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existing infant formula are limited to
changing the type of packaging of an
existing infant formula (e.g., changing
from metal cans to plastic pouches); or
(2) The manufacturer requests an
exemption and provides assurances, as
required under § 106.121(h), that
demonstrate that the change made by
the manufacturer to an existing formula
does not affect the bioavailability of the
protein.
(3) The manufacturer requests an
exemption and provides assurances, as
required under § 106.121(i), that
demonstrate that an alternative method
to the PER that is based on sound
scientific principles is available to
demonstrate that the formula supports
the quality factor for the biological
quality of the protein.
*
*
*
*
*
■ 9. In § 106.100, revise paragraphs
(f)(4), (k)(5)(ii), (m), and (o) to read as
follows:
§ 106.100

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*
*
*
*
(f) * * *
(4) Records, in accordance with
§ 106.30(f), on equipment cleaning,
sanitizing, and maintenance that show
the date and time of such cleaning,
sanitizing, and maintenance and the
production aggregate number of each
infant formula processed between
equipment startup and shutdown for
cleaning, sanitizing, and maintenance.
The person performing and checking the
cleaning, sanitizing, and maintenance
shall date and sign or initial the record
indicating that the work was performed.
*
*
*
*
*
(k) * * *
(5) * * *
(ii) The production aggregate number;
*
*
*
*
*
(m) A manufacturer shall maintain all
records required under this part in a
manner that ensures that both the
manufacturer and the Food and Drug
Administration can be provided with
access to such records within 24 hours.
The manufacturer may maintain the
records required under this part as
original records, as true copies such as
photocopies, microfilm, microfiche, or
other accurate reproductions of the
original records, or as electronic
records. Where reduction techniques,
such as microfilming, are used, suitable
reader and photocopying equipment
shall be readily available. All electronic
records maintained under this part shall
comply with part 11 of this chapter.
*
*
*
*
*
(o) The manufacturer shall maintain
quality control records that contain
sufficient information to permit a public

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DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration

10. In § 106.120, add paragraph (b)(7)
to read as follows:

21 CFR Parts 310, 314, 329, and 600

§ 106.120

[Docket No. FDA–2008–N–0334]

■

New infant formula submission.

*

*
*
*
*
(b) * * *
*
*
*
*
*
(7) If the manufacturer is requesting
an exemption under § 106.91(b)(1)(ii),
the manufacturer shall include the
scientific evidence that the
manufacturer is relying on to
demonstrate that the stability of the new
infant formula will likely not differ from
the stability of formulas with similar
composition, processing, and packaging
for which there are extensive stability
data.
*
*
*
*
*
11. In § 106.121 revise paragraphs (d)
and (i) and add paragraph (j) to read as
follows:

■

Records.

*

VerDate Mar<15>2010

health evaluation of any production
aggregate of infant formula.
*
*
*
*
*

§ 106.121 Quality factor assurances for
infant formulas.

*

*
*
*
*
(d) If the manufacturer is requesting
an exemption under § 106.96(c)(2)(ii),
the manufacturer shall include a
detailed description of the change and
an explanation of why the change made
by the manufacturer to an existing
infant formula does not the affect the
ability of the formula to support normal
physical growth.
*
*
*
*
*
(i) If the manufacturer is requesting an
exemption under § 106.96(g)(3), the
manufacturer shall include a detailed
explanation of the alternative method,
an explanation of why the method is
based on sound scientific principles,
and the data that demonstrate that the
quality factor for the biological quality
of the protein has been met.
(j) A statement certifying that the
manufacturer has collected and
considered all information and data
concerning the ability of the infant
formula to meet the requirements for
quality factors and that the
manufacturer is not aware of any
information or data that would show
that the formula does not meet the
requirements for quality factors.
Dated: June 4, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014–13384 Filed 6–9–14; 8:45 am]
BILLING CODE 4160–01–P

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RIN 9010–AF96

Postmarketing Safety Reports for
Human Drug and Biological Products;
Electronic Submission Requirements
AGENCY:

Food and Drug Administration,

HHS.
ACTION:

Final rule.

The Food and Drug
Administration (FDA or we) is
amending its postmarketing safety
reporting regulations for human drug
and biological products to require that
persons subject to mandatory reporting
requirements submit safety reports in an
electronic format that FDA can process,
review, and archive. FDA is taking this
action to improve the Agency’s systems
for collecting and analyzing
postmarketing safety reports. The
change will help the Agency to more
rapidly review postmarketing safety
reports, identify emerging safety
problems, and disseminate safety
information in support of FDA’s public
health mission. In addition, the
amendments will be a key element in
harmonizing FDA’s postmarketing
safety reporting regulations with
international standards for the
electronic submission of safety
information.
DATES: This rule is effective June 10,
2015.
FOR FURTHER INFORMATION CONTACT: For
information concerning human drug
products: Jean Chung, Center for Drug
Evaluation and Research (CDER), Food
and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 7268,
Silver Spring, MD 20993–0002, 240–
402–7911.
For information concerning human
biological products: Stephen Ripley,
Center for Biologics Evaluation and
Research (CBER) (HFM–17), Food and
Drug Administration, 1401 Rockville
Pike, Suite 200N, Rockville, MD 20852–
1448, 301–827–6210.
SUPPLEMENTARY INFORMATION:
SUMMARY:

Table of Contents
I. Introduction
A. The Proposed Rule
B. Changes to the Proposed Rule
II. Summary of the Final Rule
A. Electronic Submission of Postmarketing
Safety Reports
B. Safety Reports Not Covered by the Final
Rule

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C. Waivers
D. Individual Case Safety Report (ICSR)—
Definition and Required Information
E. Removal of Paper Format Provisions
F. Section 745A of the FD&C Act and
Electronic Format for Submissions
G. Miscellaneous Changes
III. Comments on the Proposed Rule
A. Safety Reports Covered
B. FDA Web-Based Submission Portal
C. Waivers
D. ICSR Submissions
E. International Harmonization
F. Technical Specifications
IV. Legal Authority
V. Environmental Impact
VI. Analysis of Impacts
VII. Paperwork Reduction Act of 1995
A. Reporting Costs
B. Capital Costs
VIII. Federalism
IX. Reference

I. Introduction
In the Federal Register of August 21,
2009 (74 FR 42184), FDA published a
proposed rule to require that persons
subject to mandatory postmarketing
safety reporting requirements for human
drug or biological products submit
safety reports in an electronic format
that the Agency can process, review,
and archive.
When a drug or biological product is
approved and enters the market, the
product is introduced to a larger patient
population in settings different from
clinical trials. New information
generated during the postmarketing
period offers further insight into the
benefits and risks of the product, and
evaluation of this information is
important to ensure the safe use of these
products.
FDA receives information regarding
postmarketing adverse drug
experiences 1 from safety reports
submitted to the Agency. For nearly 35
years, FDA has received these
postmarketing safety reports on paper.
Since 2001, many companies have
voluntarily submitted reports for drug
and nonvaccine biological products to
the Agency in electronic format. Data
from both the electronic and paper
reports are entered into the FDA
Adverse Event Reporting System
(FAERS) database. FAERS is a
computerized information database
designed to support FDA’s
postmarketing safety surveillance
program for drug and nonvaccine
biological products. The FAERS
database is used to store and analyze
data received in postmarketing safety
reports. Safety reporting data submitted
on paper is first converted into an
1 For purposes of this preamble, the term
‘‘adverse drug experience’’ includes an ‘‘adverse
experience’’ associated with use of a human drug
or biological product.

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electronic format before being entered
into FAERS.2 In September 2012, the
FAERS database replaced the previously
used Adverse Event Reporting System
(AERS) database described in the
preamble to the proposed rule (74 FR
42184 at 42185). The transition to the
FAERS database has been an important
step in improving FDA’s postmarketing
surveillance capabilities. FAERS
supports greater functionality and more
sophisticated pharmacovigilance tools
that enhance FDA’s ability to analyze
safety information.
The proposed rule proposed that use
of an electronic format be mandatory for
the submission of all required
postmarketing safety reports for human
drug and biological products, including
vaccines,3 a change to improve the
Agency’s systems for collecting and
analyzing these reports.
A. The Proposed Rule
In the preamble to the proposed rule
(74 FR 42184 at 42187 to 42189), we set
forth in detail the rationale for requiring
electronic submission of postmarketing
safety reports. Receiving postmarketing
safety reports in electronic format will
expedite access to safety information
and facilitate international
harmonization and exchange of this
information. This, in turn, will lead to
more efficient reviews of safety data and
will enhance our ability to rapidly
disseminate safety information to health
care providers, consumers, applicants,
sponsors, and other regulatory
authorities in support of FDA’s public
health mission. In addition, the Agency
will recognize a significant cost savings
by converting the safety reporting
system from a paper submission process
to a predominantly all-electronic system
that will increase the accuracy of
information and reduce the need for
manual data entry. We also believe this
change will benefit industry by
eliminating time and costs associated
with submitting paper reports.
In the proposed rule, FDA proposed
revising §§ 310.305, 314.80, 314.98, and
600.80 (21 CFR 310.305, 314.80, 314.98,
and 600.80) to require that
manufacturers, packers, and
distributors, and applicants with
approved new drug applications
(NDAs), abbreviated new drug
applications (ANDAs), and biological
license applications (BLAs), and those
2 Additional information regarding the FAERS
database may be found at http://www.fda.gov/cder/
aers/default.htm.
3 Data from postmarketing safety reports for
vaccines is entered into the Vaccine Adverse Event
Reporting System (VAERS). The VAERS database is
used to store and analyze data received in
postmarketing safety reports for vaccines.

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that market prescription drugs for
human use without an approved
application, submit postmarketing
safety reports (i.e., individual case
safety reports (ICSRs) and any ICSR
attachments) to the Agency in an
electronic format that FDA can process,
review, and archive. We stated that the
proposal would apply to all
postmarketing safety reports required to
be submitted to FDA under §§ 310.305,
314.80, 314.98, and 600.80 (including
vaccines) and would apply to any new
postmarketing safety reports for drug or
biological products implemented in the
future. (The preamble to the proposed
rule (74 FR 42184 at 42185 to 42186)
describes current postmarketing safety
reporting requirements.) We also
proposed revising § 600.81 (21 CFR
600.81) to require the electronic
submission of biological lot distribution
reports.
The preamble to the proposed rule (74
FR 42184 at 42186 to 42187) also
discussed the Dietary Supplement and
Nonprescription Drug Consumer
Protection Act (Public Law 109–462),
enacted on December 22, 2006, which
amended the Federal Food, Drug, and
Cosmetic Act (the FD&C Act) to create
a new section 760 (21 U.S.C. 379aa),
entitled ‘‘Serious Adverse Event
Reporting for Nonprescription Drugs.’’
As noted in the preamble, section 760
of the FD&C Act requires manufacturers,
packers, or distributors whose name
appears on the label of nonprescription
(over-the-counter or OTC) human drug
products marketed without an approved
application to report to FDA serious
adverse events associated with their
products. It does not apply to OTC drug
products marketed under applications
approved under section 505 of the FD&C
Act (21 U.S.C. 355), which are subject
to the reporting requirements under
§ 314.80, as are all other drugs marketed
under approved NDAs or ANDAs.4 The
requirement went into effect in
December 2007, and to assist entities in
complying with the requirements, FDA
issued a guidance for industry entitled
‘‘Postmarketing Adverse Event
Reporting for Nonprescription Human
Drug Products Marketed Without an
Approved Application’’ (available on
4 Section 760 of the FD&C Act provides for
mandatory safety reporting for nonprescription
human drug products not subject to NDAs or
ANDAs. Accordingly, the requirements apply to all
OTC drug products marketed without an approved
application, including those marketed under the
OTC Drug Monograph Review process (whether or
not subject to a final monograph), those marketed
outside the monograph system, and including those
that have been discontinued from marketing but for
which a report of an adverse event was received.
These reporting requirements became effective
December 22, 2007.

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FDA’s Web site at http://www.fda.gov/
Drugs/GuidanceComplianceRegulatory
Information/Guidances/default.htm). In
the preamble to the proposed rule, we
requested comment on whether to
require the electronic submission of
postmarketing safety reports required by
section 760 of the FD&C Act (referred to
in this document as section 760 reports).
We noted that our decision would be
informed by public comments received
and our experience with the submission
of these reports to date.
The proposed rule stated that FDA
would periodically issue guidance on
how to provide the electronic
submissions (e.g., method of
transmission, media, file formats,
preparation, and organization of files).
Currently, technical specifications
referenced in guidance documents rely
upon and adopt certain safety reporting
and transmission standards
recommended by the International
Conference on Harmonisation of
Technical Requirements for Registration
of Pharmaceuticals for Human Use
(ICH). ICH was formed to facilitate the
harmonization of technical
requirements for the registration of
pharmaceutical products among the
three ICH regions: The European Union
(EU), Japan, and the United States. The
proposal reaffirmed our intention to
continue to rely on ICH standards while
also providing other options for
providing electronic submissions to
FDA.
In the preamble to the proposed rule,
we explained that applicants,
manufacturers, packers, and distributors
had been voluntarily submitting
postmarketing safety reports for drugs
and nonvaccine biological products in
electronic format by sending the reports
to FDA either through FDA’s Electronic
Submission Gateway (ESG) or on
physical media (e.g., CD–ROM (sent by
mail).5 The ESG is the central
transmission point for sending
information electronically to FDA.
Among other things, the ESG allows
ICH-compatible postmarketing safety
report submissions to be transmitted
directly from the company’s database to
FDA.6 The direct database-to-database
submissions may include ICSRs, any
ICSR attachments, and descriptive
information. Once received through the
ESG, the ICSRs for drug and nonvaccine
biological products are downloaded into
5 FDA expects that, in the future, all electronic
submissions to the Agency will be sent through the
ESG and that use of physical media (e.g., CD–ROM)
for such submissions will be phased out.
6 ICH data elements for postmarketing safety
reports are available at http://www.fda.gov/
downloads/RegulatoryInformation/Guidances/
UCM129399.pdf.

