[Federal Register Volume 86, Number 123 (Wednesday, June 30, 2021)]
[Notices]
[Pages 34759-34762]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-13968]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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


Agency Information Collection Activities; Proposed Collection; 
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 an opportunity for public 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: Submit either electronic or written comments on the collection 
of information by August 30, 2021.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. Electronic comments 
must be submitted on or before August 30, 2021. The https://www.regulations.gov electronic filing system will accept comments until 
11:59 p.m. Eastern Time at the end of August 30, 2021. Comments 
received by mail/hand delivery/courier (for written/paper submissions) 
will be considered timely if they are postmarked or the delivery 
service acceptance receipt is 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.''

[[Page 34760]]

    Instructions: All submissions received must include the Docket No. 
FDA-2021-N-0515 for ``Postmarketing Adverse Experience Reporting and 
Recordkeeping for Drug and Biological Products.'' 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: 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, 
PRAStaff@fda.hhs.gov.

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 and Recordkeeping for Drug 
and Biologics Products

OMB Control Number 0910-0230--Extension

    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, 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

[[Page 34761]]

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 drug products marketed outside the monograph 
system.
    FDA estimates 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
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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 drug              285             690         196,650               6       1,179,900
 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......
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    Total 2.....................  ..............  ..............         211,464  ..............       2,035,149
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1 The reporting burden for Sec.  Sec.   310.305(c)(1), (2), and (3), and 314.80(c)(1)(i) and (ii) is covered
  under OMB control number 0910-0645.
2 The capital costs or operating and maintenance costs associated with this collection of information are
  approximately $25,000 annually.


[[Page 34762]]


                                Table 2--Estimated Annual Recordkeeping Burden 1
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                                                     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
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310.305.........................              25               1              25              16             400
314.80(j).......................             325           2,025         658,240              16      10,531,840
Recordkeeping of nonprescription             300        885.6667         265,700               8       2,125,600
 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 identify              350               1             350               8           2,800
 what reports have been stored
 and when the reporting process
 was restored...................
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    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.

    The information collection reflects adjustments resulting in an 
overall decrease in burden hours and an increase in annual responses. 
We believe these adjustments reflect expected fluctuations in burden 
and invite comment on our assumptions.

    Dated: June 25, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-13968 Filed 6-29-21; 8:45 am]
BILLING CODE 4164-01-P


