[Federal Register Volume 86, Number 212 (Friday, November 5, 2021)]
[Notices]
[Pages 61277-61279]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-24236]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2021-N-0515]


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

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) 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 December 6, 2021.

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: Domini Bean, Office of Operations, 
Food and Drug Administration, Three White Flint North, 10A-12M, 11601 
Landsdown St., North Bethesda, MD 20852, 301-796-5733, 
[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 and Recordkeeping for Drug 
and Biologics Products

OMB Control Number 0910-0230--Revision

    This information collection supports statutory provisions set forth 
in the Federal Food, Drug, and Cosmetic Act (FD&C Act) regarding the 
monitoring of FDA-regulated products. Specifically,

[[Page 61278]]

FDA must be promptly informed of adverse experiences associated with 
the use of marketed drugs, including human drugs and biological 
products. Regulations in Sec. Sec.  310.305 and 314.80 (21 CFR 310.305 
and 314.80) implement reporting and recordkeeping requirements that 
enable FDA to take action to protect the public health from adverse 
drug experiences. All applicants who have received marketing approval 
for drug products are required to report serious, unexpected adverse 
drug experiences (15-day ``Alert reports''), as well as followup 
reports (Sec.  314.80(c)(1)) to FDA. This includes reports of all 
foreign or domestic adverse experiences as well as those based on 
information from applicable scientific literature and certain reports 
from postmarketing studies. Section 314.80(c)(1)(iii) pertains to such 
reports submitted by nonapplicants.
    Under Sec.  314.80(c)(2), applicants must 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 for 10 years 
records of all adverse drug experience reports known to the applicant.
    For marketed prescription drug products without approved new drug 
applications (NDAs) or abbreviated new drug applications (ANDAs), 
manufacturers, packers, and distributors 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 
for 10 years records of all adverse drug experiences required to be 
reported.
    Section 760 of the FD&C Act (21 U.S.C. 379aa) also provides for 
mandatory safety reporting for over-the-counter (OTC) human drug 
products not subject to applications approved under section 505 of the 
FD&C Act (21 U.S.C. 355) (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 21 CFR 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,'' available at 
https://www.fda.gov/media/77193/download. 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.
    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 drug 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, and clinical 
investigators. 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 or the 
need for postmarketing studies or clinical trials and, when necessary, 
to initiate removal of a product from the market.
    In addition, this information collection includes an International 
Council for Harmonisation (ICH) guidance for industry entitled 
``Providing Postmarketing Periodic Safety Reports in the ICH E2C(R2) 
Format (Periodic Benefit-Risk Evaluation Report),'' available at 
https://www.fda.gov/media/85520/download. The guidance describes the 
conditions under which applicants may use the ICH3 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) (21 CFR 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 (PSUR) waiver is in place. The information collection 
burden for waivers of a PSUR are currently approved in OMB control 
number 0910-0771; however, it is being consolidated with this 
information collection for administrative efficiency.
    Similarly, the 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,'' available at https://www.fda.gov/media/72498/download. 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.
    Respondents to this collection of information are: (1) 
Manufacturers, packers, distributors, and applicants of FDA-regulated 
drug and biologic products; (2) manufacturers, packers, and 
distributors of marketed prescription drug products without an FDA-
approved application; and (3) manufacturers, packers, and distributors 
of marketed nonprescription drug products, including 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

[[Page 61279]]

drug products marketed outside the monograph system.
    In the Federal Register of June 30, 2021 (86 FR 34759), we 
published a 60-day notice requesting public comment on the proposed 
collection of information. No comments were received.
    We estimate the burden of this collection of information as 
follows:

                                 Table 1--Estimated Annual Reporting Burden \1\
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                                                    Number of
   21 CFR section or type of       Number of      responses per   Total annual    Average burden    Total hours
    respondent and activity       respondents      respondent       responses      per response
----------------------------------------------------------------------------------------------------------------
310.305(c)(5).................                3               1               3                1               3
314.80(c)(1)(iii).............                5               1               5                1               5
314.80(c)(2)..................              820           17.32          14,202               60         852,120
Reports of serious adverse                  285             690         196,650                6       1,179,900
 drug events (Sec.   329.100).
Applicants that have a PSUR                  55             3.4             187                1             187
 waiver for an approved
 application..................
Applicants that do not have a                29             2.3              67                2             134
 PSUR waiver for an approved
 application..................
Notifying FDA when normal                   350               1             350                8           2,800
 reporting is not feasible....
                               ---------------------------------------------------------------------------------
    Total \2\.................  ...............  ..............         211,464  ...............       2,035,149
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\1\ The capital costs or operating and maintenance costs associated with this collection of information are
  approximately $25,000 annually.


                               Table 2--Estimated Annual Recordkeeping Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                    Number of                     Average burden
  21 CFR section or FD&C act       Number of       records per    Total annual         per          Total hours
     section and activity        recordkeepers    recordkeeper       records      recordkeeping
----------------------------------------------------------------------------------------------------------------
310.305.......................               25               1              25               16             400
314.80(j).....................              352           1,870         658,240               16      10,531,840
Recordkeeping of                            300        885.6667         265,700                8       2,125,600
 nonprescription drug adverse
 event reports (Section
 760(e)(1) of the FD&C Act)...
Adding Adverse Event report                 100               1             100               50           5,000
 planning to Continuity of
 Operations Plans.............
Maintaining documentation of                350               1             350                8           2,800
 pandemic conditions and
 resultant high absenteeism...
Maintaining records to                      350               1             350                8           2,800
 identify what reports have
 been stored and when the
 reporting process was
 restored.....................
                               ---------------------------------------------------------------------------------
    Total \2\.................  ...............  ..............         924,765  ...............      12,668,440
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\1\ There are no capital costs or operating costs associated with this collection of information.
\2\ There are maintenance costs of approximately $22,000 annually.

    We have increased our estimate to reflect expected adjustments to 
the information collection since our last submission for OMB review and 
approval.

    Dated: November 1, 2021.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2021-24236 Filed 11-4-21; 8:45 am]
BILLING CODE 4164-01-P