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the FAERS database. FDA has
encouraged electronic submission of
ICSRs because it is a cost-effective and
efficient alternative to paper-based
reporting, particularly for companies
submitting large numbers of ICSRs. In
addition, electronic submission of ICSRs
enhances global pharmacovigilance by
facilitating electronic transmission and
exchange of appropriate information
from ICSRs among regulatory bodies
and regulated entities through use of
common data elements and
transmission standards.
In the preamble to the proposed rule,
we also explained that we are
developing a ‘‘Web-based submission
portal’’ to collect and process safety
information for FDA-regulated products.
We anticipated that the Web-based
submission portal would allow the
secure electronic submission of
postmarketing ICSRs directly into FDA’s
FAERS database once information was
entered into a ‘‘Web-based electronic
form.’’ We stated that the Web-based
submission portal would allow
submission of ICSRs consistent with
ICH standards and could be used as an
alternative method for reporting adverse
drug experiences to FDA electronically.
We noted that the Web-based system
would be particularly useful for entities
that submit a small number of safety
reports because it would create a
simpler and more efficient mechanism
for reporting that would not require an
internal database that is compatible
with the ICH-based direct transmission
system. (See section II.A for further
discussion of the Web-based submission
portal.)
Because in certain rare circumstances
electronic submission of safety reports
may not be feasible, we proposed (in
§§ 310.305(e)(2), 314.80(g)(2), and
600.80(g)(2)) to allow for the submission
of requests for a temporary waiver from
the electronic format requirement and
stated that waivers would be granted on
a limited basis for good cause shown.
We requested comments on
circumstances under which a waiver
should be granted. We stated that
guidance would be issued describing
the procedures for submitting a waiver
request. Elsewhere in this issue of the
Federal Register, we are announcing the
availability of a draft guidance entitled
‘‘Providing Submissions in Electronic
Format—Postmarketing Safety Reports’’
(the postmarketing safety reports
guidance) (available on FDA’s Web site
at http://www.fda.gov/Drugs/Guidance
ComplianceRegulatoryInformation/
Guidances/default.htm). It is intended
to assist persons required to submit
postmarketing safety reports in
complying with the final rule. In

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addition, the draft guidance addresses
procedures for submitting waiver
requests and other information.
We proposed to delete the specific
references to paper reporting forms in
§§ 310.305, 314.80, and 600.80. Because
the paper reporting forms would no
longer be used, we proposed to add a
list of the reportable elements to
proposed §§ 310.305(d), 314.80(f), and
600.80(f). The list of reportable elements
in the proposed rule was derived from
the elements included in Form FDA
3500A, the paper reporting form.
Moreover, the obligation to provide all
applicable information described in the
proposed rule would be the same as the
obligation to complete Form FDA 3500A
and VAERS–1. To facilitate the shift
away from the paper reporting forms,
we also proposed to adopt a generic
term for the safety reporting vehicle:
Individual case safety report (ICSR).
Proposed §§ 310.305(b) and 314.80(a)
define an ICSR as ‘‘a description of an
adverse drug experience related to an
individual patient or subject.’’ Proposed
§ 600.80(a) defines ICSR as ‘‘a
description of an adverse experience
related to an individual patient or
subject.’’
B. Changes to the Proposed Rule
We received seven submissions
containing comments on the proposed
rule. Several commenters expressed
support for requiring electronic
submission of postmarketing safety
reports, agreeing that it would help FDA
to more rapidly review safety reports
and identify emerging safety issues.
Two commenters also expressed
support for requiring the electronic
submission of safety reports required by
section 760 of the FD&C Act; no
commenters opposed this requirement
for the section 760 reports. Commenters
also requested clarification of certain
terms and requirements in the proposed
rule. We address all of the comments in
greater detail in section III.
After considering the comments and
based on our experience with
postmarketing safety reporting, we have
concluded that certain revisions to the
proposed rule are appropriate. However,
we note that the provisions applicable
to safety reporting under §§ 310.305,
314.80, and 600.80 are largely
unchanged from the proposed rule.
We have concluded that the electronic
submission requirement should extend
to safety reports required by section 760
of the FD&C Act. Therefore, the final
rule adds part 329 (21 CFR part 329),
entitled ‘‘Nonprescription Human Drug
Products Subject to Section 760 of the
Federal Food, Drug, and Cosmetic Act’’
to chapter 21 of the Code of Federal

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Federal Register / Vol. 79, No. 111 / Tuesday, June 10, 2014 / Rules and Regulations
Regulations to address the safety
reporting requirements of section 760 of
the FD&C Act described in section I.A.
This addition responds to the two
comments received on this issue, both
of which supported requiring the
electronic submission of section 760
reports. It also reflects FDA’s
determination that the electronic
submission requirement should extend
to these safety reports in furtherance of
FDA’s goal to more quickly review
postmarketing safety reports and
identify emerging safety issues.
The final rule adds new § 329.100 to
require the electronic submission of
section 760 reports. Section 329.100(a)
states that safety reports required by
section 760 of the FD&C Act must be
submitted to FDA in electronic format.
Section 329.100(b) explains that for
purposes of safety reporting under
section 760, an ICSR constitutes the
‘‘MedWatch Form’’ (the common name
for Form FDA 3500A) required to be
submitted in section 760(d) of the FD&C
Act, and sets forth the elements that are
reported in an ICSR under section 760.
As noted previously in this document
and in the preamble to the proposed
rule, we have adopted the term
‘‘individual case safety report’’ (ICSR)
because we will no longer be using the
paper reporting forms for mandatory
postmarketing safety reporting. New
§ 329.100(c)(1) states that the
submissions must be in an electronic
format that FDA can process, review,
and archive; § 329.100(c)(2) provides for
a good-cause waiver; and § 329.100(d)
addresses patient privacy. All of these
provisions are analogous to the
provisions in this final rule for reports
submitted under §§ 310.305, 314.80, and
600.80.
The final rule revises the proposed
provisions entitled ‘‘Patient privacy’’ (in
final §§ 310.305(f), 314.80(i), and
600.80(j)) to state, ‘‘the applicant should
assign a unique code for identification
of the patient.’’ 7 This addresses a
comment expressing concern that the
proposed rule was confusing because it
used two different terms to refer to the
code that must be assigned to protect
patient privacy. Section 329.100(d) uses
the revised language.
On our own initiative, we have made
revisions that are described as follows.
The final rule adds a definition for the
term ‘‘ICSR attachments’’ to
§§ 310.305(b), 314.80(a), and 600.80(a).
In §§ 310.305(b) and 314.80(a), ICSR
attachments are defined as ‘‘documents
7 The revised language in § 600.80(j) applies only
to nonvaccine biological products. ICSRs for
vaccines should not use a patient identification
code but should continue to include the patient’s
name (§ 600.80(g)).

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related to the adverse drug experience
described in an ICSR, such as medical
records, hospital discharge summaries,
or other documentation.’’ In § 600.80(a),
ICSR attachments are defined as
‘‘documents related to the adverse
experience described in an ICSR, such
as medical records, hospital discharge
summaries, or other documentation.’’
The final rule revises the proposed
provisions addressing waivers in
proposed §§ 310.305(e)(2), 314.80(g)(2),
and 600.80(g)(2). The final rule deletes
the statement that if the Agency grants
a waiver, the person who requested the
waiver must submit the required reports
on paper within the required time
periods and that FDA intends to issue
guidance on how to provide the paper
submission. This statement has been
deleted so that the rule does not specify
that safety reports that cannot be
submitted in electronic format must be
submitted on paper. We recognize that
alternate formats for safety reports, other
than paper, such as email or fax, may be
appropriate when a waiver of the
electronic submission requirement is
granted. We will specify an acceptable
alternate format at the time the waiver
is granted. The final rule also modifies
the language indicating that procedures
for how to request waivers will be set
forth in guidance. The proposed rule
stated, ‘‘Procedures for how to request
waivers of this requirement will be set
forth in guidance.’’ The final rule states,
‘‘FDA will issue guidance on requesting
a waiver of the requirements [for
electronic submission].’’ We have made
this change to indicate that the guidance
addressing waivers may include
information on other aspects of the
waiver provision, such as circumstances
under which FDA may grant waivers,
not just the procedures for how to
request waivers. (The waiver provision
for biological products has been
finalized in § 600.80(h)(2).) Section
329.100(c)(2), applicable to section 760
reports for nonprescription products
marketed without an approved
application, contains this revised
language on waivers. It is important to
note that the waiver referred to in the
final rule (as in the proposed rule)
pertains only to the electronic format
requirements. It is not a waiver from the
underlying safety reporting requirement.
On our own initiative, we have made
additional changes to the provisions
addressing patient privacy. The
proposed provisions entitled ‘‘Patient
privacy’’ (in proposed §§ 310.305(f),
314.80(i), and 600.80(i)) state that the
preferred methodology for determining
the identification code will be set forth
in guidance. FDA does not believe that
it is necessary to identify specific

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33075

elements in the final rule for which we
will be providing technical guidance or
specifications. FDA currently provides
and will continue to provide technical
guidance and specifications for many
different aspects of electronic ICSR
submission. Accordingly, we are
deleting that language from final
§§ 310.305(f), 314.80(i), and 600.80(j).
However, for drug and nonvaccine
biological products, we recommend that
no identifying information, such as
initials or birthdate, be used as part of
the patient identification code. At the
same time, under new § 600.80(g), ICSRs
for vaccine products will continue to
include the patient’s name.
In the patient privacy provisions, we
proposed that the name of the reporter
not be included when the reporter is
also the patient. The proposed provision
stated that the submitter should include
the name of the reporter from whom the
information was received, unless the
reporter is the patient. FDA is not
finalizing the proposal because we have
concluded that those submitting
mandatory safety reports should include
the name of the reporter (in the reporter
section of the ICSR), even when the
reporter is the patient. It is important for
FDA to have the name of the reporter so
that we may contact the reporter, if
necessary, to obtain followup
information about the adverse event
reported. To make clear that the name
of the reporter should be provided (in
the initial reporter information section
of the ICSR), even when the reporter is
the patient, we are amending the patient
privacy provisions in the final rule to
state, ‘‘the [submitter] should include
the name of the reporter from whom the
information was received as part of the
initial reporter information, even when
the reporter is the patient’’
(§§ 310.305(f), 314.80(i), 329.100(d), and
600.80(j)). FDA regulations prohibit the
release of the names of patients, health
care professionals, hospitals, and
geographical identifiers in adverse event
reports to the public, so it is unlikely
that the patient’s privacy will be
compromised if the patient’s name is
provided in situations where the patient
is the reporter.
The final rule modifies the language
in proposed § 600.81(b)(1) describing
the electronic format requirement for
biological product lot distribution
reports so that it reflects the language
used in analogous provisions
(§§ 310.305(e)(1), 314.80(g)(1),
329.100(c)(1), and 600.80(h)(1)).
As described later in this section, the
final rule also makes some revisions to
the proposed provisions that set forth
the reportable elements included in an
ICSR. Changes to the language

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describing certain elements, including
the addition of descriptive phrases, have
been made to clarify to what
information those elements refer. The
final rule also adds a new § 600.80(g)
and adds certain elements to proposed
§§ 310.305(d), 314.80(f), and 600.80(f) to
more accurately describe the
information currently reported on the
VAERS–1 form and Form FDA 3500A.
Accordingly, §§ 310.305(d), 314.80(f),
329.100(b), and 600.80(f) list ICSR
elements, derived from Form FDA
3500A, for drug and nonvaccine
biological products. Section 600.80(g) in
the final rule lists ICSR elements for
vaccine products derived from the
VAERS–1 form.
The new § 600.80(g) has been added
to the final rule to capture the
information reported on the VAERS–1
form that was inadvertently omitted
from the proposed rule. Section
600.80(f) applies only to nonvaccine
biological products. Section 600.80(g) in
the final rule lists ICSR elements for
vaccines that are derived from the
VAERS–1 form. The list of elements in
§ 600.80(g) (for vaccine products) is
largely the same as the list of elements
for nonvaccine biological products, but
there are some variations, including
certain additional elements applicable
only to safety reporting for vaccine
products. Reporting elements that have
been included for vaccine ICSRs that are
not applicable to ICSRs for nonvaccine
biological products include, among
others, patient name (in place of patient
identification code), birth weight for
children under 5, time of adverse
experience, illness at the time of
vaccination, anatomical site of
vaccination, number of previous vaccine
doses, time of vaccination, other
vaccine(s) administered in the 4 weeks
before the vaccination date, name of the
person who administered the vaccine,
and name of the responsible physician
at the facility where the vaccine was
administered. This information is
currently reported on the VAERS–1
form and is important for FDA to
evaluate adverse experiences associated
with the administration of vaccines. In
addition, because § 600.80(g) does not
include patient identification code as a
reporting element, FDA has revised
§ 600.80(c)(2)(ii)(A)(2) and (A)(4), which
describe how to reference and index
ICSRs in periodic reports, to note that
ICSRs for nonvaccine biological
products should be referenced and
indexed by patient identification code,
whereas ICSRs for vaccines should be
referenced and indexed by unique case
identification number.
The final rule removes from proposed
§§ 310.305(d), 314.80(f), and 600.80(f)

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the element requiring applicants to
report information on whether the
initial reporter also sent a copy of the
report to FDA. FDA does not often use
that information to identify duplicate
reports, and including that information
is not consistent with international
electronic reporting standards. The final
rule adds to all sections that contain
reporting elements the following
elements to be reported: (1) Whether the
report is a 15-day ‘‘Alert report’’ and (2)
whether the ICSR is an initial report or
a followup report. These two elements
replace the element requiring the type of
report (e.g., 15-day, periodic, followup).
We believe that it is clearer to represent
this information with two separate
elements. The final rule adds to
§§ 310.305(d), 314.80(f), and 600.80(f)
the element requiring information on
whether the product is a combination
product as defined under § 3.2(e) (21
CFR 3.2(e)).8 The final rule adds to
§§ 310.305(d), 314.80(f), and 600.80(f)
the element ‘‘whether the product is a
prescription or nonprescription
product.’’ Section 329.100(b) also lists
‘‘whether the product is a prescription
or nonprescription product’’ as an
element to be included in an ICSR. Even
though § 310.305 only applies to
prescription products and § 329.100
only applies to nonprescription
products, for consistency, we use the
same language in all sections to describe
the information to be provided. The
final rule removes from proposed
§ 310.305(d), ‘‘Basis for marketing if
nonapplication product’’ because we are
able to obtain that information based on
the status of the drug as a prescription
product and whether a drug application
number is provided. The final rule adds
to the ICSR elements for each product
type (e.g., drug, nonvaccine biological
product, vaccine) ‘‘unique case
identification number,’’ which must be
the same in the initial report and any
subsequent followup reports. The
unique case identification number is
different from the ‘‘unique code [used]
for identification of the patient.’’ The
‘‘unique case identification number’’
replaces the ‘‘Manufacturer Report
Number’’ used on Form FDA 3500A and
VAERS–1. Using a unique case
identification number (that is the same
8 For purposes of postmarketing safety reporting,
combination product, under § 3.2(e), includes: (1) A
product comprised of two or more regulated
components, i.e., drug/device, biological product/
device, drug/biological product, or drug/device/
biological product, that are physically, chemically,
or otherwise combined or mixed and produced as
a single entity and (2) two or more separate
products packaged together in a single package or
as a unit and comprised of drug and device
products, device and biological products, or
biological and drug products.

