2007 proposed rule and made several
changes to our proposed labeling and
testing requirements. Tables 1, 2, 4, and
5 in this document summarize the
labeling and effectiveness testing
requirements included in the 2007
proposed rule as well as the labeling
and effectiveness testing required by
this final rule:
• Table 1: PDP Labeling (discussed in
section III)
• Table 2: Drug Facts Labeling
(discussed in section IV)
• Table 4: SPF Test (discussed in
section VI)
• Table 5: Broad Spectrum Test
(discussed in section VIII)
Rather than summarizing all of the
revisions to the labeling and testing
included in the 2007 proposed rule, we
are highlighting what we consider to be
the most important revisions in this
section of the document.
We made the following changes to the
proposed labeling:
1. The proposed UVA ‘‘star rating’’ is
not required on the PDP.
2. A combined ‘‘Broad Spectrum SPF’’
statement is required on the PDP for
sunscreen products that pass the broad
spectrum test established in new 21 CFR
201.327(j). To pass the broad spectrum
test, the amount of UVA protection must
increase as the SPF value increases.
3. For sunscreen products that pass
the broad spectrum test established in
new 21 CFR 201.327(j) and have SPF
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values of 15 or higher in accordance
with the SPF test in 21 CFR 201.327(i):
a. The ‘‘Sun Alert’’ warning proposed
as the first warning in 2007 is not
required (Warning proposed located in
21 CFR 352.52(c)(1)).
b. A new indication statement may be
included to inform consumers that
using the product ‘‘as directed with
other sun protection measures (see
Directions [in bold italic font]) decreases
the risk of skin cancer and early skin
aging caused by the sun.’’
c. A new direction statement has been
added informing consumers that
exposure to the sun increases the risk of
skin cancer and early skin aging and
providing a list of specific sun
protection measures that can decrease
this risk.
4. For any OTC sunscreen product
that does not pass the broad spectrum
test in 21 CFR 201.327(j), or that are
broad spectrum with an SPF value less
than 15, this final rule, like the 2007
proposed rule, requires that the first
warning indicate the adverse
consequences of spending time in the
sun. The wording of this warning has
been revised to state, ‘‘Skin Cancer/Skin
Aging Alert [in bold font]: Spending
time in the sun increases your risk of
skin cancer and early skin aging. This
product has been shown only to help
prevent sunburn, not [in bold font] skin
cancer or early skin aging.’’
We also made the following changes
to the effectiveness testing proposed in
2007:
1. The number of subjects required in
the SPF test has been reduced from 20
subjects to 10 subjects.
2. One in vitro test is required to
demonstrate broad spectrum protection
rather than the two previously proposed
tests (an in vitro test and an in vivo test).
3. The broad spectrum test is a pass/
fail test based on the critical wavelength
value of 370 nm 2.
II. Administrative and Other Issues
Some of the submissions that we
received following publication of the
2007 proposed rule made the following
requests involving administrative issues
(Ref. 1):
• Extend the comment period of the
2007 proposed rule.
• Lift the stay on 21 CFR part 352,
imposed in 2001 (66 FR 67485).
• Allow interim marketing of
products containing avobenzone with
ensulizole and avobenzone with zinc
oxide.
• Set an effective date for this final
rule other than the 18 months proposed
in the 2007 proposed rule.
2 Nanometers.
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• Revise the preemption language
included in the 2007 proposed rule by
deleting any references regarding the
rule’s potential preemption of State tort
law.
Our positions on these issues are
discussed in the remainder of this
section of the document.
All of the requests to extend the
comment period were submitted before
the November 28, 2007 Federal Register
notice in which we extended the
comment period of the 2007 proposed
rule (72 FR 67264). In that notice, we
extended the close of the comment
period from November 26, 2007, to
December 26, 2007. We have not
received any more requests to extend
the comment period since December
2007.
With regard to requests to lift the stay
of 21 CFR part 352 (the OTC sunscreen
monograph), as already discussed, our
2007 proposed rule anticipated
amending the testing and labeling
provisions of that monograph and
subsequently lifting the stay. However,
comments received on the 2007
proposed rule not only addressed
labeling and effectiveness testing for
final sunscreen formulations, but also
raised other issues about the monograph
conditions for OTC sunscreen products
that require further consideration. As a
result, we are not finalizing
amendments to part 352 at this time nor
lifting the stay placed on that section as
enacted in 1999 (66 FR 67485). Rather,
this final rule establishes in 21 CFR
201.327 labeling requirements and the
effectiveness testing upon which it
relies for covered OTC sunscreen drug
products. We intend to lift the stay on
part 352 when we reach our final
conclusions on the conditions under
which sunscreen products are GRASE
and not misbranded, including a
determination regarding sunscreen
active ingredients, and publish a revised
final monograph. In the interim, the
labeling and effectiveness testing
provisions of this rule apply to covered
OTC sunscreen products.
We received a request that we allow
interim marketing of avobenzone
combinations in proposed § 352.20(a)(2)
prior to issuing a final rule for part 352.
Subject to our enforcement discretion,
we will continue to allow the marketing
of avobenzone combinations provided
for in the 1999 sunscreen final rule.
However, we are not allowing marketing
of the additional avobenzone
combinations discussed in the 2007
proposed rule until we reach a final
conclusion on the GRASE determination
for sunscreen active ingredients and
combinations of those ingredients.
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We are requiring that this final rule
become effective in 1 year, even though
we considered 18 months in the 2007
proposed rule (72 FR 49070 at 49110).
We are allowing products with annual
sales less than $25,000 to comply with
this rule in 2 years, as stated in the 2007
proposed rule. In response to the
proposed rule, we received one
submission arguing that we should
require this final rule to become
effective in 1 year (Ref. 1). The
submission stated that a later effective
date would have a negative public
health impact. We received eight
submissions arguing that we should
extend the effective date from the
proposed 18 months to 3 years (Ref. 1).
The submissions listed the following
reasons for allowing more than 18
months:
• Repackaging
• Relabeling
• Testing/retesting
• Removing products from market
• Impact on small businesses
The most common argument was that
more time would be needed to test/
retest OTC sunscreen products for broad
spectrum protection in accordance with
both the in vitro and in vivo UVA test
methods included in the proposed rule.
We agree with the submission which
stated that it would be beneficial for
consumers to have this rule become
effective within 1 year. As explained in
section VIII.A of this document, we are
not requiring manufacturers to
demonstrate broad spectrum protection
by conducting in vivo and in vitro tests.
This final rule requires that
manufacturers conduct only the simpler
and less expensive nonclinical in vitro
test to demonstrate broad spectrum
protection. In vitro tests are
substantially shorter than in vivo tests.
Therefore, we are setting an effective
date for this rule 1 year from the date
of publication in the Federal Register.
However, we are providing two years for
all products with annual sales less than
$25,000 to comply with this rule. In
addition, in order to ensure that limited
testing laboratory capacity does not
result in sunscreen shortages during the
transition to the new rule, we intend to
exercise enforcement discretion for a
period of time with regard to the SPF
test for certain OTC sunscreen products
on the market by June 17, 2011 (see our
draft guidance entitled ‘‘Guidance for
Industry: Enforcement Policy—OTC
Sunscreen Drug Products Marketed
Without An Approved Application’’
announced elsewhere in this issue of
the Federal Register).
The submissions stating that
additional time is necessary for
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repackaging and relabeling did not
submit any information or data to
support these arguments (Ref. 1). The
argument that more than 18 months is
needed to remove non-compliant
products from the market is not valid.
In the 2007 proposed rule, we indicated
that sunscreen products which are
already distributed by the effective date
of the final rule would not be expected
to be relabeled or retested in conformity
with the final rule conditions unless
these products were subsequently
relabeled or repackaged after the
effective date (72 FR 49070 at 49109).
Consistent with this statement, we do
not expect non-compliant products
introduced or delivered for introduction
into interstate commerce prior to the
compliance dates specified for this final
rule to be removed from the market.
We received a submission that
expressed concern about the agency’s
preemption discussion in the 2007
proposed rule (72 FR 49070 at 49109
and 49110) and requested that we delete
any discussion regarding the rule’s
potential preemption of State tort law
(Ref. 1). The submission claimed that
we exceeded our authority when we
stated that section 751(a) of the FD&C
Act displaces both State legislative
requirements and State common law
duties. The submission argued that
Congress intended to preserve State
common law claims by including
section 51(e), which exempts State
product liability claims from express
preemption under section 751(a) of the
FD&C Act. The commenter appears to
have construed our statement in a way
that would nullify section 751(e) of the
FD&C Act. We did not intend to suggest
that section 751(a) of the FD&C Act
preempts State product liability claims,
whether based on State legislative
enactments or common law, because
section 751(e) exempts such actions
from the express preemption provision
in section 751(a). However, it is
important to note that section 751(e) of
the FD&C Act exempts only those
common law claims that are based on
State product liability law. Our revised
preemption discussion in section XII
remains consistent with applicable law.
The submission also requested that
we delete any references to implied
preemption. In this final rule, we have
omitted any statement regarding
implied preemption because, although
implied preemption may arise, such
scenarios are necessarily case-specific.
Section XII of this document makes
clear that the sole statutory provision
giving preemptive effect to the final rule
is section 751 of the FD&C Act.
III. Principal Display Panel (PDP)
Labeling
In response to the 2007 sunscreen
proposed rule, we received 45
submissions requesting that we revise
the proposed principal display panel
(PDP) labeling (Ref. 1). We are revising
the PDP labeling based, in part, on these
submissions (see table 1 of this
document). We have decided that the
PDP labeling included in this document
will simplify the purchase decision for
consumers by allowing them to more
easily find important information
included on the PDP.
TABLE 1—SUMMARY OF PDP LABELING IN THE 2007 PROPOSED RULE AND THIS FINAL RULE USING A BROAD SPECTRUM
SPF 30 WATER RESISTANT SUNSCREEN PRODUCT AS EXAMPLE A AND AN SPF 6 SUNSCREEN THAT IS NOT BROAD
SPECTRUM AND NOT WATER RESISTANT AS EXAMPLE B
Labeled information
2007 Proposed rule
Effectiveness Rating 1 ..........
Example A:
‘‘UVB SPF 30 High’’
‘‘UVA ★★★✰ High’’
Example B:
‘‘UVB SPF 6 Low’’
‘‘No UVA Protection’’
Example A:
‘‘Water Resistant’’
Example B:
No statement on water resistance
Examples A & B:
‘‘UV rays from the sun are made of UVB and UVA. It is
important to protect against both UVA and UVB
rays.’’
Water Resistance .................
Educational Statement .........
This final rule
Example A:
‘‘Broad Spectrum SPF 30’’
Example B:
‘‘SPF 6’’
Example A:
‘‘Water Resistant (40 minutes)’’
Example B:
No statement on water resistance
Examples A & B:
No educational statement
1 The UVA rating in the 2007 proposed rule is a four-tier rating (low, medium, high, highest). The UVA testing in this final rule is pass/fail—a
product is either allowed or not allowed to include a broad spectrum statement depending on results of the test described in new 21 CFR
201.327(j) (see section VIII of this document).
emcdonald on DSK2BSOYB1PROD with RULES3
A. SPF Statement
In the 2007 sunscreen proposed rule,
we proposed redefining the acronym
‘‘SPF’’ as the ‘‘sunburn protection
factor.’’ We also proposed that the term
‘‘UVB SPF’’ would be required on the
PDP of all OTC sunscreen products
(proposed 21 CFR 352.50(a)). This term
would be followed by the numerical
value determined from SPF testing and
one of the following descriptors: ‘‘low,’’
‘‘medium,’’ ‘‘high,’’ or ‘‘highest.’’ For
example, a sunscreen product could
have contained the statement ‘‘UVB SPF
40 High’’ on the PDP.
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We received 12 submissions regarding
the SPF statement in response to the
2007 sunscreen proposed rule (Ref. 1).
Collectively, the submissions made the
following requests:
1. Do not change the definition of SPF
to ‘‘sunburn protection factor’’
2. Remove UVB from ‘‘UVB SPF’’
3. Redefine the ‘‘highest’’ product
category descriptor to include SPF 50
4. Require SPF values expressed in
multiples of 5
5. Label SPF as the percent of UVB
radiation screened
As discussed in the remainder of this
section, we agree with the first and
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second requests, but are not granting the
other three requests.
In this final rule, unlike the 2007
proposed rule, we have no express
definitional section. However, we
identify ‘‘SPF’’ as an abbreviation for
‘‘sun protection factor’’ in new 21 CFR
201.327(a)(1), and use it consistently in
this way throughout the rule. This use
of the term SPF is identical to the
definition in the 1999 stayed sunscreen
final rule (64 FR 27666). For products
that are not broad spectrum, the term
‘‘SPF’’ will appear on the PDP with the
numerical SPF value calculated
according to the test method in new 21
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CFR 201.327(i). For broad spectrum
sunscreen products, the term ‘‘Broad
Spectrum SPF’’ will appear on the PDP
along with the numerical SPF value
calculated according to the test method
in new 21 CFR 201.327(i).
The term ‘‘UVB’’ will not be required
as part of the SPF statement. We are also
not requiring the descriptor (e.g., ‘‘high’’
or ‘‘low’’). We included these two
requirements in the 2007 proposed rule
because we had concluded that the
requirements would help consumers
understand the side-by-side SPF
numerical rating in conjunction with
the UVA star rating, which included the
term ‘‘UVA’’ and the same descriptors
(72 FR 49070 at 49084). As discussed in
section III.B of this document, the UVA
star rating is not being included in this
final rule, and as discussed below, we
have concluded that neither the term
‘‘UVB’’ nor the descriptor is necessary
for consumers to understand the
effectiveness statement.
Neither the term ‘‘UVB’’ nor a
descriptor (e.g. ‘‘low’’ or ‘‘high’’) had
been included on sunscreen labels prior
to our 2007 proposal, and consumers
had been able to make purchase and use
decisions based on SPF values alone.
Under this final rule, the SPF value will
be expressed on the PDP by including
the term ‘‘SPF,’’ followed by the
numerical value determined from the
SPF test, similar to how it has appeared
on the labels of OTC sunscreen products
for more than 30 years. As described in
section III.B of this document, for
products passing the critical wavelength
test in new 21 CFR 201.327(j), the SPF
value statement will be expressed as
‘‘Broad Spectrum SPF’’ followed by the
numerical SPF value calculated
according to the test method in 21 CFR
201.327(i).
We received five submissions
objecting to the definition of SPF as
‘‘sunburn protection factor’’ and only
one submission supporting the
definition (Ref. 1). The submissions
objecting to the definition argued that,
if the term ‘‘sunburn protection factor’’
is used, consumers may mistakenly
assume that a higher SPF value means
a higher probability of sunburn.
Additionally, they argued that
sunscreen products protect against
various harmful effects of sun exposure,
such as early skin aging and skin cancer,
in addition to protecting against
sunburn. Some submissions suggested
that the term ‘‘sunburn protection
factor’’ will lead consumers with darker
skin to assume that they do not need
sunscreen products because they do not
burn easily (Ref. 1).
We agree with the arguments
provided by the submissions suggesting
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that the term ‘‘sunburn protection
factor’’ may be misleading. In the 2007
sunscreen proposed rule, we revised the
definition of SPF from ‘‘sun protection
factor’’ to ‘‘sunburn protection factor’’
because we thought that the new
definition was more descriptive of what
an SPF value represents (72 FR 49070 at
49077). The SPF value is determined
from a clinical test with sunburn as the
endpoint. However, for broad spectrum
sunscreen products, the SPF statement
also serves as a relative measure of the
magnitude of broad spectrum protection
(Ref. 4). In this final rule, while we do
not codify a separate definitional
section, we continue to use the term
‘‘SPF’’ to mean ‘‘sun protection factor,’’
as we had done in the 1999 final rule
(21 CFR 201.327(a)(1)).
In this final rule, we are also revising
the effectiveness statement so that the
term ‘‘UVB’’ is not required before the
term ‘‘SPF,’’ as proposed in the 2007
proposed rule (proposed 21 CFR
352.50(a)). We received six submissions
requesting this revision (Ref. 1). These
submissions argued that ‘‘UVB SPF’’ is
an incorrect representation of the SPF
value determined from a test using a
solar stimulator that emits both UVA
and UVB radiation. The submissions
point out that sunburn is not caused
solely by UVB radiation. It is well
known that UVA radiation contributes
up to 20 percent of the skin’s sunburn
response (Refs. 5 and 6). One
submission points out that if a
sunscreen product blocked 100 percent
of the incident UVB radiation and none
of the erythemally effective UVA
radiation, the sunscreen product would
have SPF values no higher than 11 (if
only 9 percent or 1/11 of UV radiation
reaches the skin) (Ref. 4).
We agree that UVA radiation
contributes to the development of
sunburn. Although the contribution of
UVA to sunburn is less than UVB, it is
still significant (Ref. 5). Further, as
stated in the submissions, protection
against UVA radiation is necessary to
achieve higher SPF values (Ref. 5). We
proposed including the term ‘‘UVB’’ in
the SPF statement in the 2007 proposed
rule to help consumers understand that
the SPF effectiveness rating is different
from the UVA effectiveness (star) rating
being proposed (72 FR 49070 at 49084).
However, as discussed elsewhere in this
final rule we are not requiring a UVA
effectiveness rating on the PDP (see
section III.B.). Therefore, the term
‘‘UVB’’ is not necessary as part of the
SPF statement. In this final rule, we are
not requiring the term ‘‘UVB’’ be placed
before the term ‘‘SPF.’’
In the 2007 sunscreen proposed rule,
we stated that the SPF value should be
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followed by one of the descriptors
‘‘low,’’ ‘‘medium,’’ ‘‘high,’’ or ‘‘highest’’
(proposed 21 CFR 352.50(a)). The
proposed descriptors were included to
help consumers understand the SPF
value because the label would have
included identical descriptors for the
UVA star rating. As discussed in section
III.B. of this document, we are not
requiring a UVA effectiveness rating on
the PDP. Therefore, descriptors are no
longer required to distinguish the SPF
value from the UVA rating on a
sunscreen label. Because we are not
requiring a descriptor after the SPF
value on the PDP in this document, the
request to include SPF 50 sunscreen
products in the ‘‘highest’’ category is no
longer relevant.
We received two other requests for
revision to the SPF statement with
which we do not agree. First, a
submission stated that SPF values
should only be labeled in multiples of
five to be consistent with SPF labeling
recommendations by the European
Commission (Ref. 7). Second, one
request from a submission suggested
that SPF values should be expressed as
the percent of UV absorption. The
submission argued that the current SPF
values are misleading because
consumers believe an SPF 15 sunscreen
product is not very protective even
though it screens 93 percent of UV
radiation.
We do not agree with either
submission. Based on SPF test data we
have reviewed, we find that SPF values
for sunscreen products generally can be
determined with a precision that allows
the products to be labeled with SPF
values in intervals of less than 5 units
(Ref. 1). Therefore, there is no
mathematical or statistical basis for
restricting SPF values to multiples of
five. Contrary to the second request,
consumers have relied on SPF values for
over 30 years and are familiar with this
format. Therefore, expressing SPF
values as percentages may be confusing.
It would imply that the stated
percentage of the entire UV spectrum is
absorbed by a sunscreen. However, the
SPF values only reflect protection
against the portion of the UV spectrum
that causes sunburn. Additionally, the
percentages of UV radiation screened
that the submission notes are
theoretical. The percentages are
determined in a laboratory setting and
not under actual use conditions. For
example, laboratory tests may show that
an SPF 15 sunscreen absorbs 93 percent
of UV rays, but, under actual use
conditions, the level of protection
provided by an SPF 15 sunscreen
product may be significantly below 93
percent. There are a number of factors
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that lead to this decreased protection,
the most important being underapplication of the sunscreen product (72
FR 49070 at 49092). Therefore, if SPF
values were expressed as percentages,
consumers might mistakenly believe
that the sunscreen products they are
using provide more protection than they
really do provide under actual use
conditions.
emcdonald on DSK2BSOYB1PROD with RULES3
B. Broad Spectrum Statement
In response to the 2007 proposed rule,
we received over 50 submissions
collectively making the following four
requests regarding the UVA
effectiveness rating (Ref. 1):
1. Do not require UVA 4-star rating
system.
2. Do not require ‘‘no UVA
protection’’ statement if a product does
not protect against UVA radiation.
3. Do not require the UVA statement
to be the same size as the SPF statement.
4. Perform label comprehension
studies prior to implementing proposed
PDP labeling.
The submissions included arguments,
but no data, to support these requests.
We agree with the first and second
requests. However, we are not granting
the third and fourth requests. Our
reasons for these decisions are
explained below, but we first
summarize the related provisions of this
final rule. We are not requiring a star
rating or descriptors to indicate the level
of UVA protection as proposed. Instead,
to indicate the level of UVA and UVB
protection, we are establishing a pass/
fail broad spectrum test and a broad
spectrum labeling statement. If a
sunscreen product passes the broad
spectrum test (see section VIII.B. of this
document), under this final rule, the
PDP of the product must include the
statement ‘‘Broad Spectrum SPF [insert
numerical SPF value resulting from
testing under paragraph (i) of this
section],’’ without any ‘‘UVA’’ reference
(§ 201.327(a)(1)(i)). We are requiring the
Broad Spectrum SPF statement to
appear as continuous text with no
intervening text or graphics. We are also
requiring that the entire text be the same
font style, size and color on the same
background color. (§ 201.327(a)(1)(ii)).
With regard to the submissions
received, nearly all of the 50+
submissions argued against requiring
the 4-star rating system to display the
level of UVA protection on the PDP of
OTC sunscreen products (Ref. 1). Many
submissions stated that the presence of
stars and a number (SPF) on the PDP
will lead to consumer confusion. Some
submissions argued that consumers may
be confused when determining whether
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a star is filled or empty, thereby not
knowing the UVA protection level.
Other submissions argued that
consumers are familiar with star ratings,
but that the star rating for items such as
movies and hotels are based on
recommendations and not rigorous data.
They suggested several options for
labeling UVA protection, such as a
numerical rating or another symbol
other than stars.
Some submissions suggested that the
UVA rating should be proportional to
the SPF value but requested that there
not be two ratings on the PDP. The
submissions cited the European
Commission’s recommendation that
UVA protection increase as the SPF
value increases (Ref. 7). The European
Commission recommends a minimum
UVA protection factor equal to at least
one-third of the labeled SPF or a critical
wavelength of at least 370 nm, but does
not recommend that the actual value of
the UVA protection factor or critical
wavelength be displayed. The European
Commission recommends that the main
indicator of sun protection be the SPF
value. Broad spectrum protection is
indicated by a symbol on sunscreen
labels—the acronym ‘‘UVA’’ enclosed
within a circle the diameter of which
should not exceed the height of the SPF
value.
We agree with the submissions that
the UVA star rating would likely be
confusing in conjunction with the
numerical SPF rating. We also agree
with the submissions requesting that
UVA protection should be proportional
to the SPF value. We are requiring such
proportionality in the broad spectrum
test described in this document.
Because of this proportionality, there is
no longer a need for a separate UVA
rating. Instead of a rating, we are
requiring a ‘‘broad spectrum’’ statement
on the PDP if a product has a critical
wavelength equal to or greater than 370
nm. This pass/fail ‘‘broad spectrum’’
statement is consistent with the
recommendations in the submissions
citing the recommendations of the
European Commission.
As noted, several submissions
responding to our proposal for a
separate UVA rating with stars
suggested that consumer comprehension
testing should be performed before the
proposed labeling is implemented. We
agree with the submissions that
consumer comprehension data can be
very helpful in formulating labeling
changes. In fact, in conjunction with our
1993 proposal to allow products to be
labeled as ‘‘broad spectrum’’ if they
contained sunscreen active ingredients
that absorbed UVA radiation (58 FR
28194 at 28233), we requested label
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comprehension study data to allow us to
determine consumer understanding of
the terms ‘‘broad spectrum,’’ ‘‘UVA,’’
and ‘‘UVB’’ (58 FR 28194 at 28243).
Unfortunately, the data we received
were not sufficient to allow us to
determine the level of consumer
understanding of these terms (72 FR
49070 at 49081 through 49085), and we
received no further consumer
comprehension data in response to the
2007 proposal to require the UVA star
rating. While we acknowledge the value
of consumer comprehension data, for
reasons explained below, we conclude
that conducting consumer
comprehension testing is not necessary
in this case in light of the labeling we
have selected for the final rule.
First, submissions suggesting
consumer testing were responding to the
UVA star rating in the proposed rule,
the value of which would have been
based on the results of two tests (72 FR
49070 at 49081 through 49085). As
noted, we agree with the submissions
suggesting that the 2007 UVA labeling
proposal was likely to be confusing.
Elsewhere in the document, we also
discuss our final choice of a pass-fail
test for establishing UV protection
(section VIII.B). As a result of these
changes in the underlying test method
and the submissions on the proposed
labeling, we have incorporated a much
simpler labeling statement in this final
rule. This statement designates as
‘‘broad spectrum’’ those products that
are demonstrated to have a critical
wavelength of at least 370 nm, using the
test in new 21 CFR 201.327(j).
Second, unlike in 1993 when we first
sought consumer data on the term
‘‘broad spectrum’’, and unlike the UVA
star rating that we proposed in 2007,
consumers are now likely to be familiar
with the term ‘‘broad spectrum’’ as
included in this document because
some sunscreen manufacturers have
labeled sunscreen products as ‘‘broad
spectrum’’ for over 20 years. For
example, the Johnson and Johnson
‘‘Sundown Broad Spectrum’’ line of
sunscreens was on the market in 1988
(Ref. 8). As already noted, in our 1993
proposed rule, we not only sought
consumer data, but in fact proposed that
products be permitted to be labeled as
‘‘broad spectrum’’ if they contained
sunscreen active ingredients that
absorbed UVA radiation, although we
did not at that time propose to require
a specific test to demonstrate UVA
protection (58 FR 28194 at 28233). We
continued to allow this statement in the
1999 sunscreen final rule (64 FR 27666
at 27666 through 27667).
Many consumers may also be familiar
with the term ‘‘broad spectrum’’ because
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of public health campaigns and news
articles about the importance of broad
spectrum UV protection over the last
two decades. For example, an article
appearing in Working Woman magazine
in 1990 urged women to ‘‘make sure to
look for the term ‘broad spectrum’ on
the label of a sunscreen’’ because ‘‘it
means you’re getting protection from
both types of radiation’’ (Ref. 9).
For consumers not already familiar
with the term ‘‘broad spectrum,’’ the
additional indication statement allowed
in this document for certain broad
spectrum sunscreen products should
help consumers recognize the benefit of
these products. Under ‘‘Uses’’ in Drug
Facts, broad spectrum sunscreen
products with an SPF value of 15 or
higher are allowed the following
indication statement: ‘‘if used as
directed with other sun protection
measures (see Directions [in bold italic
font]), decreases the risk of skin cancer
and early skin aging caused by the sun’’
(new 21 CFR 201.327(c)(2)).
In addition, educational campaigns
about sun protection will further inform
consumers about the benefits of using
sunscreens that include the term ‘‘broad
spectrum’’ on their labels and have an
SPF value of 15 or higher. We expect
consumers to learn that a sunscreen
labeled with the statement ‘‘Broad
Spectrum SPF’’ 15 or higher, when used
as directed with other sun protection
measures, offers more comprehensive
protection against sun-induced skin
damage than that provided by a
sunscreen that is not broad spectrum or
that are broad spectrum with an SPF
value less than 15.
It is important to note that the broad
spectrum test required in this document
captures both UVB and UVA protection
for the effectiveness of a sunscreen
product. The broad spectrum test is not
limited to UVA wavelengths as was the
case with the proposed test (see section
VIII.B of this document). By requiring
that a broad spectrum sunscreen
provide both UVB and UVA protection
in a pass/fail test, the amount of UVA
protection for a sunscreen product that
passes the test must increase as the SPF
increases. For example, a Broad
Spectrum SPF 40 sunscreen product
provides greater protection against both
UVB and UVA than a Broad Spectrum
SPF 20 sunscreen product. In contrast,
an SPF 40 sunscreen product that is not
broad spectrum provides more UVB
protection than a SPF 20 sunscreen
product that is not broad spectrum, but
may not provide more UVA protection.
This proportionality between UVB
and UVA protection is important
because consumers have been
accustomed to basing their purchase
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decision concerning protection level
primarily on the SPF value, and only
secondarily on indications of whether or
not the sunscreen provides broad
spectrum protection. For example, a
consumer seeking lower protection may
have chosen an SPF 15 sunscreen
product, whereas a consumer seeking
higher protection may have chosen an
SPF 40 sunscreen product. By creating
a clear and standardized ‘‘yes/no’’
indicator regarding broad spectrum
protection, these final labeling
requirements will enable consumers to
make better and more informed
purchase decisions by looking to see if
a product has a ‘‘Broad Spectrum SPF’’
value on the label. Thus, the ultimate
purchase decision would be based on
the numerical value associated with the
Broad Spectrum SPF statement. For
products offering broad spectrum
protection, the Broad Spectrum SPF
value on the PDP will not only indicate
the relative level of protection against
UVB radiation but will also reflect the
level of UVA protection, with increasing
SPF values indicating greater protection
against both UVA and UVB radiation.
For broad spectrum products, linking
the amount of UVA protection to the
SPF value, is consistent with the
approach taken in Europe (Ref. 7).
For broad spectrum products, we are
requiring the broad spectrum statement
on the PDP to appear in combination
with the SPF statement. For example, an
SPF 40 sunscreen product which passes
the broad spectrum test will be labeled
‘‘Broad Spectrum SPF 40’’ in a uniform
font style, size, and color and with the
same background color. This placement
will help consumers recognize that the
particular sunscreen product is broad
spectrum in conjunction with the SPF
value. As previously explained, the
broad spectrum statement and SPF
value together will provide a relative
measure of both UVB and UVA
protection. Combining the broad
spectrum and SPF statements will help
consumers become more aware of the
importance of broad spectrum
protection.
Under the 2007 proposed rule, if an
OTC sunscreen product was not tested
for or did not protect against UVA
radiation, the statement ‘‘No UVA
protection’’ would have been required
on the PDP (proposed 21 CFR
352.50(b)(1)). Ten submissions argued
against requiring this statement (Ref. 1).
Some submissions argued that this
statement is misleading because all
sunscreen products provide some UVA
protection. Submissions also stated that
a negative statement is inconsistent with
the OTC Drug Review because a drug
should only describe the indications for
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which it is effective. Other submissions
suggested that we should require all
sunscreen products to provide UVA and
UVB protection, making this statement
unnecessary.
We have concluded that the ‘‘No UVA
Protection’’ statement is not necessary
and could be misleading. Under this
final rule, the labeling on the PDP of
sunscreens no longer refers the type of
UV radiation (UVA or UVB) protection
offered; rather, products that pass the
critical wavelength test in 201.327(j) are
labeled with ‘‘Broad Spectrum SPF’’
values. Under this labeling, consumers
who see ‘‘UVA’’ on the PDP, even if it
is part of the statement ‘‘No UVA
Protection,’’ may mistakenly believe
that the product offers UVA protection.
To eliminate this potential
misunderstanding, we are not including
the ‘‘No UVA Protection’’ statement on
the PDP.
In contrast to four submissions
requesting that we make the UVA
statement less prominent than the SPF
statement, we are requiring the SPF and
broad spectrum statements to be equally
prominent on the PDP by appearing as
a combined statement. The four
submissions stated that they believe
UVB radiation contributes more to skin
cancer and photodamage than UVA
radiation and argued that more
prominence should be given to the SPF
statement. However, none of the
submissions included data to support
this argument. Some submissions
suggested that consumers are familiar
with SPF ratings and that providing
another rating with similar prominence
may mislead and confuse consumers.
It is well known that both UVA and
UVB radiation contribute to
photodamage and skin cancer (Refs. 6–
7 and 10–12). Therefore, in our view,
providing consumers with information
about the effectiveness of a sunscreen
product for UVA and UVB radiation
protection is equally important. We are
requiring that the broad spectrum
statement be displayed in combination
with the SPF statement. The two
statements must not be interrupted with
any graphics or text. In addition, the
broad spectrum statement must be the
same font style, size, and color as the
SPF statement with the same
background color. It is important for
consumers to evaluate both statements
when making a purchase decision. By
requiring this information to be
presented with identical prominence on
the PDP, consumers should be able to
quickly and easily identify sunscreen
products that provide broad spectrum
protection, as well as the SPF of all
sunscreen products. While we are not
requiring a negative statement on the
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emcdonald on DSK2BSOYB1PROD with RULES3
PDP of products that do not pass the
critical wavelength test in new
301.327(j), we caution that such
products may be misbranded if they
include statements regarding UVA
protection; such statements may
misleadingly imply that the product
provides benefits that are similar or
superior to those of products labeled
with Broad Spectrum SPF values.
