[Federal Register Volume 85, Number 204 (Wednesday, October 21, 2020)]
[Notices]
[Pages 66995-66999]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-23290]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-N-3771]


Annual Status Report Information and Other Submissions for 
Postmarketing Requirements and Commitments: Using Forms FDA 3988 and 
FDA 3989; Draft Guidance for Industry; Availability; Agency Information 
Collection Activities; Proposed Collection; Comment Request

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a draft guidance for industry entitled ``Annual 
Status Report Information and Other Submissions for Postmarketing 
Requirements and Commitments: Using Forms FDA 3988 and FDA 3989.'' 
Forms FDA 3988, Transmittal of PMR/PMC Submissions for Drugs and 
Biologics, and FDA 3989, PMR/PMC Annual Status Report for Drugs and 
Biologics, are intended to facilitate submissions by drug and 
biological product application holders of complete and accurate 
information on postmarketing requirements (PMRs) and postmarketing 
commitments (PMCs) in a consistent format. Forms FDA 3988 and 3989 are 
published in draft form in Appendix A and B of the draft guidance for 
comment and are not intended to be used until the forms are finalized. 
The forms were developed, in part, in response to the recommendations 
from the Government Accountability Office (GAO) and the Department of 
Health and Human Services (HHS) Office of the Inspector General (OIG) 
regarding the need for comparable information across annual status 
reports (ASRs) on PMRs and PMCs, to eliminate manual data entry, and to 
enhance FDA's ability to track PMRs and PMCs. These forms are expected 
to result in improved accuracy and timeliness of FDA's identification 
and review of those submissions containing information on PMRs and 
PMCs. This draft guidance covers the purpose of each form, when to use 
these forms, and how to submit these forms. The draft guidance also 
explains where applicants will be able to find the forms and 
instructions for their completion once the forms and instructions are 
finalized.

DATES: Submit either electronic or written comments on the draft 
guidance by December 21, 2020 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 
version of the guidance. Submit either electronic or written comments 
on the collection of information set forth in this document by December 
21, 2020.

ADDRESSES: You may submit comments on any guidance at any time as 
follows:

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

[[Page 66996]]