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in the initial ICSR and any followup
reports) allows FDA to link the initial
ICSR with any followup reports in the
FAERS or VAERS database. This will
allow FDA to track an individual case
over its life cycle.
II. Summary of the Final Rule
A. Electronic Submission of
Postmarketing Safety Reports
The final rule revises current
§§ 310.305, 314.80, 314.98, and 600.80
to require that manufacturers, packers,
and distributors, and applicants with
approved NDAs, ANDAs, and BLAs and
those that market prescription drugs for
human use without an approved
application submit postmarketing safety
reports to the Agency in an electronic
format that FDA can process, review,
and archive. As addressed in section I.B
of this document, the final rule also
adds part 329 to address safety reports
required by section 760 of the FD&C
Act. Section 329.100 requires that
reports required to be submitted to the
Agency under section 760 of the FD&C
Act be submitted in an electronic format
that FDA can process, review, and
archive.
Under the final rule, the following
reports must be submitted to FDA in an
electronic format: Postmarketing 15-day
Alert report ICSRs and any ICSR
attachments; periodic adverse (drug)
experience reports (including the ICSRs,
any ICSR attachments, and the
descriptive information portion); and
section 760 reports. A separate ICSR is
to be submitted for each individual
patient report of an adverse drug
experience, just as separate paper forms
have been submitted for each individual
patient report of an adverse drug
experience. Information on the formats
the Agency is able to process, review,
and archive is described in FDA
guidance and associated technical
specifications documents available on
FDA’s Web site.
For marketed products with an
approved application, manufacturers,
packers, or distributors that do not hold
the application continue to have the
option of submitting 15-day Alert
reports directly to FDA or to the
application holder under
§§ 314.80(c)(1)(iii) and 600.80(c)(1)(iii).
If they opt to submit reports directly to
FDA, they are required to do so in
electronic format. If they choose to
report to the applicant, they may submit
the report in any format acceptable to
the reporter and applicant. The
applicant, however, is required to use
electronic reporting when it
subsequently reports the information to
FDA. Similarly, for marketed

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Federal Register / Vol. 79, No. 111 / Tuesday, June 10, 2014 / Rules and Regulations
prescription drug products without an
approved application, initial safety
reports submitted to the manufacturer
by packers and distributors under
§ 310.305 may be sent in any format
agreeable to the reporter and the
manufacturer, but all safety reports
submitted to FDA must be in electronic
format. Under section 760 of the FD&C
Act, a retailer whose name appears on
the label of a nonprescription (OTC)
drug product marketed in the United
States without an approved application,
as a distributor, may, by agreement,
authorize the manufacturer or packer of
the nonprescription drug to submit the
required reports to FDA (as long as the
retailer directs to the manufacturer or
packer all adverse events associated
with the drug that are reported to the
retailer as specified in section 760). The
retailer may direct serious adverse event
reports to the manufacturer or packer in
any agreed-upon format. However, the
manufacturer or packer must then send
the required reports to FDA in an
electronic format that the Agency can
process, review, and archive.
This rule will apply to any new
postmarketing safety reports for drug or
biological products that are
implemented in the future (e.g., once
finalized, new postmarketing safety
reports in the proposed rule to amend
safety reporting requirements published
in the Federal Register of March 14,
2003, 68 FR 12406). The rule also
revises § 600.81, requiring the electronic
submission of biological lot distribution
reports.9 The specific references to
submission of postmarketing safety
reports in paper format in §§ 310.305,
314.80, 600.2, and 600.80 have been
deleted, and language has been added to
these sections which states that FDA
will issue guidance on how to provide
the electronic submissions (e.g., method
of transmission, media, file formats,
preparation, and organization of files).
In the proposed rule, we stated that
we were developing a Web-based
submission portal (for submission of
reports to FAERS) that we believed
might be preferred by entities that
submit a small number of safety reports.
The Safety Reporting Portal (SRP)
(available at http://
www.safetyreporting.hhs.gov) allows the
secure electronic submission of ICSRs
for drug and nonvaccine biological
products directly into the FAERS
database once information is typed into
the Web-based electronic form. The SRP
creates a simple and efficient
mechanism for electronic reporting that
9 As noted in § 600.81, FDA intends to issue
guidance addressing electronic submission of these
reports.

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does not require an internal ICHcompatible database. As described in
the preamble to the proposed rule, use
of the SRP does however require some
administrative support to manually
enter information for the ICSRs into a
Web-based form.
To assist entities that submit a small
number of safety reports for vaccines,
FDA has made available an eSubmitter
tool. The eSubmitter tool is a standalone application that can be
downloaded free of charge from FDA’s
Web site at http://www.fda.gov/
forindustry/fdaesubmitter. The
eSubmitter application appears as a
fillable form, and once the appropriate
fields are filled in, an ICSR in electronic
format is generated that can be
transmitted through the ESG into the
VAERS database. We believe that the
eSubmitter tool generally offers the
same benefits as the SRP. As noted in
§ 600.80(h), FDA will issue guidance
providing further information about the
electronic submission of vaccine
reports.
B. Safety Reports Not Covered by the
Final Rule
Postmarketing safety reports for drugs,
including vaccines, constitute the
largest volume of paper safety reports
received by the Agency and,
consequently, require the most
resources to input electronically. We
anticipate that this final rule will permit
FDA to manage these postmarketing
safety reports more efficiently. The final
rule only addresses electronic
submission of postmarketing safety
reports for drugs and biological
products and does not apply to
submission of the following reports:
• Investigational new drug
application (IND) safety reports
(§ 312.32 (21 CFR 312.32));
• Safety update reports for drugs
(§ 314.50(d)(5)(vi)(b) (21 CFR
314.50(d)(5)(vi)(b));
• Approved NDA and BLA annual
reports (§§ 314.81(b)(2) and 601.28 (21
CFR 314.81(b)(2) and 601.28));
• Biological product deviation reports
(BPDRs) (§§ 600.14 and 606.171 (21 CFR
600.14 and 606.171));
• Reports of complications of blood
transfusion and collection confirmed to
be fatal (§§ 606.170(b) and 640.73 (21
CFR 606.170(b) and 640.73));
• Adverse reaction reports for human
cells, tissues and cellular and tissuebased products (HCT/Ps) regulated
solely under section 361 of the Public
Health Service Act (PHS Act) (42 U.S.C.
264) (§ 1271.350(a) (21 CFR
1271.350(a)); and
• NDA-field alert reports
(§ 314.81(b)(1) (21 CFR 314.81(b)(1)).

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C. Waivers
Although this final rule requires that
all postmarketing safety reports be
submitted to FDA in electronic format,
new §§ 310.305(e)(2), 314.80(g)(2),
329.100(c)(2), 600.80(h)(2), and
600.81(b)(2) allow for a temporary
waiver from the electronic format
requirement for ‘‘good cause’’ shown.10
Details for submitting waiver requests,
such as where to send the request and
any supporting information, are
provided in the postmarketing safety
reports guidance issued today in
conjunction with this final rule. When
a temporary waiver has been granted,
FDA intends to specify an acceptable
alternate format for submitting the
safety reports. FDA anticipates that
temporary waivers of the requirement to
submit postmarketing safety reports to
the Agency in electronic format will be
needed only in rare circumstances.
Companies experiencing technical
difficulties with transmission of their
electronic submissions to FDA should
consult FDA for technical assistance
rather than submitting a waiver request.
Companies that normally use the direct
database-to-database method to submit
reports to FDA could use the SRP as a
backup method for FAERS submissions
and the eSubmitter tool as a backup
method for VAERS submissions during
short-term, temporary outages.
D. Individual Case Safety Report
(ICSR)—Definition and Required
Information
In this final rule, as in the proposed
rule, the term ‘‘individual case safety
report’’ (ICSR) is used to describe the
information contained in either an
initial or a followup report of an
individual adverse drug experience,
reported on a Form FDA 3500A, on a
Council for International Organizations
of Medical Sciences (CIOMS) I form, on
a VAERS–1 form, or in electronic
format. Because we are requiring that all
postmarketing safety reports be
submitted in electronic format, we
proposed this term to describe the safety
reporting vehicle generically, rather
than by reference to the associated
paper form. In addition, this term in
now commonly used in international
electronic reporting standards (e.g., ICH
E2B, Health Level 7 (HL7)) in reference
to such reports.
Accordingly, as proposed,
§§ 310.305(b) and 314.80(a) have been
revised to define an ICSR as a
description of an adverse drug
experience related to an individual
10 Waiver requests under §§ 600.80(h)(2) and
600.81(b)(2) must be submitted in accordance with
§ 600.90.

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patient or subject, and § 600.80(a) has
been revised to define an ICSR as a
description of an adverse experience
related to an individual patient or
subject. Because the items of
information to be reported were
specified on the paper reporting forms
that will no longer be used for reports
covered under this rule, we have added
a list of the reportable elements to the
regulations. Accordingly, §§ 310.305(d),
314.80(f), 329.100(b), 600.80(f), and
600.80(g) provide detailed lists of
specific elements (in five broad
categories for nonvaccine products and
seven broad categories for vaccine
products) that are to be reported in an
ICSR, derived from the associated paper
forms. The five categories applicable to
all products, including vaccines, and
examples of some of the types of
information in each category, are as
follows:
• Patient information (e.g., age,
gender);
• Information about the adverse
experience (e.g., date and description of
the adverse drug experience);
• Information about the suspect
medical product (e.g., drug name, dose,
indication, National Drug Code (NDC)
number);
• Information about the initial
reporter (e.g., name and contact
information); and
• Information about the drug’s
applicant or manufacturer or
responsible person (e.g., name and
contact information)
In addition, the two categories
applicable to vaccine products only are
as follows:
• Information about other vaccine(s)
administered in the previous 4 weeks;
and
• Information on the facility and
personnel where the vaccine was
administered (e.g., name of person who
administered vaccine, name of
responsible physician and facility where
the vaccine was administered).
Though there are minor wording
differences, the list of information to be
reported is derived from the information
reflected on Form FDA 3500A and
VAERS–1 for postmarketing reporting
for drugs and biological products.
Codification of the ICSR reporting
requirements is not intended to change
the obligation of manufacturers,
packers, or distributors to exercise due
diligence for purposes of completing all
of the applicable elements of an ICSR.
The obligation to provide all applicable
information described in §§ 310.305(d),
314.80(f), 329.100(b), 600.80(f), or
600.80(g) is the same as the obligation
to complete Form FDA 3500A or
VAERS–1.

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E. Removal of Paper Format Provisions
We believe that it is no longer
necessary to describe procedures for
paper format submissions in the
regulations because we anticipate that a
paper format will be used on a limited
basis, if at all. Accordingly, as proposed,
this final rule removes from the
regulations provisions describing the
details for submission of safety reports
in paper format, such as the number of
required paper copies or specific
markings or notations required on the
paper forms. We have deleted in
§§ 310.305(d), 314.80(f), and 600.80(f)
the provisions specifically describing
paper submissions and replaced them
with a paragraph (§§ 310.305(e)(1),
314.80(g)(1), and 600.80(h)(1)), which
states that ICSRs and any ICSR
attachments must be submitted to FDA
in an electronic format that we can
process, review, and archive. Additional
revisions to remove or modify
references or provisions that are specific
to paper formats include the following:
• References to the number of paper
copies required for safety report
submissions (§§ 310.305(c), 314.80(c),
and 600.80(c));
• The requirement to mark paper
reports to identify their contents as ‘‘15day Alert report’’ or ‘‘15-day Alert
report-followup,’’ (§§ 310.305(c)(4),
314.80(c)(1)(iv), 600.80(c)(1)(iv));
• The requirement to use Form FDA
3500A, CIOMS I form, or VAERS–1 form
or to determine an appropriate
alternative format for voluntary
submission in electronic format
(§§ 310.305(d)(1) and (d)(3), 314.80(f)(1)
and (f)(3), and 600.80(f)(1) and (f)(3));
• The reference to Form FDA 3500A
or other paper forms designated for
adverse drug experience reporting by
FDA for ICSRs that are submitted as part
of periodic reporting requirements
(§§ 314.80(c)(2)(ii)(b) and
600.80(c)(2)(ii)(B));
• The requirement for identifying
reports of adverse drug experiences that
occur in postmarketing studies by
separating and marking them
(§§ 314.80(e)(2) and 600.80(e)(2));
• The requirement to submit adverse
experience reports by mail to CBER’s
mailing address (§ 600.2(a)) by deleting
the phrase ‘‘adverse experience reports’’
from § 600.2(a);
• The requirement to submit adverse
experience reports by mail to CDER’s
mailing address (§ 600.2(b)(2));
• The requirement to submit VAERS
reports by mail to the VAERS mailing
address (§ 600.2(d)); and
• The requirement to submit
distribution reports on biological
products by mail (§ 600.81) by deleting

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‘‘(see mailing addresses in § 600.2)’’
from § 600.81.
As noted previously in this document,
procedural and formatting
recommendations, if applicable to
electronic submissions, will be set forth
in guidance.11
F. Section 745A of the FD&C Act and
Electronic Format for Submissions
Section 745A(a) of the FD&C Act (21
U.S.C. 379k–1), added by section 1136
of the Food and Drug Administration
Safety and Innovation Act (Pub. L. 112–
144), provides that submissions under
section 505(b), (i), or (j) of the FD&C Act
or section 351(a) or (k) of the PHS Act
shall be submitted in such electronic
format as specified by FDA in guidance.
In section 745A(a) of the FD&C Act,
Congress granted explicit statutory
authority to FDA to implement the
electronic format for submissions
requirement by guidance. This grant of
authority, however, does not preclude
FDA from implementing such
requirements by notice and comment
rulemaking (5 U.S.C. 553). At this time,
even though we conclude that certain
submissions that are addressed in this
final rule are also within the scope of
section 745A(a) of the FD&C Act, FDA
has determined that it is appropriate to
amend the current regulations on the
submission of postmarketing safety
reports to remove references to paper
submissions and to specify that such
reports be submitted in an electronic
format that FDA can process, review,
and archive. FDA may consider, at a
future date, whether certain electronic
submission requirements should be
specified in guidance pursuant to
section 745A(a) of the FD&C Act.
G. Miscellaneous Changes
As proposed, the final rule amends
§§ 310.305, 314.80, 314.98, and 600.80
by replacing the word ‘‘shall’’ with the
word ‘‘must’’ except in the first sentence
of §§ 314.80(c)(1)(iii) and
600.80(c)(1)(iii), from which the word
‘‘shall’’ has been removed for editorial
reasons. The final rule revises in
§ 314.80(c)(2) the paragraph
designations that were not in correct
format. We believe that these minor
changes clarify the regulations and
make them easier to read. The final rule,
as proposed, also changes the term
‘‘licensed manufacturer’’ to ‘‘applicant’’
in §§ 600.80, 600.81, and 600.90.
11 We are also issuing a draft guidance today in
conjunction with this final rule. The draft guidance,
when finalized, will represent FDA’s current
thinking on certain topics pertaining to the
electronic submission of postmarketing safety
reports in the context of this rulemaking.

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The mailing addresses for the
submission of postmarketing safety
reports have been removed from
§§ 310.305(c), 314.80(c), 314.98(b), and
600.80(c) because this information is no
longer necessary in light of the
requirement to submit safety reports
electronically.
Final § 310.305(c)(1)(i) requires the
submission of a current copy of the
labeling in electronic format unless it is
already on file with FDA. Previously,
under § 310.305(c)(1)(i), each report was
to be accompanied by a copy of the
labeling. However, if the Agency already
has the current labeling on file, we do
not believe it is necessary for a current
copy of the labeling to be submitted
with each report.12
For products with approved
applications, currently, reports for all
adverse experiences other than those
submitted as 15-day Alert reports or
followup reports to 15-day Alert reports
(i.e., reports of adverse experiences that
are both serious and expected or
nonserious) are required to be submitted
as a batch as part of the postmarketing
periodic safety report for the reporting
interval during which the applicant
received the report. Although the ICSRs
may be generated at any time from the
beginning of the reporting interval
through the date that the periodic report
is submitted to FDA, they are currently
retained by the applicant during this
time period and submitted to FDA in a
single batch, along with the other
(descriptive) portions of the periodic
report. The final rule includes language
in §§ 314.80(c)(2)(ii)(B) and
600.80(c)(2)(ii)(B) to give applicants the
option of submitting these ICSRs at any
time up until the due date of the
periodic report, rather than waiting to
submit them in a single batch with the
descriptive portion. All reports of
adverse experiences that are both
serious and expected or nonserious that
the applicant received during the
reporting interval must still be
submitted to the Agency by the time the
descriptive portion is due for that
period, but the final rule permits them
to be filed anytime up until the due date
of the periodic report, rather than in a
12 For products subject to § 310.305(c)(1)(i), a
copy of the labeling is submitted to FDA in
Structured Product Labeling (SPL) format as part of
the electronic drug listing process. See the guidance
for industry ‘‘Providing Regulatory Submissions in
Electronic Format—Drug Establishment Registration
and Drug Listing’’ (May 2009) available at http://
www.fda.gov/Drugs/
GuidanceComplianceRegulatoryInformation/
default.htm and FDA’s Web site on Structured
Product Labeling Resources at http://www.fda.gov/
ForIndustry/DataStandards/
StructuredProductLabeling/default.htm for
information on submitting labeling to FDA in
electronic format.