C. Water Resistance Statement
In the 2007 sunscreen proposed rule
(proposed 21 CFR 352.52), we allowed
the PDP of OTC sunscreen products to
contain the statement ‘‘water resistant’’
if a sunscreen product was shown to
retain the labeled SPF value after 40
minutes of water immersion, or ‘‘very
water resistant’’ if a sunscreen product
was shown to retain the labeled SPF
value after 80 minutes of water
immersion, according to the test in
proposed 21 CFR 352.76. We
simultaneously proposed that the
‘‘Uses’’ section of labeling (not the PDP)
indicate specifically whether the
product had been established to be
water resistant for 40 minutes or 80
minutes, and included specific
directions addressing times for
reapplication of each product,
dependent on its level of water
resistance (proposed 21 CFR
352.52(b)(1)(vii), (b)(1)(viii), (d)(2), and
(d)(3); 72 FR 49070 at 49113). In this
document, we are revising the PDP to
contain the statement ‘‘water resistant
(40 minutes)’’ or ‘‘water resistant (80
minutes)’’ as determined by the water
resistance test in new 21 CFR
201.327(i)(7). We are removing this
information from the indications section
of Drug Facts (section IV.B of this
document). We continue to include
directions based on the duration of
water resistance established under the
new water resistance test (section IV.D
of this document).
One submission stated that including
information about water resistance in
the indications section as well as in the
directions section is ‘‘redundant and
confusing’’ (Ref. 1). The submission
recommended that we delete the
indications statement. We agree with
the submission. To eliminate
redundancy and simplify the labeling
for consumers, we are relocating the
information formerly contained within
the indication statement to the PDP.
The content of the labeling as a whole
is the same as that included in the 2007
proposed rule. However the proposed
statement on the PDP did not clearly
and accurately convey to consumers the
difference between ‘‘water resistant’’
and ‘‘very water resistant’’ sunscreen
products. For example, knowing that a
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sunscreen product is ‘‘very water
resistant’’ does not give any indication
of how much time a consumer can
safely spend in the water. Under the
2007 proposed rule, a consumer would
have had to read either the ‘‘Uses’’ or
the ‘‘Directions’’ section of the Drug
Facts label to determine the duration of
water resistance for a sunscreen product
(proposed 21 CFR 352.52(b)(1)(vii) and
(b)(1)(viii) and proposed 21 CFR
352.52(d)(2) and (d)(3), respectively; 72
FR 49070 at 49113).
Providing, on the PDP, specific
information about the actual time (40 or
80 minutes) a consumer can expect a
sunscreen product to retain its labeled
SPF value is likely to be more helpful
to consumers because the information is
displayed in one place—on the PDP and
not on different parts of the labeling.
The revised statements ‘‘water resistant
(40 minutes)’’ or ‘‘water resistant (80
minutes)’’ should make it clearer and
easier for consumers to understand
water resistance as part of their
purchase decision. This water resistance
information continues to be reinforced
by information in the directions
regarding reapplication.
D. UVB and UVA Educational
Statement
In the 2007 sunscreen proposed rule,
we proposed that the following
educational statement be included on
the PDP of all OTC sunscreen products
(proposed 21 CFR 352.50(c)): ‘‘UV rays
from the sun are made of UVB and
UVA. It is important to protect against
both UVB and UVA rays to prevent
sunburn and other skin damage.’’
We received four submissions
regarding the UVB and UVA
educational statement in response to the
2007 sunscreen proposed rule (Ref. 1).
The submissions made the following
requests:
• Do not require the educational
statement on the PDP or
• Combine the educational statement
with the sun alert statement and include
the combined statement in the ‘‘Other
Information’’ section of the Drug Facts
label.
We considered including the
proposed educational statement on the
PDP. We concluded that this
information is not critical for effective
use of sunscreen products, particularly
since we are no longer requiring other
PDP statements to refer separately to
UVA and UVB protection. An
understanding that the sun produces
ultraviolet (UV) rays or that there are
two types of UV rays that reach the
earth’s surface is not necessary to ensure
the safe and effective use of sunscreen
products. The explanation of these
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concepts on sunscreen labeling is
potentially confusing and could raise
additional questions about their
meaning. We could not determine a
succinct educational statement that
would not also be potentially
misleading. Therefore, we have
concluded that an educational statement
should not be required on the PDP.
As noted, submissions also requested
that the proposed educational statement
be combined with proposed sun alert,
included in the proposed rule as a
warning. In section IV.C of this
document, we address submissions on
the sun alert warning, and explain our
decision to incorporate the information
regarding the role of certain sunscreens
in reducing the risk of skin cancer and
early skin aging into a new indication
and accompanying directions for
sunscreens with Broad Spectrum SPF
values of 15 or higher. We are retaining
a modified warning to be included as
the first warning on sunscreen products
that are either not broad spectrum or
that are broad spectrum with an SPF
value less than 15. Because we are not
requiring an educational statement on
the PDP and are either eliminating or
modifying the proposed sun alert
warning, the request to combine these
two statements is no longer relevant.
IV. Drug Facts Labeling
In September 2004 (69 FR 53801), we
delayed the May 16, 2005,
implementation date for the Drug Facts
final rule (21 CFR 201.66) for OTC
sunscreen products until further notice).
The Drug Facts final rule (21 CFR
201.66) establishes general labeling
format and content requirements for all
OTC drugs. With the additional
exception of certain OTC drug products
in ‘‘convenience size’’ packages (see 67
FR 16304 at 16306 (April 5, 2002), other
OTC drug products are already required
to comply with 201.66. We delayed
implementation of 201.66 for
sunscreens so as to avoid the potential
that sunscreen manufacturers would
have to relabel their products twice
within a short time period if a final rule
specifying labeling for sunscreens
published shortly after the original May
2005 implementation date for the
general content and format requirements
of the Drug Facts final rule. We
published the notice of delay for OTC
sunscreens’ implementation of the Drug
Facts final rule so that such products
could simultaneously implement both
the general labeling provisions of that
rule and the specific labeling provisions
for sunscreens when we published a
sunscreen labeling final rule. We are
now lifting the stay on the
implementation of the Drug Facts final
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rule for OTC sunscreen products. In this
document, we are requiring the same
implementation date for the regulations
set forth in this labeling and testing final
rule (21 CFR 201.327) and in the Drug
Facts final rule (21 CFR 201.66) as
applied to these sunscreen products.
This action will benefit both
consumers and manufacturers.
Consumers will benefit by having
sunscreen labeling presented in the
Drug Facts format that they are familiar
with. Manufacturers benefit because
they will achieve compliance with two
rules through one labeling revision
(rather than following the more
expensive course of making two labeling
changes at two different times).
In 2003 (68 FR 33362, June 4, 2003),
we also stayed the part of the skin
protectant monograph that describes
GRASE combinations of skin protectant
and sunscreen active ingredients (21
CFR 347.20(d)). Because this document
addresses the labeling and testing of
sunscreen products and not the GRASE
35629
status of individual sunscreen active
ingredients, we are not lifting the stay
of 21 CFR 347.20(d).
This document requires much of the
Drug Facts labeling included in the 2007
proposed rule. However, we have made
several revisions to the proposed
labeling. These revisions are discussed
in detail throughout the remainder of
this section. In addition, table 2 of this
document summarizes these revisions
as follows:
TABLE 2—SUMMARY OF DRUG FACTS LABELING INCLUDED IN THE 2007 PROPOSED RULE AND THIS FINAL RULE
Drug facts section
2007 Proposed rule
This final rule
Active Ingredients/
Purpose.
Uses .........................
Name and amount of ingredient(s) followed by ‘‘sunscreen’’
Name and amount of ingredient(s) followed by ‘‘sunscreen.’’
• for all sunscreen products: ‘‘helps prevent sunburn.’’
• Optional, for sunscreen products with Broad Spectrum
SPF values of 15 or higher, ‘‘if used as directed with
other sun protection measures (see Directions), decreases the risk of skin cancer and early skin aging
caused by the sun.’’
Warnings ..................
UV exposure from the sun increases the risk of skin cancer, premature skin aging, and other skin damage. It is
important to decrease UV exposure by limiting time in
the sun, wearing protective clothing, and using a sunscreen.
• [low, medium, high, or highest] UVB sunburn protection
• [low, medium, high, or highest] UVA protection
• retains SPF after 80 minutes of activity in the water
For external use only
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Directions .................
Inactive Ingredients ..
Other Information .....
Questions? ...............
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Stop use and ask a doctor if skin rash occurs
When using this product keep out of eyes. Rinse with
water to remove.
Keep out of reach of children. If swallowed, get medical
help or contact a Poison Control Center right away.
Non-Water Resistant Product
• apply liberally [# minutes] before sun exposure
• reapply at least every 2 hours and after towel drying,
swimming, or sweating
• apply and reapply as directed to avoid lowering protection
• children under 6 months: Ask a doctor
Water Resistant Product
• apply liberally [# minutes] before sun exposure
• reapply after 40 [or 80] minutes of swimming or sweating
and after towel drying. Otherwise, reapply at least every
2 hours.
• apply and reapply as directed to avoid lowering protection
• children under 6 months: Ask a doctor
Water Resistant and Non-Water Resistant Products
No statement
List inactive ingredients in alphabetical order
No required statements
No required statements
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For sunscreen products that are not broad spectrum or for
products that are broad spectrum with an SPF value less
than 15, Skin Cancer/Skin Aging Alert [in bold font]:
Spending time in the sun increases your risk of skin cancer and early skin aging. This product has been shown
only to help prevent sunburn, not [in bold font] skin cancer or early skin aging.
For all sunscreens:
For external use only
Do not use on damaged or broken skin
Stop use and ask a doctor if rash occurs
When using this product keep out of eyes. Rinse with
water to remove.
Keep out of reach of children. If swallowed, get medical
help or contact a Poison Control Center right away.
Non-Water Resistant Product
• apply liberally 15 minutes before sun exposure
• use a water resistant sunscreen if swimming or sweating
• reapply at least every 2 hours
• children under 6 months: Ask a doctor
Water Resistant Product
• apply liberally 15 minutes before sun exposure
• reapply:
• after 40 [or 80] minutes of swimming or sweating
• immediately after towel drying
• at least every 2 hours
• children under 6 months: Ask a doctor
Water Resistant and Non-Water Resistant Products
For sunscreens with Broad Spectrum SPF values of 15 or
higher:
• Sun Protection Measures [in bold font]. Spending time in
the sun increases your risk of skin cancer and early skin
aging. To decrease this risk, regularly use a sunscreen
with a Broad Spectrum SPF value of 15 or higher and
other sun protection measures including:
• limit time in the sun, especially from 10 a.m.–2 p.m.
• wear long-sleeved shirts, pants, hats, and sunglasses.
List inactive ingredients in alphabetical order.
• protect this product from excessive heat and direct sun.
No required statements.
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A. Active Ingredients/Purpose
We received one submission
regarding the listing of active
ingredients and one submission
requesting that we provide specific
details about what each ingredient does
in the product (Ref. 1). One of these
submission also requested that we
require listing of the percentage of each
active ingredient next to the ingredient
name.
We are not making any changes to the
‘‘Active ingredients/Purpose’’ section of
the Drug Facts label. The general OTC
labeling regulations specify that the
‘‘quantity of each active ingredient per
dosage unit’’ be listed with the
established name of each active
ingredient (21 CFR 201.66(c)(2)).
Therefore, every sunscreen product is
already required to include the active
ingredient names followed by the
percentage (weight per volume) in the
‘‘Active ingredients/Purpose’’ section,
as requested by the first submission.
We are not requiring specific details
about what each ingredient does in the
product. The function of each active
ingredient in an OTC drug product is
already required to be listed by 21 CFR
201.66(c)(3), which specifies that the
‘‘Active ingredients/Purpose’’ section of
the label list the ‘‘general pharmacologic
categories or principal intended actions
of each active ingredient.’’ There is not
currently a requirement to list the
purpose of inactive ingredients on OTC
drug labels. This information is not
needed to safely and effectively use
sunscreen products. Therefore, in this
document, we are not requiring the
purpose of inactive ingredients to be
listed on sunscreen labels.
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B. Uses
1. Indications Statements Proposed in
the 2007 Proposed Rule
The 2007 proposed rule included
three indication statements under
‘‘Uses’’ in Drug Facts:
1. Level of UVB sunburn protection
(proposed 21 CFR 352.52(b)(1)(i)–
(b)(1)(iv))
2. Level of UVA protection (proposed
21 CFR 352.52(b)(1)(v) and (b)(1)(vi))
3. Extent of water resistance
(proposed 21 CFR 352.52(b)(1)(vii) and
(b)(1)(viii))
The first statement would have
appeared on all monograph sunscreen
products. The second statement would
only have appeared on monograph
sunscreen products providing UVA
protection. The third statement would
only have appeared on monograph
sunscreen products that are water
resistant for either 40 or 80 minutes. We
received numerous submissions from
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the public concerning these statements
following publication of the 2007
proposed rule (Ref. 1).
We are not requiring these indication
statements in this final rule. Instead, all
sunscreen products covered by this rule
will be required to include the
indication statement ‘‘helps prevent
sunburn,’’ as required in the 1999
sunscreen final rule (64 FR 27666; new
21 CFR 201.327(c)(1)). We are requiring
this statement instead of the first
proposed statement (level of UVB
sunburn protection) because we agree
with submissions arguing that sunburn
is not caused solely by UVB radiation
(Ref. 1). We also agree with submissions
arguing that the SPF value by itself on
the PDP informs consumers of the level
of sunburn protection, so a separate
description of the level of sunburn
protection does not need to be included
as an indication.
In addition, sunscreen products
covered by this rule that provide broad
spectrum protection according to the
test in new 21 CFR 201.327(j) and have
SPF values of 15 or higher, may include
the following indication statement (new
21 CFR 201.327(c)(2)(i)): ‘‘if used as
directed with other sun protection
measures (see Directions), decreases the
risk of skin cancer and early skin aging
caused by the sun.’’ This statement
replaces the second proposed indication
statement. We are allowing this
statement for certain sunscreens covered
by this rule based on available clinical
studies, the fact that UV radiation from
the sun is harmful, and the scientific
understanding that substantially
limiting overall UVB and UVA exposure
reduces the risk of skin cancer and early
skin aging.
As discussed in the remainder of this
section of the document, it is critical
that the indication statement regarding
skin cancer and early skin aging
includes information about using the
products as directed and following other
sun protection measures (listed under
the heading Directions). We have
concluded that the reference to other
sun protection measures is necessary to
ensure that the consumer’s overall UV
exposure is substantially decreased. A
consumer who relies on the use of a
sunscreen with Broad Spectrum SPF
value of 15 or higher alone may not
obtain a meaningful net decrease from
the risk of skin cancer or early skin
aging if, because he or she is wearing
the sunscreen, the consumer spends
more time in the sun and/or wears less
protective clothing. In fact, reliance on
sunscreen use alone, without also
employing other sun protection
measures, could actually result in an
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increase in the consumer’s overall UV
exposure. Therefore, if the indication
statement regarding decreasing risk of
skin cancer and early skin aging does
not include the information about using
the product as directed, which includes
following other sun protection
measures, the statement will be
considered misleading (and thus make a
sunscreen product misbranded) (new 21
CFR 201.327(c)(3)). Similarly, sunscreen
products covered by the rule that
provide broad spectrum with SPF
values between 2 and 15 or do not
provide broad spectrum protection
should not state or imply that the use of
a sunscreen product alone will reduce
the risk of skin cancer or early skin
aging. Doing so would cause the product
to be misbranded.
We are not including the third
proposed indication statement
(regarding water resistance) in this
document. As already discussed, under
this final rule, information about water
resistance is included on the PDP, as
well as under ‘‘Directions’’ in Drug
Facts (see sections III.C and IV.D of this
document). We conclude that
information about the water resistance
of a sunscreen product is more
effectively and accurately presented on
the PDP and as a direction than as an
indication statement. The extent of
water resistance informs a consumer
about how long the SPF value is
retained following water exposure and,
therefore, how long an interval can
elapse before reapplying the sunscreen
product (40 or 80 minutes). In addition,
the PDP requirements in this document
include the time interval as part of the
water resistance statement, so that
consumers can readily distinguish
between products on this basis when
making purchasing decisions. Because
we include water resistance on the PDP
and under ‘‘Directions,’’ we are not
including a separate indication
statement about water resistance in this
document.
2. Statement Regarding Skin Cancer and
Early Skin Aging
a. Submissions Arguing For a Skin
Cancer and Early Skin Aging Indication
As already stated, in this final rule we
have adopted, for the first time, an
indication for skin cancer and early skin
aging for sunscreen products covered by
the rule that have Broad Spectrum SPF
values of 15 or higher. In our 2007
proposed rule, we had included
indication statements that indicated the
degree of protection against both UVB
and UVA radiation but that linked UVB
protection only to sunburn prevention
and did not expressly link UVA
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protection to any specific health benefit
(proposed 21 CFR 352.52(a)). At the
same time, however, we had proposed
both an educational statement on the
PDP stating that UV rays from the sun
are made of both UVB and UVA and
that it is important to protect against
both types of radiation to prevent
sunburn and other skin damage
(proposed 21 CFR 352.50 (c)). We also
proposed a ‘‘sun alert’’ statement as the
first warning. This first warning read,
‘‘UV exposure from the sun increases
the risk of skin cancer, premature skin
aging, and other skin damage. It is
important to decrease UV exposure by
limiting time in the sun, wearing
protective clothing, and using a
sunscreen.’’ (proposed 21 CFR
352.52(c)(1)).
In response to our proposed rule, we
received a total of 12 submissions
asking that we include a specific
statement regarding reduction in risk of
skin cancer and early skin aging as an
indication for covered sunscreens (Ref.
1). The submissions asked that we allow
an indication statement informing
consumers that the regular, consistent,
or continued use of a sunscreen product
reduces or helps reduce the risk or
chance of developing skin damage, early
skin aging, and some types of skin
cancer (Ref. 1). These submissions also
supported our proposed requirement of
a ‘‘sun alert’’ on the labeling to inform
consumers of the need to limit time in
the sun and wear protective clothing.
The submissions came from sunscreen
manufacturers and public health
organizations including the American
Academy of Dermatology, the American
Cancer Society, and the Skin Cancer
Foundation. Many of the submissions
provided references to studies that they
argued support the inclusion of this
indication statement. One submission
specifically requested that we allow an
anti-aging claim (without mention of
skin cancer), and one other submission
argued that no sunscreen can claim to
prevent cancer (Ref. 1). We received no
new data to accompany these requests
for a separate indication that the regular
use of sunscreen decreases the risk of
skin cancer and early skin aging.
However, on reconsideration of the data
reviewed prior to the 2007 proposed
rule, we agree with the argument that
the data underpinning our proposed
education statement and warning are
sufficient to support an appropriately
qualified skin cancer and premature
skin aging indication for one subset of
sunscreens covered by this rule—those
that have Broad Spectrum SPF values of
15 or higher. As a result, our final rule
provides different labeling for these
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sunscreens than for sunscreens covered
by the rule that are not broad spectrum
or that provide broad spectrum with
SPF values less than 15. In addition, we
conclude that such an indication should
not be included in the Warnings section
of Drug Facts. We have concluded that,
as proposed in 2007, the second
sentence of the first warning (i.e., the
‘‘Sun Alert’’ warning) is an implied
indication: ‘‘It is important to decrease
UV exposure by limiting time in the
sun, wearing protective clothing, and
using a sunscreen.’’ Because it follows
a warning that ‘‘UV exposure from the
sun increases the risk of skin cancer,
premature skin aging, and other forms of
skin damage,’’ the second sentence
implies that using any sunscreen,
regardless of SPF value or broad
spectrum protection, and following
other sun protection measures will
decrease the risks of skin cancer, early
skin aging, and other consequences of
UV exposure to the sun. We have
concluded, based on a reconsideration
of data previously reviewed in the 2007
proposed rule, that, if consumers use
broad spectrum sunscreens with SPF
values of 15 or higher and follow other
sun protection measures, they can
reduce their risk of skin cancer and
early skin aging. For these products, we
agree with the public submissions that
this information is most appropriately
placed as an indication (i.e., under Uses)
with a reference to the need to use the
product as directed with other sun
protection measures. For these products,
we include under the heading
Directions, specific reference not only to
regularly use sunscreens with Broad
Spectrum SPF values of 15 or higher
(the subset of sunscreens for which the
indication is allowed) but also to
employ the other listed sun protection
measures listed under Directions. For
sunscreen products covered by this rule
that are not Broad Spectrum or that are
broad spectrum with an SPF value less
than 15, however, we conclude that
existing data are insufficient to support
an indication for reducing risk of skin
cancer or early skin aging. In the
sections that follow, we explain the
specific scientific basis for our
conclusion, as well as explain our
rationale for the specific framing of the
labeling, as included in the final rule,
for both subsets of the sunscreens
covered by the final rule—those that
have Broad Spectrum SPF values of 15
or higher and those that do not have
Broad Spectrum or that are Broad
spectrum with SPF values less than 15.
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35631
b. Limiting Overall UV Exposure
Reduces Risk of Skin Cancer and Early
Skin Aging
For drugs subject to OTC monographs,
like sunscreen products, indication
statements about the effectiveness of the
drug products must be supported with
scientific data (21 CFR 330.10(a)(4)(ii)).
In order for an OTC drug to be
considered generally recognized as
effective (GRAE), there must be a
reasonable expectation that, in a given
proportion of the target population, the
drug will provide clinically significant
relief of the type claimed (21 CFR
330.14(a)(4)(ii)). Based on the available
data concerning the harmful effects of
UV radiation and sunscreen UV
protection, we have concluded that
sunscreens, in conjunction with the
critical behavioral steps of limiting time
in the sun particularly during the
midday hours and wearing protective
clothing (long sleeve shirt, pants, hat,
and sunglasses), provide ‘‘clinically
significant relief’’ in reducing the risk of
skin cancer and early skin aging. Based
on the available data, we have limited
this claim to broad spectrum sunscreen
products with an SPF value of 15 or
higher.
UV radiation from the sun has been
associated with nonmelanoma skin
cancers since 1927 and with melanomas
since 1952 (Ref. 13). It is estimated that
as much as 90 percent of melanomas
and nonmelanomas are caused by sun
exposure (Ref. 5). In 1992, the
International Agency for Research on
Cancer (IARC), under the auspices of the
World Health Organization, identified
UV radiation as a human carcinogen 3
(Ref. 14). More recently, broad spectrum
UV radiation was listed as a human
carcinogen in the National Toxicology
Program’s 11th Report on Carcinogens
issued in 2005 (Ref. 15). It is important
to note that this report indicates that
UVB and UVA radiation across the
spectrum are known human
carcinogens, but that either UVB
radiation alone or UVA radiation alone
is ‘‘reasonably anticipated to be a
human carcinogen.’’ This classification
is due to the fact that the exact
wavelengths of UV radiation that cause
different harmful effects (e.g., DNA
damage or loss of skin elasticity) have
not yet been identified. It is clear,
though, that broad spectrum UV
radiation causes skin cancer. Broad
spectrum UV radiation has also been
shown to cause other types of skin
damage, including early skin aging
(Refs. 6 and 16). Therefore, we agree
3 A carcinogen is anything that is known to cause
the development of cancer. UV radiation is known
to cause skin cancer.
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with the principle that a reduction, of
sufficient magnitude, in broad spectrum
UV exposure should reduce the risk of
harmful effects to the skin, including
skin cancer and early skin aging.
Broad spectrum sunscreens, by
absorbing UVA and UVB radiation,
decrease consumer exposure to both
types of UV radiation from the sun that
reach the earth’s surface. Other critical
behavioral steps, such as limiting time
in the sun and wearing protective
clothing, also decrease consumer
exposure to UVA and UVB radiation.
After considering the submissions and
other available data, we have concluded
that a claim for the reduction in risk of
skin cancer and early skin aging is
appropriate for certain sunscreen
products, when the claim also includes
the requirement that consumers use the
product as directed and the Directions
specify other sun protection measures
be followed (see section IV.D of this
document). We are basing this claim on
the scientific understanding of the harm
from UVA and UVB radiation and the
absorption and/or reflection of that UV
radiation by broad spectrum sunscreens,
as well as data from studies concerning
sunscreen use and the development of
skin cancer or precursors of skin cancer
(section IV.B.2.c of this document).
For a sunscreen to be effective (i.e.,
provide ‘‘clinically significant relief’’) in
reducing the risk of skin cancer and
early skin aging, consumers must not
increase their overall exposure to UV
radiation by overreliance on sunscreen
use. Other behavioral factors could
account for such an increase, such as
the amount of time spent in the sun and
the use of protective clothing. If
consumers rely on sunscreen use to
spend more time in the sun and/or to
wear less protective clothing, then
consumers could actually increase their
overall UV exposure, which would
eliminate the effectiveness of sunscreen
use in reducing the risk of skin cancer
and early skin aging.
To illustrate this point, it is helpful to
consider what has been termed the
‘‘compensation hypothesis.’’ As we
noted in the 2007 proposed rule, the
compensation hypothesis states that
consumers who wear high SPF
sunscreens generally spend more time
in the sun and/or wear less protective
clothing (72 FR 49070 at 49086). If the
hypothesis is true, consumers would not
reduce their risk of skin cancer or early
skin aging because their overall UV
exposure increases, even though a
properly applied (and reapplied)
sunscreen absorbs UV radiation and
helps prevent sunburn. We cited two
retrospective studies which support the
compensation hypothesis in the 2007
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proposed rule (72 FR 49070 at 49086).
Reynolds et al. published a study in
1996 finding, in a study of 509 sixthgraders, that adolescents who used
sunscreen on both Saturday and Sunday
of a Labor Day weekend spent
significantly more time in the sun than
those who used sunscreen only one day
or not at all (Ref. 17). In the second
study, parents of 503 children, aged less
than 2 to 12 years, were surveyed as to
parental attitudes about their children’s
sun exposure (Ref. 18). The authors
reported that ‘‘sunscreen use in children
was significantly associated with longer
duration of sun exposure’’ (Ref. 18).
Increased overall UV exposure might,
in fact, increase the risk of skin cancer
and early skin aging, despite the proper
use of sunscreens. Likewise, if
consumers limit time in the sun,
especially during midday, and wear
more protective clothing (such as broad
brimmed hats, long pants, and long
sleeve shirts) while outside, but do not
use sunscreens for areas of the skin
exposed to the sun (such as parts of face
and neck), then the consumer may not
decrease the risk of skin cancer and
early skin aging for sun-exposed areas.
For these reasons, for products that are
entitled to include an indication for
reducing the risk of skin cancer and
early skin aging, we continue to direct
consumers to follow a comprehensive
sun protection program that includes
use of sunscreens with Broad Spectrum
SPF values of 15 or higher, limiting time
in the sun, and wearing protective
clothing, similar to the sun protection
measures discussed in the 2007
proposed rule (72 FR 49070 at 49089).
Nearly identical multi-step behavioral
sun protection programs are advocated
by a number of medical and public
health organizations, including the
American Academy of Dermatology, the
Skin Cancer Foundation, and the
American Cancer Society.
We have concluded that a
comprehensive sun protection approach
is critical to ensure that consumers who
are seeking to obtain a reduction in the
risk of skin cancer and early skin aging
limit their overall sun exposure.
Without the reduction in consumers’
overall UV exposure, even a sunscreen
with Broad Spectrum SPF value of 15 or
higher may not be effective in
decreasing the risk of skin cancer and
early skin aging. As discussed below,
the available clinical studies do not
control for these behavioral factors and,
therefore, do not demonstrate that even
this subset of sunscreens alone reduce
the risk of skin cancer and early skin
aging. However, based on the scientific
understanding of the harm from UV
exposure and our assessment of the
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study data, we have concluded that if
consumers use sunscreens with Broad
Spectrum SPF values of 15 or higher,
limit time in the sun especially during
the midday hours, and wear protective
clothing when exposed to the sun, the
resulting reduction in overall UV
exposure will reduce the risk of skin
cancer and early skin aging. Therefore,
there is sufficient evidence of
‘‘clinically significant relief’’ to justify
the indication and related directions for
this subset of products, as set forth in
the rule. However, we conclude that the
omission of prominent information in
the indication regarding the need for
other sun protection measures would
misbrand the product, as would the
omission of the associated direction
specifying these measures. Indeed, it
would suggest a different indication
than that which available evidence
supports. Consequently, we have
included in this final rule a new
provision indicating that ‘‘Any labeling
or promotional materials that suggest or
imply that the use, alone, of any
sunscreen reduces the risk of or
prevents skin cancer or early skin aging
will cause the product to be misbranded
under section 502 of the FD&C Act (21
U.S.C. 352).’’ (new 21 CFR
201.327(c)(3)).
c. Available Scientific Data
We are not aware of any data other
than what we reviewed in the 2007
proposed rule that evaluate the
effectiveness of sunscreens in reducing
the risk of skin cancer or early skin
aging for healthy subjects. One more
recent study, published in 2009, found
that regular use of Broad Spectrum SPF
50+ sunscreen ‘‘may prevent’’ the
development of actinic keratoses and
non-melanoma skin cancer in immunecompromised organ transplant
recipients (Ref. 19). We have not relied
on this study in reaching our
conclusions regarding OTC sunscreens,
because we do not consider the
immune-compromised study population
to be representative of the general
population.
We have re-evaluated the data
originally reviewed in preparing the
2007 proposed rule to determine
whether those data support allowing the
indication for all sunscreen products or
only for certain sunscreen products.
Based on our re-evaluation, we have
concluded that the data is supportive of
an indication for broad spectrum
sunscreens having SPF values of at least
15. Further, we have determined that,
while the existing evidence does not
support a claim for the use of any
sunscreen alone, it does support an
indication that the combination of using
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a sunscreen with Broad Spectrum SPF
value of 15 or higher along with other
sun protection measures, reduces the
risk of skin cancer and early skin aging,
consistent with other positions in the
2007 proposed rule (72 FR 49070 at
49087 through 49090).
To date, there are no clinical studies
demonstrating that use of any sunscreen
alone can prevent skin cancer. There are
two prospective 4 studies that directly
examine the role of sunscreen products
in preventing skin cancer. Although it
did not show any difference in primary
endpoints, a large 1999 study conducted
in Australia demonstrated that people
who applied a Broad Spectrum SPF 15
sunscreen product on a daily basis over
a 4.5 year period had a lower overall
incidence of one type of skin cancer,
squamous cell carcinoma, on the head,
neck, arms, and forearms than study
participants who did not apply
sunscreen (28 cases in the broad
spectrum sunscreen group vs. 46 cases
in the group not using broad spectrum
sunscreen) (Ref. 20). In an extension of
that study, van der Pols et al. evaluated
the same population of subjects over an
additional 8 years, and found that the
sunscreen users continued to have a
statistically significant lower incidence
of squamous cell carcinoma over the
entire 12.5 year period (Ref. 21). Neither
study found that daily sunscreen use
had any measurable effect on the most
common form of skin cancer, basal cell
carcinoma. Further, we are not aware of
any studies examining the effect of
sunscreen use on the development of
melanoma, which is the deadliest form
of skin cancer.
Although data from clinical studies
addressing the specific end points of
cancer is limited, some prospective
studies have evaluated the effects of
regular sunscreen use on the
development of surrogate skin lesions
that can be precursors to cancer: actinic
keratoses and melanocytic nevi. A small
percentage of actinic keratoses progress
to squamous cell carcinomas (Ref. 22).
At least four studies have demonstrated
that the number of actinic keratoses is
lower for individuals regularly using
sunscreens with Broad Spectrum SPF
values of 15 or higher (Refs. 23 through
26). We are not aware of any studies
examining the potential effects on
surrogate skin lesions of sunscreens that
either are not broad spectrum or are
4 A prospective study is designed to study
subjects under pre-specified conditions. These
studies differ from retrospective studies that try to
prove hypotheses by assessing past experiences.
Generally, prospective studies are superior to
retrospective studies in demonstrating drug
effectiveness.
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broad spectrum with SPF values less
than 15.
Two prospective studies have shown
that regular use of a Broad Spectrum
SPF 30 sunscreen reduces the risk of
developing melanocytic nevi, which can
progress into melanomas (Ref. 22). In a
2000 study, Gallagher et al. examined
the formation of new melanocytic nevi
in 393 Canadian school children. The
group of children given Broad Spectrum
SPF 30 sunscreen product had fewer
new nevi over the course of the three
year study than did children not given
sunscreen products or advice on
sunscreen use (Ref. 27). The difference
was small (24 v. 28 nevi, respectively),
but statistically significant (p = 0.048).
