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[Federal Register Volume 90, Number 11 (Friday, January 17, 2025)]
[Notices]
[Pages 5895-5898]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2025-01151]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2024-N-3112]

Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Postmarketing Adverse 
Experience Reporting

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that a 
proposed collection of information has been submitted to the Office of 
Management and Budget (OMB) for review and clearance under the 
Paperwork Reduction Act of 1995.

DATES: Submit written comments (including recommendations) on the 
collection of information by February 18, 2025.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be submitted to https://www.reginfo.gov/public/do/PRAMain. Find this particular information 
collection by selecting ``Currently under Review--Open for Public 
Comments'' or by using the search function. The OMB control number for 
this information collection is 0910-0230. Also include the FDA docket 
number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: JonnaLynn Capezzuto, Office of 
Operations, Food and Drug Administration, Three White Flint North, 10A-
12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-3794, 
[email protected].

SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.

Postmarketing Adverse Experience Reporting

OMB Control Number 0910-0230--Revision

    This information collection helps support provisions found in 
sections 201, 502, 505, 701, and 760 of the Federal Food, Drug, and 
Cosmetic Act (FD&C Act) (21 U.S.C. 321, 352, 355, 371, and 379aa) 
governing adverse experience reporting (AER) and associated 
recordkeeping for FDA-regulated drug products. FDA has issued 
applicable regulations in part 4 and Sec. Sec.  310.305, 314.80, 
314.81, 314.98, and 329.100 (21 CFR part 4 and 21 CFR 310.305, 314.80, 
314.81, 314.98, and 329.100) that implement the statutory requirements, 
identify specific content and format elements, and establish reporting 
and retention schedules for the required information. Postmarketing 
safety data collection and adverse event reporting are critical 
elements of FDA's monitoring of drugs. For more information, please 
visit https://www.fda.gov/drugs/surveillance/postmarketing-adverse-event-reporting-compliance-program.
    Respondents to the information collection are manufacturers, 
packers, distributors, and applicants of FDA-regulated drug and 
biologic products marketed with or without an FDA-approved application, 
including over-the-counter (OTC) drug products marketed without an 
approved application; OTC drug products marketed under the OTC Drug 
Monograph Review process (whether subject to a final monograph or not); 
and drug products marketed outside the monograph system. All reports 
and followup reports must be submitted to FDA in electronic format, 
although waivers of the electronic requirements are available for good 
cause.
    Adverse experience reporting for products associated with drug 
marketing applications are governed by regulations in Sec. Sec.  
314.80, 314.81, and 314.98. The regulations identify required reporting 
content and format elements, as well as establish followup reporting 
requirements and mandatory reporting schedules. The regulations also 
establish associated recordkeeping and require that written procedures 
be developed for the surveillance, receipt, evaluation, and reporting 
of postmarketing adverse experiences to FDA. The regulations require 
reporting in an electronic format that FDA can process, although 
temporary waivers may be granted on a limited basis for good cause. A 
final guidance for industry entitled ``Providing Submissions in 
Electronic Format--Postmarketing Safety Reports'' (April 2022) is 
available for general information pertaining to electronic submission 
of postmarketing safety reports for certain human drugs, biological 
products, and combination products. The guidance is available at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/providing-submissions-electronic-format-postmarketing-safety-reports.
    We have established and maintain the FDA Adverse Event Reporting 
System (FAERS) at https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system-faers/fda-adverse-event-reporting-system-faers-electronic-submissions. Information may be submitted via 
FDA's Electronic Submissions Gateway or utilizing the ``Safety 
Reporting Portal,'' developed by FDA and the National Institutes of 
Health to streamline reporting and review of adverse events.
    The primary purpose of FDA's adverse drug experience reporting 
system is to enable identification of signals for potentially serious 
safety problems with marketed drugs. Although premarket testing 
discloses a general safety profile of a new drug's comparatively common 
adverse effects, the larger and more diverse patient populations 
exposed to the marketed product provide the opportunity to collect 
information on rare, latent, and long-term effects. Signals are 
obtained from a variety of sources, including reports from patients, 
treating physicians, foreign regulatory agencies, clinical 
investigators, and literature. Information derived from the adverse 
drug experience reporting system contributes directly to increased 
public