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single batch with the descriptive portion
of the periodic report. We have adopted
this change, as proposed, because we
understand that many applicants prefer
this added flexibility of submitting the
ICSRs on an ongoing basis.
To protect patient privacy, names of
individual patients are not to be
included in the patient identification
portion of the ICSRs for drug and
nonvaccine biological products. We
instead require that a unique code be
used for patient identification. As
proposed, the final rule removes from
the provisions entitled ‘‘patient
privacy’’ the language specifying an
eight character limit on the code.
Although we also proposed that the
name of the reporter not be included
when the reporter is also the patient, we
are not finalizing that proposal. FDA has
determined that it is important for us to
have the name of the reporter, even
when the patient is the reporter, because
it will allow us to contact the reporter,
if necessary, to obtain followup
information. Names of patients, health
care professionals, hospitals, and
geographical identifiers in adverse drug
experience reports are not releasable to
the public under FDA’s public
information regulations. These same
requirements addressing patient privacy
have been included in § 329.100(d),
applicable to reports required by section
760 of the FD&C Act.
As proposed, we have revised
§§ 310.305(c)(1)(i), 314.80(c)(1)(i), and
600.80(c)(1)(i) to state that 15-day Alert
reports must be submitted as soon as
possible, but no later than 15 calendar
days from initial receipt of the
information. FDA does not intend this
change to have any substantive effect. It
is being made solely to simplify the
regulatory language and improve its
readability.
III. Comments on the Proposed Rule
We received written comments from
three pharmaceutical companies, two
associations representing the drug and
biologic industries, a law firm
representing a manufacturer of
nonprescription drug products marketed
without approved applications, and an
individual (seven commenters total). A
summary of the comments contained in
the submissions received, and our
responses, follow.
A. Safety Reports Covered
(Comment 1) In the preamble to the
proposed rule, we requested public
comment on whether we should require
the use of an electronic format for
reports of serious adverse events
required by then newly enacted section
760 of the FD&C Act for nonprescription

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human drug products marketed without
an approved application. Two
commenters supported requiring the use
of an electronic format for the
submission of reports required by
section 760 of the FD&C Act. No
comments were opposed to such a
requirement.
(Response) As discussed in section
I.B, we agree that the requirement that
postmarketing safety reports be
submitted electronically should extend
to safety reports required to be
submitted by section 760 of the FD&C
Act. Electronic submission of safety
reports required to be submitted by
section 760 of the FD&C Act will allow
FDA to process, review, and archive
such reports more efficiently. Therefore,
as described previously in this
document, we have added 21 CFR part
329 to cover nonprescription human
drug products subject to section 760 of
the FD&C Act. Section 329.100 sets forth
information to be included in safety
reports that are required to be submitted
by section 760 of the FD&C Act and
requires that the reports be submitted in
an electronic format that FDA can
process, review, and archive. As with
safety reports required by §§ 310.305,
314.80, and 600.80, § 329.100 also
includes a provision allowing requests
for a temporary waiver from the
electronic submission requirement for
good cause. As noted in the preamble to
the proposed rule, nonprescription
(OTC) drug products that are marketed
under approved applications (NDAs or
ANDAs) are not covered under section
760 of the FD&C Act. Those products
are subject to the reporting requirements
of §§ 314.80 and 314.98.
(Comment 2) One comment suggested
that we develop an option to allow IND
safety reports to be submitted
electronically. The comment states that
this option would reduce the burden for
companies that must use two different
systems.
(Response) The comment is beyond
the scope of this rulemaking. This rule
addresses only the electronic
submission of postmarketing safety
reports. Premarketing safety reports are
transmitted directly to the review
division of FDA that has responsibility
for review of the IND and are not
uploaded into the FAERS database.
(Comment 3) Although this
rulemaking does not apply to biological
product deviation reports (BPDRs), in
the preamble to the proposed rule, we
requested comment on requiring the
electronic submission of BPDRs
(required by §§ 600.14 and 606.171) in
the future. One comment supported
requiring the electronic submission of
BPDRs and also suggested that the

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current Web-based form available for
the voluntary electronic submission of
BPDRs be modified to allow more than
2,000 characters in the event description
field to allow a complete description of
the event.
(Response) We appreciate the
comment. As addressed in section II.F,
section 745A(a) of the FD&C Act
provides that submissions under section
351(a) or (k) of the PHS Act, which
include BPDRs, shall be submitted in
such electronic format as specified by
FDA in guidance. The Agency intends
to address the implementation of
section 745A(a) of the FD&C Act
separately. In the meantime, parties
wishing to submit BPDRs electronically
are encouraged to do so through the
existing Web-based system. We note
that the current electronic system for
BPDR reporting has been expanded to
allow up to 3,999 characters for
narrative entries.
(Comment 4) Two comments
requested that we address the
submission of postmarketing safety
reports for combination drug and device
products in the final rule. One comment
noted specifically that reporting
requirements for drugs and biologics
differ from the reporting requirements of
devices and therefore requested that we
provide further information on how to
submit safety reports for drug and
device combination products.
(Response) These comments are
beyond the scope of this rulemaking.
This final rule requires electronic
submission of required postmarketing
safety reports for drugs and biological
products (including vaccines). We note
that on October 1, 2009, FDA published
a proposed rule entitled ‘‘Postmarketing
Safety Reporting for Combination
Products’’ (74 FR 50744). When
finalized, this new rule will clarify the
safety reporting requirements for
combination products such as drug and
device combinations.
(Comment 5) One comment noted that
the preamble to the proposed rule
indicates that developments are
underway for VAERS to receive ICSRs
for vaccines through FDA’s ESG. The
comment stated, however, that no
information is provided regarding how
and when these submissions may be
made to VAERS.
(Response) Modifications are still
underway to permit VAERS to receive
ICSRs through FDA’s ESG, which will
facilitate the submission of multiple
reports without the need for manual
data entry. FDA expects that VAERS
will be able to receive ICSRs through the
ESG by the time this final rule becomes
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B. FDA Web-Based Submission Portal
In the preamble to the proposed rule,
we explained that a ‘‘Web-based
electronic submission portal’’ was under
development to allow the secure
electronic submission of postmarketing
ICSRs directly into FDA’s AERS
database once information is entered
into a ‘‘Web-based electronic form.’’ We
noted that the Web-based submission
portal would allow electronic
submission of ICSRs consistent with
ICH standards and could be used as an
alternative method for reporting adverse
drug experiences to FDA electronically.
We noted that this alternative electronic
reporting method would be particularly
useful for entities that submit a small
number of safety reports because it
would create a simpler and more
efficient mechanism for reporting that
would not require an internal database
that is compatible with the ICH-based
direct submission system.
(Comment 6) One comment requested
clarification of the terms ‘‘Web-based
submission portal’’ and ‘‘Web-based
form,’’ noting that both terms are used
in the preamble to the proposed rule.
(Response) In the proposed rule, we
used the term ‘‘Web-based submission
portal’’ (now referred to as the Safety
Reporting Portal (SRP)) to describe a
Web-based system that any person
subject to FDA’s postmarketing safety
reporting requirements could use to
submit ICSRs to FDA electronically.
(See section II.A for further discussion
of the SRP.) We used the term ‘‘Webbased form’’ to describe the on-screen
interface into which users would enter
the ICSR data elements. Users
‘‘complete’’ the ICSR by filling in the
appropriate fields in the Web-based
form and then submit the ICSR to the
FAERS database through the Web-based
submission portal.13
(Comment 7) One comment suggested
that to eliminate any potential barriers
for small companies, no charge should
be associated with use of the Web-based
system.
(Response) There will be no charge for
electronic submission of safety reports
to the FAERS database through the SRP.
For submissions to VAERS using the
eSubmitter tool, however, a digital
security certificate will be necessary.
These certificates allow users to sign
and encrypt documents for
transmission, ensuring that any
electronic submissions are verifiable
and secure. Digital certificates are
available through many third-party
13 As described in section II.A, the eSubmitter
tool will be used instead of the SRP as an
alternative method for the electronic submission of
vaccine ICSRs into the VAERS database.

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vendors. A certificate generally lasts 1 to
3 years and typically costs $10 to $15.
A digital certificate is also necessary to
comply with FDA’s electronic
registration and listing requirements, so
most companies already have digital
certificates and will not need to obtain
one to use the eSubmitter tool. Further
information about digital security
certificates is available on FDA’s
Electronic Drug Registration and Listing
Instructions Web page at http://
www.fda.gov/ForIndustry/
ElectronicSubmissionsGateway/
ucm177328.htm.
(Comment 8) One comment asked
whether training or some type of
qualification will be required to submit
ICSRs through the Web-based system.
(Response) The SRP creates a simpler
mechanism for electronic submission of
safety reports. No special training or
qualification will be required. The
information for the ICSR is entered into
the Web-based form and then submitted
to FDA. However, prior to initial use of
the SRP, companies will need to contact
the FAERS Electronic Submissions
Coordinator at [email protected] to
establish an account to submit safety
reports through the SRP. Having an SRP
account allows for faster data entry
because certain fields will be prepopulated by information from the user
account. Having an account also allows
users to save a report and complete it
later, allows users to see a list of reports
that have been submitted, and allows for
followup submissions as more
information about the adverse drug
experience becomes available. Further
information on submitting ICSRs
through the SRP is included in the
postmarketing safety reports guidance.
For vaccine products, the eSubmitter
tool can be used, instead of the SRP, as
an alternative method for the electronic
submission of ICSRs to VAERS. The
eSubmitter tool provides a user-friendly
method for submission of these reports,
and no special training or qualification
will be necessary. Firms will, however,
need to contact FDA’s ESG Help Desk to
establish an ESG account and will need
to obtain a digital security certificate (as
described in the previous response), if
these two steps have not already been
completed to comply with FDA’s
electronic drug registration and
establishment listing requirements. The
first time firms submit a report to the
VAERS database, they will also need to
contact the CBER Electronic
Submissions Program at esgprep@
fda.hhs.gov.
(Comment 9) One comment suggested
that companies should be able to use
both the Web-based portal and the ESG

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and should not have to choose one
system.
(Response) FDA will not limit
companies to one method for creating
and transmitting ICSRs electronically to
FDA. As described in this document,
FDA offers both the direct database-todatabase method and the SRP for
submission of ICSRs into the FAERS
database, and the direct database-todatabase method and eSubmitter tool for
submission of ICSRs into the VAERS
database. FDA recommends that
companies select the submission
method that best suits their needs to
submit a given report.
(Comment 10) One comment
recommended that the Web-based portal
provide a receipt or acknowledgement
indicating whether the submission was
successfully received or if the delivery
failed. The comment noted that this will
allow companies to take appropriate
followup action.
(Response) When using the SRP to
submit postmarketing safety reports,
users will receive electronic
acknowledgement indicating whether or
not their submission was accepted into
the FAERS database.14 If notified that
the submission was not accepted, users
should resubmit the safety report to
ensure that FDA receives the report.
Further information about FAERS
submission acknowledgement is
provided in the postmarketing safety
reports guidance.
(Comment 11) One comment stated
that the Web-based portal should accept
ICH-compliant XML files that may be
generated and submitted to the Webbased portal and/or the ESG.
(Response) The SRP allows for the
submission of ICH-compliant ICSRs.
Once the data elements for the ICSR are
entered into the Web-based form and
submitted to FDA, the SRP generates an
XML file which is then uploaded into
the FAERS database (along with any
ICSR attachments that may be
included). The ESG will continue to
accept ICH-compliant XML files.
Similarly, for submission of vaccine
reports, both the eSubmitter tool and the
direct database-to-database transmission
method generate ICH-compliant XML
files that are submitted to FDA through
the ESG.
(Comment 12) One comment asked
whether followup links to the original
report will be available when submitting
14 Similarly, users submitting ICSRs for vaccines
using the eSubmitter tool will receive an electronic
confirmation. Further information about VAERS
submission acknowledgement is provided in
guidance available at http://www.fda.gov/
BiologicsBloodVaccines/
GuidanceComplianceRegulatoryInformation/
Guidances/default.htm.

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the report through the Web-based
system.
(Response) When the initial ICSR is
submitted through the SRP, users will
be able to return to the initial ICSR and
submit followup reports as more
information about the reported adverse
experience becomes available. Users
may log in to their SRP accounts, locate
the ICSR record, and modify or add to
the initial ICSR. Users may submit as
many followup reports as necessary.
More detailed information on how to
modify or add to an initial ICSR is
available on the SRP Web site.
Similarly, the eSubmitter tool, which
can be used for the submission of
vaccine reports through the ESG into
VAERS, allows for the creation and
submission of both initial reports and
followup reports as more information
regarding the adverse event becomes
available. Use of the same unique case
identification number for the initial
ICSR and any followup reports will be
essential to ensure that the reports are
linked in the database.
C. Waivers
In the proposed rule, we proposed
allowing for the submission of requests
for temporary waivers from the
electronic format requirement and
stated that waivers would be granted on
a time-limited basis for ‘‘good cause’’
shown. While noting that the details for
submitting waiver requests would be
announced in guidance, we requested
comment on what circumstances would
constitute ‘‘good cause’’ justifying a
waiver from the electronic submission
requirement.
(Comment 13) One comment
requested a categorical exemption from
the electronic reporting requirement for
small business entities, which the
comment defined as any business with
fewer than 100 employees and less than
$10,000,000 in annual sales. The
comment noted difficulties that these
entities had with FDA’s system for
electronic establishment registration
and drug listing and expressed concern
that these businesses would have
similar difficulties with the electronic
submission of safety reports.
(Response) FDA has concluded that it
will not grant a categorical exemption
from the electronic safety reporting
requirement for small business entities.
We anticipate that receiving all required
postmarketing safety reports
electronically will allow us to more
rapidly review the reports, identify
emerging safety problems, and
disseminate safety information. We
believe that any categorical exemption
from the electronic submission
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these important benefits. As we stated
in the preamble to the proposed rule, we
believe a waiver will only be needed in
rare circumstances.
We appreciate the commenter’s
concern about potential difficulties with
the electronic submission of safety
reports through FDA’s system. We
believe that the SRP provides a simple,
user-friendly system for submission of
ICSRs into the FAERS database. The
SRP is similar to systems used for
online purchases and other Web-based
transactions. FDA has been receiving
safety reports through the SRP for the
Center for Food Safety and Applied
Nutrition, the Center for Veterinary
Medicine, and the Center for Tobacco
Products since 2010. In addition, FDA
intends to provide technical assistance
to help resolve any problems.
We believe that the eSubmitter tool,
which may be used for the electronic
submission of ICSRs for vaccines,
provides a simple and straightforward
method for submitting these reports.
Furthermore, submission testing is
available so that users will have the
opportunity to try out the system before
the rule becomes effective.
FDA has been working with both large
and small companies and has been
successfully receiving voluntary
electronic submissions of ICSRs through
the ESG since 2001. We believe our
experience to date with the electronic
submission of safety reports will help us
to minimize problems with electronic
submission that regulated entities may
have, especially entities new to the
system. We also believe that the
effective date adopted in this rule will
permit the Agency and industry
sufficient time to ensure that the
systems are fully functional and that
any technical problems are worked out
by the time the requirements of this rule
become effective.
(Comment 14) One comment
recommended allowing a good cause
waiver in cases of natural or manmade
disaster. The same comment also
suggested allowing a time-limited
waiver for companies bringing their first
commercially available product to
market.
(Response) We agree that natural or
manmade disasters may present
situations where a waiver from the
electronic submission requirement
would be appropriate. For example, in
these situations, electricity may be
unavailable for an extended period of
time, and electronic submission of
safety reports would not be feasible. We
do not agree that a time-limited waiver
for companies bringing their first
commercially available product to
market will be necessary or appropriate.