In a follow-up study published in 2005,
Lee et al. evaluated the same group of
children for differences in melanocytic
nevi by location on the body and
demographic factors (Ref. 28). These
investigators found that the sunscreen
group had significantly fewer new nevi
on the trunk than the control group
(p = 0.05).
With respect to the role of sunscreen
products in decreasing the risk of early
skin aging, we are aware of only indirect
evidence that sunscreen use decreases
early skin aging. One recent study
demonstrated that a broad spectrum
sunscreen product can reduce the extent
of solar UV-induced damage to factors
associated with early skin aging even
when the SPF value is less than 10 (Ref.
29). Although this study was small,
evaluating only 12 Caucasian subjects, it
shows the importance of broad
spectrum protection. These findings
have been corroborated in a large
number of studies using broad spectrum
sunscreens with SPF values ranging
from 19 to 50, as reported by Fourtanier
et al. in two recent reviews (Refs. 10 and
30).
Neither those studies evaluating the
long term effect of regular sunscreen use
on the development of skin cancer and
early skin aging nor those evaluating the
long term effect of sunscreen use on
surrogate markers for these conditions
were adequately controlled. Such
studies, which must take place over
many years, make adequate controls
extremely difficult, if not impossible to
implement. For example, one cannot
control for time and duration of
exposure, application and re-application
amounts, or use of supplemental
behavioral measures such as wearing
protective clothing for a study which
takes place over several years.
Despite their limitation, the results of
the short-term effectiveness studies are
consistent with our understanding that
measures which significantly reduce UV
exposure decrease the risk of skin
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cancer and early skin aging. UVA and
UVB radiation is the only known
external risk factor for skin cancer and
early skin aging. Therefore, measures
that significantly reduce both UVA and
UVB exposure should decrease the risk
of skin cancer and early skin aging.
Based on this understanding, limiting
time in the sun, wearing protective
clothing and using a broad spectrum
sunscreen with an SPF value of 15 or
higher should decrease the risk of skin
cancer and early skin aging. Using a
broad spectrum sunscreen with an SPF
value of 15 or higher ensures adequate
breadth and magnitude of UVA and
UVB protection. For these products, the
broad spectrum test measures breadth
and SPF test measures magnitude of UV
protection. Consistent with this
scientific principle, the short-term
effectiveness studies demonstrate a
decrease in the development of
surrogates for skin cancer and early skin
aging. Thus, we have concluded that the
available evidence supports our finding
that sunscreen products, in conjunction
with limiting time in the sun and
wearing protective clothing, reduce the
risk of developing skin cancer or early
skin aging.
d. Indication Limited to Covered
Sunscreens With Broad Spectrum SPF
Values of 15 or Higher
In light of the submissions requesting
that we reframe our labeling information
regarding sunscreen use and reduced
risk of skin cancer and premature skin
aging as an indication, we re-evaluated
skin cancer and aging studies discussed
in the 2007 proposed rule to determine
whether the skin cancer and early skin
aging indication should apply to all
sunscreen products or be limited to
certain sunscreen products. Available
data support this indication only for
broad spectrum sunscreens with SPF
values of 15 or higher. Several reports
have indicated that UV-induced skin
damage associated with both skin
cancer and early skin aging can be
reduced by the use of broad spectrum
sunscreens (Refs. 10 and 29 through 31).
In a direct comparison of a broad
spectrum sunscreen and a non-broad
spectrum sunscreen with the same SPF,
Moyal and Fourtanier found that the
broad spectrum sunscreen provided
significantly better protection from UV
radiation-induced immunosuppression,
a factor associated with both skin cancer
and early skin aging (Ref. 32).
Furthermore, the National Toxicology
Program classified broad spectrum UV
radiation as a known human carcinogen
because it is not clear which UVB and/
or UVA wavelengths contribute to the
development of cancer (Ref. 15).
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Therefore, available data indicate that a
broad spectrum sunscreen is necessary
to reduce the risk of skin cancer.
Likewise, we do not know which UVB
and/or UVA wavelengths contribute to
early skin aging. Therefore, it is
reasonable to conclude that reducing the
risk of early skin aging also requires a
broad spectrum sunscreen (in
conjunction with limiting time in the
sun and wearing protective clothing).
With regard to SPF value, the
available study data concerning the use
of sunscreens in reducing the risk of
skin cancer is based on products with
SPF values of 15 or higher. The
sunscreen product used in the 1999
Australian study on skin cancer
(squamous cell and basal cell
carcinomas) had a Broad Spectrum SPF
value of 16, and those that were found
to reduce actinic keratoses and nevi had
SPF values ranging from 16 to 46. The
studies on early skin aging make it
difficult to know for certain whether
Broad Spectrum SPF values of 15 or
higher are necessary to reduce the risk
of early skin aging. However, we
conclude that the data regarding the
minimum sunscreen protection
necessary to reduce the risk of skin
cancer can be extrapolated to early skin
aging. In many ways, the biological
processes that take place in response to
UV radiation are similar for both
conditions. For both skin cancer and
early skin aging, UV radiation causes
damage in the skin that is not
completely repaired and leads to cancer,
fine lines, wrinkles, etc. Because the
supporting data for a skin cancer claim
are based on products with SPF values
of 15 or higher, we are only allowing the
skin cancer and early skin aging claim
for covered sunscreen products that are
broad spectrum and have SPF values of
at least 15. This rule does not preclude
approval of a new drug application
including an indication for reduction in
risk of skin cancer and early skin aging
for any sunscreen product. To be
approved, such an application must be
supported by the submission of
adequate data. This rule also does not
preclude future amendment of the
sunscreen monograph in 21 CFR part
352, if additional data are provided to
support a similar indication for other
types of sunscreens.
e. Precedent for an Indication Statement
That Includes Behavior Modification
There is at least one other OTC drug
product with an indication statement
that describes not only the drug’s
intended effect but also one or more
behavioral measures to ensure the effect.
The indication statement on the weight
loss aid orlistat states that the product
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is to be used ‘‘for weight loss in
overweight adults, 18 years and older,
when used along with a reduced-calorie
and low-fat diet’’ (Ref. 33). The
behavioral measure of reduced caloric
intake is necessary for consumers to
experience weight loss. A low-fat diet is
necessary for consumers to avoid the
undesirable side effect of diarrhea
caused by consuming a high-fat diet
while taking orlistat.
The need to include reduced caloric
intake as part of the indication
statement for orlistat is similar to the
need for including the use of other sun
protection measures as part of the
indication statement for sunscreens.
Orlistat increases the likelihood of
weight loss by preventing fat from being
absorbed as food is digested in the
stomach and intestines. If consumers
take orlistat and decrease their caloric
intake, they increase the likelihood of
losing weight. However, if consumers
increase their caloric intake while
taking orlistat, they are less likely to
lose weight. Orlistat’s effect of
preventing fat absorption could be offset
by the high number of calories being
eaten. Similarly, the reduction in UV
exposure afforded by use of broad
spectrum sunscreens with SPF values of
15 or higher can be offset if consumers
increase their UV exposure by spending
more time in the sun and/or wearing
less protective clothing. This increased
overall exposure could eliminate the
effectiveness of sunscreen use in
reducing the risk of skin cancer and
early skin aging.
The labeling of prescription
cholesterol-lowering drug products (i.e.,
statins) follows a similar principle by
emphasizing that reduction of
cholesterol levels requires not only use
of the drug product but also a healthy
diet. The National Institutes of Health
(NIH) specifies therapeutic lifestyle
changes that can be followed to lower
levels of cholesterol in the blood (Ref.
34). These changes include following a
diet restricted in saturated fat and
cholesterol, exercising regularly, and
managing weight. Used in conjunction
with cholesterol reducing drugs
(currently available only by
prescription), these lifestyle changes
improve the chance of effectively
treating high cholesterol levels.
Prescription cholesterol-lowering
drug products include the behavioral
step of following a low fat diet in the
indication statement (Ref. 35). The body
produces cholesterol, which the drug
product inhibits to produce the desired
drug effect of lowering cholesterol being
made by the body. However, the total
cholesterol circulating in the blood
reflects cholesterol made by the body
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plus cholesterol absorbed from foods
containing fats. Therefore, if consumers
use a statin and minimize the amounts
of food containing fats in their diet, then
they will reduce the total cholesterol
level in the blood. However, if
consumers do not minimize the
amounts of food containing fats in their
diet, they may not reduce the total
cholesterol in the blood. The decreased
cholesterol production in the body
caused by the statin may not be
significant compared to the high amount
of cholesterol derived from food eaten
by consumers.
In the same way that regularly taking
an OTC weight loss aid or a prescription
cholesterol-lowering drug product
without also following a healthy diet
may not result in the intended health
effect, use of a sunscreen with Broad
Spectrum SPF value of 15 or higher
without also limiting time in the sun
and covering sun-exposed areas may not
result in a net reduction in the risk of
developing skin cancer or early skin
aging. For this reason, we are requiring
that the indication statement allowed on
sunscreens with Broad Spectrum SPF
values of 15 or higher include all parts
of the sun protection program and not
suggest or imply that use of a sunscreen
alone reduces the risk of skin cancer or
early skin aging.
C. Warnings
We received submissions requesting
that we revise warnings included in the
2007 proposed rule and that we add
new warnings not included in the 2007
proposed rule (Ref. 1). In section IV.C.1
of this document, we discuss one new
and one revised warning included in
this final rule. We are adding the new
warning ‘‘Do not use on damaged or
broken skin’’ (new 21 CFR
201.327(d)(1)). We are revising the
warning about skin rash (proposed 21
CFR 352.52(c)(3)): ‘‘Stop use and ask a
doctor if skin rash occurs’’ to read ‘‘Stop
use and ask a doctor if rash occurs.’’
In section IV.C.2 of this document, we
discuss our revision to the proposed
‘‘Sun Alert’’ warning. Under this final
rule, the warning proposed for all
monograph sunscreens is replaced with
an optional indication and required
direction on covered sunscreens with
Broad Spectrum SPF values of 15 or
higher, while covered sunscreens that
are broad spectrum with SPF values less
than 15 or that do not provide broad
spectrum protection will bear a revised
warning, called the ‘‘Skin Cancer/Skin
Aging Alert.’’ (new 21 CFR
201.327(d)(2)).
In section IV.C.3 of this document, we
discuss three new warnings that were
requested in submissions, but are not
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being included in this document.
Submissions argued that we should add
warnings that the regular use of
sunscreen products may cause vitamin
D deficiency and may reduce the
photoprotective effects of tanning. We
also considered adding a warning
concerning sunscreen products
containing alpha hydroxy acids (AHAs).
We are not adding any of these warnings
because the available data do not
support the need for these warnings.
In summary, this document requires
the following warnings on all covered
OTC sunscreen products (new 21 CFR
201.327(d)):
• ‘‘Do not use on damaged or broken
skin’’
• ‘‘Stop use and ask a doctor if rash
occurs’’
• ‘‘When using this product keep out
of eyes. Rinse with water to remove.’’
For all covered sunscreen products that
either are not broad spectrum or are
broad spectrum with SPF values less
than 15, this final rule also requires a
‘‘Skin Cancer/Skin Aging Alert’’ as the
first statement under the heading
Warnings. In addition to these warnings,
all sunscreen products are required to
include the ‘‘external use’’ and ‘‘keep
out of reach of children’’ warning
statements required on all topical OTC
drug products (21 CFR 201.66(c)(5)(i)
and (c)(5)(x)).
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1. New and Revised Warnings for
Damaged or Broken Skin and Rash
The new warning that we are
requiring on all covered sunscreen drug
products reads, ‘‘do not use on damaged
or broken skin.’’ We require this
warning or a similar warning for other
topical OTC drug products:
• Acne treatments (21 CFR
333.350(c)(3))
• Skin protectants (21 CFR
347.50(c)(6))
• Antiperspirants (21 CFR
350.50(c)(1))
The safety data for these ingredients are
based on application to intact (i.e.,
unbroken or undamaged) skin. We do
not have data of the safe use of these
ingredients if the skin is not intact. For
the same reason, the warning appears on
sunscreen products marketed under
new drug applications (NDAs).5
Therefore, in this document, we are
requiring this warning for all covered
OTC sunscreen products, which are
marketed without approved
applications (new 21 CFR
201.327(d)(1)(i)).
In addition to the new warning, we
are revising the warning in proposed 21
5 NDAs
21–501, 21–502, 21–471, and 22–009.
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CFR 352.52(c)(3): ‘‘Stop use and ask a
doctor if skin rash occurs.’’ We are
deleting the word ‘‘skin’’ so that the
new warning reads: ‘‘Stop use and ask
a doctor if rash occurs’’ (new 21 CFR
201.327(d)(1)(iii)). We received two
submissions arguing that the word
’’skin’’ is unnecessary in this warning
because every rash is a skin rash (Ref.
1). We agree and are removing the word
to make the warning more concise.
Consumers will likely understand the
warning without the word ‘‘skin.’’
2. Revision of the Proposed ‘‘Sun Alert’’
Warning
In 2007, we proposed a warning,
based on the ‘‘Sun Alert’’ statement
cited in the 1999 stayed sunscreen final
rule (64 FR 27666 at 27679), as the first
statement under the heading Warnings
for all monograph sunscreen products
regardless of SPF value or broad
spectrum protection (proposed 21 CFR
352.52(c)(1)). As proposed, this warning
would have stated, ‘‘UV exposure from
the sun increases the risk of skin cancer,
premature skin aging, and other skin
damage. It is important to decrease UV
exposure by limiting time in the sun,
wearing protective clothing, and using a
sunscreen.’’ Submissions regarding this
proposed warning are discussed in
section IV.B.2 of this document. As
noted there, we agree that, as proposed,
this warning included an implied
indication that all sunscreens reduce the
risk of skin cancer and skin aging.
Under this final rule, we are no longer
requiring a ‘‘Sun Alert’’ or similar
warning on broad spectrum sunscreens
with SPF values of 15 or higher covered
by the rule. This decision is based on
our re-evaluation of the available
scientific data. We are now permitting
an indication stating that, used as
directed with other sun protection
measures, these sunscreens reduce the
risk of skin cancer and premature skin
aging (new 21 CFR 201.327 (c)(2)).
For these products we are also
requiring a new direction statement
(new 21 CFR 201.327(e)(1)(iv)). The
direction states:
Sun Protection Measures. [in bold font]
Spending time in the sun increases your risk
of skin cancer and early skin aging. To
decrease this risk, regularly use a sunscreen
with a Broad Spectrum SPF of 15 or higher
and other sun protection measures including:
[bullet] limit time in the sun, especially from
10 a.m.–2 p.m. [bullet] wear long-sleeved
shirts, pants, hats, and sunglasses
We have concluded that information
about decreasing sun exposure and
wearing protective clothing is more
appropriate in ‘‘Directions’’ than in
‘‘Warnings.’’ These measures, in
addition to use of a sunscreen with
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Broad Spectrum SPF value of 15 or
higher, are necessary for the consumers’
sun protection as part of a
comprehensive program.
For covered sunscreen products that
do not provide broad spectrum
protection or those that do provide
broad spectrum protection with SPF
values less than 15, we conclude that a
warning regarding the risks of skin
cancer and skin aging remains
necessary. In light of comments received
on the ‘‘Sun Alert’’ warning proposed in
2007, however, we are revising the text
to read as follows: ‘‘Skin Cancer/Skin
Aging Alert [in bold font]: Spending
time in the sun increases your risk of
skin cancer and early skin aging. This
product has been shown only to help
prevent sunburn, not [in bold font] skin
cancer or early skin aging.’’ (new 21
CFR 201.327(d)(2). The title ‘‘Skin
Cancer/Skin Aging Alert’’ more
accurately and specifically conveys the
nature of the warning that follows than
the proposed ‘‘Sun Alert’’ warning,
particularly since the products that will
bear this statement are indicated to help
prevent sunburn, one consequence of
sun exposure. The first sentence of this
warning is a factual statement similar in
content to the opening statement of the
warning proposed in 2007. Like the
proposed ‘‘Sun Alert’’ warning, this
statement alerts consumers to risks they
continue to incur from sun exposure,
the conditions under which they will
make use of the product. The second
sentence clarifies for users the limits on
the benefits that the product in hand has
been established to provide, specifying
that these products have been shown to
help prevent sunburn but have not been
shown to reduce the risk of skin cancer
or early skin aging. Inclusion of this
warning is critical to help ensure that
consumers do not mistakenly conclude
that all sunscreens have been
demonstrated to provide the same
benefits. It will reinforce the distinction
between sunscreens indicated only for
preventing sunburn (those that have
broad spectrum with SPF values below
15 or that are not broad spectrum) and
sunscreens that have also been shown to
reduce the risk of skin cancer and early
skin aging when used as directed with
other sun protection measures (those
with Broad Spectrum SPF values of 15
or higher). This warning serves a similar
purpose to one required on cosmetic
suntanning preparations that do not
contain a sunscreen ingredient, which
likewise is intended to assist consumers
in distinguishing among products that
they might otherwise confuse. (See 21
CFR 740.19).
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3. Warnings Requested in Submissions
But Not Included in This Final Rule
We considered adding the following
three warnings:
• Sunscreens may reduce the
photoprotective effects of tanning
• Increased sun sensitivity caused by
alpha hydroxy acids (AHAs) in
sunscreen products
• Regular use of sunscreen products
may cause vitamin D deficiency
However, as discussed in this section of
the document, we conclude that these
warnings are not needed for the safe and
effective use of sunscreen products.
We received a submission arguing
that we should require the following
warning on all OTC sunscreen products
containing UVA-protective active
ingredients (Ref. 1): ‘‘The use of this
product will prevent the development of
photo-protective facultative
pigmentation, a.k.a., a tan.’’ The
submission implies that UVA protection
is not only unnecessary but harmful to
consumers. No data were included in
the submission.
We agree that tanning caused by UVA
radiation offers some protection against
sunburn. However, tanning, particularly
when attributable to prolonged exposure
to UVA radiation in tanning beds or
booths, may also have harmful effects
on the skin (Refs. 36 and 37). In
addition, one study suggests that the
protective effects of tanning are small,
as a tan only appears to provide an SPF
value of approximately 4 (Ref. 36). As
stated in the 2007 proposed rule (72 FR
49070 at 49083), we do not know which
UVA wavelengths cause specific types
of damage (e.g., skin cancer or early skin
aging). We continue to assert, however,
that protection against UVA radiation is
important for consumers’ health (72 FR
49070 at 49083). We have concluded
that the warning suggested in the
submission is not in the best interest of
public health because the warning
discourages consumers from using
broad spectrum sunscreen products.
Therefore, we are not requiring any
warning related to tanning.
We are not adding any additional
warnings to sunscreen products
containing AHAs. In the 2007 proposed
rule, we requested comment on the need
for additional warnings or directions on
sunscreen products combined with
AHAs (72 FR 49070 at 49110). We made
this request in response to a 2005
guidance that we issued for cosmetic
products containing alpha hydroxy
acids (70 FR 1721, January 10, 2005).
The guidance recommends the
following warning be included on
cosmetic products containing alpha
hydroxy acids: ‘‘Sunburn Alert: This
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product contains an alpha hydroxy acid
(AHA) that may increase your skin’s
sensitivity to the sun and particularly
the possibility of sunburn. Use a
sunscreen and limit sun exposure while
using this product and for a week
afterwards.’’
Many cosmetic products containing
alpha hydroxy acids also contain
sunscreens because the sunscreen helps
protect the skin made sensitive to the
sun by the alpha hydroxy acids. The
guidance does not address products
combining alpha hydroxy acids and
sunscreens.
Two submissions stated that
additional warnings are not necessary
on these products (Ref. 1). We agree
with these submissions. We considered
added a warning or other labeling to
inform consumers that AHAs contained
in some sunscreen products may make
the consumer more likely to sunburn.
However, the sunscreen component of
such products would, in fact, protect
consumers from sunburn. Furthermore,
we have concluded that the addition of
sunscreen active ingredients to AHAcontaining cosmetic products provides
valuable UV protection for consumers.
Therefore, at this time, we have
concluded that a warning about AHA is
not necessary on OTC sunscreen
products.
The other new warning requested in
submissions relates to vitamin D
deficiency. We received six submissions
arguing that consumers should be
warned that frequent sunscreen use may
result in vitamin D deficiency (Ref. 1).
The submissions cite articles discussing
the negative effects of vitamin D
deficiency, such as growth retardation,
rickets, and osteoporosis (Ref. 38). The
submissions include numerous
published articles concerning vitamin
D, but only four clinical studies that
directly examine the effect of sunscreen
use on vitamin D levels. In the
remainder of this section, we discuss
the four studies included in
submissions, as well as three additional
studies that we located through a
literature search. Collectively, the
studies do not demonstrate that the use
of sunscreen causes vitamin D
deficiency.
The term ‘‘vitamin D’’ refers to several
forms of the vitamin, but the two forms
important to humans are vitamin D2
(ergocalciferol) and vitamin D3
(cholecalciferol) (Ref. 39). Vitamin D2 is
obtained by eating vitamin D-rich foods
such as fish or food fortified with
vitamin D. The skin makes vitamin D3
when it is exposed to sunlight (Ref. 40)
and, therefore, vitamin D production
may vary depending on the following
factors: (1) Skin pigmentation, (2) age,
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(3) clothing, (4) season, (5) latitude, (6)
time of day, (7) weather conditions, and
(8) sunscreen application (Refs. 40–43).
Vitamin D deficiency has long been
associated with Ricketts, but recent
research suggests that vitamin D
deficiency may also be associated with
other diseases (Ref. 38). However, the
threshold of vitamin D blood levels that
constitutes a deficiency is currently
being re-evaluated by scientific experts
(Refs. 40, 44, and 45).
To determine whether sunscreen use
causes vitamin D deficiency, we
reviewed four clinical studies included
in the submissions that explored the
effect of sunscreen use on vitamin D
levels as well as three studies that we
identified in a literature search:
• Matsuoka et al 1987 (Ref. 46)
• Matsuoka et al 1988 (Ref. 47)
• Marks et al. 1995 (Ref. 48)
• Farrerons et al. 1998 (Ref. 49)
• Kimlin et al., 2007 (Ref. 50)
• Cusack et al., 2008 (ref. 51)
• Hoesl et al., 2010 (Ref. 52).
All but one of these studies assessed 25hydroxyvitamin D levels because 25hydroxyvitamin D is typically used as
the biological marker for vitamin D (in
the D2 or D3 form) (Ref. 53). Much of the
data available in the literature involves
nonclinical studies, which can be
difficult to extrapolate to consumer
(human) actual use conditions. Studies
with clinical data provide more
meaningful results because, if
adequately designed, they can be more
easily extrapolated to consumer actual
use conditions. Therefore, we are
focusing discussion in this document on
the clinical studies.
In the 1987 study by Matsuoka et al.,
four subjects applied a sunscreen
product with an unknown SPF to the
entire body, while four control subjects
did not apply any topical product (Ref.
46). All of the subjects were exposed to
1 MED 6 of UV radiation (260–330 nm 7)
and then vitamin D3 levels were
monitored for 15 days. The subjects
using sunscreen product applied the
sunscreen product 1 hour before UV
exposure. The level of vitamin D3 was
determined one day before UV exposure
to serve as the baseline measure.
The level of vitamin D3 in the control
group (no sunscreen) increased
significantly over baseline 1 day after
UV exposure (from ∼2 ng/ml 8 to 25 ng/
ml) and then decreased gradually,
returning to baseline 15 days after UV
exposure. In contrast, the levels of
vitamin D3 in the sunscreen group did
6 MED refers to the lowest dose of UV radiation
that produces perceptible reddening of the skin.
7 Nanometers.
8 Nanograms per milliliter.
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not change significantly from the
baseline level (5 ng/ml) at each time
point.
Based on this preliminary study,
Matsuoka et al. conducted another
study in 1988 (Ref. 47). This study
enrolled 40 subjects from Illinois and
Pennsylvania with 20 subjects in the
control group and 20 subjects in the
sunscreen group. Each time they went
outdoors for 1 year, the subjects in the
sunscreen group, who had a history of
skin cancer, applied a sunscreen
product with an unknown SPF to all
sun-exposed areas of the body.
Serum 25-hydroxyvitamin D levels
were measured in each group at the
conclusion of the study and were
significantly lower in the sunscreen
group than the control group: 40.2 and
91.3 nmol/L,9 respectively. The
difference in 25-hydroxyvitamin D
levels between the two groups was
statistically significant (p < 0.001).
Marks et al. conducted a randomized,
double-blind controlled clinical study
over a summer period in Australia (Ref.
48). In this study, 113 subjects over 40
years old who exhibited at least one
solar keratosis (a precursor of carcinoma
of the skin) were recruited and divided
into two groups. The first group of 56
subjects applied an SPF 17 sunscreen
cream. Fifty-five subjects in the control
group applied a placebo cream. Subjects
in both groups were asked to apply their
cream on the head, neck, forearm and
dorsal side of each hand once a day in
the morning and more frequently if
sweating, swimming, or involved in
activities that might rub off the cream.
The mean levels of 25hydroxyvitamin D rose significantly by
almost the same amount in both groups
over the period of the study. The mean
level in the placebo group increased by
12.8 mmol/L, whereas the mean level in
the sunscreen group increased by 11.8
mmol/L. The difference between these
increases from baseline values was not
statistically significant.
In 1998, Farrerons et al. carried out a
study to examine the effects of
sunscreen use on vitamin D levels in
elderly individuals (Ref. 49). In this 2year study, 24 subjects (10 men and 14
women with a mean age of 71 years)
were enrolled in the sunscreen group.
The subjects had actinic keratosis, basal
cell carcinoma, or squamous cell
carcinoma. None of the subjects had
previously used sunscreen products, but
were instructed to apply an SPF 15
sunscreen product to sun-exposed areas
of the body each morning, avoid midday sun, and wear UV-protective
clothing during the spring and autumn.
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The control group of 19 subjects did not
use sunscreen product, but had the
same skin characteristics. Mean serum
levels of 25-hydroxyvitamin D were
measured at eight different time points
(four in the autumn and four in the
spring) over the two-year study period.
The mean serum levels of 25hydroxyvitamin D were statistically
lower in the sunscreen group as
compared to the control group at one
spring and one autumn time point
(p < 0.05). However, the mean serum
levels of 25-hydroxyvitamin D were not
statistically different between the
groups at the other 6 spring and autumn
time points.
In 2007, Kimlin et al. reported that
there was ‘‘no association’’ between use
of sunscreens with SPF values higher
than 15 and blood levels of 25hydroxyvitamin D in a study of 126
Australian adults 18–87 years of age
(Ref. 50). However, the authors stated
that mean levels of 25-hydroxy vitamin
D increased with increasing frequency
of sunscreen use. Interestingly, study
‘‘participants who ‘usually’ or ‘almost
always’ wore a hat when outdoors’’
were significantly more likely to have
higher serum 25-hydroxy vitamin D
levels than those who wore hats less
often (Ref. 50). On the other hand, study
participants who usually or almost
always wore long sleeve shirts or pants
while outside were statistically more
likely to have lower serum 25hydroxyvitamin D levels than those who
wore these types of protective clothing
less often (Ref. 50).
In 2008, Cusack et al. reported that
decreased levels of 25-hydroxyvitamin
D levels were only ‘‘weakly correlated’’
with sunscreen usage in 52 Irish
patients with cutaneous lupus
erythematosus (Ref. 51). This study
population was specifically selected
because patients with lupus are
particularly sensitive to exposure to the
sun. While an analysis of the effects of
daily sunscreen use on serum levels of
25-hydroxyvitamin D showed the
relationship between these two
parameters to be significant, a
multivariate analysis of the same data
was not significant (Ref. 51).
Most recently, in 2010, Hoesl et al.
reported ‘‘no statistically significant
association’’ between serum levels of
25-hydroxyvitamin D and use of the
sunscreen drometrizole trisiloxane in a
cohort of 15 patients with Xeroderma
pigmentosum (Ref. 52). Like those with
lupus ertythematosus, patients with
Xeroderma pigmentosum are extremely
sensitive to the sun. The authors
reported that reductions in serum levels
of 25-hydroxyvitamin D are ‘‘not
associated with any type or duration of
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35637
sun protection applied by these
patients’’ (Ref. 52).
These seven clinical studies are
inconclusive because the results were
contradictory. Two studies suggest that
sunscreens decrease vitamin D levels
and the other five studies suggest that
sunscreens do not decrease vitamin D
levels. In addition, the studies were
relatively small, only enrolling 8 to 126
subjects. The study with the greatest
number of participants was
inconclusive showing that people who
regularly used sunscreens and wore hats
had increased levels of vitamin D,
whereas people who regularly wore
pants outside had decreased levels
(Ref. 50).
Because the preponderance of
currently available data suggests that
sunscreen use does not cause clinically
meaningful decreases in vitamin D
levels (i.e., decreases that lead to
vitamin D deficiency and/or disease
caused by low levels of vitamin D), we
are not including a warning regarding
vitamin D deficiency on OTC sunscreen
products. In addition, determining
whether decreases in vitamin D levels
result in vitamin D deficiency is
especially difficult because the
threshold of vitamin D blood levels that
constitutes a deficiency is currently
being re-evaluated by scientific experts
(Refs. 38, 44, and 45). We recognize that
certain subpopulations may be at
increased risk of vitamin D deficiency,
as pointed out in one submission.
However, there are many factors that
determine the amount of sun exposure
necessary to ensure adequate vitamin D
levels (e.g., geographical location,
season, skin pigmentation, dietary
vitamin D intake). Because of these
many other factors, it is difficult for us
to determine a meaningful message in
sunscreen product labeling for
consumers, especially in the absence of
conclusive data. If we become aware of
data from adequate and well-controlled
studies demonstrating that regular use
of sunscreen causes vitamin D
deficiency, we will re-evaluate this
issue.
D. Directions
We received numerous submissions
requesting that we revise directions
included in the 2007 proposed rule (Ref.
1). In response to those requests and our
reevaluation of OTC sunscreen labeling,
we are revising the following directions:
• ‘‘Reapply after [select one of the
following: ‘40 minutes of’ or ‘80 minutes
of’ ’’ for products that satisfy either the
water resistant or very water resistant
test procedures in proposed paragraphs
352.76(a) and (b), respectively]
swimming or [select one of the
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following: ‘sweating’ or ‘perspiring’] and
after towel drying. Otherwise, reapply at
least every 2 hours’’ (proposed 21 CFR
352.52(d)(2)).
• ‘‘Reapply at least every 2 hours after
towel drying, swimming, or sweating’’
(proposed 21 CFR 352.52(d)(3)).
These two directions are the
reapplication instructions for water
resistant and non-water resistant
products, respectively. We also received
five submissions requesting that we
revise the direction: ‘‘Apply [select one
of the following: ‘liberally’ or
‘generously’] [and, as an option: ‘and
evenly’] [insert appropriate time
interval, if a waiting period is needed]
before sun exposure’’ (proposed 21 CFR
352.52(d)(1)(i)). As discussed in this
section, we are not revising this
direction statement.
In addition to the revisions to these
provisions (described in more detail in
this section of the document), we are no
longer requiring the following proposed
direction: ‘‘Apply and reapply as
directed to avoid lowering protection’’
(proposed 21 CFR 352.52(d)(1)(ii)).
As already discussed, for covered
sunscreen products with Broad
Spectrum SPF values of 15 or higher, we
are requiring the following direction:
‘‘Sun Protection Measures. [in bold font]
Spending time in the sun increases your risk
of skin cancer and early skin aging. To
decrease this risk, regularly use a sunscreen
with a Broad Spectrum SPF of 15 or higher
and other sun protection measures including:
[bullet] limit time in the sun, especially from
10 a.m.–2 p.m. [bullet] wear long-sleeved
shirts, pants, hats, and sunglasses’’
(new 21 CFR 201.327(e)(1)(iv)). For
these products, this direction most
appropriately conveys the information
proposed in the ‘‘Sun Alert’’ warning
included in the 2007 proposed rule, and
provides the necessary directions to
complement the new indication
permitted for these products.
In addition to the required directions,
we will allow the optional direction
heading ‘‘for sunscreen use’’ (new 21
CFR 201.327(e)(1)(i)).
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1. Revised Directions
We are revising the directions for
water resistant sunscreen products (new
21 CFR 201.327(e)(2)) to read:
• Reapply:
• After 40 [or 80] minutes of
swimming or sweating
• Immediately after towel drying
• At least every 2 hours
We are also revising the directions for
non-water resistant sunscreen products
(new 21 CFR 201.327(e)(3)) to read:
‘‘[Bullet] reapply at least every 2 hours
[bullet] use a water resistant sunscreen
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if swimming or sweating.’’ These
revisions should clarify the directions.
We are removing reapplication
directions concerning swimming and
sweating from non-water resistant
products because these products should
not be used when swimming or
sweating. Instead, we are requiring more
accurate directions instructing
consumers to use a different sunscreen
product—a water resistant sunscreen
product—if swimming or sweating.