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 should include the Docket 
No. FDA-2018-N-3771 for ``Annual Status Report Information and Other 
Submissions for Postmarketing Requirements and Commitments: Using Forms 
FDA 3988 and FDA 3989.'' Received comments 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.
     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.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    Submit written requests for single copies of the draft guidance to 
the Division of Drug Information, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10001 New Hampshire Ave., 
Hillandale Building, 4th Floor, Silver Spring, MD 20993-0002; or the 
Office of Communication, Outreach, and Development, Center for 
Biologics Evaluation and Research, Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002. 
Send one self-addressed adhesive label to assist that office in 
processing your requests. See the SUPPLEMENTARY INFORMATION section for 
electronic access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT: Kathy Weil, Center for Drug Evaluation 
and Research, Food and Drug Administration, 10903 New Hampshire Ave., 
Bldg. 22, Rm. 5367, Silver Spring, MD 20993-0002, 301-796-6054; or 
Stephen Ripley, Center for Biologics Evaluation and Research, Food and 
Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, 
Silver Spring, MD 20993-0002, 240-402-7911.
    With regard to the proposed collection of information: 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, PRAS[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Annual Status Report Information and Other Submissions for 
Postmarketing Requirements and Commitments: Using Forms FDA 3988 and 
FDA 3989.'' This draft guidance is intended for applicants that are 
required to report annually on the status of postmarketing studies and 
clinical trials for human drug and biological products under section 
506B of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 
356b) and its implementing regulations at Sec. Sec.  314.81(b)(2)(vii) 
and 601.70 (21 CFR 314.81(b)(2)(vii) and 601.70). These forms are 
expected to result in improved accuracy and timeliness of FDA's 
identification and review of those submissions containing information 
on PMRs and PMCs. The purpose of the draft guidance is to explain why 
Forms FDA 3988 and FDA 3989 were created, describe the contents of the 
forms, and explain how to submit the forms electronically. The draft 
guidance also explains where applicants will be able to find the forms 
and instructions for their completion once the forms and instructions 
are finalized. Forms FDA 3988 and 3989 are published in draft form in 
Appendix A and B of the draft guidance for comment and are not intended 
to be used until the forms are finalized.
    PMRs and PMCs are studies or clinical trials conducted by the 
applicant after FDA has approved a drug or biological product for 
marketing or licensing. These studies or clinical trials can be 
required under statute or regulation (PMRs) or agreed upon in writing 
by FDA and the applicant (PMCs). Section 130(a) of the Food and Drug 
Administration Modernization Act of 1997 amended the FD&C Act by adding 
section 506B of the FD&C Act (21 U.S.C. 356b). Under section 506B of 
the FD&C Act and its implementing regulations at Sec. Sec.  
314.81(b)(2)(vii) and 601.70, applicants must submit an ASR on PMRs and 
PMCs.\1\ This report must address the progress of the PMR/PMC or the 
reasons for failing to conduct the requirement or commitment (section 
506B(a) of the FD&C Act).
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    \1\ The FDA defines postmarketing studies or clinical trials for 
which annual status reports (ASRs) must be submitted under section 
506B of the FD&C Act as those concerning a human drug or biological 
product's clinical safety, clinical efficacy, clinical pharmacology, 
or nonclinical toxicology that are either required by FDA (PMRs) or 
that are committed to, in writing, (PMCs) either at the time of 
approval of an application or a supplement or after approval of an 
application or supplement. See Sec. Sec.  314.81(b)(2)(vii) and 
601.70. FDA interprets section 506B of the FD&C Act to apply to 
postmarketing studies and clinical trials that are required under 
the Pediatric Research Equity Act (section 505B of the FD&C Act (21 
U.S.C. 355c); Sec. Sec.  314.55(b) and 601.27(b)), the animal 
efficacy rule (Sec. Sec.  314.610(b)(1) and 601.91(b)(1)), 
accelerated approval (section 506(c)(2)(A) of the FD&C Act; 
Sec. Sec.  314.510 and 601.41), and the Food and Drug Administration 
Amendments Act of 2007 (section 505(o)(3) of the FD&C Act (21 U.S.C. 
355(o)(3)).
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    This draft guidance does not apply to postmarketing studies or 
clinical trials

[[Page 66997]]

that are not subject to the reporting requirements of section 506B of 
the FD&C Act.\2\ For example, the draft guidance does not apply to 
voluntary studies or clinical trials performed by an applicant or on an 
applicant's behalf that are neither required nor agreed upon in 
writing. This draft guidance also does not apply to PMCs related to 
chemistry, manufacturing, and controls or stability studies.
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    \2\ Under Sec.  314.81(b)(2)(viii), applicants submitting an 
annual report for human drug products must include a status report 
of postmarketing studies and clinical trials not included under 
Sec.  314.81(b)(2)(vii) that are being performed by, or on behalf 
of, the applicant.
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    In a December 2015 report from the GAO entitled ``Drug Safety: FDA 
Expedites Many Applications, but Data for Postapproval Oversight Need 
Improvement,'' \3\ the GAO recommended that FDA improve its data 
tracking to ensure the completeness, timeliness, and accuracy of 
information in its database on PMRs/PMCs. Additionally, in a July 2016 
HHS OIG study entitled ``FDA is Issuing More Postmarketing 
Requirements, but Challenges with Oversight Persist,'' \4\ the HHS OIG 
noted that FDA continued to have problems with its data management 
system and work processes, thereby hindering its ability to track PMRs. 
OIG recommended that FDA provide standardized forms for ASRs, ensure 
that the forms are complete, and require applicants to submit the forms 
electronically.
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    \3\ Available at https://www.gao.gov/products/GAO-16-192.
    \4\ Available at https://oig.hhs.gov/oei/reports/oei-01-14-00390.asp.
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    Based in part on the recommendations from GAO and HHS OIG, FDA 
created Forms FDA 3988 and FDA 3989 to improve its collection, 
identification, and use of information regarding PMRs and PMCs. Form 
FDA 3988 was developed to accompany an applicant's PMR/PMC-related 
submissions (e.g., draft protocols, final protocols, interim reports, 
final reports, and PMR/PMC-related correspondence), except the ASR on 
PMRs and PMCs. Form FDA 3988 allows applicants to identify, in a 
standardized format, the type of PMR/PMC-related submission the 
applicant is making (e.g., draft protocol) and the PMR or PMC to which 
the submission applies. Form FDA 3989 was developed so that applicants 
may provide ASR information on their PMRs and PMCs in a standardized 
format. The purpose of these forms is to assist applicants in providing 
clearly identified PMR/PMC-related submissions and in meeting their 
annual reporting requirements under section 506B of the FD&C Act and 
Sec. Sec.  314.81(b)(2)(vii) and 601.70.
    Use of Form FDA 3988 and 3989 is optional, but FDA encourages their 
use because the forms should facilitate FDA management and review of 
the applicant's submissions, as well as enhance the accuracy of data 
within FDA's electronic document archiving systems. FDA uses these 
archiving systems as a source from which to obtain data published 
annually in the Federal Register as required under section 506B(c) of 
the FD&C Act and to provide quarterly status updates of the PMR and PMC 
data on FDA's Postmarket Requirements and Commitments public web page 
(available at https://www.accessdata.fda.gov/scripts/cder/pmc/index.cfm).
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the current thinking of FDA on ``Annual 
Status Report Information and Other Submissions for Postmarketing 
Requirements and Commitments: Using Forms FDA 3988 and FDA 3989.'' It 
does not establish any rights for any person and is not binding on FDA 
or the public. You can use an alternative approach if it satisfies the 
requirements of the applicable statutes and regulations.