[[Page 5896]]

health protection because the information enables FDA to make important 
changes to the product's labeling (such as adding a new warning), to 
make decisions about risk evaluation and mitigation strategies; the 
need for postmarketing studies or clinical trials; and, when necessary, 
to initiate removal of a product from the market.
    In the Federal Register of September 23, 2024 (89 FR 77515), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. No comments were received.
    FDA estimates the burden of this collection of information as 
follows:

                                Table 1--Estimated Annual Reporting Burden 1 2 3
----------------------------------------------------------------------------------------------------------------
                                                     Number of
   21 CFR section or guidance;       Number of     responses per   Total annual   Average burden    Total hours
            activity                respondents     respondent       responses     per response
----------------------------------------------------------------------------------------------------------------
310.305(c)(5); AERs for                       36            88.8           3,197               1           3,197
 prescription products not the
 subject of a marketing
 application....................
314.80(c)(1); 15-day alerts for              682        1,832.84       1,250,000               1       1,250,000
 approved products..............
314.80(c)(2); periodic reports               682        1,228.73         838,000              60      50,280,000
 for approved products..........
329.100; AERs for non-                       312          62.522          19,507               6         117,042
 prescription drug products.....
ICH E2C(R2) Guidance; Periodic               471           8.885           4,185               1           4,185
 safety updates; Applicants w/
 waiver for an approved
 application (section III.A.)...
ICH E2C(R2) Guidance; Periodic             1,115          16.254          18,123               2          36,246
 safety updates; Applicants w/no
 waiver for an approved
 application (section III.B.)...
AER During Pandemic Guidance;                  1               1               1               8               8
 notifying FDA when normal
 reporting is not feasible
 (section III.C.)...............
4.103, 4.104, 4.105, 310.305,                  1               1               1              24              24
 314.80, 314.98, 329.100(c);
 Waiver requests from electronic
 reporting requirements.........
                                 -------------------------------------------------------------------------------
    Total.......................       \4\ 2,618  ..............       2,133,014  ..............      51,690,702
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\1\ There are no capital costs associated with this collection. The operating and maintenance costs associated
  with this collection of information are approximately $25,000 annually.
\2\ The reporting burdens for Sec.   310.305(c)(1), (2), and (3), and voluntary reports by healthcare providers
  received under Sec.   314.80(c)(1)(i) and (ii) are covered under OMB control number 0910-0291.
\3\ Totals may not sum due to rounding.
\4\ Total of unique respondents.

                               Table 2--Estimated Annual Recordkeeping Burden 1 2
----------------------------------------------------------------------------------------------------------------
                                                    Number of                     Average burden
   21 CFR section or guidance       Number of      records per    Total annual         per          Total hours
       section; activity          recordkeepers   recordkeeper       records      recordkeeping
----------------------------------------------------------------------------------------------------------------
 310.305; AER records--                      36            88.8           3,197               16          51,152
 prescription product not the
 subject of a marketing
 application...................
314.80(j); AER records--product             841      1,814.0606       1,525,625               16      24,410,000
 associated w/marketing
 application...................
Postmarket AER for                          312         62.5224          19,507                8         156,056
 Nonprescription Drug Products
 Guidance; (Sec.   329.100)....
AERs During Pandemic Guidance;              100               1             100               50           5,000
 Continuity of operations
 planning (section III.B.).....
AERs During Pandemic Guidance;              350               1             350                8           2,800
 documenting conditions and
 resultant high absenteeism
 (section III.C.2).............
AERs During Pandemic Guidance;              350               1             350                8           2,800
 documenting AER process
 (section III.C.1.)............
4.105; Postmarketing safety                  11              18             198  0.1 (6 minutes)            19.8
 recordkeeping for combination
 products and constituent parts
                                --------------------------------------------------------------------------------
    Total......................  ..............  ..............       1,549,327  ...............    24,627,827.8
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\1\ There are no capital costs associated with this collection of information. There are operating and
  maintenance costs associated with this collection of information of approximately $22,000 annually.
\2\ Totals may not sum due to rounding.