We considered revising the 2-hour
reapplication timeframe because some
of the submissions objected to this
specific timeframe (Ref. 1). The
submissions argued that we should
require the word ‘‘often’’ instead of a 2hour reapplication timeframe because
there are no data supporting this
timeframe. The submissions also point
out that the American Academy of
Dermatology (AAD) no longer supports
a 2-hour timeframe, even though we
cited AAD as supporting the 2-hour
timeframe in the 2007 proposed rule (72
FR 49070 at 49093).
In its submission following the 2007
proposed rule, the AAD does not state
its support for the 2-hour timeframe.
However, all of the public education
materials from AAD instruct consumers
to reapply sunscreen at least every 2
hours (Refs. 54 through 58). In addition,
other public health organizations such
as the Centers for Disease Control and
Prevention (CDC) and the U.S.
Environmental Protection Agency (EPA)
recommend reapplication at least every
2 hours (Refs. 59 and 60).
We disagree with the submissions
stating that data do not support this
timeframe. In the 2007 proposed rule,
we described two studies demonstrating
a significantly decreased sunburn risk if
sunscreen product were applied at least
every 2 hours (72 FR 49070 at 49092
through 49093). Wright et al. found that
subjects who reapplied sunscreen every
1 to 2 hours and after swimming were
not sunburned (Ref. 61). Similarly, Rigel
et al. reported that people who
reapplied sunscreen every two hours or
sooner were five times less likely to
sunburn compared to those who
reapplied sunscreen only after 2.5 hours
or longer (Ref. 62).
One of the submissions following the
2007 proposed rule included results
from a computer-simulation of
sunscreen product reapplication based
on a mathematical model (Ref. 1). The
results of this simulation suggested that
sunscreen products should be reapplied
15 to 30 minutes after sun exposure
begins. The results also suggested that
further reapplication of sunscreen
product is necessary after vigorous
activity that could remove sunscreen
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product, such as swimming, toweling,
excessive sweating, or rubbing. No other
reapplication time is suggested. The
usefulness of this study in determining
whether to revise the directions is
limited. In particular, we do not know
whether this simulation was validated,
because it has not been confirmed with
clinical studies. Until we receive
clinical studies demonstrating that
consumers do not experience skin
damage when sunscreen is reapplied at
longer timeframes, we will continue to
require the 2-hour reapplication
timeframe. As discussed in the 1999
final rule, manufacturers may seek
approval of different reapplication
directions by submitting specific and
substantive supporting data to us under
an NDA deviation (described in 21 CFR
330.11).
2. Proposed Directions Not Being
Revised
We are not revising proposed 21 CFR
352.52(d)(1)(i): ‘‘Apply [select one of the
following: ‘Liberally’ or ‘generously’]
[and, as an option: ‘And evenly’] [insert
appropriate time interval, if a waiting
period is needed] before sun exposure.’’
Several submissions requested that we
allow ‘‘smoothly’’ to be included in this
statement (Ref. 1). However, we
continue to consider this word to be
vague (72 FR 49070 at 49072 and
49092). Some submissions also
requested that we include a specific
application amount in place of the terms
‘‘generously’’ and ‘‘liberally’’ (Ref. 1).
For example, the submissions suggested
that the statement could read ‘‘apply 2
tablespoonsful.’’ The submissions
argued that more specific directions
would lead to consumers applying more
sunscreen product, reflecting the 2
milligrams per square centimeter (mg/
cm2) used during the SPF test. However,
specifying a certain amount in the
directions will not accomplish this goal.
The amount of sunscreen product that
needs to be applied to reach 2 mg/cm2
varies for each sunscreen product and
depends on the amount of skin surface
area being covered. For example, the
volume of sunscreen oil applied to the
neck and face will differ greatly from
the amount needed to apply a sunscreen
lotion to every sun-exposed area of the
body. Therefore, we are continuing to
require the terms ‘‘generously’’ and
‘‘liberally.’’
3. Proposed Directions Not Being
Required
We are not requiring the proposed
statement ‘‘apply and reapply as
directed to avoid lowering protection’’
(proposed 21 CFR 352.52(d)(1)(ii)). We
included this statement in the 2007
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proposed rule because reapplication
time appears to be critical to achieve
proper sun protection (72 FR 49070 at
49093). However, we have concluded
that this statement is redundant with
more specific reapplication directions
and may confuse consumers. It is not
clear that consumers will understand
the intent of this statement to emphasize
the need to follow reapplication
instructions. Therefore, we are not
requiring the statement in this
document.
4. New Directions Resulting From
Submissions on the Proposed Rule
For covered sunscreens with Broad
Spectrum SPF values of 15 or higher, we
are requiring a new Directions statement
that emphasizes the need not only to
regularly use such a sunscreen, but also
to follow other sun protection measures.
For these sunscreens, the statement will
read, ‘‘[bullet] Sun Protection Measures.
[in bold font] Spending time in the sun
increases your risk of skin cancer and
early skin aging. To decrease this risk,
regularly use a sunscreen with a Broad
Spectrum SPF of 15 or higher and other
sun protection measures including:
[Bullet] limit time in the sun, especially
from 10 a.m.–2 p.m. [bullet] wear longsleeved shirts, pants, hats, and
sunglasses (new 21 CFR
201.327(e)(1)(iv)). This statement is
taken from the proposed warning ‘‘UV
exposure from the sun increases the risk
of skin cancer, premature skin aging,
and other skin damage. It is important
to decrease UV exposure by limiting
time in the sun, wearing protective
clothing, and using a sunscreen.’’
(proposed 21 CFR 352.52(c)(1)). As
discussed in section IV.C. of this
document, this warning is no longer
being required for sunscreens with
Broad Spectrum SPF values of 15 or
higher. Rather, as discussed in section
IV.B of this document, submissions
suggested that the information proposed
as a warning is better understood as an
indication, with the supporting
conditions for achieving effectiveness.
As described in section IV.B, on
reexamination of the scientific data, we
agree that an appropriately limited
indication for reduction in risk of skin
cancer and early skin aging is supported
for sunscreens with Broad Spectrum
SPF values of 15 or higher. For these
products, the direction instructs users
how to use the product in a manner that
supports that indication.
In this final rule, we are being more
specific about the need to limit time in
the sun especially during the midday
hours of 10 a.m. to 2 p.m. when the
intensity of solar radiation is greatest
because the sun is at its zenith (i.e.,
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directly overhead). In our 1993
proposed rule, we stated that, ‘‘on any
day of the year, the intensity of the UV
energy of sunlight is greatest between 10
a.m. and 2 p.m.’’ (58 FR 28194 at
28199). We have concluded that this
information is important to consumers
trying to protect themselves from the
sun and are including the information
in the new direction statement. This
change is also responsive to the
concerns of two submissions on the
portion of the proposed sun alert that
referred to ‘‘limiting time in the sun,’’
both of which suggested alternatives
intended to provide more concrete
information for consumers to act on
(Ref. 1).
Several submissions argued that we
should allow different Drug Facts
labeling for cosmetics containing
sunscreens so that consumers will apply
the product appropriately for its
intended cosmetic use (Ref. 1). For
example, the submissions argued that
reapplication every 2 hours may not be
appropriate for cosmetic-sunscreen
products. We disagree with these
submissions. Cosmetic-sunscreen
combinations that are intended for use
as drugs require adequate labeling for
their drug use. (See 21 CFR 700.35). The
Drug Facts label communicates
information to the consumer so that the
cosmetic-sunscreen product can be used
safely and effectively. To help
consumers understand that the
sunscreen directions apply to the use of
the product as a drug, for sun
protection, we are allowing the optional
statement ‘‘for sunscreen use:’’ to appear
as the first line under ‘‘Directions.’’
Consumers who are using these
products primarily for cosmetic use will
be more likely to understand that they
might not receive the intended sun
protection if they do not follow the
directions in the Drug Facts label.
E. Constitutionality of Labeling
Statements Regarding Skin Cancer and
Skin Aging
Two submissions questioned the
constitutionality of the labeling
provisions in the 2007 sunscreen
proposed rule. Specifically, the
submissions contended that our
proposed restriction on any claims
about the prevention of skin cancer,
early skin aging, and related skin
damage would violate the sunscreen
manufacturers’ commercial speech
rights under the First Amendment to the
U.S. Constitution.
In the 2007 proposed rule preamble,
we had concluded that our proposed
restriction on claims about the
prevention of skin cancer, early skin
aging, and related skin damage would
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35639
be permissible under the First
Amendment, in part, because, at that
time, we tentatively concluded that
there were insufficient scientific data to
support inclusion of such claims in the
sunscreen monograph. As described
elsewhere in this document, we
received numerous submissions in
response to the 2007 proposed rule,
some of which contained references to
clinical studies we had reviewed in
preparing the 2007 proposed rule about
the effectiveness of sunscreens in
protecting against the harmful effects of
UV radiation. As already described in
section IV.B.2, based in part on our reevaluation of the data from these
studies, as well as the scientific fact that
reducing exposure to both UVB and
UVA radiation by a substantial amount
(i.e., equivalent to that provided by a
broad spectrum sunscreen with an SPF
value of 15 or higher) decreases the risk
of damaging the skin, we find that the
science supports the conclusion that
one subset of sunscreens covered by this
rule, broad spectrum sunscreen
products with an SPF value of 15 or
higher, in conjunction with limiting
time in the sun and wearing protective
clothing, reduce the risk of developing
skin cancer and early skin aging. Our
conclusion is reflected in the
permissible indication described in this
final rule for covered products with
Broad Spectrum SPF values of 15 or
higher. Although we have decided to
permit a claim about the prevention of
skin cancer and early skin aging for
certain covered sunscreens, as requested
in the submissions, we have
nevertheless conducted a First
Amendment analysis of our
requirements concerning the skin
cancer/early skin aging claim in this
final rule (hereinafter ‘‘skin cancer/early
aging indication’’), as well as the ‘‘Skin
Cancer/Skin Aging Alert’’ required as a
warning for covered products that do
not provide broad spectrum protection
with an SPF value of 15 or higher. For
the following reasons, we have
concluded that these requirements do
not violate the First Amendment.
This rule establishes effectiveness
testing methods and labeling that are
appropriate for the safe and effective use
of OTC sunscreen products covered by
this rule. Any covered sunscreen
product that deviates from the
requirements set forth in this labeling
regulation and any other applicable
labeling regulation would be considered
misbranded under section 502 of the
FD&C Act. In particular, sunscreen
products covered by this rule would be
misbranded if they are labeled with a
skin cancer/early aging indication but
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do not provide broad spectrum
protection with an SPF value of 15 or
higher. Such products would also be
misbranded if they do not include the
‘‘Skin Cancer/Skin Aging Alert’’
described in this rule (see 21 CFR
201.327(d)(2)). Covered sunscreen
products that do provide broad
spectrum protection with an SPF value
of 15 or higher would be misbranded if
they are labeled with the permissible
skin cancer/early aging indication but
do not include reference to the need to
use the product as directed with other
sun protection measures (21 CFR
201.327(c)(3)). Manufacturers of covered
sunscreen products that comply with
the labeling requirements in this
document would not be subject to
enforcement actions on the basis that
the products are misbranded, provided
they comply with all other requirements
under section 502 of the FD&C Act.
Because this rule applies only to
products marketed without approved
applications, manufacturers who wish
to deviate from the testing or labeling
requirements in this document may do
so by means of a new drug application
(NDA) under section 505 of the FD&C
Act.
We have concluded that the labeling
requirements in this rule satisfy the
applicable tests governing commercial
speech, as set forth by the Supreme
Court. The requirements for the ‘‘Skin
Cancer/Skin Aging Alert’’ and the
information in the skin cancer/early
aging indication about using the product
as directed with other sun protection
measures, are permissible under the
First Amendment because they are
reasonably related to the Government’s
interest in protecting public health (see
Zauderer v. Office of Disciplinary
Counsel, 471, U.S. 626, 651 (1985)).
We are requiring covered sunscreen
products that do not provide broad
spectrum protection with an SPF value
of 15 or higher to include the ‘‘Skin
Cancer/Skin Aging Alert’’ under the
‘‘Warnings’’ heading on the label to
ensure that consumers are aware of the
continued risks of skin cancer and early
skin aging that occur from sun exposure,
the conditions under which they will be
using the product, and that they
understand that the product has been
shown only to help protect against
sunburn. Without this warning,
consumers could fail to distinguish
between these sunscreen products and
other sunscreen products that have been
proven to help provide protection
against skin cancer and early skin aging.
Providing this information is important
for consumers to be able to make
informed choices about the selection
and use of sunscreens.
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For covered sunscreen products that
do provide broad spectrum protection
with an SPF value of 15 or higher, we
are requiring that the additional
information about using the product as
directed with other sun protection
measures be included in the indication
so that consumers are not misled about
how to use these sunscreens effectively
or about the conditions under which
these sunscreens are effective. Use of a
sunscreen alone—even a broad
spectrum sunscreen with an SPF value
of 15 or higher—has not been shown to
reduce the risk of skin cancer or early
skin aging if a consumer increases
overall UV exposure by spending greater
time in the sun and/or wearing less
protective clothing. The additional
information required in the skin cancer/
early aging indication about using the
product as directed with additional sun
protection measures clarifies how the
use of sunscreens is part of a
comprehensive sun protection program.
Displaying this information elsewhere
would underemphasize its importance
in relation to the use of these sunscreens
for protection against skin cancer and
early skin aging (see N.Y. State Rest.
Ass’n v. N.Y. City Bd. of Health, 556
F.3d 114 (2d Cir. 2009); see also 21
U.S.C. 352(c)). Thus, these disclosure
requirements will promote the proper
use of covered sunscreens and are,
therefore, reasonably related to the
Government’s interest in protecting
public health.
Our requirements concerning the skin
cancer/early aging indication would
also be permissible under the First
Amendment using the analytical
framework provided in Central Hudson
Gas & Electric Corporation v. Public
Service Commission, 447 U.S. 557
(1980). Under Central Hudson,
commercial speech that is false,
misleading, or concerns unlawful
activity is not entitled to protection
under the First Amendment. While
commercial speech that concerns lawful
activity and is not misleading receives
some protection under the First
Amendment, it may nonetheless be
regulated by the Government if the
following conditions are met: (1) The
asserted governmental interest is
substantial; (2) the regulation directly
advances the asserted governmental
interest; and (3) the regulation is not
more restrictive than necessary to serve
that interest (Id. at 566). The Supreme
Court has explained that the last
element of the Central Hudson test is
not a ‘‘least restrictive means’’
requirement but, rather, requires narrow
tailoring (i.e., ‘‘a fit that is not
necessarily perfect, but reasonable’’
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between means and ends) (Board of
Trustees of the State Univ. of N.Y. v.
Fox, 492 U.S. 469, 480 (1989)). In
subsequent decisions, the Court has also
clarified that ‘‘misleading’’ in the first
element of the test refers to speech that
is inherently or actually misleading.
Based on the data currently available,
we have concluded that the following
statements or omissions would be false
or inherently misleading: (1) Use of the
skin cancer/early aging indication on
the labeling of a sunscreen product that
does not provide broad spectrum
protection with an SPF value of 15 or
higher, (2) the omission of the ‘‘Skin
Cancer/Skin Aging Alert’’ under the
‘‘Warnings’’ heading of the labeling for
sunscreen products that do not provide
broad spectrum protection with an SPF
value of 15 or higher, and (3) use of the
skin cancer/early aging indication that
omits the required information about
using the product as directed with other
sun protection measures.
Use of the skin cancer/premature
aging indication on the labeling of
covered sunscreen products that do not
provide broad spectrum protection with
an SPF value of 15 or higher would be
false or inherently misleading for
several reasons. As discussed elsewhere
in this document, only broad spectrum
UV radiation is classified as a known
human carcinogen, according to the
National Toxicology Program.
Therefore, covered sunscreen products
that do not provide broad spectrum UV
protection may not reduce the risk of
skin cancer. Furthermore, since the
precise wavelengths of UV radiation
that cause skin cancer and early skin
aging are unknown, a covered sunscreen
product that only provides protection
against part of the UV spectrum may not
ensure a reduction in the risk of
developing skin cancer or early skin
aging. In addition, all of the scientific
data that support the skin cancer/early
aging indication for certain covered
sunscreens were derived from studies
that used sunscreen products with an
SPF value of 15 or higher. Therefore, the
skin cancer/early aging indication
would be false or inherently misleading
on covered sunscreen products that do
not provide this level of protection,
because there is a lack of any evidence
demonstrating that these products
would reduce the risk of skin cancer or
early skin aging. Similarly, omitting the
‘‘Skin Cancer/Skin Aging Alert’’ on
these products, which are identified on
their labels as ‘‘sunscreens,’’ would be
inherently misleading because
consumers who are using these products
for sun protection would not be
sufficiently alerted to the fact that these
products have been shown only to
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protect against sunburn, while sun
exposure also increases the risks of skin
cancer and early skin aging.
A skin cancer/early aging indication
on a covered product with Broad
Spectrum SPF value of 15 or higher that
omits the required information about
using the product as directed with other
sun protection measures would also be
false or inherently misleading because
sunscreen use alone has not been shown
to reduce the risk of skin cancer or early
skin aging if a consumer increases
overall UV exposure by spending greater
time in the sun and/or wearing less
protective clothing. As discussed above
in this section and elsewhere in this
document, without the reduction in
consumers’ overall UV exposure, a
covered sunscreen product may not be
effective in reducing consumers’ risk of
skin cancer and early skin aging.
We also conclude that the labeling
claims and omissions described above
would cause the product to be
misbranded and, therefore, relate to an
unlawful activity. As described earlier
in this section and elsewhere in this
document, labeling regulations establish
certain requirements that help ensure
the safe and effective use of OTC drug
products. The false or misleading
labeling described above would cause
covered products to be misbranded
under section 502 of the act. Therefore,
such labeling would concern the illegal
sale of misbranded drugs. Under the
Central Hudson test, then, we have not
violated the First Amendment with
these requirements, which simply
prohibit false or inherently misleading
labeling.
Although we conclude that the
labeling described above would not be
entitled to First Amendment protection
under the threshold inquiry of the
Central Hudson test, we conclude that
our regulation directly advances a
substantial Government interest and is
no more extensive than necessary, and
therefore would also pass muster under
the test’s three remaining steps. Under
the first remaining step, we have a
substantial interest in protecting public
health (see Pearson v. Shalala, 164 F.3d
650, 656 (DC Cir. 1999) (citing Rubin v.
Coors Brewing Co., 514 U.S. 476, 484–
485 (1995)).
Under the second remaining step of
the Central Hudson test, our labeling
requirements discussed in this section
directly advance the Government’s
interests in protecting public health
because they help ensure that covered
sunscreen products are adequately
labeled for safe and effective use by
consumers.
As stated previously in this
document, scientific evidence only
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supports the skin cancer/premature
aging indication for sunscreen products
that provide broad spectrum protection
with an SPF value of 15 or higher.
Allowing the skin cancer/early aging
indication on sunscreen products for
which it is not scientifically supported
would lead to consumers unjustifiably
relying on such products for protection
against skin cancer and early skin aging.
Furthermore, the ‘‘Skin Cancer/Skin
Aging Alert’’ allows consumers to be
aware that spending time in the sun
increases their risk of skin cancer and
early skin aging, and that products on
which this alert appears have not been
shown to provide this type of
protection. The requirement for
information in the skin cancer/early
aging indication about using sunscreens
as directed with sun protection
measures also directly advances our
interest in protecting public health
because these elements are essential for
consumers to reduce their overall UV
exposure and, consequently, their risk
of developing skin cancer and early skin
aging. Thus, these requirements directly
advance the Government’s interest in
protecting public health through the
safe and effective use of sunscreens.
Under the final remaining step of the
Central Hudson test, our requirements
concerning the skin cancer/early aging
indication are not more restrictive than
necessary, because there are not
numerous and obvious alternatives
(Cincinnati v. Discovery Network, 507
U.S. 410, 418 n. 13 (1993)) to achieve
the Government’s substantial interests.
By permitting the skin cancer/early
aging indication only for covered
sunscreen products with Broad
Spectrum SPF values of 15 or higher,
and requiring the ‘‘Skin Cancer/Skin
Aging Alert’’ for products that do not
offer this level of protection, we are
ensuring that consumers do not
mistakenly rely on sunscreen products
that have not been demonstrated to be
effective for protection against skin
cancer and early skin aging. In addition,
labeling that omits a statement regarding
the use of other sun protection measures
as directed from the skin cancer/early
aging indication could lead to
consumers foregoing other sun
protection measures, thereby negating
the protective effect of the sunscreen.
Including a statement in the skin
cancer/early aging indication regarding
the need to follow other sun protection
measures as well as the related
directions ensures that consumers
understand how to use sunscreens to
reduce their risk of skin cancer and
early skin aging.
It is important to note that
manufacturers of OTC sunscreens
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covered by this rule have several
alternatives for adding labeling
information that is not included in this
labeling regulation. For example, such
manufacturers can file an NDA under
section 505 of the FD&C Act or submit
a petition under 21 CFR 10.30 to amend
the labeling regulation. In either case,
the manufacturer need only submit the
requisite evidence to support the
indication or other labeling for the
product that differs from that addressed
by the regulation. Therefore, we are not
being more restrictive than necessary
when these viable alternatives are
available for manufacturers.
Reacting to the fact that our proposed
rule did not permit any indication
statement for any sunscreen regarding
prevention of skin cancer and early skin
aging, one submission asserted that we
must consider use of a disclaimer as an
alternative means of addressing the
limits of the product’s effectiveness. As
noted previously in this document, this
final labeling regulation permits an
appropriately limited indication for
broad spectrum sunscreens with SPF
values of 15 or higher—one stating that
when used as directed with other sun
protection measures, such products
decrease the risk of skin cancer and
early skin aging caused by the sun. The
claim is authorized for this subset of
covered sunscreen products because
available scientific data discussed
elsewhere in this document are
sufficient to substantiate the claim for
these products. Because we have
included a skin cancer/early skin aging
claim in these labeling regulations, we
no longer view the submission’s request
as being applicable.
In any event, we note that the use of
disclaimers on drug labeling to qualify
inadequately supported or unapproved
indications is not an effective, less
restrictive means of achieving FDA’s
substantial interests in protecting public
health and preserving the integrity of its
premarket approval systems. Indeed,
disclaimers on drug labeling would
severely undermine the Government’s
interests here. For over 100 years,
Congress has charged FDA with
enforcing misbranding laws to protect
public health. In 1962, Congress
amended the FD&C Act to require that
all new drugs be approved as both safe
and effective prior to marketing.
Congress found that a premarket
approval system, requiring specific
types of supporting evidence (see 21
U.S.C. 355(d)), and misbranding
provisions, among other requirements,
were necessary to avoid further
tragedies involving unsafe and
ineffective drugs. Using disclaimers for
drugs would completely undermine the
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regulatory framework established by
Congress for the protection of public
health. FDA’s labeling regulations help
ensure the safety and effectiveness of
OTC drugs and establish the conditions
under which a drug is not misbranded
under the FD&C Act. If a manufacturer
of a covered sunscreen would like to
label its sunscreen product in a way that
does not conform to this labeling
regulation, it cannot circumvent the
premarket NDA process.
In summary, we conclude that the
labeling requirements provided in this
document do not violate the First
Amendment.
F. Other Information
We received submissions requesting
that we add a new statement about
storage conditions under ‘‘Other
information’’ in the Drug Facts label
(Ref. 1). The submissions argued that
sunscreen products in containers are
often exposed to heat when used at the
beach, swimming pools, etc. The
concern expressed in the submissions
was that heat could cause sunscreen
formulations inside containers to
change, resulting in less sun protection.
We agree with the submissions.
Sunscreen products within containers
should not be exposed to direct sun and
can be protected by wrapping them in
towels and/or keeping them in shaded
environments (e.g., under an umbrella
and/or in a purse or bag). Consumers
could also store sunscreen product
containers in coolers while outside
during hot periods. In this final rule we
are requiring the following statement in
the ‘‘Other information’’ section of the
Drug Facts label: ‘‘[Bullet] protect the
product in this container from excessive
heat and direct sun’’ (new 21 CFR
201.327(f)).
In addition to the statement about
storage conditions, we received
numerous submissions requesting that
we relocate the proposed ‘‘sun alert’’
warning to the ‘‘Other information’’
section of the Drug Facts label. The
submissions argued that the ‘‘sun alert’’
is an educational statement and not a
warning: ‘‘UV exposure from the sun
increases the risk of skin cancer,
premature skin aging, and other skin
damage. It is important to decrease UV
exposure by limiting time in the sun,
wearing protective clothing, and using a
sunscreen.’’
As already discussed, in light of our
re-evaluation of the evidence supporting
the indications for sunscreens, we have
made changes to the labeling to more
accurately convey appropriate
information to consumers about the
benefits, directions, and limitations of
two different groups of products
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covered by the rule—those that provide
broad spectrum protection with an SPF
value of 15 or higher, and those that do
not. We do not agree that this
information belongs under the heading
‘‘Other information’’ but have included
it in modified form under the headings
Uses and Directions for products with
Broad Spectrum SPF values of 15 or
higher (new 201.327(c)(2) and (e)(2),
and under a revised ‘‘Skin Cancer/Skin
Aging Alert’’ under the heading
Warnings for other sunscreens (new
201.327(d)(2)).
In this document, we are also
removing the optional ‘‘Other
information’’ statements in proposed 21
CFR 352.52(e):
1. ‘‘Low,’’ ‘‘medium,’’ ‘‘high’’ or
‘‘highest’’ ‘‘sunburn protection product’’
2. ‘‘Higher SPF products give more
sun protection, but are not intended to
extend the time spent in the sun.’’
According to the 2007 proposed rule,
these statements could appear in ‘‘Other
information’’ or anywhere outside Drug
Facts. However, in this rule, we have
revised the labeling and are no longer
requiring the principal display panel to
characterize the level the sunburn
protection. Rather, for broad spectrum
products, the rule requires only the
statement ‘‘Broad Spectrum SPF [fill in
tested SPF value]’’ to appear on the
principal display panel. In light of this
revised approach to labeling, we are
concerned that including the
characterizations of the product as
providing ‘‘low,’’ ‘‘medium,’’ ‘‘high’’ or
‘‘highest’’ ‘‘sunburn protection would be
confusing or misleading, and are no
longer including it as an option.
We have concluded that the second
statement, although truthful, is not
necessary. Consumers likely understand
the first part of this statement (higher
SPF values represent more sun
protection) based on the long-standing
inclusion on SPF values on OTC
sunscreen products. The second part of
the statement (higher SPF products are
not intended to extend time spent in the
sun) is redundant with the information
already provided under ‘‘Uses’’ and
‘‘Directions,’’ particularly concerning
the need for limiting time in the sun
(see sections IV.B and IV.D). Although
we are not requiring inclusion of the
second statement under ‘‘Other
information,’’ the statement may appear
outside the Drug Facts label because it
is truthful and nonmisleading.
G. Reduced Labeling
Five submissions requested changes
to our proposed regulations allowing
reduced labeling for sunscreen products
sold in small packages (i.e., packages
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which meet the requirements in 21 CFR
201.66(d)(10)) that are labeled for use
only on small areas of the face. One
submission stated that all cosmetic
products labeled with sunscreen
indications should be required to
include all sunscreen product labeling.
After reassessing the criteria for
reduced labeling, we are not allowing
the reduced labeling included in the
2007 proposed rule. OTC drug labeling
regulations (21 CFR 201.66(d)(10)) allow
reduced labeling for any OTC drug
product sold in a small package,
including sunscreen products. In the
2007 proposed rule, we proposed
additional reductions in labeling for
three types of sunscreen products sold
in small packages and intended for use
on small areas of the face:
• Proposed 21 CFR 352.52(f)(1)(i)–
(f)(1)(iv): Sunscreen products sold in
small packages and labeled for use
specifically on the lips, nose, ears, and/
or around the eyes (i.e., small areas of
the face)
• Proposed 21 CFR 352.52(f)(1)(v):
Sunscreen-lip protectant combination
products sold in small packages
• Proposed 21 CFR 352.52(f)(1)(vi):
Sunscreen products formulated as
lipsticks, lip products that prolong wear
of lipstick, lip gloss, and lip balms
Three submissions argued that we
should not restrict labeling exemptions
only to sunscreen products sold in small
packages and labeled for use on small
areas of the face. The submissions stated
that reduced labeling provisions should
apply to all sunscreen products sold in
small packages whether or not they are
labeled for use on small parts of the
face. Two of the submissions argued
that such a restriction violates the
Administrative Procedures Act (APA).
The submissions cite Bracco
Diagnostics, Inc., v. Shalala 963 F.
Supp. 20, 27–28 (D.D.C. 1997) as
evidence that the courts oppose
regulations requiring ‘‘two sets of
similar products to run down two sets
of separate [regulatory] tracks * * * for
no apparent reason.’’
In this document, we continue to
allow the reduced labeling specified in
21 CFR 201.66(d)(10). Therefore, if the
information listed under Drug Facts
requires more than 60 percent of the
total available surface area, the Drug
Facts labeling can be reduced by making
the formatting changes specified in 21
CFR 201.66(d)(10)(i)–(d)(10)(v).
However, in contrast to the 2007
proposed rule, we are not allowing
additional reductions in labeling for any
sunscreen products.
When we proposed the additional
reduced labeling, we recognized that
many of the sunscreen products sold in
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small packages and labeled for use on
small areas of the face could not
accommodate full Drug Facts labeling.
However, in the last several years,
manufacturers have introduced new
label designs that permit full Drug Facts
labeling on very small packages. For
example, some stick products, including
lip protectant-external analgesic
combinations marketed in 0.15 oz.
amounts, have been labeled with wraparound labels that contain full Drug
Facts labeling. If these products can be
labeled to accommodate full Drug Facts
labeling, then all sunscreen products
should be able to accommodate full
Drug Facts labeling. Requiring full Drug
Facts labeling should not discourage
manufacturers from including sunscreen
ingredients because of limited labeling
space, as stated in the 2007 proposed
rule (72 FR 49070 at 49075 through
49077). Therefore, in this document, we
are eliminating all of the allowances for
reduced labeling in proposed 21 CFR
352.52(f). Sunscreen products can only
have reduced labeling for formatting if
they meet the criteria in 21 CFR
201.66(d)(10).
V. Miscellaneous Labeling Outside Drug
Facts
We received several submissions
regarding various performance claims,
including comments asking us to allow
claims for protection immediately upon
application (instant protection) and for
extended duration between applications
(extended wear) and comments asking
us not to allow terms such as
‘‘sunblock,’’ ‘‘waterproof,’’ and
‘‘sweatproof’’ (Ref. 1). These kinds of
claims were not included in the 2007
proposed rule (Ref. 1).
We are not including labeling in 21
CFR 201.327 permitting these claims on
OTC sunscreen products covered by the
rule. The current record does not
contain support for any of these kinds
of claims. To clarify the status of these
kinds of claims, we are finalizing two
provisions. We include instant
protection and extended wear claims,
which are claims that we think may be
capable of substantiation, in 21 CFR
310.545(a)(29)(ii). While these claims
may not be included on products
marketed without approved
applications, including them in this
provision makes it clear that these
claims may be substantiated for an
individual product by the submission of
adequate data in an NDA.
We agree with the submissions that
argue that ‘‘sunblock,’’ ‘‘waterproof,’’
and ‘‘sweatproof’’ claims are false or
misleading, as we have stated in
previous sunscreen rulemakings (58 FR
28194 at 28228; 64 FR 27666 at 27676
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through 27680). These terms are
essentially exaggerations of performance
that FDA does not think can be
substantiated. Accordingly, in this final
rule, we codify these as terms or phrases
that would be false or misleading on
covered products, and are therefore
prohibited (21 CFR 201.327(g)).
In addition to submissions requesting
that we allow certain labeling outside
Drug Facts, we also received a
submission requesting that we require
information about the UV index (UVI).
A stated in the 2007 proposed rule, we
have determined that the usage
information provided on OTC sunscreen
products applies regardless of the UVI
value (72 FR 49070 at 49073). Therefore,
we will allow but do not require
information about the UV index to be
included on sunscreen products outside
the Drug Facts label.
A submission requested that we
require that the UV index appear on
sunscreen product labels because this
information would help consumers
understand and use the UV index to
determine their risk of sunburn. The UV
index was developed in 1995 by the
National Weather Service,
Environmental Protection Agency, and
Centers for Disease Control and
Prevention to provide a forecast of the
expected risk of overexposure to UV
rays. The UV index is calculated using
ozone data, atmospheric pressure,
temperature, and cloudiness. As stated
in the 2007 proposed rule, we are not
requiring labeling of UV index
information because it is not necessary
for consumers to understand this index
in order to safely and effectively use
OTC sunscreen products (72 FR 49070
at 49073). However, manufacturers may
include truthful and nonmisleading
information about the UV index in the
labeling outside of Drug Facts if they
choose.