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We believe the electronic submission
systems are easy to use and will be fully
functional by the time this rule becomes
effective. Furthermore, as explained in
the previous response, FDA is prepared
to assist companies to ensure that any
problems with electronic submission are
resolved.
(Comment 15) One comment
suggested that temporary waivers
should be granted for unplanned,
extended-duration ESG downtime;
business continuity or disaster recovery
situations where a company’s
pharmacovigilance system access may
be down for a period of time and the
volume of reports is too high to use the
Web-based system requiring manual
entry; or where human resources are
greatly diminished, for example, as a
result of pandemic or terror attack.
(Response) We agree that disaster
recovery situations, pandemics, or terror
attacks may present circumstances in
which a waiver from the electronic
submission requirement would be
appropriate. We believe it is unlikely
that the ESG would experience
unplanned downtime of extended
duration such that a waiver from the
electronic submission requirement
would be necessary. However, if such a
situation were to occur, a waiver might
be appropriate.
(Comment 16) One comment
suggested that the components of a
request for a waiver could include the
nature of the inability to comply, the
anticipated time to recover, and a crisis
manager contact for the company who
would be accountable to FDA for
followup and resolution. The comment
also requested that FDA include in its
guidance the type of documentation that
must be kept and the documentation
FDA will provide as a record of the
situation for future inspections or
audits.
(Response) We agree with the
suggestion that a waiver request should
include the nature of the inability to
comply, the anticipated time to recover,
and a company contact. Though
additional relevant information could
also be included in a waiver request, the
components suggested for inclusion
would allow us to assess the
reasonableness of a waiver request and
would ensure that we are able to limit
the waiver to the time necessary.
Accordingly, in the postmarketing safety
reports guidance issued today in
conjunction with this rule, we have
stated that a waiver request should
include the reason for the request and
a proposed end date for the waiver. To
follow up with the company, FDA
intends to contact the individual who
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addressed in the postmarketing safety
reports guidance, we believe that in the
normal course of business, it would be
usual and customary for companies to
maintain adequate records of the
situation leading to a waiver request and
documentation related to the waiver
request.
(Comment 17) Two comments stated
that FDA should provide a telephone
contact for requesting a temporary
waiver, because during a crisis
situation, it may be difficult to put
together a comprehensive request. One
of the comments also suggested fax as
an alternative for submitting a waiver
request.
(Response) Consistent with the
procedures for requesting waivers of
other FDA requirements, requests for
waivers of the electronic safety
reporting requirement should be
submitted to FDA in writing by mail as
described in the postmarketing safety
reports guidance issued today. The
Agency is exploring other methods that
may facilitate submission of waiver
requests, and we will update the
postmarketing safety reports guidance,
as appropriate, to reflect any changes in
waiver request procedures.
D. ICSR Submissions
1. Content
(Comment 18) One comment
requested clarification on the types of
attachments that are required as part of
an ICSR submission.
(Response) The final rule includes a
definition of ‘‘ICSR attachments’’ for
clarification, but the rule does not
change the types of attachments that
may be necessary as part of an ICSR
submission. As noted previously in this
document, in the proposed rule, and in
final §§ 310.305(b), 314.80(a), and
600.80(a), examples of ICSR attachments
that may be necessary include
published articles that must accompany
ICSRs based on scientific literature
(§§ 314.80(d) and 600.80(d)) and other
supporting information, such as hospital
discharge summaries and autopsy
reports.
(Comment 19) One comment asked
whether the ICSR attachments will be
made public and whether companies
will be required to redact the patient
information from the attachments. The
comment noted that requiring the
company to redact patient information,
such as address and birth date would
create a significant additional burden.
(Response) FDA will not publicly
release names or any other identifying
information about patients contained in
ICSR attachments. FDA redacts patient
names and other identifying information

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before publicly releasing information
contained in postmarketing safety
reports. Persons submitting reports
should not redact information contained
in ICSRs or ICSR attachments before
submitting them to FDA. We understand
that companies may receive documents
from reporters that are already redacted.
Those documents should be submitted
to FDA as received from the reporter
and should not be redacted any further.
(Comment 20) Proposed
§ 310.305(c)(1)(i) stated that each 15-day
‘‘Alert report’’ must be accompanied by
the ‘‘current content of the labeling’’ in
electronic format unless it is already on
file at FDA. One comment requested
clarification of what ‘‘content of the
labeling’’ means, suggesting that it could
refer to the entire label or only certain
sections or certain types of information
in the labeling.
(Response) As set forth in
§ 314.50(l)(1)(i), the ‘‘content of
labeling’’ refers to the contents of the
package insert or professional labeling.
It is the information required by
§§ 201.56, 201.57, and 201.80, in the
format specified. For products subject to
§ 310.305(c)(1)(i), the content of labeling
is submitted to FDA in Structured
Product Labeling (SPL) format as part of
the electronic drug listing process.
Further information about electronic
submission of content of labeling and
SPL format is provided in the guidance
for industry entitled ’’Providing
Regulatory Submissions in Electronic
Format—Drug Establishment
Registration and Drug Listing’’ and the
draft guidance ‘‘SPL Standard for
Content of Labeling—Technical Qs &
As’’ (available on FDA’s Web site at
http://www.fda.gov/Drugs/Guidance
ComplianceRegulatoryInformation/
Guidances/default.htm) which, when
finalized, will represent the Agency’s
current thinking.
(Comment 21) Proposed
§§ 310.305(d)(1)(i), 314.80(f)(1)(i), and
600.80(f)(1)(i) listed ‘‘patient
identification code’’ as an element to be
included in each ICSR. Proposed
§§ 310.305(f), 314.80(i), and 600.80(i),
entitled ‘‘Patient privacy,’’ stated: ‘‘An
applicant should not include in reports
under this section the names and
addresses of individual patients;
instead, the applicant should assign a
unique code to each report.’’ 15 One
comment requested that we clarify
15 Both proposed and final § 310.305(f) use the
phrase ‘‘manufacturers, packers, and distributors’’
in place of the term ‘‘applicant,’’ because § 310.305
applies to prescription drugs for human use without
approved NDAs. Proposed § 600.80(i) and final
§ 600.80(j) addressing patient privacy state: ‘‘For
nonvaccine biological products, an applicant
should not include in reports . . .’’

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whether the term ‘‘patient identification
code’’ (used in proposed
§§ 310.305(d)(1)(i), 314.80(f)(1)(i), and
600.80(f)(1)(i)) and the term ‘‘unique
code for each report’’ as used in the
provisions addressing patient privacy
(proposed §§ 310.305(f), 314.80(i), and
600.80(i)) are intended to be different
codes.
(Response) The ‘‘patient identification
code’’ listed as a reporting element to be
included in ICSRs (in
§§ 310.305(d)(1)(i), 314.80(f)(1)(i), and
600.80(f)(1)(i)) and the ‘‘unique code for
each report’’ discussed in the provision
on patient privacy (in proposed
§§ 310.305(f), 314.80(i), and 600.80(i))
are referring to the same code. Entities
that submit ICSRs for drug and
nonvaccine biological products should
not include names and contact
information for patients in the ICSRs.
Rather, a unique code should be used
instead of the patient’s name and
contact information in the patient
information section of the ICSR.16 The
intent of using such a code is to protect
the privacy of patients who have
experienced adverse events that are
being reported to FDA, while allowing
the submitter to know the patient’s
identity and contact information for
reference purposes. We agree that as
proposed, the requirement is unclear.
Therefore, we are revising the sections
entitled ‘‘Patient privacy’’ (§§ 310.305(f),
314.80(i), and 600.80(j)) to state: ‘‘. . .
should not include in reports under this
section the names and addresses of
individual patients; instead, the
applicant should assign a unique code
for identification of the patient.’’ We
believe this change to the final rule will
make clearer that the ‘‘patient
identification code’’ included in the list
of ICSR reporting elements (for drug and
nonvaccine biological products) and the
code described in the sections on
patient privacy are referring to the same
code, which is intended to protect the
identity of patients. Section 329.100(d)
also uses the same language.
We note, however, that §§ 310.305(d),
314.80(f), 329.100(b), and 600.80(f) and
(g) that set forth the ICSR reporting
elements, as finalized, also require a
‘‘unique case identification number’’ for
each ICSR. This unique case
identification number is distinct from
the patient identification code. The
16 The patient’s name and contact information
should only be included in an ICSR when the
patient is the reporter. Under those circumstances,
the patient-reporter’s name and contact information
should be included in the initial reporter section of
the ICSR but not in the patient information section
of the ICSR. In the patient information section of
the ICSR, a unique code should be used instead of
the patient-reporter’s name and contact
information.

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unique case identification number,
which must be the same in the initial
ICSR and any subsequent followup
ICSR(s), was referred to as the
Manufacturer Report Number on Form
FDA 3500A and VAERS–1, and it allows
FDA to track an individual case over its
life cycle.
(Comment 22) One comment noted
that, in the past, the ESG has accepted
ICSRs for which the applicant does not
have all categories of information. The
comment sought to confirm that ICSRs
would not be rejected by the ESG if
there are any gaps in categories of
information.
(Response) The ESG will continue to
operate as it has and will accept ICSRs
for which the applicant may not have all
categories of information. Even though
the ESG and SRP accept ICSRs for
which there are gaps in certain
categories of information, it is important
for applicants to include all information
about the reported event that is known
to the applicant.
2. Timing of Report Submissions
(Comment 23) One comment
requested confirmation that the ESG
will be available 24 hours a day, 7 days
a week, and that ICSRs submitted
outside of business hours will be
considered timely (if submitted within
the required time frame). The comment
also requested that we provide guidance
on procedures for planned and
unplanned downtime of the ESG and
how the downtime affects submission
deadlines.
(Response) FDA intends to make the
ESG available 24 hours a day, 7 days a
week to receive electronic submissions.
Additional information explaining how
submission dates are calculated if the
ESG and/or the FAERS database is
temporarily unavailable is provided in
the postmarketing safety reports
guidance issued today. We note that
FDA also intends to make the SRP
available 24 hours a day, 7 days a week
to receive submissions.
E. International Harmonization
(Comment 24) One comment
suggested that we reference the ICH
Harmonized Tripartite Guideline
instead of listing, in the rule, categories
of information to be included in ICSRs.
(Response) We set forth the categories
of information to be included in ICSRs
because we believe that this is a clear
and concise way to communicate the
information to be included when
reporting adverse events to FDA and to
move away from reliance on paper
forms. We considered the ICH
guidelines when creating these
categories and believe that the

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33083

categories included are either consistent
with international standards or can be
accommodated as local requirements
using international transmission
standards.
(Comment 25) One comment asked
what version of the ICH E2B standard
(i.e., the ICH guideline on data elements
for transmission of ICSRs) will be
accepted.
(Response) It has been FDA’s practice
to accept both the latest version of the
ICH E2B standard in addition to the
previous version. This practice has
allowed applicants reasonable time to
transition to the updated ICH E2B
standard. Any changes to submission
standards will be provided in guidance,
as appropriate.17
(Comment 26) One comment noted
that the EU Drug Regulatory Authorities
Pharmacovigilance system
(EudraVigilance) has different validators
than FDA’s reporting system. As a
result, some ICSRs would be accepted
by FDA that would not be accepted by
the European Medicines Agency. The
comment requested that if new
validators are placed on the ESG they be
aligned with the EudraVigilance
validators so that both systems accept
the same reports.
(Response) It would not be
functionally workable or practical to
commit, in advance, to incorporating
changes made by other regulatory
bodies to ensure complete consistency
among the reporting systems. FDA will
continue to work with international
standards organizations when
developing new technical specifications
so that differences in those
specifications are kept to a minimum.
F. Technical Specifications
The proposed rule indicated that
standards and technical specifications
will be addressed in guidance
documents rather than set forth in the
final rule.
(Comment 27) One comment noted
that changes to technical standards or
specifications can increase costs to
companies. The comment expressed
concern that by adopting changes in
guidance documents, the changes can
occur more quickly and more
frequently, resulting in a greater burden
to companies. The comment stated that
it is important that required technical
standards or specifications not be
changed frequently and that when they
17 Further information about E2B message
standards accepted by FAERS is available on the
FAERS Electronic Submissions Web page at http://
www.fda.gov/Drugs/
GuidanceComplianceRegulatoryInformation/
Surveillance/AdverseDrugEffects/ucm115894.htm.

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are changed, adequate time be allowed
for public comment.
(Response) We understand the
concern that frequent changes in
technical standards and specifications
may increase the cost of compliance to
companies. FDA does not anticipate
frequent changes. However, it is
important for FDA to retain flexibility so
that we can be responsive to the rapidly
changing technological environment.
We believe that the use of guidance
documents to communicate technical
specifications will benefit both
companies and the Agency. If FDA were
to set forth technical specifications in
regulations, the result could be that
companies would be bound to standards
and specifications that are outdated.
Maintaining older systems can also be a
resource burden to companies.
IV. Legal Authority
FDA’s legal authority to amend its
regulations governing the submission of
postmarketing safety reports for human
drugs and biological products derives
from sections 201, 301, 501, 502, 503,
505, 505A, 506, 506A, 506B, 506C, 510,
701, 704, 705, 745A, 760, and 801 of the
FD&C Act (21 U.S.C. 321, 331, 351, 352,
353, 355, 355a, 356, 356a, 356b, 356c,
360, 371, 374, 375, 379k–1, 379aa, and
381); and the PHS Act (42 U.S.C. 241,
262, and 264).

emcdonald on DSK67QTVN1PROD with RULES

V. Environmental Impact
The Agency has determined under 21
CFR 25.30(h) 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.
VI. Analysis of Impacts
FDA has 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). FDA
believes that this final rule is not a
significant regulatory action as defined
by Executive Order 12866.
The Regulatory Flexibility Act
requires Agencies to analyze regulatory
options that would minimize any
significant impact of a rule on small

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entities. Because the average small
entity submits few safety reports and the
Agency’s Web-based system for
submitting reports electronically will
require little additional cost per report,
the Agency believes that this final rule
will not 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 $141
million, using the most current (2013)
Implicit Price Deflator for the Gross
Domestic Product. FDA does not expect
this final rule to result in any 1-year
expenditure that would meet or exceed
this amount.
The final rule requires the submission
of all postmarketing safety reports,
including periodic reports, to FDA in an
electronic format. In addition,
manufacturers of products distributed
under a biologic license are required to
submit lot distribution reports
electronically. The public health
benefits of this final rule, quicker access
to postmarketing safety information,
were not quantified. The final rule will
generate an annual savings for the
Agency of about $0.8 million, which is
primarily a savings in the cost of
processing paper. Total one-time costs
to industry will be between $5.9 million
to $7.5 million; the costs are for
changing standard operating procedures
(SOPs) and for training personnel.
Annualized over 10 years at a 7 percent
discount rate, the costs are from $0.8
million to $1.1 million. At a 3 percent
discount rate over 10 years, the
annualized costs are $0.7 million to $0.9
million.
The full assessment of economic
impacts is available in Docket No. FDA–
2008–N–0334 and at http://
www.fda.gov/AboutFDA/
ReportsManualsForms/Reports/
EconomicAnalyses/default.htm (Ref. 1).
VII. Paperwork Reduction Act of 1995
This final rule contains information
collection provisions that are subject to
review by the Office of Management and
Budget (OMB) under the Paperwork
Reduction Act of 1995 (44 U.S.C. 3501–
3520). The title, description, and
respondent description of the
information collection provisions are