II. Paperwork Reduction Act of 1995

    Under the Paperwork Reduction Act of 1995 (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 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.

Annual Status Report Information and Other Submissions for 
Postmarketing Requirements and Commitments: Using Forms FDA 3988 and 
FDA 3989

    The draft guidance describes the purpose and content of Form FDA 
3988, Transmittal of PMR/PMC Submissions for Drugs and Biologics, and 
Form FDA 3989, PMR/PMC Annual Status Report for Drugs and Biologics. 
These forms are intended for applicants that are required by statute or 
regulation, or that have agreed in writing, to conduct postmarketing 
studies or clinical trials concerning the clinical safety, clinical 
efficacy, clinical pharmacology, or nonclinical toxicology of a human 
drug or biological product as PMRs or PMCs. Applicants are required to 
submit ASRs on PMCs and PMRs under section 506B of the FD&C Act and its 
implementing regulations at Sec. Sec.  314.81(b)(2)(vii) and 601.70, 
and this information collection is approved under OMB control numbers 
0910-0001 and 0910-0338, respectively. For this reason, these existing 
control numbers will be updated to account for Forms FDA 3988 and FDA 
3989.
    Form FDA 3988 would include the following information:
     Applicant's name, Center that approved or licensed the 
application (Center for Drug Evaluation and Research or Center for 
Biologics Evaluation and Research), application type (new drug 
application (NDA), biologics license application (BLA), abbreviated new 
drug application (ANDA), or investigational new drug application 
(IND)), and submission date.
     Six-digit application number and supplement number(s) as 
applicable.
     Drug or biologic product's established name (e.g., proper 
name, U.S. Pharmacopeia/U.S. Adopted Name) and proprietary (trade) 
name(s), if any.
     Information for all PMRs and PMCs addressed in the 
submission, including type (PMR or PMC), PMR or PMC number, 
establishment date, and National Clinical Trial (NCT) number (if 
applicable).
     PMR/PMC submission type, including draft protocol, final 
protocol, interim report, final report, general correspondence, 
Pediatric Research

[[Page 66998]]