We also received a submission
requesting that we allow a claim of
‘‘instant protection’’ and to allow claims
for extended periods of protection
between applications (i.e., longer than
the 2 hours specified in ‘‘Directions’’ in
the 2007 proposed rule). The
submission argued that several
marketed products provide sunburn
protection immediately upon
application, as demonstrated by test
results included in the submissions. In
this document, SPF testing requires a
15-minute waiting period between
sunscreen application and UV exposure
of the test site. It appears that the
submitted test method included the
same 15-minute waiting period.
Therefore, the assertion that this
product provides ‘‘instant protection’’
does not appear to be substantiated. We
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35643
also did not receive any data regarding
claims for extended periods of use, so it
is not clear whether these claims are
truthful. Claims that a product provides
for an extended period of protection
between applications or immediately
upon application would have to be
supported by data. Therefore, these
claims could be made only under
approved new drug applications (NDAs)
with the required data.
In this document, we are specifically
identifying these claims as not allowed
on any OTC sunscreen product,
regardless of SPF value or broad
spectrum protection, without an
approved application containing
sufficient substantiation to support the
claim. (new 21 CFR 310.545(a)(29)(ii)):
• Instant protection or protection
immediately upon application
• Claims for ‘‘all-day’’ protection or
extended wear claims citing a specific
number of hours of protection that are
inconsistent with the directions for
application in 21 CFR 201.327.
In addition, we are identifying the
terms ‘‘sunblock’’ ‘‘waterproof,’’ and
‘‘sweatproof’’ as false and misleading, as
we have stated in previous sunscreen
rulemakings:
• Sunblock (64 FR 27666 at 27679
and 27680)
• Sweatproof (58 FR 28194 at 28227
through 28228)
• Waterproof (58 FR 28194 at 28227
through 28228).
We have previously identified these
claims as ones that would render a
product misbranded but are addressing
them again in this document because
OTC sunscreen products currently
marketed without approved
applications continue to contain the
claims. In this final rule, we are listing
these false and misleading terms in 21
CFR 201.327(g). These terms may not be
included on any OTC sunscreen
products covered by the rule.
Finally, in the 2007 proposed rule, we
proposed to specify other optional
statements that could be included
outside of Drug Facts in proposed 21
CFR 352.52(e)(3):
• ‘‘Broad spectrum sunscreen’’
• ‘‘Provides [select one of the
following: ‘UVA and UVB’ or ‘broad
spectrum’] protection’’
• ‘‘Protects from UVA and UVB
[select one of the following: ‘rays’ or
‘radiation’]’’
• ‘‘[Select one of the following:
‘absorbs’ or ‘protects’] within the UVA
spectrum.’’
This final rule is not a monograph,
and we do not consider it necessary in
this rule to codify optional statements
for use outside of ‘‘Drug Facts.’’ The
labeling required in this document
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should provide consumers with the
information that they need to safely and
effectively use the sunscreen products
that it addresses. Under this final rule,
products marketed without approved
applications that provide broad
spectrum protection according to the
test in new 21 CFR 201.327(j) of this
document will be identified on the PDP
by use of the term ‘‘Broad
Spectrum SPF.’’ In light of this
requirement in the rule for use of the
term ‘‘broad spectrum’’ on these
particular products, including a
statement anywhere in the labeling of a
product that does not pass the broad
spectrum test in 21 CFR 201.327(j) that
suggests or implies that the product
provides broad spectrum protection
would misbrand that product. We
likewise caution against references to
‘‘UVA’’ (or ‘‘UVA/UVB’’) protection on
products that do not provide broad
spectrum protection as demonstrated by
the test in 21 CFR 201.327(j). Such
labeling would misbrand the products if
it misleadingly suggests that the
products provide protection that is
equivalent or greater to that provided by
products labeled with ‘‘Broad Spectrum
SPF’’ values or is otherwise false or
misleading.
VI. SPF Test Parameters
The 2007 proposed rule included the
SPF test from the 1999 final rule with
revisions to a few test parameters. In
response to the 2007 proposed rule, we
received numerous submissions
requesting that we revise additional test
parameters (Ref. 1). In this document,
we have rewritten the regulations
describing the SPF test in an effort to
make it easier to read and understand
and to more closely follow the order in
which steps of the SPF testing
procedure are conducted. We have also
made several revisions to the test
parameters. However, we did not make
all of the revisions requested in the
submissions. Table 4 of this document
summarizes test parameters that we
considered revising. The table identifies
the parameters that we are changing in
this document as well as those that we
are not changing. Detailed discussion of
each test parameter appears throughout
the remainder of this section.
TABLE 4—SUMMARY OF SPF TEST PARAMETERS INCLUDED IN THE 2007 PROPOSED RULE AND THIS FINAL RULE
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2007 Proposed rule
This final rule
21 CFR 352.70(a). Standard sunscreens
Two standards:
8% homosalate (SPF 2— ≤ 15)
7% padimate, 3% oxybenzone (SPF > 15)
HPLC reference standard:
no limits set for accuracy of oxybenzone & padimate O
21 CFR 201.327(i)(2). SPF standard
One standard:
7% padimate, 3% oxybenzone (all SPFs)
21 CFR 352.70(b). Light source (solar simulator)
Emission spectrum specifications:
(1) COLIPA 1 1994 (Ref. 63)
(2) no specifications for UVA
Calibration:
every 6 months
Total irradiance:
1500 Watts/square meter (W/m2)
Beam uniformity:
within 20 percent
21 CFR 201.327(i)(1). UV source (solar simulator)
Emission spectrum specifications:
(1) COLIPA 1 2006 (Ref. 64)
(2) specifications for UVA I and UVA II percentages of total UV
Calibration:
at least annually
Total irradiance:
1500 Watts/square meter (W/m2)
Beam uniformity:
within 20 percent
21 CFR 352.70(c)(7). Number of subjects
SPF < 30:
20–25 subjects; ≥ 20 valid results
SPF ≥ 30:
25–30 subjects; ≥ 25 valid results
21 CFR 201.327(i)(3). Test subjects
All SPFs:
• 10–13 subjects; ≥ 10 valid results
21 CFR 352.70(c)(4). Test site delineation/subsite
test site area:
≥ 50 cm2
test subsite area:
≥ 1 cm2
Distance between subsites:
≥ 1 cm
21 CFR 201.327(i)(4)(i) and (ii). Test site/subsite
test site area:
≥ 30 cm2
test subsite area:
≥ 0.5 cm2
Distance between subsites:
≥ 0.8 cm
21 CFR 352.70(c)(5). Application of test materials
Application amount:
2 milligrams per square centimeter (mg/cm2)
Presaturation of finger cot:
Required
Water-resistant statement requirements:
20 minute water immersion times
20 minute drying times
21 CFR 201.327(i)(4)(iii). Applying test materials
Application amount:
2 milligrams per square centimeter (mg/cm2)
Presaturation of finger cot:
not required
Water-resistant statement requirements:
20 minute water immersion times
15 minute drying times
21 CFR 352.70(d)(3). Determination of individual SPF values
Definitions of MED:
(1) MED(PS) = MED for protected skin
(2) MED(US) = MED for unprotected skin
21 CFR 201.327(i)(5). UV exposure
Definitions of MED:
(1) ssMEDp = MED for skin protected by sunscreen standard
(2) tpMEDp = MED for skin protected by test product
(3) initial MEDu = MED for unprotected skin prior to testing test
product
(4) final MEDu = MED for unprotected skin determined when testing test product
UV doses for initial MEDu:
HPLC reference standard:
limit set to within 5% of theoretical for accuracy of oxybenzone &
padimate O
UV doses for MED(US):
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TABLE 4—SUMMARY OF SPF TEST PARAMETERS INCLUDED IN THE 2007 PROPOSED RULE AND THIS FINAL RULE—
Continued
2007 Proposed rule
This final rule
five doses
21 CFR 352.70(c)(8) Response criteria
Maximal UV exposure:
‘‘no more than twice the total energy of the minimal exposure’’
number of doses not specified
21 CFR 201.327(i)(5). UV exposure
Maximal UV exposure:
not specified
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1 Draft test method entitled ‘‘International Sun Protection Factor (SPF) Test Method’’ developed by the European Cosmetic, Toiletry and Perfumery Association (COLIPA).
We are not making some of the
requested changes to certain test
parameters because we lack adequate
data to determine whether these
changes would change the accuracy or
reproducibility of the SPF test. We are
making changes to some test parameters
based on the following developments
since the 2007 proposed rule published:
• New data (submitted by the public
or published in the scientific literature)
• Technical improvement of SPF
testing equipment
• Accumulating experience in the
performance of SPF testing
• Efforts towards international
harmonization of SPF testing
procedures
In support of the requested changes,
several submissions (Ref. 1) cited
differences between the SPF test in the
2007 proposed rule and the COLIPA
SPF test (Ref. 64). The COLIPA SPF test
is a joint effort by the cosmetic industry
trade associations in Europe, Japan,
South Africa, and the United States to
harmonize SPF test procedures. The
International Organization for
Standardization (ISO) is currently
developing an SPF test method. Because
harmonization of testing methods is
important, we are actively involved in
the ISO working group responsible for
developing methods for assessing the
efficacy of sun protection products.
We are revising our proposed SPF test
method to be as consistent as possible
with the COLIPA SPF test. We
acknowledge the merits of harmonizing
test methods and are an active
participant in ongoing harmonization
efforts. However, some of the test
parameters in this document differ from
comparable parameters in the COLIPA
SPF test because we have concluded
that the data do not support using the
COLIPA SPF test parameters.
Throughout the remainder of this
section, we discuss whether test
parameters in this document match or
do not match those in the COLIPA SPF
methods.
A. Solar Simulator
Several submissions recommended
adopting the solar simulator
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specifications in the COLIPA SPF test
(Ref. 1). We are revising solar simulator
specifications to:
• Allow the use of smaller beam,
multiport simulators
• Adjust the relative cumulative
erythemal effectiveness (RCEE) range
specifications for each wavelength band
• Specify that UVA II (320–340 nm)
and UVA I (340–400 nm) irradiance
should equal or exceed 20 percent and
60 percent, respectively, of the total UV
(290–400 nm) irradiance
• Change the regular calibration
period from every 6 months to at least
once a year
These changes are consistent with the
COLIPA SPF test. More importantly,
these revisions will allow the SPF test
to continue to be accurate and
reproducible. For example, we received
calibration data demonstrating that solar
simulators and their UV lamps are
stable for periods longer than 1 year.
Therefore, the requirement in the 2007
proposed rule to calibrate every 6
months is unnecessary. The test results
should be the same whether calibration
is done annually or every 6 months.
In contrast, we are not changing the
following solar simulator specifications
because changes to these specifications
could reduce test accuracy and/or
reproducibility:
• Total irradiance limit of 1500 W/m2
• Total irradiance range of 250–1400
nm
• 20 percent beam uniformity
requirement.
These test specifications differ from the
COLIPA SPF test, which recommends a
1600 W/m2 limit and a 10 percent beam
uniformity requirement.
Two submissions (Ref. 1) objected to
limiting total solar simulator irradiance
to 1500 W/m2 for all wavelengths
between 250 and 1400 nm (proposed
21 CFR 352.70(b)(1)). We proposed the
1500 W/m2 limit because we were
concerned that solar simulators
operating above this limit could cause
excessive heat. Excessive heat could
harm test subjects and/or cause loss of
dose reciprocity, the correlation
between UV dose and resulting
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erythema. One submission argued that
no data indicate that exceeding 1500 W/
m2 causes excessive heat or affects SPF
test results. The submission argued that
higher intensities should be allowed as
long as they are thermally tolerated by
test subjects, because allowing higher
intensities enables faster SPF testing.
We are not changing the 1500 W/m2
total irradiance limit. We do not have
data demonstrating that exceeding 1500
W/m2 leads to loss of dose reciprocity.
However, we conclude that the limit
should be retained to protect test
subjects. The COLIPA SPF test cites a
study showing that total irradiance of
1600 W/m2 induces heat and pain in a
majority of test subsites, and
recommends keeping total irradiance
below 1600 W/m2 (Ref. 64). Therefore,
we are keeping the 1500 W/m2 total
irradiance limit (new 21 CFR
201.327(i)(1)(i)).
One submission also objected to the
250–1400 nm range over which total
irradiation should be monitored (Ref. 1).
The submission argued that portable
spectroradiometers are typically
incapable of measuring wavelengths out
to 1400 nm. According to the
submission, emissions from longer
wavelengths have not been shown to
affect SPF testing.
We are not changing the requirement
that total irradiation be monitored over
a range of 250–1400 nm. We have
concluded that monitoring over this
range of wavelengths helps protect SPF
test subjects from being exposed to
undesirable, unnecessary radiation. The
requirement should not impose undue
hardship, because longer wavelengths
can be monitored using a thermopile,
pyroelectric, or similar detectors.
We received two submissions
addressing the requirement in proposed
21 CFR 352.70(b)(2) that a solar
simulator have ‘‘good beam uniformity
(within 20 percent) in the exposure
plane’’ (Ref. 1). One submission argued
that advances in equipment and
monitoring allow for a stricter beam
uniformity requirement (<20 percent),
which would result in less variability in
SPF test results. Another submission
argued that the beam uniformity
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requirement is only important for large
diameter beams and has no impact on
SPF testing using small beams.
We are not changing the 20 percent
beam uniformity requirement because
accurate determination of SPF values
relies upon good beam uniformity for all
beam sizes. In the 2007 proposed rule,
we described how small diameter beams
can be tested for beam uniformity (see
72 FR 49070 at 49098). The submission
requesting stricter requirements did not
include data showing that current solar
simulators can reasonably be expected
to have beam uniformity less than
20 percent. We conclude that a 20
percent beam uniformity requirement is
adequate to produce reliable SPF
results. Therefore, we are keeping the
requirement that solar simulators
demonstrate good beam uniformity
(within 20 percent) in new 21 CFR
201.327(i)(1) (iii).
B. Sunscreen Standards
The 2007 proposed rule include two
sunscreen standards for use in SPF
testing. The two proposed sunscreen
standards were a 7 percent padimate
O/3 percent oxybenzone standard (mean
SPF value of 16.3) and an 8 percent
homosalate standard (mean SPF value of
4.47). For SPF testing of sunscreen
products with SPF values of 2 to 15,
either the padimate O/oxybenzone
standard or the homosalate standard
would have been required to be tested
along with the test sunscreen product.
Tests for sunscreen products with SPF
values over 15 would have required use
of the padimate O/oxybenzone standard.
We received two requests to include
an additional sunscreen standard with
an SPF value of 30 or higher to test
sunscreen products with SPF values of
30 or more (Ref. 1). Neither request
specified any particular sunscreen
standard formulation with an SPF in
this range. If a particular sunscreen
standard formulation were specified, we
would also need validation data to
support including the additional
sunscreen standard in the monograph.
Therefore, we are not including a
sunscreen standard with an SPF value
of 30 or more in this document.
We also received a request to include
the JCIA SPF 15 ‘P3’ sunscreen standard
containing 0.5-percent avobenzone, 3percent octyl methoxycinnamate, and
2.78-percent phenylbenzimidazole
sulfonic acid. To support including the
‘‘P3’’ standard, the request included a
table showing mean, maximum, and
minimum SPF values from tests
conducted in labs in Europe, Japan,
Australia, and South Africa. We
recognize that the ‘‘P3’’ standard has
been widely used and is included in the
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COLIPA SPF test, but we are not
including the ‘‘P3’’ standard in this
document. In the 2007 proposed rule
(72 FR 49070 at 49095 to 49095), we
requested further data to show that
testing using the ‘‘P3’’ standard could be
performed with:
• Low level interlaboratory variation
• Sufficient sensitivity to detect
experimental error
• A reasonable degree of accuracy
The submitted data (i.e. the table of SPF
values) fail to show that the ‘‘P3’’
standard meets these performance
requirements because they do not show:
• Individual lab results
• The number of tests conducted in
each lab
• The number of test subjects used in
each test
• Calculated standard errors for each
test
Without these data, we cannot assess
interlaboratory variability, sensitivity to
experimental error, or test result
accuracy. In addition, the advantage of
using the ‘‘P3’’ standard instead of the
padimate O/oxybenzone standard is
unclear, because both these standards
have approximately the same SPF value
of 16. Therefore, we are not including
the ‘‘P3’’ standard in this document.
We are also eliminating the proposed
homosalate standard with an SPF value
of 4.47 because the padimate O/
oxybenzone standard with an SPF value
of 16.3 is adequate for validating all test
methodologies. In the 2007 proposed
rule, we stated that the sunscreen
standards were ‘‘method controls rather
than calibration tools.’’ As a method
control, the purpose of the sunscreen
standard is verifying proper and
consistent performance of test
equipment and procedures, rather than
verifying the accuracy of the SPF value
determined for sunscreen test products.
Therefore, we conclude that it is not
critical for the SPF value of the
sunscreen standard to be close to the
SPF value of the sunscreen test product.
It is more important that the sunscreen
standard demonstrate consistency of test
performance. Consequently, we have
concluded that including multiple
sunscreen standards is unnecessary, and
that the padimate O/oxybenzone
standard is a suitable sunscreen
standard for all sunscreen products. We
favor including the padimate O/
oxybenzone standard over the
homosalate standard because the
homosalate standard was only proposed
for use for SPF testing of sunscreen
products with SPF values lower than 15.
Because most currently marketed
sunscreen products have SPF values of
15 or higher, the padimate O/
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oxybenzone standard is used much
more frequently than the homosalate
standard.
We received one submission
identifying errors in the ‘‘Composition
of the Padimate O/Oxybenzone
Standard Sunscreen’’ table that appears
in the 2007 proposed rule. As suggested
by the submission, we are moving the
inactive ingredient ‘‘propylparaben’’
from ‘‘Part A’’ to ‘‘Part B,’’ as it appears
in the COLIPA SPF test. We are not
revising the listing of the inactive
ingredient ‘‘glyceryl monostearate’’ to
read ‘‘glyceryl monostearate (Glyceryl
Stearate SE),’’ as suggested. The United
States Pharmacopeia defines ‘‘glyceryl
monostearate’’ as an ‘‘emulsifying and/
or solubilizing agent,’’ which adequately
describes the ingredient that is
appropriate for use in the formulation.
C. Test Subjects
In the 2007 proposed rule, we
proposed requiring the following
numbers of test subjects providing valid
results:
• 20 to 25 subjects for sunscreen
products with SPF less than 30
• 25 to 30 subjects for sunscreen
products with SPF value of 30 or more
We explained that a minimum of 20
subjects would be required to provide
an acceptably accurate SPF result (i.e.,
low standard error of the mean). We had
concluded that sunscreen products with
SPF values of 30 or more required a
greater number of test subjects because
we suspected higher test result
variability for these sunscreen products.
However, the data used for determining
appropriate test subject numbers were
limited and dated. Therefore, we invited
submission of additional data
demonstrating what subject numbers
would be adequate.
Several submissions recommend
requiring 10 to 25 test subjects as in the
COLIPA SPF test (Ref. 1). These
submissions include data demonstrating
that SPF testing can be performed with
suitable accuracy and precision with as
few as 10 test subjects. The submissions
further argued that SPF testing using a
minimum of 10 test subjects has been
practiced globally for many years, even
for sunscreen products with high SPF
values.
We agree with the submissions and
are lowering the number of test subjects
required for SPF testing. We are
requiring that a test panel produce a
minimum of 10 valid test results. A
maximum of three subjects may be
rejected from the panel. Therefore, if 3
subjects would be rejected, a test panel
would have had to include 13 subjects.
We are reducing the number of test
subjects in this document because the
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data we received demonstrate that SPF
testing can be conducted with adequate
accuracy and precision using as few as
10 test subjects, even when testing high
SPF products. The submissions include
SPF test results for several sunscreen
formulations using panels of 20 to 25
test subjects. We randomly selected 10
subjects within each of these panels to
determine if using fewer subjects
significantly decreased test accuracy
and precision. For each of these panels,
the mean SPF value and standard error
calculated from a randomly selected
subset of 10 subjects were not
significantly different from those
calculated from all 20 to 25 subjects in
the panel. Therefore, these data indicate
that using as few as 10 test subjects will
not compromise SPF test accuracy or
precision. Consequently, fewer test sites
and subsites need to be tested and fewer
test results need to be rejected, thereby
decreasing the number of test subjects
needed. Our revised SPF test subject
number requirement is similar to the
COLIPA SPF test requirement. The only
significant difference related to test
subject number is that we are not
including a statistical requirement or
allowing individual subjects to be added
incrementally to a test panel as allowed
under the COLIPA SPF test.
D. Test Sites and Subsites
Several submissions requested the
following revisions of the minimum size
specifications for test sites and subsites
proposed in the 2007 proposed rule
(Ref. 1):
• Test site: proposed 50 cm2 revised
to 30 cm2
• Test subsite: proposed 1 cm2
revised to 0.5 cm2
• Subsite separation: proposed 1 cm
revised to 0.8 cm
According to the submissions, these
smaller revised minimum sizes would
allow multiport solar simulators to be
used, while the larger proposed sizes
would not. These revised specifications
have also been adopted in the COLIPA
SPF test (Ref. 64).
We are revising the test site and
subsite size specifications as requested
by these submissions. Our previously
proposed specifications were based on
single port solar simulators. Some new
multiport solar simulators cannot meet
these proposed specifications. In the
2007 proposed rule, we stated that
reducing test site/subsite size
specifications would be considered if
data were submitted showing that these
reductions would not compromise
testing accuracy (72 FR 49070 at 49100).
New data show that SPF testing can still
be accurately performed using the
recommended reduced test site/subsite
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size specifications (Ref. 1). Therefore,
we are revising the test site/subsite size
specifications to accommodate new
equipment and to harmonize our
specifications with global SPF test
methods.
E. Finger Cot
In the 2007 proposed rule, we
proposed that a finger cot, presaturated
with sunscreen, be used to apply the
sunscreen in the SPF test (proposed
21 CFR 352.70(c)(5)):
Use a finger cot compatible with the
sunscreen to spread the product as evenly as
possible. Pretreat the finger cot by saturating
with the sunscreen and then wiping off
material before application. Preteatment is
meant to ensure that sunscreen is applied at
the correct density of 2 mg/cm 2.
We received one submission that
objected to the use of finger cots because
consumers do not typically use finger
cots when applying sunscreens (Ref. 1).
Other submissions argued that the
presaturation requirement for finger cots
is unnecessary and introduces
variability in applied amounts (Ref. 1).
Other submissions requested the
optional use of sponge applicators for
testing powder formulations, because
they argued that sponge applicators
distribute powder formulations more
evenly than finger cots (Ref. 1). We are
not addressing issues regarding the use
of sponge applicators for the testing of
powders in this rule. Elsewhere in this
issue of the Federal Register, we
publish an advance notice of proposed
rulemaking that discusses sunscreen
dosage forms, including powders. We
may address this issue in a future
rulemaking..
While we acknowledge that
consumers do not use finger cots to
apply sunscreens, we are continuing to
require the use of finger cots in the SPF
test. The use of finger cots seems to
increase reproducibility of test results,
which was why we originally proposed
requiring use of finger cots (72 FR 49070
at 49100 through 49101). We agree with
the submissions that the presaturation
requirement is unnecessary and are
removing this requirement. We
proposed requiring finger cot
presaturation to prevent sunscreen
product from adhering to the finger cot
instead of being transferred to the test
subject’s skin, resulting in sunscreen
product being applied at less than the
intended 2 mg/cm 2. We received study
results showing that a residual amount
of sunscreen product may adhere to
non-presaturated finger cots, but the
amount was small (approximately
2 percent) (Ref. 1). In this study, each of
100 finger cots (without presaturation)
was weighed before and after sunscreen
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35647
product application at 2 mg/cm 2
(100 mg sunscreen product applied over
50 cm 2). However, the study did not
include a comparison to presaturated
finger cots. Therefore, it is difficult to
determine the effect of presaturation on
residual sunscreen amounts.
In addition, we reassessed the basis
for presaturation. We are now
concerned that performing the
presaturation step may lead to
overestimation of SPF values, because
the residual amount normally left on a
finger cot with presaturation may
increase the amount of sunscreen
applied to the skin This could lead to
overestimation of SPF values.
Overestimation of SPF may, in turn,
lead to increased incidence of sunburn
because consumers may anticipate
greater protection than a sunscreen
product actually provides. This
overestimation risk is a sufficient basis
to remove the presaturation step from
the proposed SPF test method.
We also received data showing that
testing without the presaturation step
can produce highly reproducible results
(Ref. 1). In a test of 20 subjects without
the presaturation step, a control
sunscreen product yielded a mean SPF
value of 4.19 with a standard error of
0.06 (i.e., 1.4 percent error), while a test
sunscreen product yielded a mean SPF
value of 15.54 with a standard error of
0.22 (i.e., 1.4 percent error). These errors
are small, suggesting that the calculated
SPF values did not vary significantly
between test subjects. If lack of
presaturation increased variability, then
the errors would be expected to be
larger. Therefore, we are removing the
presaturation requirement because of
the risk of overestimation of SPF values
and our conclusion that the removal of
the presaturation step will not affect the
reproducibility of SPF test results.
F. Application Amount
We are continuing to require that 2
mg/cm2 sunscreen product be applied
for the SPF test (proposed 21 CFR
352.70(c)(5); new 21 CFR
201.327(i)(4)(iii)). Several submissions
argued for a lower application amount
that better reflects the actual amount
used by consumers, which they argued
is commonly 1 mg/cm2 or less (Ref. 1).
These submissions argued that the
unrealistically high 2 mg/cm2
application amount results in SPF
values that overstate the actual sun
protection provided by the amounts
consumers typically apply. Other
submissions supported the 2 mg/cm2
application amount (Ref. 1). These
submissions argued that SPF values are
relative, not absolute, values that allow
comparison of sun protection provided
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by different sunscreen products.
According to the submissions, changing
the application amount will affect the
ability of consumers to make this
comparison.
We are not changing the sunscreen
product application amount because we
have concluded that the advantages of
continuing to require 2 mg/cm2 exceed
the disadvantages of lowering the
amount. Requiring the 2 mg/cm2
sunscreen product application amount
is consistent with SPF test methods
used in other countries. The 2 mg/cm2
application amount is being used in
Europe, Australia, Canada, Korea, and
Japan (Refs. 65–67). If we lower the
application amount, sunscreen products
available in the United States will have
significantly lower SPF values than
similar products available in other
countries. This discrepancy in SPF
values is counterproductive to our
global harmonization efforts and would
likely mislead consumers traveling to
other countries about the SPF protection
of foreign sunscreen products.
Another advantage of continuing to
require a 2 mg/cm2 sunscreen product
application amount is greater
reproducibility of SPF test results.
Bimczok et al. compared the SPF values
determined using sunscreen product
application amounts of 0.5, 1, and 2 mg/
cm2 (Ref. 68). The SPF values
determined using 2 mg/cm2 sunscreen
product were more reliable and
reproducible than SPF values
determined using the lower application
amounts. A sunscreen product
application amount of 2 mg/cm2 is a
large enough amount to allow
visualization of the distribution of
sunscreen product as it is applied. This
allows for more consistent and uniform
application of the sunscreen used in
testing. Therefore, the 2 mg/cm2
sunscreen product application amount
is more likely to generate reproducible
results.
G. Water Resistance
In the 2007 proposed rule, sunscreen
products tested with two 20-minute
immersion periods (i.e., 40 minutes
total) would be allowed to include a
‘‘water resistant’’ statement and
sunscreen products tested with four 20minute immersion periods (i.e., 80
minutes total) would be allowed to
include a ‘‘very water resistant’’
statement. There is a 20-minute drying
period between each immersion period.
For example, a ‘‘water resistant’’
sunscreen product would be tested by
having test subjects in the water for 20
minutes, out of the water for 20
minutes, and in the water for 20
minutes.
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We received various requests to revise
the test (Ref. 1). One submission
recommended longer water immersion
times equal to those in water resistance
tests used in Australia and New
Zealand. Another submission included
data from an in vitro water resistance
test to support removing the in vivo
water resistance test. A third submission
stated the test should be eliminated
because it is not validated and requires
too much time. Further, the submission
argued that directions for frequent
reapplication make the test unnecessary.
We are continuing to include a water
resistance test because water resistance
is an important property of sunscreen
products that can benefit consumers.
The water resistance test indicates that
a sunscreen product’s labeled SPF
protection is retained for a certain
period of time after immersion in water.
This is useful information to consumers.
Therefore, we conclude that a water
resistance statement based on the test
should be allowed (see section III.C of
this document).
We are not changing the 20-minute
water immersion periods or the number
of immersion periods required. We
based these time periods on marketing
data indicating that individuals at the
beach or the pool spend an average of
21 minutes in the water and go into the
water an average of 3.6 times (43 FR
38206 at 38263, August 25, 1978). We
have not received any other data
supporting different time periods. We
have concluded that more or longer
water immersion periods are not
needed.
We are, however, reducing the drying
period from 20 minutes to 15 minutes.
We are making this change to decrease
the time required for testing. Shorter
testing time may increase test accuracy
and reproducibility, especially for high
SPF sunscreens that retain their water
resistance for 80 minutes. In addition,
15 minutes is adequate time to allow for
drying. It is possible that sunscreens
may lose water resistance with repeated
wetting and drying. However, we have
concluded that a 15-minute drying
period mimics consumer behavior and
ensures that the water resistant
properties of a sunscreen do not change
with multiple cycles of water immersion
and drying.
VII. SPF Test Issues (Other than Test
Parameters)
A. Pass/Fail (Binomial) SPF Test
Several submissions requested the
optional use of a pass/fail (binomial)
test to determine the SPF value of a
sunscreen product (Ref. 1). These
submissions promote the pass/fail test
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because it would expose fewer subjects
to UV irradiation, cost less, and save
time. The pass/fail test is based on the
hypothesis that a sunscreen product of
a certain SPF has a 50:50 probability of
preventing the MED response when
irradiated with a UV dose correlated
with that SPF. For example, a sunscreen
product with an expected SPF value of
30 or more should prevent the MED
response in greater than 50 percent of
test subsites irradiated with a UV dose
equivalent to 30 times the UV dose that
causes the MED response on
unprotected skin. If a test sunscreen
product prevents the MED response in
a significant number of the subsites (i.e.,
significantly more subsites that ‘‘pass’’
versus ‘‘fail’’), then the test sunscreen
product would be allowed to be labeled
with the SPF correlated to the UV dose.
We are not including the optional use
of a pass/fail test for SPF testing. We
considered a pass/fail SPF test in the
2007 proposed rule (72 FR 49070 at
49094 to 49095). We stated that a pass/
fail test could be a reasonable substitute
for our proposed SPF test for sunscreen
products with SPF values of 30 or more
if certain modifications were made and
validation data demonstrated that the
test could be performed similarly
between labs.
In response to our invitation for
public comment, one submission
included two studies comparing a pass/
fail SPF test to the proposed SPF test:
(1) A single center study of four
sunscreen products with different SPF
values and (2) a multicenter (four
laboratories) study of two high SPF
sunscreen products. After reviewing
these data, we have determined that the
pass/fail test has the following
drawbacks:
• Each test subsite evaluation is
biased towards ‘‘pass’’ because the
evaluator expects that no skin reaction
should occur on subsites protected by
the test sunscreen product.
• The test fails to reject test sites
where all of the subsites show positive
responses or all of the subsites show
negative responses.
• The validity of treating each subsite
as an independent variable is
questionable.
• The test endpoint (any observed
reaction) differs from the endpoint in
the proposed SPF test (clearly defined
erythema).
• A passing test result for the
sunscreen standard does not
demonstrate that the test is being
performed correctly.
• Test results do not include data for
water resistant sunscreen products.
• Allowing this test as an option
would yield products with different UV
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protection levels labeled with the same
SPF.
• SPF test methods developed by
various standards-setting organizations
do not include a pass/fail test.
• The study report includes statistical
errors that overstate the statistical power
of the test to distinguish whether a test
sunscreen product provides significant
UV protection.
Therefore, we are not including a pass/
fail test in the SPF test procedure,
because including a pass/fail test would
present numerous complications and
the available data indicate that a pass/
fail test has disadvantages compared to
the SPF test included in this document.
B. Photostability
Several submissions expressed
concern about the loss of UV protection
by sunscreen products due to
breakdown of ingredients from exposure
to sunlight (Ref. 1). These submissions
recommended a test to ensure that
sunscreen products exposed to sunlight
retain sufficient UV protection.