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shown below with an estimate of the
annual reporting burden. Included in
the estimate is the time for reviewing
instructions, searching existing data
sources, gathering and maintaining the
data needed, and completing and
reviewing each collection of
information.
Title: Postmarketing Safety Reports for
Human Drug and Biological Products:
Electronic Submission Requirements.
Description: The final rule amends
FDA’s postmarketing safety reporting
regulations for human drug and
biological products under parts 310,
314, and 600, and adds part 329, to
require that persons subject to
mandatory reporting requirements
submit safety reports in an electronic
format that FDA can process, review,
and archive. Under §§ 310.305, 314.80,
314.98, and 600.80, manufacturers,
packers, and distributors, and
applicants with approved NDAs,
ANDAs, and BLAs and those that
market prescription drugs for human
use without an approved application
must submit postmarketing safety
reports to the Agency. Section 760 of the
FD&C Act requires manufacturers,
packers, or distributors whose name
appears on the label of nonprescription
human drug products marketed without
an approved application to report
serious serious adverse events
associated with their products. Under
§ 600.81, applicants with approved
BLAs must submit biological lot
distribution reports to the Agency. In
this rule, FDA is requiring that these
postmarketing reports be submitted to
the Agency in an electronic format that
FDA can process, review, and archive.
The final rule also states that FDA will
issue guidance on how to provide the
electronic submissions (e.g., method of
transmission, media, file formats,
preparation and organization of files).
This rule does not change the content of
these postmarketing reports. It only
requires that they be submitted in an
electronic format. Under
§§ 310.305(e)(2), 314.80(g)(2),
329.100(c)(2), 600.80(h)(2), and
600.81(b)(2), we are also permitting
those subject to mandatory reporting
requirements to request a waiver from
the electronic format requirement.
We currently have OMB approval for
submission of postmarketing safety
reports to FDA under parts 310, 314,
and 600. The information collection for
part 310 and part 314 is approved under
OMB control numbers 0910–0291 (Form
FDA 3500A) and 0910–0230. The
information collection for part 600 is
approved under OMB control numbers
0910–0291 (Form 3500A) and 0910–
0308. The burdens currently estimated

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Federal Register / Vol. 79, No. 111 / Tuesday, June 10, 2014 / Rules and Regulations
under parts 310, 314, and 600, for
submission of postmarketing safety
reports to FDA for human drugs and
biological products, do not change as a
result of this final rule. This is because:
(1) Current burden estimates associated
with these regulatory requirements have
taken into account voluntary
submission of these reports in an
electronic format and those applicants,
manufacturers, packers, and distributors
that already submit these reports in an
electronic format would have no new
reporting burdens and (2) new burdens
for establishing the means for
submitting postmarketing safety reports
in electronic form to comply with this
final rule, including obtaining an
electronic certificate, revising SOPs, and
becoming familiar with the system,

would be negated by the savings in
burden from not having to print out the
report and mail it to FDA. These
assumptions also apply to applicants
submitting biological lot distribution
reports under § 600.81.
OMB has approved the burden
associated with submissions required by
section 760 of the FD&C Act under OMB
control number 0910–0636.
In table 1 of this document, we have
estimated the burdens associated with
the submission of waivers, under
§§ 310.305(e)(2), 314.80(g)(2),
329.100(c)(2), 600.80(h)(2), and
600.81(b)(2). We expect few waiver
requests (see section II.C). We estimate
that approximately one manufacturer
will request a waiver annually under
§§ 310.305(e)(2), 329.100(c)(2), and

33085

600.81(b)(2), and five manufacturers
will request a waiver annually under
§§ 314.80(g)(2) and 600.80(h)(2). We
estimate that each waiver request will
take approximately 1 hour to prepare
and submit to us.
Description of Respondents:
Manufacturers, packers, and distributors
of marketed prescription drug products
that are not the subject of approved
applications, applicants with approved
NDAs, ANDAs, and BLAs, and those
that market nonprescription drugs for
human use without an approved
application.
Burden Estimate: Table 1 of this
document provides an estimate of the
new annual reporting burden for
submitting requests under the waiver
requirement in this final rule.

TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN
Number of
responses per
respondent

Number of
respondents

21 CFR Sections

Total annual
responses

Hours per
response

Total hours

Waivers—Electronic Format for Submissions
310.305(e)(2) .......................................................................
314.80(g)(2) .........................................................................
329.100(c)(2) ........................................................................
600.80(h)(2) .........................................................................
600.81(b)(2) .........................................................................

1
5
1
5
1

1
1
1
1
1

1
5
1
5
1

1
1
1
1
1

1
5
1
5
1

Total Reporting Burden ................................................

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

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

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

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

13

A. Reporting Costs
Based on the average hourly wage
($79) as calculated in section VI
(Analysis of Impacts) of the final rule,
the cost to respondents would be $1,027
(13 × $79).

Tables 2 through 5 of this document
provide an estimate of the annual
reporting burden currently covered
under existing OMB control numbers
0910–0291, 0910–0230, 0910–0308, and
0910–0636. As explained previously, we
believe that any burden increases

associated with electronic reporting are
offset by burden decreases associated
with not printing out reports and
mailing them to FDA. Therefore, we
believe that the burden estimates for
these information collections will not
change.

emcdonald on DSK67QTVN1PROD with RULES

TABLE 2—OMB CONTROL NUMBER 0910–0291 ‘‘MEDWATCH: THE FDA MEDICAL PRODUCTS REPORTING PROGRAM’’
21 CFR Sections

Number of
respondents

Number of
responses per
respondent

Total annual
responses

Hours per
response

Total hours

Form FDA 3500A (MedWatch: The FDA Safety Information and Adverse Event Reporting Program—Mandatory) (§§ 310.305—Records and reports concerning adverse drug experiences on marketed prescription drugs
for human use without approved new drug applications,
314.80—Postmarketing reporting of adverse drug experiences, 314.98—Postmarketing reports, and 600.80—
Postmarketing reporting of adverse experiences) ...........

600

683

409,608

1.1

450,568

Based on the average hourly wage
($79) as calculated in section VI
(Analysis of Impacts) of the proposed

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rule, the cost to respondents would be
$39,895,948 (505,012 × $79).

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Federal Register / Vol. 79, No. 111 / Tuesday, June 10, 2014 / Rules and Regulations
TABLE 3—OMB CONTROL NUMBER 0910–0230 ‘‘ADVERSE DRUG EXPERIENCE REPORTING’’
Number of
responses per
respondent

Number of
respondents

21 CFR Sections

Total annual
responses

Hours per
response

Total hours

310.305(c)(5)—Reporting requirements ............................
314.80(c)(2)—Periodic adverse drug experience reports

1
642

1
17.88

1
11,478

1
60

1
688,680

Total ............................................................................

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

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

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

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

688,681

Based on the average hourly wage
($79) as calculated in section VI of the

proposed rule, the cost to respondents
would be $54,405,799 (688,681 × $79).

TABLE 4—OMB CONTROL NUMBER 0910–0308 ‘‘ADVERSE EXPERIENCE REPORTING FOR LICENSED BIOLOGICAL
PRODUCT; AND GENERAL RECORDS’’
Number of
responses per
respondent

Number of
respondents

21 CFR Sections

Total annual
responses

Hours per
response

Total hours

600.80(c)(1)—Postmarketing 15-day ‘‘Alert reports’’ and
600.80(e)—Postmarketing studies .................................
600.80(c)(2)—Periodic adverse experience reports ..........
600.81—Distribution Reports .............................................
600.90—Waivers ................................................................

108
108
108
21

801.69
530.55
3.23
1

86,583
57,300
349
21

1
28
1
1

86,583
1,604,400
349
21

Total ............................................................................

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

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

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

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

1,691,353

Based on the average hourly wage
($79) as calculated in section VI of the
proposed rule, the cost to respondents

would be $133,616,887 (1,691,353 ×
$79).

TABLE 5—OMB CONTROL NUMBER 0910–0636 ‘‘GUIDE FOR INDUSTRY ON LABELING OF NONPRESCRIPTION HUMAN
DRUG PRODUCTS MARKETED WITHOUT AN APPROVED APPLICATION AS REQUIRED BY THE DIETARY SUPPLEMENT AND
NONPRESCRIPTION DRUG CONSUMER PROTECTION ACT’’

Reports of serious adverse drug events under section 760
of the FD&C Act (21 U.S.C. 379aa((b) and (c)) ..............

emcdonald on DSK67QTVN1PROD with RULES

Based on the average hourly wage
($79) as calculated in section VI of the
proposed rule, the cost to respondents
would be $1,975,000 (25,000 × $79).
B. Capital Costs
As explained in section VI (Analysis
of Impacts), total one-time costs to
industry would be between $5.9 million
to $7.5 million; the costs are for
changing standard SOPs and training
personnel. Annualized over 10 years at
a 7 percent discount rate, the costs will
be from 0.8 million to $1.1 million. At
a 3 percent discount rate over 10 years,
the annualized costs are $0.7 million to
$0.9 million.
The information collection provisions
of this final rule have been submitted to
OMB for review. Prior to the effective
date of this final rule, FDA will publish
a notice in the Federal Register
announcing OMB’s decision to approve,
modify, or disapprove the information

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Number of
respondents

Number of
responses per
respondent

Total annual
responses

Hours per
response

Total hours

50

250

12,500

2

25,000

collection provisions in this final rule.
An Agency may not conduct or sponsor,
and a person is not required to respond
to, a collection of information unless it
displays a currently valid OMB control
number.
VIII. Federalism
FDA has analyzed this final rule in
accordance with the principles set forth
in Executive Order 13132. FDA has
determined that the rule does not
contain policies that have substantial
direct effects on the States, on the
relationship between the National
Government and the States, or on the
distribution of power and
responsibilities among the various
levels of government. Accordingly, the
Agency has concluded that the rule does
not contain policies that have
federalism implications as defined in
the Executive order and, consequently,

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a federalism summary impact statement
is not required.
IX. Reference
The following reference has been
placed on display in the Division of
Dockets Management (HFA–305), Food
and Drug Administration, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852
and may be seen by interested persons
between 9 a.m. and 4 p.m., Monday
through Friday, and is available
electronically at http://
www.regulations.gov.
1. Regulatory Impact Analysis, Regulatory
Flexibility Analysis, and Unfunded Mandates
Reform Act Analysis for Postmarketing Safety
Reports for Human Drug and Biological
Products; Electronic Submission
Requirements; Final Rule, available at http://
www.fda.gov/AboutFDA/
ReportsManualsForms/Reports/
EconomicAnalyses/default.htm.

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Federal Register / Vol. 79, No. 111 / Tuesday, June 10, 2014 / Rules and Regulations
List of Subjects
21 CFR Part 310
Administrative practice and
procedure, Drugs, Labeling, Medical
devices, Reporting and recordkeeping
requirements.
21 CFR Part 314
Administrative practice and
procedure, Confidential business
information, Drugs, Reporting and
recordkeeping requirements.
21 CFR Part 329
Administrative practice and
procedure, Over-the-counter drugs,
Reporting and recordkeeping
requirements.
21 CFR Part 600
Biologics, Reporting and
recordkeeping requirements.
Therefore, under the Federal Food,
Drug, and Cosmetic Act, the Public
Health Service Act, and under authority
delegated to the Commissioner of Food
and Drugs, 21 CFR parts 310, 314, and
600 are amended and a new part 329 is
added as follows:
PART 310—NEW DRUGS
1. The authority citation for 21 CFR
part 310 is revised to read as follows:

■

Authority: 21 U.S.C. 321, 331, 351, 352,
353, 355, 360b–360f, 360j, 361(a), 371, 374,
375, 379e, 379k–1; 42 U.S.C. 216, 241, 242(a),
262, 263b–263n.

2. Section 310.305 is amended by:
a. Removing the word ‘‘shall’’ each
time it appears and by adding in its
place the word ‘‘must’’;
■ b. Adding alphabetically in paragraph
(b) the definitions of ‘‘Individual case
safety report (ICSR)’’ and ‘‘ICSR
attachments’’;
■ c. Revising paragraph (c) introductory
text, paragraph (c)(1)(i), and the second
sentence of paragraph (c)(3)
introductory text; removing the last
sentence in paragraph (c)(2), and
removing and reserving paragraph (c)(4);
■ d. Revising paragraph (d); and
■ e. Redesignating paragraphs (e)
through (g) as paragraphs (f) through (h),
adding a new paragraph (e), revising
newly redesignated paragraph (f), and in
newly redesignated paragraph (g)(1)
removing ‘‘(c)(4)’’ and adding in its
place ‘‘(c)(3)’’ to read as follows:
emcdonald on DSK67QTVN1PROD with RULES

■
■

§ 310.305 Records and reports concerning
adverse drug experiences on marketed
prescription drugs for human use without
approved new drug applications.

*

*
*
*
*
(b) * * *
Individual case safety report (ICSR). A
description of an adverse drug

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experience related to an individual
patient or subject.
ICSR attachments. Documents related
to the adverse drug experience
described in an ICSR, such as medical
records, hospital discharge summaries,
or other documentation.
*
*
*
*
*
(c) Reporting requirements. Each
person identified in paragraph (c)(1)(i)
of this section must submit to FDA
adverse drug experience information as
described in this section. Except as
provided in paragraph (e)(2) of this
section, 15-day ‘‘Alert reports’’ and
followup reports, including ICSRs and
any ICSR attachments, must be
submitted to the Agency in electronic
format as described in paragraph (e)(1)
of this section.
(1) Postmarketing 15-day ‘‘Alert
reports’’. (i) Any person whose name
appears on the label of a marketed
prescription drug product as its
manufacturer, packer, or distributor
must report to FDA each adverse drug
experience received or otherwise
obtained that is both serious and
unexpected as soon as possible, but no
later than 15 calendar days from initial
receipt of the information by the person
whose name appears on the label. Each
report must be accompanied by the
current content of labeling in electronic
format as an ICSR attachment unless it
is already on file at FDA.
*
*
*
*
*
(3) Submission of reports. * * * If a
packer or distributor elects to submit
these adverse drug experience reports to
the manufacturer rather than to FDA, it
must submit, by any appropriate means,
each report to the manufacturer within
5 calendar days of its receipt by the
packer or distributor, and the
manufacturer must then comply with
the requirements of this section even if
its name does not appear on the label of
the drug product. * * *
*
*
*
*
*
(4) [Reserved]
*
*
*
*
*
(d) Information reported on ICSRs.
ICSRs include the following
information:
(1) Patient information.
(i) Patient identification code;
(ii) Patient age at the time of adverse
drug experience, or date of birth;
(iii) Patient gender; and
(iv) Patient weight.
(2) Adverse drug experience.
(i) Outcome attributed to adverse drug
experience;
(ii) Date of adverse drug experience;
(iii) Date of ICSR submission;
(iv) Description of adverse drug
experience (including a concise medical
narrative);

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33087

(v) Adverse drug experience term(s);
(vi) Description of relevant tests,
including dates and laboratory data; and
(vii) Other relevant patient history,
including preexisting medical
conditions.
(3) Suspect medical product(s).
(i) Name;
(ii) Dose, frequency, and route of
administration used;
(iii) Therapy dates;
(iv) Diagnosis for use (indication);
(v) Whether the product is a
combination product as defined in
§ 3.2(e) of this chapter;
(vi) Whether the product is a
prescription or nonprescription product;
(vii) Whether adverse drug experience
abated after drug use stopped or dose
reduced;
(viii) Whether adverse drug
experience reappeared after
reintroduction of drug;
(ix) Lot number;
(x) Expiration date;
(xi) National Drug Code (NDC)
number; and
(xii) Concomitant medical products
and therapy dates.
(4) Initial reporter information.
(i) Name, address, and telephone
number;
(ii) Whether the initial reporter is a
health care professional; and
(iii) Occupation, if a health care
professional.
(5) Manufacturer, packer, or
distributor information.
(i) Manufacturer, packer, or
distributor name and contact office
address;
(ii) Telephone number;
(iii) Report source, such as
spontaneous, literature, or study;
(iv) Date the report was received by
manufacturer, packer, or distributor;
(v) Whether the ICSR is a 15-day
‘‘Alert report’’;
(vi) Whether the ICSR is an initial
report or followup report; and
(vii) Unique case identification
number, which must be the same in the
initial report and any subsequent
followup report(s).
(e) Electronic format for submissions.
(1) Each report required to be submitted
to FDA under this section, including the
ICSR and any ICSR attachments, must
be submitted in an electronic format
that FDA can process, review, and
archive. FDA will issue guidance on
how to provide the electronic
submission (e.g., method of
transmission, media, file formats,
preparation and organization of files).
(2) Each person identified in
paragraph (c)(1)(i) of this section may
request, in writing, a temporary waiver
of the requirements in paragraph (e)(1)

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of this section. These waivers will be
granted on a limited basis for good
cause shown. FDA will issue guidance
on requesting a waiver of the
requirements in paragraph (e)(1) of this
section.
(f) Patient privacy. Manufacturers,
packers, and distributors should not
include in reports under this section the
names and addresses of individual
patients; instead, the manufacturer,
packer, and distributor should assign a
unique code for identification of the
patient. The manufacturer, packer, and
distributor should include the name of
the reporter from whom the information
was received as part of the initial
reporter information, even when the
reporter is the patient. The names of
patients, individual reporters, health
care professionals, hospitals, and
geographical identifiers in adverse drug
experience reports are not releasable to
the public under FDA’s public
information regulations in part 20 of
this chapter.
*
*
*
*
*
PART 314—APPLICATIONS FOR FDA
APPROVAL TO MARKET A NEW DRUG
3. The authority citation for 21 CFR
part 314 is revised to read as follows:

■

Authority: 21 U.S.C. 321, 331, 351, 352,
353, 355, 356, 356a, 356b, 356c, 371, 374,
379e, 379k–1.

