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