Submitted data show that the
composition of sunscreen products can
change from exposure to UV radiation.
The submissions argue that the
published photostability studies are
inconclusive because the studies
employ artificial test conditions that
may not be appropriately extrapolated
to actual use of sunscreens:
• Tested sunscreen active ingredients
were contained in solutions rather than
in typical sunscreen product
formulations
• Tested sunscreen products
contained active ingredients that are not
representative of the active ingredients
included in typical sunscreen products
• Products were tested over a limited
range of the UV spectrum
The submissions argue that
understanding the photostability of
sunscreen active ingredients alone is not
useful. Rather, the submissions argue
that it is critical to understand the
photostability of sunscreen active
ingredients as part of an overall
sunscreen product.
We agree that the available data have
limitations. Although the submissions
argue that the inconclusive data support
including a test for photostability, we
have concluded that the data do not
justify requiring a photostability test at
this time. We are not able to establish
specific photostability test procedures
or specifications based on the available
data. We have not received data
validating the performance of a
photostability test, nor have we received
data demonstrating that the
effectiveness of any particular sunscreen
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product is significantly diminished
because of photodegradation. We
maintain that the proposed SPF test
procedure does account for
photostability to some extent, because
the SPF test exposes sunscreen products
to UV radiation before an SPF value is
determined. Consequently, sunscreen
products susceptible to
photodegradation have correspondingly
lower SPF values. One submission
argued that the SPF test does not fully
account for photostability because the
solar simulator emission spectrum is
different than natural sunlight.
However, this difference is an
unavoidable limitation in testing
because solar simulators cannot
perfectly replicate natural sunlight.
We acknowledge that UV radiation
can change the composition of
sunscreen products if the products are
not photostable, as demonstrated by the
submitted data. However, we are not
certain that these data are applicable
under actual use conditions. The data
regarding the effects of UV radiation on
the protection provided by sunscreen
active ingredients are limited and
inconclusive. Therefore, we are not
creating a photostability test as part of
the SPF test procedure in this
document.
C. In Vitro SPF Test
One submission suggested replacing
the proposed in vivo SPF test with an
in vitro SPF test (Ref. 1). An in vitro SPF
test would have advantages of faster
performance, lower expense, and no
exposure of subjects to UV radiation.
We agree that an in vitro SPF test has
these advantages. However, we are not
replacing the in vivo SPF test with an
in vitro SPF test for the same reasons we
stated in the 2007 proposed rule (72 FR
49070 at 49095). One shortcoming of an
in vitro test is the lack of data on the
performance characteristics of in vitro
test substrates, such as quartz or
artificial skin. In the 2007 proposed
rule, we stated that data failed to show
that a substrate adequately mimicked
the physiological characteristics of
human skin. We stated that we would
consider an in vitro test if validating
data demonstrated that the performance
of the in vitro test was equivalent to the
in vivo test. We have not received
adequate data to validate an in vitro SPF
test. Therefore, we are not including an
in vitro test in this document.
D. Anti-Inflammatory Ingredients
One submission recommended
requiring a test to verify that sunscreen
products do not contain antiinflammatory ingredients that
significantly decrease erythemic
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35649
response to UV radiation (Ref. 1). The
submission did not identify specific
anti-inflammatory ingredients. The
submission argued that, by decreasing
the erythemal response, these
ingredients could falsely inflate SPF
values determined in SPF testing. In
addition, these anti-inflammatory
ingredients may increase the likelihood
of unwanted harmful effects from sun
exposure because sunburn, a cue to
avoid sun exposure, would be less
evident.
Although the submission raises a
serious concern, we are not aware of any
data confirming that this problem exists.
Therefore, a test to show that antiinflammatory ingredients may be
decreasing erythemic response to UV
radiation is not required at this time. It
seems unlikely that anti-inflammatory
ingredients will affect SPF values
because their anti-erythemic effect is
relatively short-lived compared to the
16–24 hour interval between UV
exposure and erythema observation in
the SPF test.
VIII. Broad Spectrum Test
In this document, we are referring to
testing involving the UVA part of the
spectrum as ‘‘broad spectrum testing.’’
The term ‘‘broad spectrum’’ more
accurately describes the test as covering
the full extent of the terrestrial solar UV
spectrum (i.e., UVA and UVB radiation).
Section VIII.A. of this document
provides our rationale for no longer
requiring an in vivo test assessing the
persistent pigment darkening associated
with UVA radiation. Section VIII.B. of
this document explains why the in vitro
test should be changed from a modified
Diffey-Robson ratio to the critical
wavelength test. Section VIII.C. defines
the testing parameters to be employed in
evaluating the critical wavelength of an
OTC sunscreen product.
A. In Vivo Test Method: Not Required
We stated in the 2007 proposed rule
that an assessment of UVA protection
should include determination of both
the magnitude and breadth of
absorption in the UVA part of the
spectrum (72 FR 49070 at 49102 through
49106). We proposed that an in vivo
Persistent Pigment Darkening (PPD) test
be used to evaluate the magnitude of
absorption and an in vitro test be used
to evaluate the breadth of absorption.
The PPD test, a modification of the PPD
test accepted by JCIA 10 since 1996, is
almost identical to the SPF test. It is
recognized as a standard for the in vivo
assessment of UVA protection by the
JCIA and the European Commission
10 Japanese
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(Ref. 7). The most significant differences
in the PPD test compared to the SPF test
are (1) the light source emits only UVA
radiation (320–400 nm) and (2) the
endpoint is darkening of the skin
(tanning) rather than reddening of the
skin (erythema).
We have concluded that the PPD test
is not necessary to establish that a
sunscreen product provides protection
against UVA radiation. The magnitude
of absorption over the solar terrestrial
UV portion of the spectrum (both UVA
and UVB) can be effectively assessed
based on the SPF test in combination
with a pass/fail broad spectrum in vitro
test (see Section VIII.B of this
document). If sunscreen products pass
the in vitro broad spectrum test, then
the amount of UVA radiation protection,
as well as UVB radiation protection,
must increase as the SPF value
increases. For example, a Broad
Spectrum SPF 40 sunscreen product
must provide more UVB and UVA
radiation protection than a Broad
Spectrum SPF 20 sunscreen product.
For sunscreen products that pass the
in vitro broad spectrum test, we have
concluded that the SPF and PPD tests
are redundant of each other, but we
have reasons to prefer the SPF test. The
SPF and PPD tests are both clinical and
indicative of the magnitude of
absorbance of UV radiation.
Furthermore, both tests depend on the
skin type of the individual. The SPF test
measures skin reddening, which is due
primarily to UV radiation in the UVB
and UVA II regions (290–340 nm). The
PPD test measures skin darkening,
which is due primarily to UV radiation
in the UVA II part of the spectrum (320–
340 nm). Therefore, the UV radiation
range covered by the PPD test is also
covered by the SPF test. In both tests,
the endpoint is indicative of how much
UV radiation is absorbed. As the
magnitude of UV radiation absorbance
increases for a sunscreen product, both
the SPF and PPD ratings increase.
We have identified several
disadvantages of the PPD test as
described in the proposed rule (72 FR
49070 at 49103):
• Human subjects are exposed to high
doses of UVA radiation with unknown
health consequences.
• Exposure to UVA radiation alone
(i.e., in the absence of UVB radiation) is
never encountered in nature, and the
biological effects of such exposure may
differ greatly from those due to exposure
to natural sunlight.
• Because it is unclear how tanning
relates to the harmful effects of sunlight,
it is unclear whether persistent pigment
darkening represents a clinically
meaningful endpoint.
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Other disadvantages are pointed out by
Nash et al. (Ref. 4):
• The physical properties of
sunscreen products may differ when
sunscreen products are exposed to UVA
radiation alone.
• The PPD test is expensive, time
consuming, and labor intensive.
• The ability to identify small
differences in pigmentation requires a
high degree of expertise and
interpretation of pigmentation changes
will be dependent on the examiner.
• There may be a high degree of
variability in test results between
subjects in the same test panel as well
as between different test panels for the
same sunscreen product.
• The test results may not be
reproducible between labs.
Because of these disadvantages of
conducting the PPD test, and the fact
that information obtained from such
tests is already provided by SPF testing
for sunscreen products that pass the in
vitro broad spectrum test, we are
eliminating the requirement to conduct
a PPD or any other in vivo UVA test in
this final rule.
B. In Vitro Test Method: Critical
Wavelength
Many submissions objected to our
proposal to use a modification of the
Boots adaptation of the Diffey/Robson
ratio as an in vitro measure of UVA
protection (Ref. 1). The Diffey/Robson
ratio evaluates UVA protection relative
to UVB protection. The ratio is
calculated as the area under the
absorbance curve in the UVA region
(320–400 nm) divided by the area under
the absorbance curve in the UVB region
(290–320 nm). As the degree of
protection against UVA radiation
increases, the ratio increases.
We proposed a modification of this
ratio to be calculated as the area under
the absorbance curve in the UVA I
region (340–400 nm) divided by the area
under the absorbance curve over total
UVB and UVA range (290–400 nm). We
indicated that this modification was
necessary because we were concerned
that a sunscreen product absorbing
strongly in the UVA II region (320–340
nm), but not absorbing strongly in the
UVA I region, might produce a
disproportionately high ratio value (72
FR 49070 at 49105). We would not
consider this sunscreen product to be a
good broad spectrum sunscreen product
even though it has a high ratio value.
We noted the importance of ensuring
that protection extends well into the
UVA I region (340–400 nm), because
neither SPF nor PPD measurements
provide much information about the
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longer wavelengths of UVA radiation.
Therefore, we modified the ratio to give
more emphasis to the UVA I area under
the absorbance curve.
Many submissions argued that we
should require a determination of
critical wavelength rather than the
proposed ratio to determine broad
spectrum protection (Ref. 1). We agree
with the arguments made in the
submissions. Therefore, in this
document, we are requiring that broad
spectrum protection be assessed by
determining the critical wavelength of a
sunscreen formulation. The submissions
noted the following disadvantages with
the proposed ratio:
• The proposed ratio places too much
emphasis on the UVA I region, which is
not generally considered to contribute
significantly to the harmful effects of
exposure to UV radiation.
• A large ratio could result if one or
more ingredients absorb radiation in the
shorter wavelength UVA II region but
not at all or only minimally in the
longer wavelength UVA I region. For
example, oxybenzone absorbs radiation
at 340–360 nm, and inclusion of this
ingredient at higher concentrations
might result in a high ratio even though
it does not provide true broad spectrum
protection.
• The proposed ratio is not a
validated measure of UVA protection
and is not used anywhere else in the
world.
• To achieve high ratios with existing
GRASE active ingredients, the
concentrations of ingredients that
absorb in the UVB and UVA II parts of
the spectrum have to be reduced,
lowering protection in these parts of the
spectrum (i.e., the SPF has to be lowered
to increase the ratio).
We agree that our proposed ratio is
not the most appropriate in vitro
measure of broad spectrum protection.
In agreement with many of the
submissions, we have concluded that
the ratio places too much emphasis on
absorption in the UVA I part of the
spectrum. Although there is some
evidence that UVA I radiation
contributes to immune suppression and
an increase in p53-positive cells, the
effects of UVA I radiation on these
processes are 100 to 1000 times less
than the effects attributed to UVB and
UVA II radiation (Ref. 4). We also
acknowledge that there is no experience
using the proposed ratio. Further, we
received some data in the submissions
that demonstrate the need to reduce SPF
values in order to achieve high ratio
values. We are concerned that, in an
effort to gain UVA protection,
consumers may be more susceptible to
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35651
sunburn because SPF values could be
lower in products with higher ratios.
In agreement with many of the
submissions, we have concluded that
the critical wavelength method provides
a better measure of broad spectrum
protection. The critical wavelength (λc)
is derived from the same data as the
modified ratio. The critical wavelength
is the wavelength at which the area
under the absorbance curve represents
90 percent of the total area under the
curve in the UV region. This is
expressed mathematically as:
In this expression, A(λ) is the mean
absorbance at each wavelength, and dλ
is the wavelength interval between
measurements.
Like the proposed ratio, the critical
wavelength measures the breadth of the
UV absorbance curve. Unlike the
proposed ratio, the critical wavelength
does not emphasize certain parts of the
UV spectrum, but is a measure of
absorbance across the entire solar
terrestrial UV spectrum (UVB and UVA
radiation). Sunscreen products offering
primarily UVB protection would have a
critical wavelength less than 320 nm,
whereas those providing both UVB and
UVA protection would have critical
wavelengths between 320 and 400 nm.
The critical wavelength method is
simple, reproducible, and inexpensive.
It has been used by sunscreen
manufacturers to evaluate UVA
protection for over a decade and is one
of the most commonly used UVA tests.
This is evidenced by the organizations
that recommend its use for determining
broad spectrum protection, including
the European Commission, the
American Academy of Dermatology, the
American Society for Dermatologic
Surgery, and the Skin Cancer
Foundation (Ref. 1).
In this document, we are requiring
that sunscreen products have a critical
wavelength of at least 370 nm (the mean
value must be equal to or greater than
370 nm) to be labeled as providing
broad spectrum protection (see section
VIII.B.). This differs from the tiered
rating (low, medium, high, and highest)
that we included in the 2007 proposed
rule (proposed 21 CFR 352.50(b)(2)). We
have concluded that the threshold
critical wavelength for a broad spectrum
statement should be 370 nm. This
wavelength is sufficiently difficult to
achieve and will ensure that sunscreen
products meeting this threshold provide
a significant amount of broad spectrum
protection. On the other hand, it is not
so difficult to formulate sunscreen
products to achieve this critical
wavelength that manufacturers cannot
develop broad spectrum sunscreen
products. We have concluded that UV
radiation in the range of 370—400 nm
is not very harmful based on the
available action spectra for sunburn and
skin cancer. We conclude that most of
the harmful effects from the sun are
caused by UV radiation in the range of
290—370 nm. Further, we conclude that
critical wavelength (breadth of UVB and
UVA protection) coupled with the SPF
value (magnitude of UVB and UVA
protection) provides a complete
measure of broad spectrum protection
provided by a sunscreen product.
C. Critical Wavelength Test Parameters
Although the proposed ratio and
critical wavelength calculations are
different, both tests are based on the
construction of a transmittance curve
over the range of UV wavelengths from
290 to 400 nm. We received several
submissions requesting that we change
or, in some cases, better define aspects
of the methodology used to measure
transmittance over these wavelengths
(Ref. 1). Although the submissions, in
most cases, referred specifically to the
proposed ratio test, the points made
regarding methodology apply equally to
the critical wavelength test.
We are making several revisions to the
section we referred to as the ‘‘UVA in
vitro testing procedure’’ in the 2007
proposed rule (proposed 21 CFR
352.71). To more accurately describe the
test as covering both the UVB and UVA
regions of the spectrum, we now refer to
the test as the ‘‘broad spectrum test.’’
The revisions are listed in Table 5 in the
order in which they appear in this
section of the document.
TABLE 5—SUMMARY OF REVISIONS TO THE PROPOSED IN VITRO BROAD SPECTRUM TEST INCLUDED IN THIS FINAL RULE
Plate .....................................
Term ‘‘spectroradiometer’’ ...
Light source for transmittance measurements.
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Input optics: Bandwidth ........
Dynamic range of the spectrometer.
Application of sunscreen
drug product to plate.
Pre-Irradiation dose .............
Number of transmittance
measurements.
Calculation of critical wavelength.
2007 proposed rule
This final rule
Quartz plate (21 CFR 352.71(b))
Spectroradiometer
(21 CFR 352.71(c) and (d))
Solar simulator
(21 CFR 352.71(a))
5 nanometers
(21 CFR 352.71(d))
Not specified
2.0 mg/cm2 with single-phase spreading (21 CFR
352.71(e))
Proportional to SPF value (21 CFR 352.71(f))
12 measurements of mean transmittance on 5 different
plates (21 CFR 352.71(g) and (i))
Not applicable
PMMA1 plate (21 CFR 201.327(j)(1)(i))
Spectrometer
(21 CFR 201.327(j)(1)(ii), (iv), and (v))
Produce a continuous spectral distribution of UV radiation from 290 to 400 nanometers
(21 CFR 201.327(j)(1)(iii)
1 nanometer
(21 CFR 201.327(j)(1)(iv))
Sufficient to measure transmittance accurately through
highly absorbing sunscreen (21 CFR 201.327(j)(1)(v))
0.75 mg/cm2 with 2-phase spreading (21 CFR
201.327(j)(2))
Fixed at 800 J/m2-eff (21 CFR 201.327(j)(3))
5 measurements of mean transmittance on 3 different
plates (21 CFR 201.327(j)(4) and (6))
21 CFR 201.327(j)(7))
1 Polymethylmethacrylate
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We re-organized the broad spectrum
test parameters in this final rule so that
they are listed in the order that the test
is done. This section of the document
begins with a description of the plates
to be used and the requirements for UV
spectrometry. The next section
addresses application of the sunscreen
product to the plate, and the following
section addresses the pre-irradiation
procedure. The last sections included
under broad spectrum test parameters
address measuring the amount of
radiation transmitted through the
sunscreen product, converting these
measurements to absorbance values, and
calculating the critical wavelength of a
sunscreen product.
All of the proposed test parameters
were re-evaluated in the preparation of
this document. Some of the parameters
did not require revision. Test
parameters not revised include:
• Sample holder
• Input optics (other than slit width)
• Light source for pre-irradiation
• Calculation of mean transmittance
values
• Calculation of mean absorbance
values
The parameters defined in this section
are based on our review of submitted
data (Ref. 1) and peer-reviewed
literature. Wherever possible and
consistent with sound science, we have
attempted to harmonize the parameters
with existing standards, including those
of the European Commission (Ref. 7)
and COLIPA (Ref. 69). As stated earlier
in this document, we are also actively
involved in the ISO working group
responsible for developing
methodologies for assessing sun
protection (both UVB and UVA
protection).
1. Plate
Many submissions argued that we
should specify that roughened PMMA
(polymethylmethacrylate) plates be used
as a substrate rather than roughened
quartz included in the 2007 proposed
rule (Ref. 1). The submissions stated
that they prefer PMMA plates because
these plates are:
• Less expensive than quartz
• Disposable—no need to clean or reroughen
• Readily available with roughened
surface
• Validated in COLIPA ring tests and
in widespread use for more than a
decade
• Recommended by the European
Commission and COLIPA
We agree with these submissions and
are specifying, in this document, that
PMMA plates be used as the substrate
in this document. We are specifying the
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use of PMMA plates primarily because
the vast majority of validation data we
have reviewed was collected using
PMMA rather than quartz plates.
Further, we agree with the submissions
noting that PMMA plates are less
expensive than quartz and, therefore,
can be disposable. The disposability of
the PMMA plates will eliminate the
requirements for cleaning and reroughening the surface characteristic of
quartz plates.
Consistent with COLIPA, we are also
specifying the degree of roughness and
size of the application area on these
plates. Plates should be roughened on
one side to a three-dimensional surface
topography measure (Sa) between 2 and
7 micrometers. These Sa values are
supported by validation studies (Ref. 70)
and are comparable to those
recommended by COLIPA (Ref. 69). The
application area must be at least 16
square centimeters with no side shorter
than 4 centimeters. We are also
replacing the word ‘‘substrate’’ with the
simpler and more widely used term
‘‘plate.’’
These changes are included in 21 CFR
201.327(j)(1)(i) of this document.
Specifying standardized roughness and
size parameters will result in more
accurate and reproducible intra- and
inter-laboratory measurements of broad
spectrum photoprotection. Because
these PMMA plates of specified
roughness and size are already being
used in many parts of the world and are
recommended by COLIPA, we have
concluded that they can be employed in
broad spectrum testing in this country
with minimal expense or training of
personnel.
2. ‘‘Spectroradiometer’’ vs.
‘‘Spectrometer’’
Four submissions asked us to replace
the term ‘‘spectroradiometer’’ with the
more generally used term
‘‘spectrophotometer’’ (Ref. 1). We
originally chose the term
‘‘spectroradiometer’’ because UV
radiation is not detectable by the human
eye and, therefore, is not gauged by
photometry (which measures visible
light). However, the term
‘‘spectrophotometer’’ is often used
interchangeably with the term
‘‘spectroradiometer.’’ In this document,
we are replacing the term
‘‘spectroradiometer’’ with the more
inclusive term ‘‘spectrometer.’’ Use of
the term ‘‘spectrometer’’ allows the use
of either a spectroradiometer or
spectrophotometer and will make the
language more consistent with current
COLIPA guidelines (Ref. 69).
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3. Light Source for Transmittance
Measurements
Four submissions (Ref. 1) asserted
that it is inappropriate to specify a solar
simulator as the light source for
measuring transmittance (proposed 21
CFR 352.71(a)). Three of the
submissions argued that radiation
emitted from a solar simulator is filtered
such that there is very low energy
output in the UV region below 300 nm
(Ref. 1). One submission noted that a
light source filtered in this way cannot
provide sufficient energy to measure
transmittance through highly absorbing
sunscreen products. The same
submission suggested that there may not
be enough transmittance at wavelengths
less than 300 nm to exceed the noise
level of the system even in the absence
of a sunscreen product (when
transmittance should be maximal).
We agree with the submissions and,
in 21 CFR 201.327(j)(1)(iii) of this
document, are specifying that the light
source for transmittance measurements
provide continuous, full spectrum
radiation from 290 to 400 nanometers.
The use of such a light source should
maximize instrument transmission
properties while retaining full
sensitivity. We note that this type of
light source is recommended by
COLIPA (Ref. 69).
4. Wavelength Interval Between
Transmittance Measurements
Two submissions argued that we
should reduce the wavelength intervals
between transmittance measurements
from the proposed 5 nm to 1 nm (Ref.
1). The submissions stated that
specifying a smaller interval would
produce more accurate results and
noted that current spectrometers are
capable of making measurements at 1
nm intervals. We agree with the
submissions. Additionally, we are aware
that the COLIPA guideline (Ref. 69)
specifies that transmittance
measurements are to be taken at 1 nm
intervals. Therefore, we are revising the
required input slit bandwidth in this
document to specify that it be less than
or equal to 1 nm (new 21 CFR
201.327(j)(1)(iv)). We are also revising
the measurement interval (new 21 CFR
201.327(j)(4)) to state that transmittance
values should be measured at 1 nm
intervals.
5. Dynamic Range of the Spectrometer
We are adding new 21 CFR
201.327(j)(1)(v) to specify that the
dynamic range of the spectrometer be
‘‘sufficient to measure transmittance
accurately through a highly absorbing
sunscreen product at all UV
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wavelengths (between 290 and 400
nm).’’ The information in this section
had been included in the section
entitled ‘‘Calculation of the spectral
transmittance at each wavelength
interval’’ in the proposed rule (proposed
21 CFR 352.71(g)). We considered
requiring a minimum dynamic range of
2.2 absorbance units, as specified in the
COLIPA guidelines (Ref. 69). However,
we have concluded that it is not
necessary to include this requirement
because nearly all current spectrometers
are capable of measuring a dynamic
range of 2.2 absorbance units or better.
6. Application of Sunscreen Product to
PMMA Plate
Thirteen submissions (Ref. 1)
expressed one or more concerns over
the method by which we proposed
applying sunscreen product to the plate
(proposed 21 CFR 352.71(e)). Eleven of
the thirteen submissions recommended
we reduce the amount applied from 2
milligrams per square centimeter (mg/
cm2) to between 0.75 and 1.2 mg/cm2.
Three submissions suggested we specify
that the sunscreen product be applied
with a better defined spreading action.
Two submissions requested we consider
requiring that a saturated fingertip be
used to apply the product rather than a
gloved finger.
We are reducing the application
amount in this document because
transmittance of UV radiation through a
film of 2 mg/cm2 thickness is low and,
therefore, can result in inaccurate and/
or irreproducible measures of UVA
protection. UV detectors have a range of
UV radiation that they can accurately
measure referred to as the dynamic
range. If UV radiation is outside the
dynamic range (either lower or higher),
measurements from the detector become
less accurate and often less
reproducible. We received validation
data demonstrating that application
amounts lower than 2 mg/cm2 are more
accurate and reproducible than an
application of 2 mg/cm2 (Ref. 1). The
2007 proposed rule required an
application amount of 2 mg/cm2
because this is the amount specified in
the proposed in vivo SPF and PPD tests.
We are not including the PPD test in
this document and we have concluded
that consistency with the SPF test is not
warranted given the concerns about
inaccurate and/or irreproducible results
with an application amount of 2 mg/cm2
in the in vitro UVA method. A reduced
application amount is consistent with
the COLIPA guidelines (Ref. 69). Both of
these documents specify an application
amount of 0.75 mg/cm2. Data we have
reviewed from the Personal Care
Product Council demonstrate that
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application of 0.75 to 1.0 mg/cm2 results
in good transmission within the
dynamic range of UV detectors (Ref. 1).
Therefore, in this document, we are
reducing the application amount to 0.75
mg/cm2 to ensure the UV radiation
transmitted through sunscreens is
within the dynamic range of UV
detectors (21 CFR 201.327(j)(2)).
We are also specifying the type of
spreading action to be employed when
applying sunscreen product to a plate.
One submission noted that the type of
spreading action employed would
depend on the type of product being
applied. The submission argued that it
might take 30 seconds to evenly spread
thicker water resistant creams, but only
10 seconds to evenly spread lotions or
oils. We recognize that the very light
spreading action for 10 seconds we
proposed may not be sufficient to
evenly distribute all dosage forms on a
plate (proposed 21 CFR 352.71(e)). One
submission provided data from a ring
test involving 7 different laboratories
showing that the UVAI/UV absorbance
ratio is affected by the amount of
pressure applied during application. A
second submission referenced a paper
by Ferrero et al. which shows that light
pressure applied to some sunscreen
products results in different ratios than
application with greater pressure (Ref.
70). Both submissions recommended
adopting a two-phase application
process like that recommended by
COLIPA (Ref. 69).
We agree that a two-phase spreading
action is a more effective means of
achieving a film of uniform thickness
and distribution for a variety of
sunscreen dosage forms than is the
proposed 10 seconds of light spreading.
This type of spreading action is more
reflective of actual use than the method
we proposed. Therefore, we are
harmonizing the standard with the
COLIPA guidelines by specifying that a
two-phase process be used. Section
201.327(j)(2) in this document specifies
that ‘‘spreading should be done with a
very light spreading action for
approximately 30 seconds followed by
spreading with greater pressure for
approximately 30 seconds.’’
Two submissions argued that we
should specify a saturated fingertip be
used rather than a gloved finger. We do
not agree for the reasons specified in
section VI.E of this document.
7. Pre-Irradiation Dose
Several submissions expressed
concern that the pre-irradiation dose we
proposed to account for differences in
photostability is too high, particularly if
we reduce the application amount (Ref.
1). We proposed that the pre-irradiation
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dose be proportional to the SPF value of
a sunscreen product (proposed 21 CFR
352.71(f)). This was to account for the
possibility that consumers may spend
more time in the sun with higher SPF
products. Proportional pre-irradiation
dosing is also recommended in the
testing procedure published by COLIPA
(Ref. 69). In these documents, the preirradiation dose is determined relative
to the UVA protection factor. Preirradiation dose increases as the UVA
protection factor increases.
Two submissions suggested that we
use a fixed or absolute dose rather than
a relative dose proportional to the SPF
value of a sunscreen product (Ref. 1).
The submissions noted that, at the same
time and location on the earth’s surface,
all sunscreen products are exposed to
the same intensity of sunlight.
Therefore, sunscreen products with
higher SPF values or UVA protection
factors should not be exposed to higher
pre-irradiation doses.
We agree with these two submissions.
It is appropriate to evaluate sunscreen
product photostability using a fixed
exposure intensity. We have data
demonstrating that avobenzonecontaining sunscreen products undergo
almost complete photodegradation
when exposed to doses between 2 and
3 MEDs 11 (Ref. 71). At a dose of 4
MEDs, there were no further decreases
in UVB and UVA absorption of five
different sunscreen products containing
2.5- to 3- percent avobenzone. These
data reflect the worst case scenario for
photodegradation because avobenzone
appears to be the least photostable
active ingredient in the sunscreen
monograph. Therefore, all sunscreen
products marketed under the
monograph are likely to be completely
degraded after 4 MEDs. Based on this
data, we are specifying a fixed preirradiation dose equivalent to 4 MEDs.
As we noted in the 2007 proposed rule,
one MED for a skin type II individual is
200 J/m2-eff (72 FR 49070 at 49107).
Therefore, in this document, we are
specifying a pre-irradiation dose of 4
times 200 J/m2-eff (800 J/m2-eff).
8. Number of Transmittance
Measurements
Two submissions (Ref. 1) stated that
requiring 12 transmittance
measurements on each plate as
proposed is excessive and not
statistically warranted (proposed 21
CFR 352.71(g)). One submission
provided data showing that there are no
significant differences in UVAI/UV
ratios calculated based on 3, 5, 8, or 12
11 Minimal erythema dose—the lowest UV dose
that produces skin reddening (erythema).
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sub-sites per plate. The submission
argued that we should reduce the
number of required test sites per sample
to 6. The other submission proposed
that we require only one transmittance
measurement per plate. The submission
suggested that, rather than taking
multiple measurements from several
small areas on the plate, one
measurement could be made over a
relatively broad area.
One of the submissions also argued
that it is not necessary to evaluate
transmittance on five different plates
(proposed 21 CFR 352.71(j)). The
submission provided data showing that
the UVAI/UV ratio for an SPF 15
sunscreen product is not significantly
different whether it is measured on 1, 2,
3, or 5 plates (with 12 measurements per
plate). We note that the COLIPA
guidelines (Ref. 69) recommend that 3
separate plates be used.
We agree with the submissions that
requiring 12 discrete measurements on
each plate is not necessary to obtain an
accurate transmittance spectrum. The
submitted data demonstrate that there
are no significant differences in UVAI/
UV ratios based on 3, 5, 8, or 12 test
sites. Similarly, we agree with the
submissions that requiring
measurements for five plates is not
necessary to obtain an accurate
transmittance spectrum. Determining 12
transmittance measurements on five
plates, as proposed, results in a total of
60 transmittance measurements. Based
on the submitted data, a total of 15
transmittance measurements should
produce an accurate transmittance
spectrum. Therefore, we are requiring 5
or more measurements on at least 3
different plates (21 CFR 201.327(j)(6) in
this document.
9. Determination of Critical Wavelength
Critical wavelength is to be
determined as described in section
VIII.B of this document.
IX. Analysis of Impacts
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A. Final Regulatory Impact Analysis
We have examined the impacts of the
final rule under Executive Order 12866,
Executive Order 13563, 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 and 13563 direct agencies to
assess all costs and benefits 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). OMB
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has determined that this final rule is a
significant regulatory action under
Executive Order 12866. Consistent with
Executive Order 13563, the approach
taken here maintains ‘‘flexibility and
freedom of choice for the public,’’ above
all by providing ‘‘information for the
public in a form that is clear and
intelligible.
The Regulatory Flexibility Act
requires agencies to analyze regulatory
options that would minimize any
significant impact of a rule on small
entities. Because we lack information
characterizing the number of products
by firm-size and because most affected
entities are considered small, we
conclude that this final rule will have a
significant economic impact on a
substantial number of small entities.
Section 202(a) of the Unfunded
Mandates Reform Act of 1995 requires
that agencies 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 current threshold
after adjustment for inflation is $136
million, using the most current (2010)
Implicit Price Deflator for the Gross
Domestic Product. We do not expect
this final rule to result in any 1-year
expenditure that would meet or exceed
this amount.
1. Background
The purpose of this rule is to finalize
labeling and testing conditions under
which OTC sunscreen drug products
marketed without approved
applications are not misbranded. This
rule addresses labeling and testing
requirements for both UVB and UVA
radiation protection. The rule modifies
the existing SPF test, specifies a test for
broad spectrum protection, and requires
changes to the product label that affect
both the front of the package (the
principal display panel or PDP) and the
Drug Facts section. In addition, the rule
lifts the stay of effective date applied to
the 1999 Drug Facts labeling final rule
(64 FR 13254) specifically for sunscreen
products (66 FR 67485). All
manufacturers of sunscreens will incur
some labeling costs due to revisions to
both the PDP and the Drug Facts section
of the product label (see section IX.A.4
of this document). In addition, many
manufacturers will incur additional
broad spectrum testing costs unless they
have already tested their products
according to the broad spectrum test
required in this rule. Manufacturers of
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sunscreens will also incur SPF testing
costs (see section IX.A.5 of this
document). Some manufactures will
also have to relabel products that are
currently labeled with claims that are
not allowed under this final rule
(§ 201.327(g) and § 310.545(a)(29)(ii)).