Equity Act PMR deferral extension request, response to information 
request, request for revised milestones, and ``other,'' and a brief 
description of the submission's content or rationale.
     Name and title of the applicant's Responsible Official, 
and (as applicable) telephone and facsimile numbers, and email and 
mailing addresses.
     Signature of the applicant's Responsible Official or other 
Authorized Official, countersignature of the Authorized U.S. Agent, and 
date that the form is signed.
    Form FDA 3989 would include the following information:
     Applicant's name, Center that approved or licensed the 
application, application type, and submission date.
     Six-digit application number and date of U.S. approval.
     Drug or biologic product's established name (e.g., proper 
name, U.S. Pharmacopeia/U.S. Adopted Name) and proprietary (trade) 
name(s), if any.
     Alternate annual status report due date (i.e., a date 
other than the approval date that FDA has allowed the applicant to use 
for annual reporting).
     Period covered by the report.
     PMR/PMC update for each ``Open'' PMR/PMC. Information 
includes PMR/PMC number, establishment date, supplement number as 
applicable, description, study or clinical trial title as applicable, 
current and expected enrollment of studies and clinical trials as 
applicable, study or clinical trial status, explanation of status, and 
milestone information (e.g., milestone type, original date, revised 
date as applicable, the reason for the revision).
     Name and title of the applicant's Responsible Official, 
and (as applicable) telephone and facsimile numbers, and email and 
mailing addresses.
     Signature of the applicant's Responsible Official or other 
Authorized Official, countersignature of the Authorized U.S. Agent, and 
date that the form is signed.
    Forms FDA 3988 and FDA 3989 are fillable forms supporting 
electronic signatures. Based on the number of applicants required by 
statute or regulation, or that have agreed in writing, to conduct 
postmarketing studies or clinical trials as PMRs or PMCs, and based on 
the number of PMR/PMC-related submissions that we currently receive 
annually, we estimate receiving approximately 1,908 Forms FDA 3988 and 
636 Forms FDA 3989, annually, in accordance with the description in the 
draft guidance. We estimate that approximately 318 \5\ applicants will 
submit these forms, and that each form, as described in the draft 
guidance, will take approximately 1 hour to prepare and electronically 
submit to FDA.
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    \5\ This number is based on information from ``The Food and Drug 
Administration Report on the Performance of Drugs and Biologics 
Firms in Conducting Postmarketing Requirements and Commitments. 
Fiscal Year 2018'' available at https://www.fda.gov/media/129657/download.
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    FDA estimates the burden of this collection of information as 
follows:

                                 Table 1--Estimated Reporting Burden \1\ \2\ \3\
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                                                     Number of
          Sec.   314.81              Number of     responses per   Total annual   Average burden    Total hours
                                    respondents     respondent       responses     per response
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Form FDA 3988...................             226               6           1,356               1           1,356
Form FDA 3989...................             226               2             452               1             452
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    Total.......................  ..............  ..............  ..............  ..............           1,808
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.
\2\ Total hours for Form FDA 3989 in this table includes and replaces the burden that applicants currently incur
  to complete the ASR on PMRs and PMCs that is currently submitted as part of the annual report under Sec.
  314.81(b)(2).
\3\ Burden associated with OMB Control No. 0910-0001: Applications for FDA Approval to Market a New Drug.


                                 Table 2--Estimated Reporting Burden \1\ \2\ \3\
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                                                     Number of
          Sec.   601.70              Number of     responses per   Total annual   Average burden    Total hours
                                    respondents     respondent       responses     per response
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Form FDA 3988...................              92               6             552               1             552
Form FDA 3989...................              92               2             184               1             184
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    Total.......................  ..............  ..............  ..............  ..............             736
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.
\2\ Total hours for Form FDA 3989 in this table includes and replaces the burden that applicants currently incur
  to complete the ASR on PMRs and PMCs that is currently submitted pursuant to Sec.   601.70.
\3\ Burden associated with OMB Control No. 0910-0338: General Licensing Provisions: Biologics License
  Application, Changes to an Approved Application, Labeling, Revocation and Suspension, Postmarketing Studies
  Status Reports, and Form FDA 356h (21 CFR part 601).


[[Page 66999]]

III. Electronic Access

    Persons with access to the internet may obtain the draft guidance 
at https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics, or 
https://www.regulations.gov.

    Dated: October 13, 2020.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2020-23290 Filed 10-20-20; 8:45 am]
BILLING CODE 4164-01-P