4. Section 314.80 is amended:
a. By removing the word ‘‘shall’’ each
time it appears and by adding in its
place the word ‘‘must’’;
■ b. In paragraph (a) by alphabetically
adding the definitions for ‘‘Individual
case safety report (ICSR)’’ and ‘‘ICSR
attachments’’;
■ c. In paragraph (c)(1)(i) by removing
the phrase ‘‘in no case later than 15
calendar days of’’ and by adding in its
place the phrase ‘‘no later than 15
calendar days from’’;
■ d. By removing the last sentence of
paragraph (c)(1)(ii);
■ e. By removing paragraph (c)(1)(iv);
■ f. By revising paragraph (c)
introductory text, the first and third
sentences of paragraph (c)(1)(iii)
introductory text, and paragraph
(c)(2)(ii);
■ g. By removing paragraph (d)(2) and
by redesignating paragraph (d)(1) as
paragraph (d) and revising the first
sentence of newly redesignated
paragraph (d);
■ h. By removing paragraph (e)(2) and
by redesignating paragraph (e)(1) as
paragraph (e);
■ i. By revising paragraph (f);
■ j. By redesignating paragraph (g)
through paragraph (k) as paragraph (h)

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■
■

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through paragraph (l); and by revising
newly redesignated paragraph (i); and
■ k. By adding new paragraph (g) to read
as follows:
§ 314.80 Postmarketing reporting of
adverse drug experiences.

(a) * * *
Individual case safety report (ICSR). A
description of an adverse drug
experience related to an individual
patient or subject.
ICSR attachments. Documents related
to the adverse drug experience
described in an ICSR, such as medical
records, hospital discharge summaries,
or other documentation.
*
*
*
*
*
(c) Reporting requirements. The
applicant must submit to FDA adverse
drug experience information as
described in this section. Except as
provided in paragraph (g)(2) of this
section, these reports must be submitted
to the Agency in electronic format as
described in paragraph (g)(1) of this
section.
(1) * * *
(iii) Submission of reports. The
requirements of paragraphs (c)(1)(i) and
(c)(1)(ii) of this section, concerning the
submission of postmarketing 15-day
Alert reports, also apply to any person
other than the applicant whose name
appears on the label of an approved
drug product as a manufacturer, packer,
or distributor (nonapplicant). * * * If a
nonapplicant elects to submit adverse
drug experience reports to the applicant
rather than to FDA, the nonapplicant
must submit, by any appropriate means,
each report to the applicant within 5
calendar days of initial receipt of the
information by the nonapplicant, and
the applicant must then comply with
the requirements of this section. * * *
*
*
*
*
*
(2) * * *
(ii) Each periodic report is required to
contain:
(A) Descriptive information. (1) A
narrative summary and analysis of the
information in the report;
(2) An analysis of the 15-day Alert
reports submitted during the reporting
interval (all 15-day Alert reports being
appropriately referenced by the
applicant’s patient identification code,
adverse reaction term(s), and date of
submission to FDA);
(3) A history of actions taken since the
last report because of adverse drug
experiences (for example, labeling
changes or studies initiated); and
(4) An index consisting of a line
listing of the applicant’s patient
identification code, and adverse
reaction term(s) for all ICSRs submitted

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under paragraph (c)(2)(ii)(B) of this
section.
(B) ICSRs for serious, expected, and
nonserious adverse drug experiences.
An ICSR for each adverse drug
experience not reported under
paragraph (c)(1)(i) of this section (all
serious, expected and nonserious
adverse drug experiences). All such
ICSRs must be submitted to FDA (either
individually or in one or more batches)
within the timeframe specified in
paragraph (c)(2)(i) of this section. ICSRs
must only be submitted to FDA once.
*
*
*
*
*
(d) Scientific literature. A 15-day
Alert report based on information in the
scientific literature must be
accompanied by a copy of the published
article. * * *
*
*
*
*
*
(f) Information reported on ICSRs.
ICSRs include the following
information:
(1) Patient information.
(i) Patient identification code;
(ii) Patient age at the time of adverse
drug experience, or date of birth;
(iii) Patient gender; and
(iv) Patient weight.
(2) Adverse drug experience.
(i) Outcome attributed to adverse drug
experience;
(ii) Date of adverse drug experience;
(iii) Date of ICSR submission;
(iv) Description of adverse drug
experience (including a concise medical
narrative);
(v) Adverse drug experience term(s);
(vi) Description of relevant tests,
including dates and laboratory data; and
(vii) Other relevant patient history,
including preexisting medical
conditions.
(3) Suspect medical product(s).
(i) Name;
(ii) Dose, frequency, and route of
administration used;
(iii) Therapy dates;
(iv) Diagnosis for use (indication);
(v) Whether the product is a
prescription or nonprescription product;
(vi) Whether the product is a
combination product as defined in
§ 3.2(e) of this chapter;
(vii) Whether adverse drug experience
abated after drug use stopped or dose
reduced;
(viii) Whether adverse drug
experience reappeared after
reintroduction of drug;
(ix) Lot number;
(x) Expiration date;
(xi) National Drug Code (NDC)
number; and
(xii) Concomitant medical products
and therapy dates.
(4) Initial reporter information.

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(i) Name, address, and telephone
number;
(ii) Whether the initial reporter is a
health care professional; and
(iii) Occupation, if a health care
professional.
(5) Applicant information.
(i) Applicant name and contact office
address;
(ii) Telephone number;
(iii) Report source, such as
spontaneous, literature, or study;
(iv) Date the report was received by
applicant;
(v) Application number and type;
(vi) Whether the ICSR is a 15-day
‘‘Alert report’’;
(vii) Whether the ICSR is an initial
report or followup report; and
(viii) Unique case identification
number, which must be the same in the
initial report and any subsequent
followup report(s).
(g) Electronic format for submissions.
(1) Safety report submissions, including
ICSRs, ICSR attachments, and the
descriptive information in periodic
reports, must be in an electronic format
that FDA can process, review, and
archive. FDA will issue guidance on
how to provide the electronic
submission (e.g., method of
transmission, media, file formats,
preparation and organization of files).
(2) An applicant or nonapplicant may
request, in writing, a temporary waiver
of the requirements in paragraph (g)(1)
of this section. These waivers will be
granted on a limited basis for good
cause shown. FDA will issue guidance
on requesting a waiver of the
requirements in paragraph (g)(1) of this
section.
*
*
*
*
*
(i) Patient privacy. An applicant
should not include in reports under this
section the names and addresses of
individual patients; instead, the
applicant should assign a unique code
for identification of the patient. The
applicant should include the name of
the reporter from whom the information
was received as part of the initial
reporter information, even when the
reporter is the patient. The names of
patients, health care professionals,
hospitals, and geographical identifiers
in adverse drug experience reports are
not releasable to the public under FDA’s
public information regulations in part
20 of this chapter.
*
*
*
*
*
■ 5. Section 314.98 is revised to read as
follows:
§ 314.98

Postmarketing reports.

(a) Each applicant having an approved
abbreviated new drug application under

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§ 314.94 that is effective must comply
with the requirements of § 314.80
regarding the reporting and
recordkeeping of adverse drug
experiences.
(b) Each applicant must make the
reports required under § 314.81 and
section 505(k) of the Federal Food,
Drug, and Cosmetic Act for each of its
approved abbreviated applications.
■ 6. Part 329 is added to read as follows:
PART 329—NONPRESCRIPTION
HUMAN DRUG PRODUCTS SUBJECT
TO SECTION 760 OF THE FEDERAL
FOOD, DRUG, AND COSMETIC ACT
Authority: 21 U.S.C. 321, 331, 351, 352,
353, 355, 371, 379aa.
§ 329.100 Postmarketing reporting of
adverse drug events under section 760 of
the Federal Food, Drug, and Cosmetic Act.

(a) Reporting requirements. Reports of
serious adverse events required by
section 760 of the Federal Food, Drug,
and Cosmetic Act (FD&C Act) must
include the information specified in this
section, as applicable. Except as
provided in paragraph (c)(2) of this
section, these reports must be submitted
to the Agency in electronic format as
described in paragraph (c)(1) of this
section.
(b) Contents of reports. For purposes
of reporting serious adverse events
under section 760 of the FD&C Act, an
individual case safety report (ICSR)
constitutes the MedWatch form required
to be submitted by section 760(d) of the
FD&C Act. ICSRs include the following
information:
(1) Patient information.
(i) Patient identification code;
(ii) Patient age at the time of adverse
drug experience, or date of birth;
(iii) Patient gender; and
(iv) Patient weight.
(2) Adverse event.
(i) Outcome attributed to adverse drug
event;
(ii) Date of adverse drug event;
(iii) Date of ICSR submission;
(iv) Description of adverse drug event
(including a concise medical narrative);
(v) Adverse drug event term(s);
(vi) Description of relevant tests,
including dates and laboratory data; and
(vii) Other relevant patient history,
including preexisting medical
conditions.
(3) Suspect medical product(s).
(i) Name;
(ii) Dose, frequency, and route of
administration used;
(iii) Therapy dates;
(iv) Diagnosis for use (indication);
(v) Whether the product is a
combination product as defined in
§ 3.2(e) of this chapter;

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33089

(vi) Whether the product is a
prescription or nonprescription product;
(vii) Whether adverse drug event
abated after drug use stopped or dose
reduced;
(viii) Whether adverse drug event
reappeared after reintroduction of drug;
(ix) Lot number;
(x) Expiration date;
(xi) National Drug Code (NDC)
number; and
(xii) Concomitant medical products
and therapy dates.
(4) Initial reporter information.
(i) Name, address, and telephone
number;
(ii) Whether the initial reporter is a
health care professional; and
(iii) Occupation, if a health care
professional.
(5) Responsible person (as defined in
section 760(b) of the FD&C Act)
information.
(i) Name and contact office address;
(ii) Telephone number;
(iii) Report source, such as
spontaneous;
(iv) Date the report was received by
responsible person;
(v) Whether the ICSR is a 15-day
report;
(vi) Whether the ICSR is an initial
report or followup report; and
(vii) Unique case identification
number, which must be the same in the
initial report and any subsequent
followup report(s).
(c) Electronic format for submissions.
(1) Each report required to be submitted
to FDA under section 760 of the FD&C
Act, accompanied by a copy of the label
on or within the retail package of the
drug and any other documentation (as
ICSR attachments), must be in an
electronic format that FDA can process,
review, and archive. FDA will issue
guidance on how to provide the
electronic submission (e.g., method of
transmission, media, file formats,
preparation, and organization of files).
(2) The responsible person may
request, in writing, a temporary waiver
of the requirements in paragraph (c)(1)
of this section. These waivers will be
granted on a limited basis for good
cause shown. FDA will issue guidance
on requesting a waiver of the
requirements in paragraph (c)(1) of this
section.
(d) Patient privacy. The responsible
person should not include in reports
under this section the names and
addresses of individual patients;
instead, the responsible person should
assign a unique code for identification
of the patient. The responsible person
should include the name of the reporter
from whom the information was
received as part of the initial reporter

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Federal Register / Vol. 79, No. 111 / Tuesday, June 10, 2014 / Rules and Regulations

information, even when the reporter is
the patient. The names of patients,
health care professionals, hospitals, and
geographical identifiers in adverse drug
event reports are not releasable to the
public under FDA’s public information
regulations in part 20 of this chapter.
PART 600—BIOLOGICAL PRODUCTS:
GENERAL
7. The authority citation for 21 CFR
part 600 is revised to read as follows:

■

Authority: 21 U.S.C. 321, 351, 352, 353,
355, 360, 360i, 371, 374, 379k–1; 42 U.S.C.
216, 262, 263, 263a, 264, 300aa–25.
§ 600.2

[Amended]

8. Section 600.2 is amended:
a. In paragraph (a) by removing the
phrase ‘‘paragraphs (c) or (d)’’ and
adding in its place ‘‘paragraph (c)’’, and
by removing the phrase ‘‘adverse
experience reports’’;
■ b. In paragraph (b) introductory text
by removing the phrase ‘‘paragraphs
(b)(1), (b)(2), (b)(3), or (c)’’ and adding
in its place ‘‘paragraphs (b)(1), (b)(2), or
(c) ‘‘
■ c. By removing paragraph (b)(2) and
redesignating paragraph (b)(3) as
paragraph (b)(2);
■ d. By removing paragraph (d) and
redesignating paragraphs (e) and (f) as
paragraphs (d) and (e).
■ e. In newly redesignated paragraph (e)
by removing the Web address ‘‘http://
www.fda.gov/cber/pubinquire.htm’’ and
adding in its place ‘‘http://www.fda.gov/
BiologicsBloodVaccines/default.htm’’
and by removing the Web address
‘‘http://www.fda.gov/cder/biologics/
default.htm’’ and adding in its place
‘‘http://www.fda.gov/Drugs/
default.htm’’.
■ 9. Section 600.80 is amended:
■ a. By removing the word ‘‘shall’’ each
time it appears and by adding in its
place the word ‘‘must’’;
■ b. By removing the phrase ‘‘licensed
manufacturer’’ or ‘‘licensed
manufacturers’’ each time it appears and
by adding in its place the word
‘‘applicant’’ or ‘‘applicants’’
respectively;
■ c. By removing the phrase ‘‘Licensed
manufacturer’’ or ‘‘Licensed
manufacturers’’ each time it appears and
by adding in its place the word
‘‘Applicant’’ or ‘‘Applicants’’
respectively;
■ d. In paragraph (a) by alphabetically
adding the definitions for ‘‘Individual
case safety report (ICSR)’’ and ‘‘ICSR
attachments’’;
■ e. In paragraph (c)(1)(i) by removing
the phrase ‘‘in no case later than 15
calendar days of’’ and by adding in its
place the phrase ‘‘no later than 15
calendar days from’’;

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■

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f. In paragraph (c)(1)(ii) by removing
the last sentence;
■ g. By removing paragraph (c)(1)(iv);
■ h. By revising paragraph (c)
introductory text, the first and third
sentences of paragraph (c)(1)(iii)
introductory text, and paragraph
(c)(2)(ii);
■ i. By removing paragraph (d)(2) and by
redesignating paragraph (d)(1) as
paragraph (d) and revising the first
sentence of paragraph (d);
■ j. By removing paragraph (e)(2) and by
redesignating paragraph (e)(1) as
paragraph (e);
■ k. By revising paragraph (f);
■ l. By redesignating paragraph (g)
through paragraph (l) as paragraph (i)
through paragraph (n) and by revising
newly redesignated paragraph (j); and
■ m. By adding new paragraphs (g) and
(h) to read as follows:
■

§ 600.80 Postmarketing reporting of
adverse experiences.