2. Benefits
As discussed in section IV.B of this
document, the regular use of a Broad
Spectrum SPF 15 or higher sunscreen
product, when combined with limiting
time in the sun and wearing clothing to
protect sun-exposed areas, reduces the
risk of skin cancer and early skin aging.
The National Cancer Institute estimates
that there are more than one million
new cases of non-melanoma skin cancer
and more than 68,000 new cases of
melanoma per year in the United States
(Refs. 72 and 73). According to the
National Cancer Institute, about 8,700
persons will die of melanoma in 2010.
Fatal cases of non-melanoma skin
cancer are less common but nonetheless
number several hundred per year. The
labeling requirements in this rule, in
conjunction with implementing the
format and content requirements in 21
CFR 201.66, which were stayed for
sunscreens but are being lifted in this
rule, will provide consumers with clear
and concise information about
sunscreen use and protection, and about
the role of sun exposure in increasing
the risk of skin cancer and early skin
aging. Consumers will be able to more
easily identify products that reduce the
risks of skin cancer and early skin aging,
when used as directed. The new
requirements for product testing will
ensure the accuracy of the SPF value
and broad spectrum claim on the
product label.
Although we are unable to quantify
the effects of clear and concise
information, the final rule will provide
clearer and more consistent information
on the benefits of certain sunscreens in
regard to skin cancer risk reduction than
is available on current labels. By
requiring better information on levels of
protection, the rule should contribute to
reduced exposure to UVB and UVA
radiation and thereby reduce the
incidence of skin cancer.
The benefits from reduced incidence
of skin cancer will equal the value of the
illnesses averted. The most appropriate
measure of that value is based on the
average willingness to pay to reduce the
probability of skin cancer. We would
then multiply the value per illness
averted by the likely number of illnesses
averted to determine the benefits of this
final rule. Because we lack estimates of
the likely numbers of illnesses averted,
we present estimates of the value per
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illness averted to illustrate the gains per
averted case.
We estimated the value per case of
preventing skin cancer for fatal and nonfatal cases of melanoma and nonmelanoma skin cancer. The estimated
average medical cost of treatment, lost
productivity, and willingness to pay to
avoid some symptoms and other effects
represents a plausible lower bound on
willingness to pay to avoid a non-fatal
case of skin cancer. For melanoma, the
estimated total cost is about $2,860 per
non-fatal case; for non-melanoma skin
cancer, the total cost is about $1,400 per
non-fatal case; (Refs. 74 and 75).
The largest potential public health
gains from this final rule would likely
come from averted deaths. We can
calculate the monetary value of averted
fatal cases as either the value of
statistical lives saved or the value of
statistical life-years saved. Although
skin cancers occur at all ages, most
cases occur at older ages. For that
reason, we estimate the benefit from
preventing fatal cases using the value of
life years saved. According to the
National Cancer Institute, the average
age of death from melanoma is 68 (Ref.
73); life expectancy for a person
between the ages of 68 and 69 is about
16 years (Ref. 76). If we discount the
average years of life saved for averted
fatal melanoma with rates of 3 and 7
percent, we get discounted statistical
life-years saved equal to 12.6 and 9.4
years. The various studies of fatal cases
of non-melanoma skin cancer find mean
or median ages of death in the 77 to 82
range (Refs. 77–79). The life expectancy
for someone between the ages of 79 and
80 is about 9 years (Ref. 76). If we
discount the average years of life saved
for fatal non-melanoma skin cancers
with discount rates of 3 and 7 percent,
we get discounted years saved equal to
7.9 and 6.5 years.
In other analyses of life-years saved,
we have used values for a statistical lifeyear in the $107,000 to $322,000 range
(74 FR 33030, July 9, 2009; updated to
current prices). For this illustrative
analysis, we use a medium value of
$214,000 per statistical life-year. We
multiply the value of a statistical lifeyear by the discounted life-years saved
per fatal case of melanoma, which
yields $2.69 million using a 3 percent
rate of discount and $2.02 million using
a 7 percent rate of discount. If we
multiply the value of a statistical lifeyear by discounted life-years saved per
fatal case of non-melanoma skin cancer,
we get $1.67 million using a 3 percent
rate of discount and $1.39 million using
a 7 percent rate of discount.
The development of melanoma and
non-melanoma skin cancer from chronic
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exposure to sunlight, as well as any
preventative effects of sunscreen (or any
other intervention), occur with a long
lag. To estimate the monetary value of
an averted case of melanoma or nonmelanoma skin cancer through
combining other protective measures
with increased broad spectrum and at
least SPF 15 protection, we adjust for
the lag between increased protection
and a decrease in the incidence of nonmelanoma skin cancer. The only
available long-term study finds a
minimum lag of 5 years before any
significant risk reduction would occur
(Refs. 20 and 21). Substantial reductions
occur with a much longer lag, probably
15 to 25 years; we use a 20-year lag in
this illustrative analysis. With a 20-year
lag discounted at 3 percent, the value
per averted statistical case of non-fatal
melanoma is $1,586; if we discount for
at 7 percent, the value per averted case
is $740. With a 20-year lag discounted
at 3 percent per year, the monetary
value per averted statistical case of nonmelanoma skin cancer is $773; if we
discount at 7 percent, the value per
averted case is $361.
For fatal cases, with the 20-year lag
discounted at 3 percent per year, the
monetary value per averted statistical
case of fatal melanoma is $1.49 million;
discounted at 7 percent, the value per
averted fatal case is $520,000. With a
20-year lag and a 3 percent rate of
discount, the discounted value per
averted case of non-melanoma skin
cancer is $920,000 million; with a 7
percent rate of discount, value per
averted fatal case is $360,000.
We have four estimates of the
discounted value per averted cases of
melanoma and non-melanoma skin
cancer, with values corresponded to
non-fatal and fatal cases. The annual
benefits of this final rule will be the
numbers of cases of each type averted
multiplied by the value of each type. We
do not, however, have estimates of the
numbers of actual or statistical cases
that will be averted. Although there is
wide agreement among experts that the
use of more effective sunscreens reduces
the risk of sun-related skin cancer, we
are unaware of any studies that quantify
the reduced risk. Without quantitative
estimates of the risk reduction
associated with broad spectrum
protection, we are unable to quantity the
overall effects of this final rule on
public health.
3. Number of Products Affected
Estimating the number of products
affected by this rule is difficult because
we do not have complete data on the
number of OTC sunscreen products
currently marketed. Our Drug Listing
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System does not have accurate
information on the number of marketed
OTC sunscreen products. In the 2007
proposed rule (72 FR 49070 at 49108),
we estimated that there were about
3,000 OTC sunscreen drug products,
including cosmetic products containing
sunscreen, with about 12,000 SKUs.12
In response to the 2007 proposed rule,
we received a submission arguing that
our estimates of the number of products
and SKUs were low but the submission
did not suggest a corrected value. We
contracted with the consulting firm
Eastern Research Group (ERG) to profile
the sunscreen market and assess the cost
to reformulate a sunscreen product.
ERG’s full report can be found in Docket
No. FDA–1978–N–0018 (Ref. 80). ERG
did an extensive search using the
internet and other sources and found
fewer dosage forms and SKUs than we
had estimated. ERG estimates that there
are about 3,065 to 3,600 SKUs. More
recently, the new FDA labeling cost
model estimates that about 3,591
sunscreen SKUs are marketed, with up
to 2,348 different formulations. Because
these data are based on a recent survey
of the market, we conclude that they are
more representative of the number of
products affected than the estimates in
the proposed rule. For this analysis, we
therefore use 3,591 SKUs to represent
the number of affected sunscreen labels
and 2,348 for the number of
formulations.
To comply with the rule, sunscreen
products currently marketed as
providing broad spectrum protection
that were already tested using the test
method in this rule will have to be relabeled but will not have to be retested
for broad spectrum protection. Other
products will be tested for broad
spectrum protection and, if they pass
and, will be relabeled with the broad
spectrum protection claim.
Manufacturers may also choose to
reformulate their products to pass the
test or discontinue production of the
products.
We have not attributed any
reformulation costs to this final rule but
realize that some manufacturers may
choose to reformulate their product if it
does not pass the broad spectrum test.
4. Cost To Relabel Sunscreen Products
The cost to relabel varies greatly
depending on the printing method and
number of colors used. In the 2007
proposed rule, we stated that the
majority of sunscreen products are
packaged in plastic bottles or tubes with
the label printed directly on the
12 SKUs refers to ‘‘stock keeping units,’’ which are
individual products, packages, and sizes.
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container or applied as a decal or paper
label during the packaging process.
The labeling requirements in this rule
will change both the PDP and the Drug
Facts section of the package and are
considered a major redesign. Frequent
label redesigns are typical for OTC
sunscreen products, with redesigns
generally implemented every 1 to 2
years. If a scheduled redesign coincides
with relabeling required by this rule, the
incremental labeling cost will be lower
than if the labeling change takes place
before scheduled changes. To estimate
the cost to relabel, we are assuming that
all products will be relabeled and none
are discontinued.
In the 2007 proposed rule, we used a
model developed for us by the
consulting firm RTI International to
derive an estimate of the cost to relabel
sunscreen products (Ref. 81). The model
was developed to estimate the cost of
food labels, which are similar to the
labels on the products affected by this
final rule. In response to the 2007
proposed rule, we received a
submission disagreeing with our
estimates of how sunscreens are
packaged and the cost to relabel these
products (Ref. 1). The submission
argued that many sunscreen products,
particularly sunscreen-cosmetic
combinations, have a secondary
container and, therefore, an additional
label. The submission also argued that
some sunscreen products would require
a fold-out label or new secondary carton
to accommodate the labeling required in
this rule. Furthermore, the submission
argued that relabeling these products
would cost $15,000 to $17,000 per SKU.
The submission did not include any
data or information to support its
estimate.
We agree that cosmetic packaging and
labeling is generally more costly than
OTC drug labeling. We also agree that
manufacturers of sunscreen-cosmetic
products would use the packaging norm
of the cosmetic industry because those
are the products they are competing
with. The cost estimates we are using
now demonstrate a large variation in the
price per SKU to account for the
differences in packaging. If the standard
content and format changes required by
the OTC labeling final rule (64 FR
13254) are being implemented for the
first time, there could be increases in
the size of container and carton labels.
Since we are allowing, in this rule, for
a compliance period of 1 year for most
products but 2 years for products with
low sales volume ($25,000 annually),
inventory losses for unused packaging
and labels are minimized and accounted
for in this analysis.
For this final rule, we use the new
FDA labeling cost model developed by
RTI International, which includes
estimates for changing sunscreen labels.
The one-time costs for a major labeling
change to sunscreen labels are $7,454 to
$18,785, depending on the type of
labeling and packaging. The medium
estimate is $11,572 per major labeling
changes. These costs include mostly
labor and materials, with some cost for
lost inventory.
We estimate that the timing of
scheduled relabeling will coincide with
the relabeling required by this rule for
50 percent of the 3,591 SKUs . We
estimate the total labeling cost for the
SKUs with coinciding scheduled
redesign would be minimal
administrative costs or about $550 ($310
to $790). Therefore, the total one-time
cost for relabeling would be about $13.9
million to $35.1 million, with a medium
estimate of $21.8 million (1,796 ×
$11,572 + 1,796 × $550).
5. Cost To Test or Retest Products To
Determine SPF Values
Manufacturers will incur SPF testing
costs because the rule requires labeling
for OTC sunscreen products to include
SPF values determined in accordance
with the specific test method that it
describes. We will publish draft
guidance entitled ‘‘Guidance for
Industry: Enforcement Policy—OTC
Sunscreen Drug Products Marketed
Without An Approved Application’’
that describes our intended enforcement
policy regarding these OTC sunscreen
products. In the draft guidance, we
propose to exercise enforcement
discretion for a period of 2 years after
the publication of this final rule with
regard to the SPF testing requirements
for certain OTC sunscreen products on
the market prior to June 17, 2011. We
estimate that 65 to 75 percent of
sunscreen reformulations, or 1,526 to
1,761 will require SPF retesting. The
cost of an SPF test depends on whether
the product is also making water
resistance claims and the SPF value
being tested; the cost of water resistant
testing is much higher than static testing
(see Table 6). In their analysis of the
sunscreen market ERG found that about
5 percent of products claimed water
resistance and SPF values less than 30,
3 percent of products claimed water
resistance with SPF greater than 30,
while the remaining 92 percent could
use the static SPF test. We use those
percentages to estimate total SPF testing
costs of $3.2 to $5.9 million (see Table
6). The midpoint of estimated SPF
testing costs is $4.6 million.
TABLE 6—COST OF SPF TESTING
Estimated number of
formulations
Type of test
emcdonald on DSK2BSOYB1PROD with RULES3
Low
Cost of test
Low
High
Total cost
High
Low
High
Water resistant, SPF < 30 .......................
Water resistant, > 30 ...............................
SPF static test ..........................................
76
46
1,404
88
53
1,620
$4,500
4,500
1,900
$4,860
5,130
3,240
$343,395
260,037
2,667,798
$427,923
271,018
5,249,189
Total Cost for SPF testing ................
........................
........................
........................
........................
3,217,230
5,948,130
6. Cost to Test or Retest Products for
Broad Spectrum Protection
In the proposed rule, we estimated
that about 75 percent of sunscreen
products would need to be tested for
broad spectrum protection. We received
a submission arguing that our estimate
was too low and that at least 90 percent
of products would need to be tested
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(Ref. 1). The argument in the submission
was based on the four-tier UVA star
rating in the proposed rule. The
submission stated that sunscreen
products with ‘‘low,’’ one-star
protection would need to be tested. We
have now changed the rating criteria to
pass-fail, where a critical wavelength of
at least 370 nm is necessary to make the
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broad spectrum statement. Over the
years, there has been a steady increase
in the number of products with claims
of broad spectrum protection. A recent
survey of marketed products found that
65 percent of the products surveyed met
the criteria for the broad spectrum
statement (Ref. 82). Products that were
tested in accordance with the broad
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spectrum test in this rule would not
need to be re-tested.
Because the broad spectrum test in
this rule is different than the proposed
test, we assume that all affected
products would need to be tested. In the
2007 proposed rule, we estimated a onetime testing cost of approximately $5.4
million for products that have broad
spectrum protection claims. This
estimate was based on 2,250 sunscreen
products (75 percent of marketed
products) being tested with a test cost of
$2,400. The test costs were estimated as
$2,200 for the proposed in vivo test and
$200 for the proposed in vitro test. In
this rule, we are not requiring the in
vivo test.
In response to the proposed rule, we
received two submissions arguing that
our estimate of $200 for the cost of the
in vitro test was too low (Ref. 1). The
first submission states that the cost of an
in vitro test is $500, and the second
states that the cost is $800. The first
submission, from a sunscreen
manufacturer, states that $500 is the
price charged by an independent testing
laboratory to test its product. The
second submission does not provide any
basis for its estimate. Although the in
vitro test in this rule is different than
the in vitro test in the 2007 proposed
rule, the cost to conduct the tests is the
same. ERG found that the cost of the test
ranges from $300 to $800 (Ref. 80).
Assuming all affected marketed product
formulations (1,526 to 1,761
formulations) will be tested for broad
spectrum protection at a cost ranging
from $300 to $800, the total cost to test
sunscreen products for broad spectrum
protection is estimated to be $457,860 to
$1,408,800 [(1,526 × $300) to (1,761 ×
$800)].
emcdonald on DSK2BSOYB1PROD with RULES3
7. Total Incremental Costs
Because we took steps earlier to
mitigate the impact of labeling changes
on the sunscreen industry by staying the
requirements in earlier rules, the
labeling costs in this rule incorporate
the labeling costs from three final rules:
1. 1999 OTC drug labeling final rule
(64 FR 13254)
2. 1999 Sunscreen final rule (64 FR
27666)
3. This rule.
Manufacturers were able to postpone
compliance costs when we chose to stay
the labeling requirements for the 1999
final rule that standardized the format
and content requirements for labeling
OTC drug products (21 CFR part 201),
which would have become effective for
all sunscreens by 2005 (69 FR 53801).
We include, as part of labeling costs, the
cost of increased container labels and
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package size to accommodate the Drug
Facts format.
The estimated total one-time
incremental cost of this rule range $17.6
to 42.5 million [($13.9 million labeling
cost + $3.2 million SPF testing cost +
$0.5 million broad spectrum testing
cost) to ($35.1 million labeling cost +
$5.9 million SPF testing cost + $1.4
million broad spectrum testing cost)].
The medium estimated one-time
incremental costs are $27.3 million.
Annualized over 10 years, the costs are
$2.1 to $5 million using a 3 percent rate
of discount and $2.5 to $6.1 million
using a 7 percent rate of discount.
Annualized medium costs are $3.2
million using a 3 percent rate of
discount and $3.9 million using a 7
percent rate of discount. If some
manufacturers of sunscreen products
have already complied with the 1999
final rule and would not otherwise have
to relabel products as a result of this
final rule, then these estimates may
overstate actual total costs.
8. Analysis of Alternatives
The principal alternatives we
identified were the inclusion of several
provisions from the 2007 proposed rule.
In the 2007 proposed rule, we required
in vivo and in vitro tests for determining
UVA protection. In this rule, we have
eliminated the in vivo test requirement,
reducing compliance costs by about $5
million. We also proposed labeling on
the PDP that would indicate the level of
UVA protection. In this rule, we
changed the in vitro test to one that
measures both UVB and UVA protection
(i.e., broad spectrum protection). We
also established a pass/fail broad
spectrum protection statement on the
PDP in place of a UVA rating.
We considered requiring a negative
statement on the PDP indicating that a
product did not have broad spectrum
protection if it failed the in vitro test.
Numerous submissions from
manufacturers opposed this
requirement, and we are concerned that
the statement could be misinterpreted
by consumers. Moreover, as noted
previously, this alternative is beyond
the scope of this final rule, which
applies only to products that do provide
broad spectrum protection.
B. Small Business Impact (Final
Regulatory Flexibility Analysis)
We estimate that about 78 percent of
the approximately 100 domestic
companies that manufacture OTC
sunscreen products would be
considered small business entities
(defined by the Small Business
Administration as having fewer than
750 employees). Because most affected
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35657
entities are considered small, we
conclude that this final rule will have a
significant economic impact on a
substantial number of small entities.
Consequently, this analysis, together
with other relevant sections of this
document, serves as the Final
Regulatory Flexibility Analysis, as
required under the Regulatory
Flexibility Act.
The average one-time incremental
cost per firm will be about $185,000 to
$445,000, with a medium of about
$285,000. This burden, described in
more detail in section IX.A of this
document, includes labeling costs, SPF
testing costs, and broad spectrum testing
costs. The economic impact will vary by
firm, depending on the number of
products requiring testing and the
number of SKUs requiring labeling.
Also, firm-specific impact will vary
inversely with the product sales; the per
firm burden will be lower for firms with
products with high sales volumes.
Because the relative economic impact of
product retesting is greater for products
with lower sales volume, which could
disproportionately affect smaller firms,
we are providing a longer
implementation period (2 years) for
products with annual sales of less than
$25,000. Because the OTC drug industry
is highly regulated, all firms are
expected to have access to the necessary
professional skills on staff or to have
contractual arrangements to comply
with the testing requirements of this
rule.
X. Paperwork Reduction Act of 1995
This final rule contains certain
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. 3501–3520). Specifically, the
final rule establishes requirements for
SPF labeling based on specified testing
of covered products, (21 CFR
201.327(a)(1) and (i)). This rule also lifts
the delay of implementation date for
§ 201.66 (21 CFR 201.66), the general
OTC Drug Facts labeling format
regulation, which has applied to all
OTC sunscreen products (69 FR 53801).
The information collections associated
with § 201.66 have been approved in
accordance with the PRA under OMB
Control Number 0910–0340, but this
approval does not currently include
application of these provisions to OTC
sunscreens. (76 FR 9022, February 16,
2011). The lifting of the stay of effective
date of § 201.66 for OTC sunscreens will
modify this information collection.
Elsewhere in this issue of the Federal
Register, in accordance with section
3506(c)(2)(A) of the PRA (44 U.S.C.
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3506(c)(2)(A)), we are publishing a 60day notice soliciting public comment on
the collections of information resulting
from this final rule and will then submit
these information collection provisions
to OMB for approval. These
requirements will not be effective until
we obtain OMB approval. We will
publish a notice concerning OMB
approval of these requirements in the
Federal Register prior to the effective
date of this final rule.
With the exceptions noted above, we
conclude that the other provisions of
this rule are not subject to OMB review
under the PRA. Section 201.327
contains specific labeling information,
including directions and warnings,
which are a ‘‘public disclosure of
information originally supplied by the
Federal Government to the recipient for
the purpose of disclosure to the public’’
(5 CFR 1320.3(c)(2)) and, therefore, are
not collections of information. The
requirements for obtaining certain
medical history information and
informed consent from test subjects (21
CFR 201.327(i)(3)(ii) and (i)(3)(iv)) are
not collections of information because
information collected from subjects of
clinical testing does not constitute
information under 5 CFR 1320.3(h)(5).
There are no recordkeeping provisions
associated with the SPF and broad
spectrum testing (i.e., effectiveness
testing) described in this rule. The
burdens of SPF testing as relevant to
labeling (third party disclosures) are
addressed in the notice published
elsewhere in this issue of the Federal
Register.
emcdonald on DSK2BSOYB1PROD with RULES3
XI. Environmental Impact
FDA has determined under 21 CFR
25.31(a) that this action is of a type that
does not individually or cumulatively
have a significant effect on the human
environment. Therefore, neither an
environmental assessment nor an
environmental impact statement is
required.
XII. Federalism
FDA has analyzed this final rule in
accordance with the principles set 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.’’ The sole statutory
provision giving preemptive effect to the
final rule is section 751 of the FD&C Act
(21 U.S.C. 379r). We have complied
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18:47 Jun 16, 2011
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with all of the applicable requirements
under the Executive order and have
determined that the preemptive effects
of this rule are consistent with
Executive Order 13132.
XIII. References
The following references are on
display in the Division of Dockets
Management (HFA–305), Food and Drug
Administration, 5630 Fishers Lane, rm.
1061, Rockville, MD 20857, under
Docket No. FDA–1978–N–0018
(formerly 1978N–0038) and may be seen
by interested persons between 9 a.m.
and 4 p.m., Monday through Friday.
(FDA has verified all Web site
addresses, but FDA is not responsible
for any subsequent changes to the Web
sites after this document publishes in
the Federal Register.
1. FDA List of Docket Submissions
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Issue.
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31–National Formulary 26, The United
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3. The United States Pharmacopeia
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4. Nash, J. F. et al., ‘‘Ultraviolet A
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5. Sayre, R. M. et al., ‘‘Commentary on
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6. Vainio, H. and F. Bianchini,
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8. Document No. FDA–1978–N–0018–
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9. Calvacca, L., ‘‘Screening the New
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123, 1990.
10. Fourtanier, A. et al., ‘‘Sunscreens
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11. De Gruijl, F., ‘‘UV Radiation, DNA
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12. Lucas, R. et al., ‘‘Solar Ultraviolet
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13. Armstrong, B. K. et al., ‘‘Sun
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14. World Health Organization, IARC,
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15. ‘‘Report on Carcinogens, Eleventh
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16. Rabe, J. et al., ‘‘Photoaging:
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24. Darlington, S. et al., ‘‘A
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Sunscreen Application and Beta
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28. Lee, T. K. et al., ‘‘Site-Specific
Protective Effect of Broad-Spectrum
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52:786–792, 2005.
29. Seite, S. and A. Fourtanier, ‘‘The
Benefit of Daily Photoprotection,’’
Journal of the American Academy of
Dermatology, 58:S160–S166, 2008.
30. Fourtanier, A. et al., ‘‘Protection of
Skin Biological Targets by Different
Types of Sunscreens,’’
Photodematology, Photoimmunology,
and Photomedicine, 22:22–32, 2006.
31. Young, A. R. et al., ‘‘The
Detrimental Effects of Daily SubErythemal Exposure on Human Skin In
Vivo Can Be Prevented by a Daily-Care
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2007.
32. Moyal, D. D. and A. M. Fourtanier,
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Better Protection From Solar UltravioletSimulated Radiation and Natural
Sunlight-Induced Immunosuppression
In Human Beings,’’ Journal of the
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33. ‘‘Label Information for AlliTM
Weight Loss Aid,’’ http://www.access
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34. ‘‘Your Guide to Lowering Your
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37. Dowdy, J. C. et al., ‘‘Indoor
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40. Holick, M. F., ‘‘Sunlight, UV–
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42. Salih, F. M., ‘‘Effect of Clothing
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45. Wolpowitz, D. and B. A. Gilchrest,
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Do You Need And How Should You Get
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46. Matsuoka, L. Y. et al.,
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64:1165–1168, 1987.
47. Matsuoka, L. Y. et al., ‘‘Chronic
Sunscreen Use Decreases Circlulating
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A preliminary Study,’’ Archives of
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48. Marks, R. et al., ‘‘The Effect of
Regular Sunscreen Use on Vitamin D
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49. Farrerons, J. et al., ‘‘Clinically
Prescribed Sunscreen (Sun Protection
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Either to Induce Changes in Parathyroid
Function or in Metabolic Markers,’’
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139:422–427, 1998.
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51. Cusack, C et al., ‘‘Photoprotective
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52. Hoesl, M. et al., ‘‘Vitamin D Levels
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56. The American Academy of
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http://www.aad.org/public/
publications/pamphlets/sun_sun.html,
February 1, 2009.
57. The American Academy of
Dermatology, ‘‘The Darker Side of
Tanning,’’ http://www.aad.org/public/
publications/pamphlets/sun_darker.
html, February 1, 2009.
58. The American Academy of
Dermatology, ‘‘Skin Cancer,’’ http://
www.aad.org/public/publications/
pamphlets/sun_skin.html, February 1,
2009.
59. Centers for Disease Control and
Prevention, ‘‘Sunscreen for Your Sun
Day,’’ http://www.cdc.gov/cancer/skin/
chooseyourcover/index.htm, October 23,
2009.
60. ‘‘Sunwise Program: Action Steps
for Sun Safety,’’ http://www.epa.gov/
sunwise/actionsteps.html, February 1,
2009.
61. Wright, M.W. et al., ‘‘Mechanisms
of Sunscreen Failure,’’ Journal of the
American Academy of Dermatology,
44:781–784, 2001
62. Rigel, D., ‘‘American Academy of
Dermatology’s Melanoma/Skin Cancer
Detection and Prevention Month Press
Release,’’ April 25, 2001.
63. European Cosmetic, Toiletry and
Perfumery Association (COLIPA); JCIA;
CTFA–SA; CTFA, ‘‘Sun Protection
Factor Test Method,’’ 1994.
64. European Cosmetic, Toiletry and
Perfumery Association (COLIPA); JCIA;
CTFA–SA; CTFA, ‘‘International Sun
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35660
Federal Register / Vol. 76, No. 117 / Friday, June 17, 2011 / Rules and Regulations
Protection Factor (SPF) Test Method,’’
2006.
65. Standards Australia and Standards
New Zealand, ‘‘Australian/New Zealand
Standard Sunscreen Products
Evaluation and Classification,’’ AS/NZS
2604:1998,’’ 1998.
66. Health Canada, ‘‘Category IV
Monograph Sunburn Protectants.
Procedure for Determining an SPF,’’
2002.
67. Korea Food and Drug
Administration, ‘‘Korean Measurement
Standards for UV Protection Efficacy,’’
2001.
68. Bimczok, R. et al., ‘‘Influence of
Applied Quantity of Sunscreen Products
on the Sun Protection Factor—A
Multicenter Study Organized by the
DGK Task Force Sun Protection,’’ Skin
Pharmacology and Physiology, 20:57–
64, 2007.
69. COLIPA (The European Cosmetics
Association), ‘‘Method for the In Vitro
Determination of UVA Protection
Provided by Sunscreen Products,’’
COLIPA Guidelines, 2007a.
70. Ferrero, L. et al., ‘‘Importance of
Substrate Roughness for In Vitro Sun
Protection Assessment,’’ IFSCC
Magazine, 9:97–108, 2006.
71. Sayre, R. M. and J. C. Dowdy,
‘‘Photostability Testing of Avobenzone,’’
Cosmetics and Toiletries, 114:85–91,
1999.
72. National Cancer Institute, ‘‘Skin
Cancer,’’ http://www.cancer.gov/cancer
topics/types/skin, April 17, 2009.
73. National Cancer Institute,
‘‘Surveillance Epidemiology and End
Results: Melanoma of the Skin,’’
http://seer.cancer.gov/statfacts/html/
melan.html, November 10, 2010.
74. Bickers, D.R. et al., ‘‘The Burden
of Skin Diseases: 2004,’’ Journal of the
American Academy of Dermatology,
55:490–500, 2006.
75. Freedberg, K.A. et al., ‘‘Screening
for Mealignant Melanoma: A CostEffective Analysis,’’ Journal of the
American Academy of Dermatology,
41:738–745, 1999.
76. Arias, E., B.L. Rostron, and B.
Tejada-Vera, ‘‘United States Life tables,
2005,’’ National Vital Statistics Reports,
58:1–132, 2010.
77. Lewis, K.G. and M.A. Weinstock,
‘‘Nonmelanoma Skin Cancer Mortality
(1988–2000),’’ Archives of Dermatology,
140:837–842, 2004.
78. Nolan, R.C., M. T.-L. Chan, and
P.J. Heenan, ‘‘A Clinicopathologic
Review of Lethal Nonmelanoma Skin
Cancers in Western Australia,’’ Journal
of the American Academy of
Dermatology, 52:101–108, 2005.
79. Girschik, J. et al., ‘‘Deaths from
Non-Melanoma Skin Cancer in Western
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20:46 Jun 16, 2011
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Australia,’’ Cancer Causes & Control,
19:879–885, 2008.
80. Eastern Research Group (2010)
‘‘Sunscreen Drug Formulations for Overthe-Counter Human Use,’’ Task Order
No. 21, Contract No. 223–03–8500.
81. RTI International, ‘‘FDA Labeling
Cost Model, Final Report,’’ prepared by
Mary Muth, Erica Gledhill, and Shawn
Karns, RTI. Prepared for Amber Jessup,
FDA Center for Food Safety and
Applied Nutrition, Revised January
2003.
82. ‘‘Sunscreen Market Analysis: The
Evolution and Use of UVA–1 Actives,’’
The Proctor and Gamble Company,
Sharon Woods Technical Center,
Cincinatti, OH, 2004.
List of Subjects
21 CFR Part 201
Drugs, Incorporation by reference,
Labeling, Reporting and recordkeeping
requirements.
21 CFR Part 310
Administrative practice and
procedure, Drugs, Labeling, Medical
devices, Reporting and recordkeeping
requirements.
Therefore, under the Federal Food,
Drug, and Cosmetic Act and under
authority delegated to the Commissioner
of Food and Drugs, 21 CFR part 201 is
amended as follows:
PART 201—LABELING
1. The authority citation for 21 CFR
part 201 continues to read as follows:
■
Authority: 21 U.S.C. 321, 331, 351, 352,
353, 355, 358, 360, 360b, 360gg–360ss, 371,
374, 379e; 42 U.S.C. 216, 241, 262, 264.
2. Section 201.327 is added to subpart
G to read as follows:
■
§ 201.327 Over-the-counter sunscreen
drug products; required labeling based on
effectiveness testing.
The following provisions apply to
sunscreen products containing
aminobenzoic acid, avobenzone,
cinoxate, dioxybenzone, ensulizole,
homosalate, meradimate, octinoxate,
octisalate, octocrylene, oxybenzone,
padimate O, sulisobenzone, titanium
dioxide, trolamine salicylate, or zinc
oxide, alone or in combination. The
provisions do not apply to sunscreen
products marketed under approved new
drug applications or abbreviated new
drug applications.
(a) Principal display panel. In
addition to the statement of identity in
paragraph (b) of this section, the
following labeling shall be prominently
placed on the principal display panel:
(1) Effectiveness claim. (i) For
products that pass the broad spectrum
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test in paragraph (j) of this section. (A)
The labeling states ‘‘Broad Spectrum
SPF [insert numerical SPF value
resulting from testing under paragraph
(i) of this section]’’.
(B) Prominence. The Broad Spectrum
SPF statement shall appear as
continuous text with no intervening text
or graphic. The entire text shall appear
in the same font style, size, and color
with the same background color.
(ii) For sunscreen products that do
not pass the broad spectrum test in
paragraph (j) of this section. The
labeling states ‘‘SPF [insert numerical
SPF value resulting from testing under
paragraph (i) of this section]’’. The
entire text shall appear in the same font
style, size, and color with the same
background color.
(2) Water resistance statements. (i) For
products that provide 40 minutes of
water resistance according to the test in
paragraph (i)(7)(i) of this section. The
labeling states ‘‘Water Resistant (40
minutes)’’.