[[Page 5897]]

                           Table 3--Estimated Annual Third-Party Disclosure Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of
                                     Number of      disclosures    Total annual       Average
    21 CFR section; activity        respondents         per         disclosures     burden per      Total hours
                                                    respondent                      disclosure
----------------------------------------------------------------------------------------------------------------
4.103; Postmarketing Safety                   11              18             198        0.35 (21            69.3
 reporting for combination                                                              minutes)
 products--Sharing information
 with other constituent part
 applicants.....................
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    All applicants who have received marketing approval for drug 
products (including combination products that are administered as drug 
products) are required to report serious, unexpected adverse drug 
experiences (15-day ``Alert reports'') (Sec.  314.80(c)(1)(i)), as well 
as followup reports (Sec.  314.80(c)(1)(ii)) to FDA. These include all 
foreign or domestic AERs as well as AERs based on information from 
applicable scientific literature and certain reports from post 
marketing studies. Section 314.80(c)(1)(iii) pertains to AERs submitted 
by nonapplicants.
    For operational efficiency, we have adjusted this information 
collection and burden table to include all 15-day alert reports 
submitted by applicants, manufacturers, packers, and distributors. 
Voluntary reports from healthcare providers are included under OMB 
control number 0910-0291.
    Under Sec.  314.80(c)(2), applicants (including combination 
products that are administered as drug products) must also provide 
periodic reports of adverse drug experiences. For the reporting 
interval, a periodic report includes reports of serious, expected 
adverse drug experiences, all nonserious adverse drug experiences, and 
an index of these reports; a narrative summary and analysis of adverse 
drug experiences; an analysis of the 15-day Alert reports submitted 
during the reporting interval; and a history of actions taken because 
of adverse drug experiences. Under Sec.  314.80(j), applicants must 
keep records of all adverse drug experience reports known to the 
applicant for 10 years.
    For marketed prescription drug products without approved new drug 
applications (NDAs) or abbreviated new drug applications (ANDAs), 
manufacturers, packers, and distributors of these products are required 
to report to FDA serious, unexpected adverse drug experiences as well 
as followup reports (Sec.  310.305(c)). Section 310.305(c)(5) pertains 
to the submission of followup reports to reports forwarded to the 
manufacturers, packers, and distributors by FDA. Under Sec.  
310.305(g), each manufacturer, packer, and distributor shall maintain 
records of all adverse drug experiences required to be reported for 10 
years. All 15-day Alert reports and followup reports must be submitted 
to FDA in electronic format.
    Section 760 of the FD&C Act also provides for mandatory safety 
reporting for over-the-counter human drug products not subject to 
applications approved under section 505 of the FD&C Act (NDAs or 
ANDAs). These 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. Under Sec.  329.100, respondents must 
submit reports according to section 760 of the FD&C Act in an 
electronic format.
    To assist respondents with implementation of section 760 of the 
FD&C Act, FDA developed the guidance for industry entitled 
``Postmarketing Adverse Event Reporting for Nonprescription Human Drug 
Products Marketed Without an Approved Application'' (July, 2009), 
available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/postmarketing-adverse-event-reporting-nonprescription-human-drug-products-marketed-without-approved. The 
guidance document discusses what should be included in a serious 
adverse drug event report submitted under section 760(b)(1) of the FD&C 
Act, including how to submit these reports and followup reports under 
section 760(c)(2) of the FD&C Act. Section 760(e) of the FD&C Act also 
requires that responsible persons maintain records of nonprescription 
drug adverse event reports, whether the event is serious or not, for a 
period of 6 years. FDA's guidance recommends that respondents maintain 
records of efforts to obtain the minimum data elements for a report of 
a serious adverse drug event and any followup reports.
    In addition, this information collection includes an International 
Council for Harmonisation of Technical Requirements for Pharmaceuticals 
for Human Use (ICH) guidance for industry entitled ``Providing 
Postmarketing Periodic Safety Reports in the ICH E2C(R2) Format 
(Periodic Benefit-Risk Evaluation Report), (November 2016)'' available 
at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/providing-postmarket-periodic-safety-reports-ich-e2cr2-format-periodic-benefit-risk-evaluation. The ICH E2C(R2) guidance 
describes the conditions under which applicants may use the ICH E2C(R2) 
Periodic Benefit-Risk Evaluation Report format for certain types of 
adverse event reporting.
    FDA regulations in Sec. Sec.  314.80(c)(2) and 600.80(c)(2) require 
applicants to submit postmarketing periodic safety reports for each 
approved application. The reports must be submitted quarterly for the 
first 3 years following the U.S. approval date and annually thereafter 
and must contain the information described in Sec. Sec.  
314.80(c)(2)(ii) and 600.80(c)(2)(ii) (the information collection 
associated with 21 CFR part 600--Biological Products, is approved under 
OMB control number 0910-0308). The Agency guidance assists respondents 
with satisfying the regulatory requirements in an alternative format, 
noting that the process differs depending on whether an applicable 
periodic safety update report waiver is in place.
    Similarly, this information collection accounts for burden that may 
be applicable to the guidance document, ``Postmarketing Adverse Event 
Reporting for Medical Products and Dietary Supplements During a 
Pandemic (May 2020),'' available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/postmarketing-adverse-event-reporting-medical-products-and-dietary-supplements-during-pandemic. In 
response to the Coronavirus Disease

