Document ID: FDA-2009-D-0283-0022
Agency: fda
Document Type: Notice
Title: Postmarketing Studies and Clinical Trials—Implementation of Section 505(o)(3) of the Federal Food, Drug, and Cosmetic Act; Draft Guidance for Industry; Availability
Posted Date: 2019-10-25T04:00Z

[Federal Register Volume 84, Number 207 (Friday, October 25, 2019)]
[Notices]
[Pages 57452-57454]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-23312]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2009-D-0283]

Postmarketing Studies and Clinical Trials--Implementation of 
Section 505(o)(3) of the Federal Food, Drug, and Cosmetic Act; Draft 
Guidance for Industry; Availability

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the availability of a draft guidance for industry entitled 
``Postmarketing Studies and Clinical Trials--Implementation of Section 
505(o)(3) of the Federal Food, Drug, and Cosmetic Act.'' This draft 
guidance revises the guidance for industry of the same name issued 
April 1, 2011. The draft guidance is being revised to describe the 
multiple factors that FDA considers, before requiring a postmarketing 
study or clinical trial for the purposes described in the Federal Food, 
Drug, and Cosmetic Act (FD&C Act), when determining the sufficiency of 
the reports under the FD&C Act and the active postmarket risk 
identification and analysis (ARIA) system available under the FD&C Act 
to meet these purposes. The draft guidance is also being revised to 
reflect certain provisions enacted under the Substance Use-Disorder 
Prevention that Promotes Opioid Recovery and Treatment (SUPPORT) for 
Patients and Communities Act as they relate to postmarketing studies 
and clinical trials.

[[Page 57453]]

DATES: Submit either electronic or written comments on the draft 
guidance by December 24, 2019 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 
version of the guidance.

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 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-2009-D-0283 for ``Postmarketing Studies and Clinical Trials--
Implementation of Section 505(o)(3) of the Federal Food, Drug, and 
Cosmetic Act; Draft Guidance for Industry; Availability.'' 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.gpo.gov/fdsys/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 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: Ayanna Augustus, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 6426, Silver Spring, MD 20993-0002, 301-
796-3980; 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.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled, ``Postmarketing Studies and Clinical Trials--Implementation 
of Section 505(o)(3) of the Federal Food, Drug, and Cosmetic Act.''
    Section 505(o)(3) of the FD&C Act \1\ (21 U.S.C. 355(o)) authorizes 
FDA to require certain postmarketing studies or clinical trials for 
prescription drugs to obtain more information about a serious risk that 
may be associated with a drug. In some cases, FDA may be concerned 
about a serious risk that is potentially or known to be associated with 
a drug but may not know enough about the risk to determine if or how to 
address it, such as by describing the risk in labeling. Section 
505(o)(3)(B) of the FD&C Act states that postmarketing studies and 
clinical trials may be required for any or all of the following 
purposes: (1) To assess a known serious risk related to the use of the 
drug; (2) to assess signals of serious risk related to the use of the 
drug; or (3) to identify an unexpected serious risk when available data 
indicates the potential for a serious risk.
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    \1\ Section 901 of Title IX of the Food and Drug Administration 
Amendments Act of 2007 (Pub. L. 110-85) amended the FD&C Act by 
adding section 505(o).
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    Prior to requiring a postmarketing study or clinical trial, FDA 
must find that the reports under section 505(k)(1) of the FD&C Act and 
the ARIA system \2\ made available under section 505(k)(3) of the FD&C 
Act will not be sufficient to meet the purposes described in section 
505(o)(3)(B) of the FD&C Act.\3\ Similarly, before requiring a 
postmarketing clinical trial, FDA must find that a postmarketing study 
will not be sufficient to meet the purposes

