[Federal Register Volume 89, Number 184 (Monday, September 23, 2024)]
[Notices]
[Pages 77515-77519]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-21675]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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


Agency Information Collection Activities; Proposed Collection; 
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 or Agency) is announcing 
an opportunity for public

[[Page 77516]]

comment on the proposed collection of certain information by the 
Agency. Under the Paperwork Reduction Act of 1995 (PRA), Federal 
Agencies are required to publish notice in the Federal Register 
concerning each proposed collection of information, including each 
proposed extension of an existing collection of information, and to 
allow 60 days for public comment in response to the notice. This notice 
solicits comments on postmarketing reporting and recordkeeping of 
adverse experiences for drug and biological products.

DATES: Either electronic or written comments on the collection of 
information must be submitted by November 22, 2024.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. The https://www.regulations.gov electronic filing system will accept comments until 
11:59 p.m. Eastern Time at the end of November 22, 2024. Comments 
received by mail/hand delivery/courier (for written/paper submissions) 
will be considered timely if they are received on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2024-N-3112 for ``Postmarketing Adverse Experience Reporting.'' 
Received comments, those filed in a timely manner (see ADDRESSES), will 
be placed in the docket and, except for those submitted as 
``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. 
and 4 p.m., Monday through Friday, 240-402-7500.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852, 240-402-7500.

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: Under the PRA (44 U.S.C. 3501-3521), Federal 
Agencies must obtain approval from the Office of Management and Budget 
(OMB) for each collection of information they conduct or sponsor. 
``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR 
1320.3(c) and includes Agency requests or requirements that members of 
the public submit reports, keep records, or provide information to a 
third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) 
requires Federal Agencies to provide a 60-day notice in the Federal 
Register concerning each proposed collection of information, including 
each proposed extension of an existing collection of information, 
before submitting the collection to OMB for approval. To comply with 
this requirement, FDA is publishing notice of the proposed collection 
of information set forth in this document.
    With respect to the following collection of information, FDA 
invites comments on these topics: (1) whether the proposed collection 
of information is necessary for the proper performance of FDA's 
functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's estimate of the burden of the 
proposed collection of information, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information to be collected; and (4) ways 
to minimize the burden of the collection of information on respondents, 
including through the use of automated collection techniques, when 
appropriate, and other forms of information technology.

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

[[Page 77517]]

promulgated 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 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.
    FDA estimates the burden of this collection of information as 
follows:

                             Table 1--Estimated Annual Reporting Burden \1\ \2\ \3\
----------------------------------------------------------------------------------------------------------------
                                                               Number of       Total      Average
    21 CFR section or guidance; activity        Number of    responses per    annual     burden per  Total hours
                                               respondents    respondent     responses    response
----------------------------------------------------------------------------------------------------------------
310.305(c)(5); AERs for prescription                    36            88.8       3,197            1        3,197
 products not the subject of a marketing
 application................................
314.80(c)(1); 15-day alerts for approved               682        1,832.84   1,250,000            1    1,250,000
 products...................................
314.80(c)(2); periodic reports for approved            682        1,228.73     838,000           60   50,280,000
 products...................................
329.100; AERs for non-prescription drug                312          62.522      19,507            6      117,042
 products...................................
ICH E2C(R2) Guidance; Periodic safety                  471           8.885       4,185            1        4,185
 updates; Applicants w/waiver for an
 approved application (section III.A.)......
ICH E2C(R2) Guidance; Periodic safety                1,115          16.254      18,123            2       36,246
 updates; Applicants w/no waiver for an
 approved application (section III.B.)......
AER During Pandemic Guidance; notifying FDA              1               1           1            8            8
 when normal reporting is not feasible
 (section III.C.)...........................
4.103, 4.104, 4.105, 310.305, 314.80,                    1               1           1           24           24
 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\
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                                                                     Number of       Total
  21 CFR section or guidance section; activity      Number of       records per      annual         Average burden per recordkeeping        Total hours
                                                  recordkeepers    recordkeeper     records
--------------------------------------------------------------------------------------------------------------------------------------------------------
310.305; AER records--prescription product not                36            88.8        3,197  16.......................................          51,152
 the subject of a marketing application.
314.80(j); AER records--product associated w/                841      1,814.0606    1,525,625  16.......................................      24,410,000
 marketing application.

[[Page 77518]]

 
Postmarket AER for Nonprescription Drug                      312         62.5224       19,507  8........................................         156,056
 Products Guidance; (Sec.   329.100).
AERs During Pandemic Guidance; Continuity of                 100               1          100  50.......................................           5,000
 operations planning (section III.B.).
AERs During Pandemic Guidance; documenting                   350               1          350  8........................................           2,800
 conditions and resultant high absenteeism
 (section III.C.2).
AERs During Pandemic Guidance; documenting AER               350               1          350  8........................................           2,800
 process (section III.C.1.).
4.105; Postmarketing safety recordkeeping for                 11              18          198  0.1 (6 minutes)..........................            19.8
 combination products and constituent parts.
                                                --------------------------------------------------------------------------------------------------------
    Total......................................        \3\ 1,650  ..............    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.
\3\ Total of unique respondents.


                                               Table 3--Estimated Annual Third-Party Disclosure Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                    Number of
            21 CFR section; activity                Number of    disclosures per  Total annual         Average burden per disclosure         Total hours
                                                   respondents     respondent      disclosures
--------------------------------------------------------------------------------------------------------------------------------------------------------
4.103; Postmarketing Safety reporting for                   11                18           198  0.35 (21 minutes)..........................         69.3
 Combination 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

[[Page 77519]]

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 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 61,615,010.1 hours and 2,546,310 responses as compared to 
the previous renewal. We invite comment on our assumptions.

    Dated: September 18, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-21675 Filed 9-20-24; 8:45 am]
BILLING CODE 4164-01-P