[[Page 5898]]

2019 public health emergency, we revised the Agency guidance document 
to provide recommendations for recordkeeping applicable to any 
pandemic, not just influenza, including recommendations for planning, 
notification, and documentation for continuity of operations for firms 
that report postmarketing adverse events during any pandemic.
    For operational efficiency, on March 20, 2023, OMB approved the 
addition of burden attributable to provisions related to postmarketing 
safety reporting for combination products as outlined in part 4, 
subpart B, and previously included in OMB control number 0910-0834. 
When information regarding an event that involves a death or serious 
injury, or an adverse event, associated with the use of a combination 
product that includes a drug product, is received by the product 
sponsor, the information must be provided to the other constituent part 
applicant(s) no later than 5 calendar days after receipt under Sec.  
4.103 (21 CFR 4.103). Relatedly, 21 CFR 4.104 explains how and where to 
submit reports for combination products, and 21 CFR 4.105 provides for 
associated recordkeeping. For combination products that are 
administered as drug products with a constituent part, adverse event 
reports are submitted to the drug application under 21 CFR part 314, 
and constituent applicants are notified of the AER under Sec.  4.103. 
These provisions are also described in the guidance document 
``Postmarketing Safety Reporting for Combination Products'' (July 
2019), available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/postmarketing-safety-reporting-combination-products.
    Our estimates of the number of respondents and the total annual 
responses are based on reports submitted to the Agency. This 
information collection incorporates revisions to include the two 
guidances for industry regarding submission of adverse event reports 
(``Postmarketing Adverse Event Reporting for Medical Products and 
Dietary Supplements During a Pandemic'' and ``Providing Submissions in 
Electronic Format--Postmarketing Safety Reports'') and adjustments to 
include 15-day alert reports from applicants, manufacturers, 
distributors, and packers that were not recorded previously in this 
information collection. We also believe adjustments in the information 
collection reflect anticipated fluctuations in burden after pandemic 
conditions, adjustments by reporters' and changes in electronic 
reporting methodologies use of updated technology including updates and 
redefinitions of reporting software, and changes of company business 
practices over time. All reports and followup reports must be submitted 
to FDA in electronic format. Waivers of the electronic requirements are 
available. As a result of these revisions and adjustments, including 
the additional reports, the inclusion of guidance document 
recommendations and the consolidation of the burden from OMB control 
number 0910-0834 (previously added to this information collection March 
2023), the total burden hours of the information collection have 
increased by 61,614,921 hours and 2,546,112 responses as compared to 
the previous renewal. While no changes have been made to the estimates 
in the 60-day notice, due to a clerical error, we are clarifying in 
this notice that the total burden hour increase is slightly lower (a 
difference of 198 burden hours and 89 responses).

    Dated: January 7, 2025.
P. Ritu Nalubola,
Associate Commissioner for Policy.
[FR Doc. 2025-01151 Filed 1-16-25; 8:45 am]
BILLING CODE 4164-01-P
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