(a) * * *
Individual case safety report (ICSR). A
description of an adverse experience
related to an individual patient or
subject.
ICSR attachments. Documents related
to the adverse experience described in
an ICSR, such as medical records,
hospital discharge summaries, or other
documentation.
*
*
*
*
*
(c) Reporting requirements. The
applicant must submit to FDA
postmarketing 15-day Alert reports and
periodic safety reports pertaining to its
biological product as described in this
section. These reports must be
submitted to the Agency in electronic
format as described in paragraph (h)(1)
of this section, except as provided in
paragraph (h)(2) of this section.
(1) * * *
(iii) Submission of reports. The
requirements of paragraphs (c)(1)(i) and
(c)(1)(ii) of this section, concerning the
submission of postmarketing 15-day
Alert reports, also apply to any person
whose name appears on the label of a
licensed biological product as a
manufacturer, packer, distributor,
shared manufacturer, joint
manufacturer, or any other participant
involved in divided manufacturing.
* * * If a person elects to submit
adverse experience reports to the
applicant rather than to FDA, the person
must submit, by any appropriate means,
each report to the applicant within 5
calendar days of initial receipt of the
information by the person, and the
applicant must then comply with the
requirements of this section. * * *
*
*
*
*
*
(2) * * *

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(ii) Each periodic report is required to
contain:
(A) Descriptive information. (1) A
narrative summary and analysis of the
information in the report;
(2) An analysis of the 15-day Alert
reports submitted during the reporting
interval (all 15-day Alert reports being
appropriately referenced by the
applicant’s patient identification code
for nonvaccine biological product
reports or by the unique case
identification number for vaccine
reports, adverse reaction term(s), and
date of submission to FDA);
(3) A history of actions taken since the
last report because of adverse
experiences (for example, labeling
changes or studies initiated);
(4) An index consisting of a line
listing of the applicant’s patient
identification code for nonvaccine
biological product reports or by the
unique case identification number for
vaccine reports and adverse reaction
term(s) for ICSRs submitted under
paragraph (c)(2)(ii)(B) of this section;
and
(B) ICSRs for serious, expected and,
nonserious adverse experiences. An
ICSR for each adverse experience not
reported under paragraph (c)(1)(i) of this
section (all serious, expected and
nonserious adverse experiences). All
such ICSRs must be submitted to FDA
(either individually or in one or more
batches) within the timeframe specified
in paragraph (c)(2)(i) of this section.
ICSRs must only be submitted to FDA
once.
*
*
*
*
*
(d) Scientific literature. A 15-day
Alert report based on information in the
scientific literature must be
accompanied by a copy of the published
article. * * *
*
*
*
*
*
(f) Information reported on ICSRs for
nonvaccine biological products. ICSRs
for nonvaccine biological products
include the following information:
(1) Patient information.
(i) Patient identification code;
(ii) Patient age at the time of adverse
experience, or date of birth;
(iii) Patient gender; and
(iv) Patient weight.
(2) Adverse experience.
(i) Outcome attributed to adverse
experience;
(ii) Date of adverse experience;
(iii) Date of report;
(iv) Description of adverse experience
(including a concise medical narrative);
(v) Adverse experience term(s);
(vi) Description of relevant tests,
including dates and laboratory data; and

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Federal Register / Vol. 79, No. 111 / Tuesday, June 10, 2014 / Rules and Regulations
(vii) Other relevant patient history,
including preexisting medical
conditions.
(3) Suspect medical product(s).
(i) Name;
(ii) Dose, frequency, and route of
administration used;
(iii) Therapy dates;
(iv) Diagnosis for use (indication);
(v) Whether the product is a
combination product as defined in
§ 3.2(e) of this chapter;
(vi) Whether the product is a
prescription or nonprescription product;
(vii) Whether adverse experience
abated after product use stopped or dose
reduced;
(viii) Whether adverse experience
reappeared after reintroduction of the
product;
(ix) Lot number;
(x) Expiration date;
(xi) National Drug Code (NDC)
number, or other unique identifier; and
(xii) Concomitant medical products
and therapy dates.
(4) Initial reporter information.
(i) Name, address, and telephone
number;
(ii) Whether the initial reporter is a
health care professional; and
(iii) Occupation, if a health care
professional.
(5) Applicant information.
(i) Applicant name and contact office
address;
(ii) Telephone number;
(iii) Report source, such as
spontaneous, literature, or study;
(iv) Date the report was received by
applicant;
(v) Application number and type;
(vi) Whether the ICSR is a 15-day
‘‘Alert report’’;
(vii) Whether the ICSR is an initial
report or followup report; and
(viii) Unique case identification
number, which must be the same in the
initial report and any subsequent
followup report(s).
(g) Information reported on ICSRs for
vaccine products. ICSRs for vaccine
products include the following
information:
(1) Patient information.
(i) Patient name, address, telephone
number;
(ii) Patient age at the time of
vaccination, or date of birth;
(iii) Patient gender; and
(iv) Patient birth weight for children
under age 5.
(2) Adverse experience.
(i) Outcome attributed to adverse
experience;
(ii) Date and time of adverse
experience;
(iii) Date of report;
(iv) Description of adverse experience
(including a concise medical narrative);

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(v) Adverse experience term(s);
(vi) Illness at the time of vaccination;
(vii) Description of relevant tests,
including dates and laboratory data; and
(viii) Other relevant patient history,
including preexisting medical
conditions.
(3) Suspect medical product(s),
including vaccines administered on the
same date.
(i) Name;
(ii) Dose, frequency, and route or site
of administration used;
(iii) Number of previous vaccine
doses;
(iv) Vaccination date(s) and time(s);
(v) Diagnosis for use (indication);
(vi) Whether the product is a
combination product (as defined in
§ 3.2(e) of this chapter);
(vii) Whether the adverse experience
abated after product use stopped or dose
reduced;
(viii) Whether the adverse experience
reappeared after reintroduction of the
product;
(ix) Lot number;
(x) Expiration date;
(xi) National Drug Code (NDC)
number, or other unique identifier; and
(xii) Concomitant medical products
and therapy dates.
(4) Vaccine(s) administered in the 4
weeks prior to the vaccination date.
(i) Name of vaccine;
(ii) Manufacturer;
(iii) Lot number;
(iv) Route or site of administration;
(v) Date given; and
(vi) Number of previous doses.
(5) Initial reporter information.
(i) Name, address, and telephone
number;
(ii) Whether the initial reporter is a
health care professional; and
(iii) Occupation, if a health care
professional.
(6) Facility and personnel where
vaccine was administered.
(i) Name of person who administered
vaccine;
(ii) Name of responsible physician at
facility where vaccine was
administered; and
(iii) Name, address (including city,
county, and state), and telephone
number of facility where vaccine was
administered.
(7) Applicant information.
(i) Applicant name and contact office
address;
(ii) Telephone number;
(iii) Report source, such as
spontaneous, literature, or study;
(iv) Date received by applicant;
(v) Application number and type;
(vi) Whether the ICSR is a 15-day
‘‘Alert report’’;
(vii) Whether the ICSR is an initial
report or followup report; and

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33091

(viii) Unique case identification
number, which must be the same in the
initial report and any subsequent
followup report(s).
(h) Electronic format for submissions.
(1) Safety report submissions, including
ICSRs, ICSR attachments, and the
descriptive information in periodic
reports, must be in an electronic format
that FDA can process, review, and
archive. FDA will issue guidance on
how to provide the electronic
submission (e.g., method of
transmission, media, file formats,
preparation and organization of files).
(2) Persons subject to the
requirements of paragraph (c) of this
section may request, in writing, a
temporary waiver of the requirements in
paragraph (h)(1) of this section. These
waivers will be granted on a limited
basis for good cause shown. FDA will
issue guidance on requesting a waiver of
the requirements in paragraph (h)(1) of
this section. Requests for waivers must
be submitted in accordance with
§ 600.90.
*
*
*
*
*
(j) Patient privacy. For nonvaccine
biological products, an applicant should
not include in reports under this section
the names and addresses of individual
patients; instead, the applicant should
assign a unique code for identification
of the patient. The applicant should
include the name of the reporter from
whom the information was received as
part of the initial reporter information,
even when the reporter is the patient.
The names of patients, health care
professionals, hospitals, and
geographical identifiers in adverse
experience reports are not releasable to
the public under FDA’s public
information regulations in part 20 of
this chapter. For vaccine adverse
experience reports, these data will
become part of the CDC Privacy Act
System 09–20–0136, ‘‘Epidemiologic
Studies and Surveillance of Disease
Problems.’’ Information identifying the
person who received the vaccine or that
person’s legal representative will not be
made available to the public, but may be
available to the vaccinee or legal
representative.
*
*
*
*
*
■ 10. Section § 600.81 is amended:
■ a. By removing the phrase ‘‘licensed
manufacturer’’ each time it appears and
by adding in its place the word
‘‘applicant’’;
■ b. By removing the word ‘‘shall’’ each
time it appears and by adding in its
place the word ‘‘must’’;
■ c. By designating the existing text as
paragraph (a) and by adding a heading
for newly designated paragraph (a);

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Federal Register / Vol. 79, No. 111 / Tuesday, June 10, 2014 / Rules and Regulations

d. In newly designated paragraph (a),
by removing from the first sentence the
phrase ‘‘(see mailing addresses in
§ 600.2)’’; and
■ e. By adding new paragraph (b) to read
as follows:
■

§ 600.81

Distribution reports.

(a) Reporting requirements. * * *
(b)(1) Electronic format. Except as
provided for in paragraph (b)(2) of this
section, the distribution reports required
under paragraph (a) of this section must
be submitted to the Agency in an
electronic format that FDA can process,
review, and archive. FDA will issue
guidance on how to provide the
electronic submission (e.g., method of
transmission, media, file formats,
preparation and organization of files).
(2) Waivers. An applicant may
request, in writing, a temporary waiver
of the requirements in paragraph (b)(1)
of this section. These waivers will be
granted on a limited basis for good
cause shown. FDA will issue guidance
on requesting a waiver of the
requirements in paragraph (b)(1) of this
section. Requests for waivers must be
submitted in accordance with § 600.90.
§ 600.90

[Amended]

11. Section 600.90 is amended by
removing the phrase ‘‘licensed
manufacturer’’ or ‘‘licensed
manufacturer’s’’ each time it appears
and by adding in its place the word
‘‘applicant’’ or ‘‘applicant’s’’
respectively.

■

Dated: June 4, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014–13480 Filed 6–9–14; 8:45 am]
BILLING CODE 4160–01–P

DEPARTMENT OF EDUCATION
34 CFR Chapter III
[Docket ID: ED–2014–OSERS–0013]

Final Priority. National Institute on
Disability and Rehabilitation
Research—Rehabilitation Research
and Training Centers
[CFDA Number: 84.133B–4.]

Office of Special Education and
Rehabilitative Services, Department of
Education.
ACTION: Final priority.

emcdonald on DSK67QTVN1PROD with RULES

AGENCY:

The Assistant Secretary for
Special Education and Rehabilitative
Services announces a priority for the
Rehabilitation Research and Training
Center (RRTC) Program administered by
the National Institute on Disability and

SUMMARY:

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Rehabilitation Research (NIDRR).
Specifically, we announce a priority for
an RRTC on Health and Function of
Individuals with Physical Disabilities.
The Assistant Secretary may use this
priority for competitions in fiscal year
(FY) 2014 and later years. We take this
action to focus research attention on an
area of national need. We intend the
priority to contribute to improved
outcomes of health and function of
individuals with physical disabilities.
DATES: This priority is effective July 10,
2014.
FOR FURTHER INFORMATION CONTACT:
Patricia Barrett, U.S. Department of
Education, 400 Maryland Avenue SW.,
Room 5142, Potomac Center Plaza
(PCP), Washington, DC 20202–2700.
Telephone: (202) 245–6211 or by email:
[email protected].
If you use a telecommunications
device for the deaf (TDD) or a text
telephone (TTY), call the Federal Relay
Service (FRS), toll free, at 1–800–877–
8339.
SUPPLEMENTARY INFORMATION: Purpose of
Program: The purpose of the Disability
and Rehabilitation Research Projects
and Centers Program is to plan and
conduct research, demonstration
projects, training, and related activities,
including international activities, to
develop methods, procedures, and
rehabilitation technology that maximize
the full inclusion and integration into
society, employment, independent
living, family support, and economic
and social self-sufficiency of individuals
with disabilities, especially individuals
with the most severe disabilities, and to
improve the effectiveness of services
authorized under the Rehabilitation Act
of 1973, as amended (Rehabilitation
Act).
Rehabilitation Research and Training
Centers
The purpose of the RRTCs, which are
funded through the Disability and
Rehabilitation Research Projects and
Centers Program, is to achieve the goals
of, and improve the effectiveness of,
services authorized under the
Rehabilitation Act through welldesigned research, training, technical
assistance, and dissemination activities
in important topical areas. These
activities are designed to benefit
rehabilitation service providers,
individuals with disabilities, family
members, policymakers, and other
research stakeholders. Additional
information on the RRTC program can
be found at: http://www2.ed.gov/
programs/rrtc/index.html.
Program Authority: 29 U.S.C. 762(g) and
764(b)(2).

PO 00000

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Applicable Program Regulations: 34
CFR part 350.
We published a notice of proposed
priority (NPP) for this program in the
Federal Register on March 3, 2014 (79
FR 11738). That notice contained
background information and our reasons
for proposing the particular priority.
There are no differences between the
proposed priority and this final priority.
Public Comment: In response to our
invitation in the notice of proposed
priority, six parties submitted comments
on the proposed priority.
Generally, we do not address
technical and other minor changes, or
suggested changes the law does not
authorize us to make under the
applicable statutory authority. In
addition, we do not address general
comments that raised concerns not
directly related to the proposed priority.
Analysis of Comments and Changes:
An analysis of the comments and of any
changes in the priority since publication
of the NPP follows.
Comment: One commenter questioned
the need for this priority.
Discussion: This priority, creating an
RRTC on Health and Function of
Individuals with Physical Disabilities,
would help achieve the goals of, and
improve the effectiveness of services
authorized under, the Rehabilitation
Act. By creating an RRTC on Health and
Function for Individuals with Physical
Disabilities, we are fulfilling the
purposes established in NIDRR’s LongRange Plan for Fiscal Years 2013–2017
(Plan), which was published in the
Federal Register on April 4, 2013 (78 FR
20299). More specifically, as we discuss
in the NPP, there is a need to better
understand how specific health
problems are interrelated with optimal
health and function; how they may
affect community participation, work
productivity, and quality of life; and
how they may be prevented or
mitigated. We believe this priority will
focus research attention on this area of
national need.
Changes: None.
Comment: One commenter
recommended that the RRTC should
focus on technology-based interventions
to improve health and function
outcomes of individuals with
disabilities.
Discussion: NIDRR agrees that
technology can be used to improve the
health and function outcomes of
individuals with physical disabilities.
This is one of five broad areas described
in the priority, under which applicants
can propose research and related
activities. NIDRR does not wish to limit
applicants’ ability to address the other
areas in the priority by requiring a focus

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