(ii) For products that provide 80
minutes of water resistance according to
the test in paragraph (i)(7)(ii) of this
section. The labeling states ‘‘Water
Resistant (80 minutes)’’.
(b) Statement of identity. The labeling
of the product contains the established
name of the drug, if any, and identifies
the drug as a ‘‘sunscreen.’’
(c) Indications. The labeling of the
product states, under the heading
‘‘Uses,’’ the phrases listed in this
paragraph (c), as appropriate. Other
truthful and nonmisleading statements,
describing only the uses that have been
established and listed in this paragraph
(c), may also be used, as provided in
§ 330.1(c)(2) of this chapter, subject to
the provisions of section 502 of the
Federal Food, Drug, and Cosmetic Act
(the FD&C Act) relating to misbranding
and the prohibition in section 301(d) of
the FD&C Act against the introduction
or delivery for introduction into
interstate commerce of unapproved new
drugs in violation of section 505(a) of
the FD&C Act.
(1) For all sunscreen products, the
following indication statement must be
included under the heading ‘‘Uses’’:
‘‘[Bullet] helps prevent sunburn’’. See
§ 201.66(b)(4) of this chapter for
definition of bullet.
(2) For sunscreen products with a
Broad Spectrum SPF value of 15 or
higher according to the tests in
paragraphs (i) and (j) of this section, the
labeling may include the following
statement in addition to the indication
in § 201.327(c)(1): ‘‘[Bullet] if used as
directed with other sun protection
measures (see Directions [in bold italic
E:\FR\FM\17JNR3.SGM
17JNR3
font]), decreases the risk of skin cancer
and early skin aging caused by the sun’’.
(3) Any labeling or promotional
materials that suggest or imply that the
use, alone, of any sunscreen reduces the
risk of or prevents skin cancer or early
skin aging will cause the product to be
misbranded under section 502 of the
FD&C Act (21 U.S.C. 352).
(d) Warnings. The labeling of the
product contains the following warnings
under the heading ‘‘Warnings’’.
(1) For all sunscreen products. (i) The
labeling states ‘‘Do not use [bullet] on
damaged or broken skin’’.
(ii) The labeling states ‘‘When using
this product [bullet] keep out of eyes.
Rinse with water to remove.’’
(iii) The labeling states ‘‘Stop use and
ask a doctor if [bullet] rash occurs’’.
(2) For sunscreen products that are
broad spectrum with SPF values of at
least 2 but less than 15 according to the
SPF test in paragraph (i) of this section
or that do not pass the broad spectrum
test in paragraph (j) of this section. The
first statement under the heading
‘‘Warnings’’ states ‘‘Skin Cancer/Skin
Aging Alert [in bold font]; Spending
time in the sun increases your risk of
skin cancer and early skin aging. This
product has been shown only to help
prevent sunburn, not [in bold font] skin
cancer or early skin aging.’’
(e) Directions. The labeling of the
product contains the following
statements, as appropriate, under the
heading ‘‘Directions.’’ More detailed
directions applicable to a particular
product formulation may also be
included.
(1) For all sunscreen products. (i) As
an option, the labeling may state ‘‘For
sunscreen use:’’.
(ii) The labeling states ‘‘[bullet] apply
[select one of the following: ‘Liberally’
or ‘generously’] [and, as an option: ‘And
evenly’] 15 minutes before sun
exposure’’.
(iii) As an option, the labeling may
state ‘‘[bullet] apply to all skin exposed
to the sun’’.
(iv) The labeling states ‘‘[bullet]
children under 6 months of age: Ask a
doctor’’.
(2) For sunscreen products with a
Broad Spectrum SPF value of 15 or
higher according to the tests in
paragraphs (i) and (j) of this section.
The labeling states ‘‘[bullet] Sun
Protection Measures. [in bold font]
Spending time in the sun increases your
risk of skin cancer and early skin aging.
To decrease this risk, regularly use a
sunscreen with a Broad Spectrum SPF
value of 15 or higher and other sun
protection measures including: [Bullet]
limit time in the sun, especially from 10
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a.m.–2 p.m. [bullet] wear long-sleeved
shirts, pants, hats, and sunglasses’’.
(3) For products that satisfy the water
resistance test in paragraph (i)(7) of this
section. The labeling states ‘‘[bullet]
reapply: [Bullet] after [select one of the
following determined by water
resistance test: ‘40 minutes of’ or ‘80
minutes of’] swimming or sweating
[bullet] immediately after towel drying
[bullet] at least every 2 hours’’.
(4) For products that do not satisfy the
water resistance test in paragraph (i)(7)
of this section. The labeling states
‘‘[bullet] reapply at least every 2 hours
[bullet] use a water resistant sunscreen
if swimming or sweating’’.
(f) Other information. The labeling of
the product contains the following
statement under the heading ‘‘Other
information:’’ ‘‘[bullet] protect the
product in this container from excessive
heat and direct sun’’.
(g) False and misleading claims.
There are claims that would be false
and/or misleading on sunscreen
products. These claims include but are
not limited to the following:
‘‘Sunblock,’’ ‘‘sweatproof,’’ and
‘‘waterproof.’’ These or similar claims
will cause the product to be misbranded
under section 502 of the FD&C Act (21
U.S.C. 352).
(h) Labeling of products containing a
combination of sunscreen and skin
protectant active ingredients.
Statements of identity, indications,
warnings, and directions for use,
respectively, applicable to each
ingredient in the product may be
combined to eliminate duplicative
words or phrases so that the resulting
information is clear and understandable.
Labeling provisions in § 347.50(e) of this
chapter shall not apply to these
products.
(i) SPF test procedure. (1) UV source
(solar simulator). (i) Emission spectrum.
A single port or multiport solar
simulator should be filtered so that it
provides a continuous emission
spectrum from 290 to 400 nanometers
(nm) with a limit of 1,500 Watts per
square meter (W/m2) on total irradiance
for all wavelengths between 250 and
1,400 nm.
(A) The solar simulator should have
the following percentage of erythemaeffective radiation in each specified
range of wavelengths:
35661
SOLAR SIMULATOR EMISSION
SPECTRUM—Continued
Wavelength range (nm)
290–310
290–320
290–330
290–340
290–400
..........................
..........................
..........................
..........................
..........................
Percent erythemal
contribution 1
49.0–65.0
85.0–90.0
91.5–95.5
94.0–97.0
99.9–100.0
1 Calculation of erythema action spectrum
described in § 201.327(i)(1)(ii) of this section.
(B) In addition, UVA II (320–340 nm)
irradiance should equal or exceed 20
percent of the total UV (290–400 nm)
irradiance. UVA I (340–400 nm)
irradiance should equal or exceed 60
percent of the total UV irradiance.
(ii) Erythema action spectrum. (A)
Calculate the erythema action spectrum
weighting factor (Vi) at each wavelength
λ:
(1) Vi (λ) = 1.0 (250 < λ ≤ 298 nm)
(2) Vi (λ) =
100.094 * (298 ndash; lambda;) (298 < λ
≤ 328 nm)
(3) Vi (λ) =
100.015 * (140 ndash; lambda;) (328 < λ
400 nm)
(B) Calculate the erythema-effective
UV dose (E) delivered by a solar
simulator as follows:
Where Vi(λ) = erythema action spectrum
weighting factor at each wavelength λ
I(λ) = irradiance (Watts per square meter)
at each wavelength λ
t = exposure time (seconds)
Erythema-effective dose (E) is expressed
as effective Joules per square meter (J/
m2-eff).
(C) The emission spectrum must be
determined using a handheld
radiometer with a response weighted to
match the spectrum in ISO 17166 CIE S
007/E entitled ‘‘Erythemal reference
action spectrum and standard erythema
dose,’’ dated 1999 (First edition, 1999–
12–15; corrected and reprinted 2000–
11–15), which is incorporated by
reference in accordance with 5 U.S.C.
552(a) and 1 CFR part 51. You may
obtain a copy from the ISO Copyright
Office, Case Postale 56, CH–1211,
Geneva 20, Switzerland, telephone +41–
22–749–01–11 or fax +41–22–74 -09–47.
http://www.iso.org. You may inspect a
copy at the Center for Drug Evaluation
SOLAR SIMULATOR EMISSION
and Research, 10903 New Hampshire
SPECTRUM
Ave., Bldg. 22, Silver Spring, MD 20993,
call 301–796–2090, or at the National
Percent erythemal
Wavelength range (nm)
Archives and Records Administration
1
contribution
(NARA). For information on the
< 290 ..............................
< 0.1 availability of this material at NARA,
290–300 ..........................
1.0–8.0 call 202–741–6030, or go to: http://
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Federal Register / Vol. 76, No. 117 / Friday, June 17, 2011 / Rules and Regulations
www/archives.gov/federal_register/
code_offederal_regulations/ibr_
locations.html. The solar simulator
output should be measured before and
after each phototest or, at a minimum,
at the beginning and end of each test
day. This radiometer should be
calibrated using side-by-side
comparison with the spectroradiometer
(using the weighting factors determined
according to paragraph (i)(1)(ii)(A) of
this section) at the time of the annual
spectroradiometric measurement of the
solar simulator as described in
paragraph (i)(1)(iv) of this section.
(iii) Operation. A solar simulator
should have no significant time-related
fluctuations (within 20 percent) in
radiation emissions after an appropriate
warm-up time and demonstrate good
beam uniformity (within 20 percent) in
the exposure plane. The delivered dose
to the UV exposure site must be within
10 percent of the expected dose.
(iv) Periodic measurement. To ensure
that the solar simulator delivers the
appropriate spectrum of UV radiation,
the emission spectrum of the solar
simulator should be measured at least
annually with an appropriate and
accurately calibrated spectroradiometer
system (results should be traceable to
the National Institute for Standards and
Technology). In addition, the solar
simulator must be recalibrated if there is
any change in the lamp bulb or the
optical filtering components (i.e., filters,
mirrors, lenses, collimating devices, or
focusing devices). Daily solar simulator
radiation intensity should be monitored
with a broadband radiometer with a
response weighted to match the
erythema action spectrum in ISO 17166
CIE S 007/E entitled ‘‘Erythemal
reference action spectrum and standard
erythema dose,’’ which is incorporated
by reference in paragraph (i)(1)(ii)(C) of
this section. If a lamp must be replaced
due to failure or aging during a
phototest, broadband device readings
consistent with those obtained for the
original calibrated lamp will suffice
until measurements can be performed
with the spectroradiometer at the
earliest possible opportunity.
(2) SPF standard. (i) Preparation. The
SPF standard should be a formulation
containing 7-percent padimate O and 3percent oxybenzone.
COMPOSITION OF THE PADIMATE O/
OXYBENZONE SPF STANDARD
Part A:
Lanolin ...................................
Cocoa butter .........................
Glyceryl monostearate ..........
Stearic acid ...........................
Padimate O ...........................
Oxybenzone ..........................
Part B:
Purified water USP ...............
Sorbitol solution ....................
Triethanolamine, 99 percent
Methylparaben ......................
Propylparaben .......................
Part C:
Benzyl alcohol .......................
Part D:
Purified water USP ...............
1
18:47 Jun 16, 2011
Jkt 223001
4.50
2.00
3.00
2.00
7.00
3.00
71.60
5.00
1.00
0.30
0.10
0.50
QS 1
Quantity sufficient to make 100 grams.
Step 1. Add the ingredients of Part A
into a suitable stainless steel kettle
equipped with a propeller agitator. Mix
at 77 to 82 °C until uniform.
Step 2. Add the water of Part B into
a suitable stainless steel kettle equipped
with a propeller agitator and begin
mixing at 77 to 82 °C. Add the
remaining ingredients of Part B and mix
until uniform.
Step 3. Add the batch of Step 1 to the
batch of Step 2 and mix at 77 to 82 °C
until smooth and uniform. Slowly cool
the batch to 49 to 54 °C.
Step 4. Add the benzyl alcohol of Part
C to the batch of Step 3 at 49 to 54 °C.
Mix until uniform. Continue to cool
batch to 35 to 41 °C.
Step 5. Add sufficient water of Part D
to the batch of Step 4 at 35 to 41 °C to
obtain 100 grams of SPF standard. Mix
until uniform. Cool batch to 27 to 32 °C.
(ii) HPLC assay. Use the following
high performance liquid
chromatography (HPLC) procedure to
verify the concentrations of padimate O
and oxybenzone in the SPF standard:
(A) Instrumentation. (1) Equilibrate a
suitable liquid chromatograph to the
following or equivalent conditions:
(i) Column .....
(ii) Mobile
Phase.
(iii) Flow Rate
(iv) Temperature.
(v) Detector ...
(vi) Attenuation.
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Percent by
weight
Ingredients
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C–18, 250 millimeters (mm)
length, 4.6 mm inner diameter (5 microns)
85:15:0.5 methanol: water:
acetic acid
1.5 milliliters (mL) per
minute
Ambient
UV spectrophotometer at
308 nanometers
As needed
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(2) Use HPLC grade reagents for
mobile phase.
(B) Preparation of the HPLC reference
standard. (1) Weigh 0.50 gram (g) of
oxybenzone USP reference standard into
a 250-mL volumetric flask. Dissolve and
dilute to volume with isopropanol. Mix
well.
(2) Weigh 0.50 g of padimate O USP
reference standard into a 250-mL
volumetric flask. Dissolve and dilute to
volume with isopropanol. Mix well.
(3) Pipet 3.0 mL of the oxybenzone
solution and 7.0 mL of the padimate O
solution into a 100-mL volumetric flask.
Dilute to volume with isopropanol and
mix well.
(C) HPLC system suitability. (1) Make
three replicate 10-microliter injections
of the HPLC reference standard
(described in paragraph (i)(2)(ii)(B) of
this section). The relative standard
deviation in peak areas should not be
more than 2.0 percent for either
oxybenzone or padimate O.
(2) Calculate the resolution (R)
between the oxybenzone and padimate
O peaks from one chromatogram as
follows:
Where to = retention time for oxybenzone
tp = retention time for padimate O
Wo = oxybenzone peak width at baseline
Wp = padimate O peak width at baseline
If the resolution (R) is less than 3.0,
adjust the mobile phase or replace the
column.
(D) SPF standard assay.
(1) The SPF standard is diluted to the
same concentration as the HPLC
reference standard according to the
following steps:
(i) Step 1. Weigh 1.0 g of the SPF
standard (described in paragraph (i)(2)(i)
of this section) into a 50-mL volumetric
flask.
(ii) Step 2. Add approximately 30 mL
of isopropanol and heat with swirling
until contents are evenly dispersed.
(iii) Step 3. Cool to room temperature
(15 to 30 °C) and dilute to volume with
isopropanol. Mix well.
(iv) Step 4. Pipet 5.0 mL of the
preparation into a 50-mL volumetric
flask and dilute to volume with
isopropanol. Mix well.
(2)(i) Inject 10-microliter of diluted
SPF standard from paragraph (i)(2)(D)(1)
of this section and calculate the amount
of oxybenzone and padimate O as
follows:
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35662
(ii) The percent of oxybenzone and
padimate O in the SPF standard should
be between 95 and 105.
(3) Test subjects. (i) Number of
subjects. A test panel should include
enough subjects to produce a minimum
of 10 valid test results. A maximum of
three subjects may be rejected from this
panel based on paragraph (i)(5)(v)) of
this section.
(ii) Medical history. (A) Obtain a
medical history from each subject with
emphasis on the effects of sunlight on
the subject’s skin. Determine that each
subject is in good general health with
skin type I, II, or III as follows:
(1) Always burns easily; never tans
(sensitive).
(2) Always burns easily; tans
minimally (sensitive).
(3) Burns moderately; tans gradually
(light brown) (normal).
(4) Burns minimally; always tans well
(moderate brown) (normal).
(5) Rarely burns; tans profusely (dark
brown) (insensitive).
(6) Never burns; deeply pigmented
(insensitive).
(B) Skin type is based on first 30 to
45 minutes of sun exposure after a
winter season of no sun exposure.
Determine that each subject is not taking
topical or systemic medication that is
known to alter responses to UV
radiation. Determine that each subject
has no history of sensitivities to topical
products and/or abnormal responses to
sunlight, such as a phototoxic or
photoallergic response.
(iii) Physical examination. Conduct a
physical examination to determine the
presence of sunburn, suntan, scars,
active dermal lesions, and uneven skin
tones on the areas of the back to be
tested. A suitable source of low power
UVA, such as a Woods lamp, is helpful
in this process. If any of these
conditions are present, the subject is not
qualified to participate in the study. The
presence of nevi, blemishes, or moles
will be acceptable if, in the physician’s
judgment, they will neither compromise
the study nor jeopardize a subject’s
safety. Subjects with dysplastic nevi
should not be enrolled. Excess hair on
the back is acceptable if the hair is
clipped. Shaving is unacceptable
because it may remove a significant
portion of the stratum corneum and
VerDate Mar<15>2010
18:47 Jun 16, 2011
Jkt 223001
temporarily alter the skin’s response to
UV radiation.
(iv) Informed consent. Obtain legally
effective written informed consent from
all test subjects.
(4) Sunscreen application. (i) Test
site. Test sites are locations on each
subject’s back, between the beltline and
the shoulder blades (scapulae) and
lateral to the midline, where skin
responses to UV radiation are
determined. Responses on unprotected
skin (no test material applied) and
protected skin (sunscreen test product(s)
or SPF standard applied) are determined
at separate unprotected and protected
test sites, respectively. Test sites should
be randomly located in a blinded
manner. Each test site should be a
minimum of 30 square centimeters and
outlined with indelible ink.
(ii) Test subsite. Test subsites are the
locations to which UV radiation is
administered within a test site. At least
five test subsites should receive UV
doses within each test site. Test subsites
should be at least 0.5 square centimeters
(cm2) in area and should be separated
from each other by at least 0.8 cm. Each
test subsite should be outlined with
indelible ink.
(iii) Applying test materials. Apply
the sunscreen test product and the SPF
standard at 2 milligrams per square
centimeter (mg/cm2) to their respective
test sites. Use a finger cot compatible
with the sunscreen to spread the
product as evenly as possible.
(iv) Waiting period. Wait at least 15
minutes after applying a sunscreen
product before exposing the test sites to
UV radiation as described in paragraph
(i)(5)) of this section. For water resistant
sunscreen products, proceed with the
water resistance testing procedure
described in paragraph (i)(7) of this
section after waiting at least 15 minutes.
(5) UV exposure. (i) Definition of
minimal erythema dose (MED). The
minimal erythema dose (MED) is the
smallest UV dose that produces
perceptible redness of the skin
(erythema) with clearly defined borders
at 16 to 24 hours after UV exposure. The
MED for unprotected skin (MEDu) is
determined on a test site that does not
have sunscreen applied. The MED for
protected skin (MEDp) is determined on
a test site that has sunscreen applied.
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35663
An MEDp is determined for the SPF
standard (ssMEDp). An MEDp is
determined for the sunscreen test
product (tpMEDp).
(ii) UV exposure for initial MEDu. For
each test subject, administer a series of
UV radiation doses expressed as J/m2-eff
(as determined according to paragraph
(a)(2) of this section) to the test subsites
within an unprotected test site using an
accurately calibrated solar simulator.
Select doses that are a geometric series
represented by 1.25n (i.e., each dose is
25 percent greater than the previous
dose).
(iii) UV exposure for final MEDu,
ssMEDp, and tpMEDp. For each subject,
determine the final MEDu, ssMEDp, and
tpMEDp by administering a series of five
UV doses to the appropriate test sites.
The middle dose (X) in each of these
dose series (i.e., the third dose) should
equal the initial MEDu times the
expected SPF. Note that the expected
SPF equals 1 and 16.3 for the final
MEDu and ssMEDp, respectively. The
remaining UV doses in the series
depend upon the expected SPF value of
the sunscreen test product(s).
For products with an expected SPF
less than 8, administer UV doses that
increase by 25 percent with each
successive dose (i.e., 0.64X, 0.80X,
1.00X, 1.25X, and 1.56X). For products
with an expected SPF from 8 to 15,
administer UV doses that increase by 20
percent with each successive dose (i.e.,
0.69X, 0.83X, 1.00X, 1.20X, and 1.44X).
For products with an expected SPF
higher than 15, administer UV doses
that increase by 15 percent with each
successive dose (i.e., 0.76X, 0.87X,
1.00X, 1.15X, and 1.32X).
(iv) Evaluation of test subsites. In
order that the person who evaluates the
test subsites is not biased, he/she should
not be the same person who applied the
sunscreen drug product to the test site
or administered the UV doses. After UV
doses are administered, all immediate
responses should be recorded. These
may include an immediate darkening or
tanning, typically grayish or purplish in
color, which fades in 30 to 60 minutes;
an immediate reddening at the subsite,
due to heating of the skin, which fades
rapidly; and an immediate generalized
heat response, spreading beyond the
subsite, which fades in 30 to 60
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ER17JN11.004
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Federal Register / Vol. 76, No. 117 / Friday, June 17, 2011 / Rules and Regulations
(ii) Calculate the mean
emcdonald on DSK2BSOYB1PROD with RULES3
and the standard deviation (s) from the
SPFi values. Calculate the standard error
(SE), which equals s/√n (where n equals
the number of subjects who provided
valid test results). Obtain the t value
from Student’s t distribution table
corresponding to the upper 5-percent
point with n—1 degrees of freedom.
Determine the labeled SPF value, which
equals the largest whole number less
than
In order for the SPF determination of
a test product to be considered valid,
the SPF value of the SPF standard
should fall within the standard
deviation range of the expected SPF
(i.e., 16.3 ± 3.43).
(7) Determination of water resistance.
The following procedure should be
performed in an indoor fresh water
pool, whirlpool, and/or hot tub
maintained at 23 to 32 °C. Fresh water
is clean drinking water that meets the
standards in 40 CFR part 141. The pool
and air temperature and the relative
humidity should be recorded.
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(i) Water resistance (40 minutes). The
labeled SPF should be determined after
40 minutes of water immersion using
the following procedure:
(A) Step 1: Apply the sunscreen as
described in paragraph (d) of this
section.
(B) Step 2: Perform moderate activity
in water for 20 minutes.
(C) Step 3: Rest out of water for 15
minutes. Do not towel test site(s).
(D) Step 4: Perform moderate activity
in water for 20 minutes.
(E) Step 5: Allow test sites to dry
completely without toweling.
(F) Step 6: Apply the SPF standard as
described in paragraph (d) of this
section.
Step 1. Expose test sites to UV doses
as described in paragraph (e) of this
section.
(ii) Water resistance (80 minutes). The
labeled SPF should be determined after
80 minutes of water immersion using
the following procedure:
(A) Step 1: Apply the sunscreen as
described in paragraph (d) of this
section.
(B) Step 2: Perform moderate activity
in water for 20 minutes.
(C) Step 3: Rest out of water for 15
minutes. Do not towel test site(s).
(D) Step 4: Perform moderate activity
in water for 20 minutes.
(E) Step 5: Rest out of water for 15
minutes. Do not towel test site(s).
(F) Step 6: Perform moderate activity
in water for 20 minutes.
(G) Step 7: Rest out of water for 15
minutes. Do not towel test site(s).
(H) Step 8: Perform moderate activity
in water for 20 minutes.
(I) Step 9: Allow test sites to dry
completely without toweling.
(J) Step 10: Apply the SPF standard as
described in paragraph (d) of this
section.
(K) Step 11: Expose test sites to UV
doses as described in paragraph (e) of
this section.
(j) Broad spectrum test procedure. (1)
UV Spectrometry. (i) Plate. Use opticalgrade polymethylmethacrylate (PMMA)
plates suitable for UV transmittance
measurements. The plate should be
roughened on one side to a three
dimensional surface topography
measure (Sa) between 2 and 7
micrometers and must have a
rectangular application area of at least
16 square centimeters (with no side
shorter than 4 cm).
(ii) Sample holder. The sample holder
should hold the PMMA plate in a
horizontal position to avoid flowing of
the sunscreen drug product from one
edge of the PMMA plate to the other. It
should be mounted as close as possible
to the input optics of the spectrometer
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to maximize capture of forward
scattered radiation. The sample holder
should be a thin, flat plate with a
suitable aperture through which UV
radiation can pass. The PMMA plate
should be placed on the upper surface
of the sample holder with the
roughened side facing up.
(iii) Light source. The light source
should produce a continuous spectral
distribution of UV radiation from 290 to
400 nanometers.
(iv) Input optics. Unless the
spectrometer is equipped with an
integrating sphere, an ultraviolet
radiation diffuser should be placed
between the sample and the input optics
of the spectrometer. The diffuser will be
constructed from any UV radiation
transparent material (e.g., Teflon® or
quartz). The diffuser ensures that the
radiation received by the spectrometer
is not collimated. The spectrometer
input slits should be set to provide a
bandwidth that is less than or equal to
1 nanometer.
(v) Dynamic range of the
spectrometer. The dynamic range of the
spectrometer should be sufficient to
measure transmittance accurately
through a highly absorbing sunscreen
product at all terrestrial solar UV
wavelengths (290 to 400 nm).
(2) Sunscreen product application to
PMMA plate. The accuracy of the test
depends upon the application of a
precisely controlled amount of
sunscreen product with a uniform
distribution over the PMMA plate. The
product is applied at 0.75 mg per square
centimeter to the roughened side of the
PMMA plate. The sunscreen product
should be applied in a series of small
dots over the entire PMMA plate and
then spread evenly using a gloved
finger. Spreading should be done with
a very light spreading action for
approximately 30 seconds followed by
spreading with greater pressure for
approximately 30 seconds. The plate
should then be allowed to equilibrate
for 15 minutes in the dark before the
pre-irradiation described in paragraph
(c) of this section.
(3) Sunscreen product pre-irradiation.
To account for lack of photostability,
apply the sunscreen product to the
PMMA plate as described in paragraph
(b) of this section and then irradiate
with a solar simulator described in
section 352.70(b) of this chapter. The
irradiation dose should be 4 MEDs
which is equivalent to an erythemal
effective dose of 800 J/m2 (i.e., 800 J/m2eff).
(4) Calculation of mean transmittance
values. After pre-irradiation described
in paragraph (c) of this section, mean
transmittance values should be
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ER17JN11.009
minutes. After the immediate responses
are noted, each subject should shield
the exposed area from further UV
radiation until the MED is determined.
Determine the MED 16 to 24 hours after
UV exposure. Because erythema is
evaluated 16 to 24 hours after UV
exposure, the final MEDu, ssMEDp, and
tpMEDp are typically determined the
day following determination of the
initial MEDu. Evaluate the erythema
responses of each test subsite using
either tungsten or warm white
fluorescent lighting that provides at
least 450 lux of illumination at the test
site. For the evaluation, the test subject
should be in the same position as when
the test site was irradiated.
(v) Invalid test data. Reject test data
for a test subject if erythema is not
present on either the unprotected or
protected test sites; or erythema is
present at all subsites; or the responses
are inconsistent with the series of UV
doses administered; or the subject was
noncompliant (e.g., the subject
withdraws from the test due to illness
or work conflicts or does not shield the
exposed testing sites from further UV
radiation until the MED is determined).
(6) Determination of SPF. (i) Calculate
an SPF value for each test subject (SPFi)
as follows:
ER17JN11.012
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ER17JN11.005
35664
Federal Register / Vol. 76, No. 117 / Friday, June 17, 2011 / Rules and Regulations
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
AGENCY:
5. Section 310.545 is amended by
revising paragraphs (a)(29) and (d)(31)
and by adding new paragraph (d)(40) to
read as follows:
§ 310.545 Drug products containing
certain active ingredients offered over-thecounter (OTC) for certain uses.
(a) * * *
(29) Sunscreen drug products.
(i) Ingredients.
Where n ≥ 5
(5) Calculation of mean absorbance
values. (i) Mean transmittance values,
Diethanolamine methoxycinnamate
Digalloyl trioleate
Ethyl 4-[bis(hydroxypropyl)]
aminobenzoate
Glyceryl aminobenzoate
Lawsone with dihydroxyacetone
Red petrolatum
are converted into mean absorbance
values,
emcdonald on DSK2BSOYB1PROD with RULES3
at each wavelength by taking the
negative logarithm of the mean
transmittance value as follows:
(ii) The calculation yields 111
monochromatic absorbance values in 1
nanometer increments from 290 to 400
nanometers.
(6) Number of plates. For each
sunscreen product, mean absorbance
values should be determined from at
least three individual PMMA plates.
Because paragraph (d) of this section
requires at least 5 measurements per
plate, there should be a total of at least
15 measurements.
(7) Calculation of the critical
wavelength. The critical wavelength is
identified as the wavelength at which
the integral of the spectral absorbance
curve reaches 90 percent of the integral
over the UV spectrum from 290 to 400
nm. The following equation defines the
critical wavelength:
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18:47 Jun 16, 2011
Jkt 223001
(ii) Any ingredients labeled with any
of the following or similar claims.
Instant protection or protection
immediately upon application.
Claims for ‘‘all-day’’ protection or
extended wear claims citing a specific
number of hours of protection that is
inconsistent with the directions for
application in 21 CFR 201.327.
*
*
*
*
*
(d) * * *
(31) December 31, 2002, for products
subject to paragraph (a)(29)(i) of this
section.
*
*
*
*
*
(40) June 18, 2012, for products
subject to paragraph (a)(29)(ii) of this
section. June 17, 2013, for products with
annual sales less than $25,000.
Dated: June 9, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011–14766 Filed 6–14–11; 8:45 am]
BILLING CODE 4160–01–P
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ACTION:
Notice of availability.
The Food and Drug
Administration (FDA) is announcing the
availability of a draft guidance for
industry entitled ‘‘Enforcement Policy—
OTC Sunscreen Drug Products Marketed
Without an Approved Application.’’
The draft guidance is intended to inform
manufacturers of over-the-counter
(OTC) sunscreen products about our
enforcement policy for certain OTC
sunscreen products marketed without
an approved new drug application. The
draft guidance describes our intended
approach to enforcement for certain
OTC sunscreen products prior to an
effective final monograph.
DATES: Although you can comment on
any guidance at any time (see 21 CFR
10.115(g)(5)), to ensure that the Agency
considers all comments on this draft
guidance before it begins work on the
final version of the guidance, submit
either electronic or written comments
on the draft guidance by August 16,
2011. Submit written comments on the
proposed collection of information by
August 16, 2011.
ADDRESSES: Submit written requests for
single copies of the draft guidance to the
Division of Drug Information, Center for
Drug Evaluation and Research, Food
and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, rm. 2201,
Silver Spring, MD 20993–0002. Send
one self-addressed adhesive label to
assist that office in processing your
requests. See the SUPPLEMENTARY
INFORMATION section for electronic
access to the draft guidance document.
Submit electronic comments on the
draft guidance to http://
www.regulations.gov. Submit written
comments to the Division of Dockets
Management (HFA–305), Food and Drug
Administration, 5630 Fishers Lane, rm.
1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT:
Reynold Tan, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
SUMMARY:
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ER17JN11.007
Authority: 21 U.S.C. 321, 331, 351, 352,
353, 355, 360b–360f, 360j, 361(a), 371, 374,
375, 379e; 42 U.S.C. 216, 241, 242(a), 262,
263b–263n.
Food and Drug Administration,
HHS.
ER17JN11.008
4. The authority citation for 21 CFR
part 310 continues to read as follows:
■
■
is the ratio of the mean of the C(λ)
values to the mean of the P(λ) values, as
follows:
Draft Guidance for Industry on
Enforcement Policy for Over-theCounter Sunscreen Drug Products
Marketed Without an Approved
Application; Availability
ER17JN11.011
PART 310—NEW DRUGS
[Docket No. FDA–2010–D–0509]
ER17JN11.010
A mean critical wavelength of 370 nm
or greater is classified as broad spectrum
protection.
21 CFR Parts 201 and 310
ER17JN11.006
Where λc = critical wavelength
A(λ) = mean absorbance at each wavelength
dλ = wavelength interval between
measurements
ER17JN11.010
determined for each wavelength λ over
the full UV spectrum (290 to 400
nanometers). The transmittance values
should be measured at 1 nanometer
intervals. Measurements of spectral
irradiance transmitted for each
wavelength λ through control PMMA
plates coated with 15 microliters of
glycerin (no sunscreen product) should
be obtained from at least 5 different
locations on the PMMA plate [C1(λ),
C2(λ), C3(λ), C4(λ), and C5(λ)]. In
addition, a minimum of 5 measurements
of spectral irradiance transmitted for
each wavelength λ through the PMMA
plate covered with the sunscreen
product will be similarly obtained after
pre-irradiation of the sunscreen product
[P1(λ), P2(λ), P3(λ), P4(λ), and P5(λ)].
The mean transmittance for each
wavelength,
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| File Type | application/pdf |
| File Modified | 2011-06-17 |
| File Created | 2011-06-17 |