[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
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Number of
21 CFR section or guidance; Number of responses per Total annual Average burden Total hours
activity respondents respondent responses per response
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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.........
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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 Average burden
21 CFR section or guidance Number of records per Total annual per Total hours
section; activity recordkeepers recordkeeper records recordkeeping
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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
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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\
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Number of
Number of disclosures Total annual Average
21 CFR section; activity respondents per disclosures burden per Total hours
respondent disclosure
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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