[[Page 57454]]

described in section 505(o)(3)(B) of the FD&C Act.\4\
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    \2\ Section 505(k)(3) of the FD&C Act mandates that FDA 
establish an active surveillance system for monitoring drugs, using 
electronic data from healthcare information holders. The Sentinel 
System draws on existing healthcare data from multiple sources to 
actively monitor the safety of medical products. The ARIA system is 
a subcomponent of the Sentinel System.
    \3\ Section 505(o)(3)(D)(i) of the FD&C Act.
    \4\ Section 505(o)(3)(D)(ii) of the FD&C Act.
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    In April 2011, FDA issued a guidance describing how it would 
implement section 505(o) of the FD&C Act. At that time, the ARIA system 
was still in early development. The ARIA system is now officially 
launched, and FDA must consider the system's sufficiency to meet the 
purposes of section 505(o)(3)(B) of the FD&C Act to determine if a 
postmarketing study or clinical trial is necessary. This draft guidance 
revises the guidance for industry of the same name issued on April 1, 
2011 (76 FR 18226). Significant changes from the 2011 version include 
explaining how FDA considers the reporting under section 505(k)(1) of 
the FD&C Act and the ARIA system when determining their sufficiency for 
the purposes under section 505(o)(3)(B) of the FD&C Act. The guidance 
is also being revised to provide examples of postmarketing requirements 
under section 505(o)(3) of the FD&C Act to assess a potential reduction 
in the expected effectiveness of a drug under certain circumstances. 
FDA's authority to require these types of studies or trials was 
clarified by a modification to the definition of adverse drug 
experience at section 505-1(b)(1)(E) of the FD&C Act (21 U.S.C. 505-
1(b)(1)(E)) enacted under section 3041 of the SUPPORT Act (Pub. L. 115-
271).
    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 on implementation of 
section 505(o)(3)(B) of the FD&C Act. 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

    This draft guidance refers to previously approved collections of 
information found in FDA regulations. These collections of information 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520).
    The following collections of information for postmarketing reports 
and clinical data in 21 CFR 314.50, 314.80, 314.81, 314.98, 314.430, 
and 314.610(b), subpart I have been approved under OMB control number 
0910-0001: (1) Preparing and submitting reports pertaining to safety, 
postmarketing commitments and preparing and submitting spontaneous and 
periodic reports, including active postmarket risk identification 
(using electronic health care data) and any milestones or submissions 
for which projected dates were specified as part of the postmarketing 
commitment; (2) submitting a proposed timetable of the postmarketing 
commitments; (3) preparing registries and submitting them when 
appropriate; (4) designing meta-analyses to evaluate statistical 
analyses of data; (5) preparing assay procedures; and (6) prepare a 
plan or approach for approval an NDA when human efficacy studies are 
not ethical or feasible.
    The following collections of information for postmarketing studies 
and clinical trials (including various patient populations) in 21 CFR 
312.23 have been approved under OMB control number 0910-0014: (1) 
Conducting in vitro laboratory tests and studies to compare pregnancy 
incidence an pregnancy outcomes and/or child outcomes for patients 
exposed to a drug; (2) submitting an introductory statement and general 
investigational plan, including a drug's pharmacological class; and (3) 
submitting protocols for drug safety and pharmacology and toxicology 
information.
    The collections of information in 21 CFR 310.305, 314.80, and 
314.98 for submitting adverse event information to the FDA Adverse 
Event Reporting System have been approved under OMB control numbers 
0910-0230 and 0910-0291; the collections of information in 21 CFR 
312.47 and 312.82 for submitting a meeting request to appeal the 
conduct of a postmarketing study or clinical trial have been approved 
under OMB control number 0910-0430 (and guidance for industry and 
review staff entitled ``Formal Dispute Resolutions: Appeals Above the 
Division Level'' (available at https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm343101.pdf).
    The following collection of information in Sec.  314.510 has been 
approved under OMB control number 0910-0765: Requests for serious or 
life-threatening diseases or conditions that may be granted accelerated 
approval if FDA determines the product has an effect on a surrogate 
endpoint that is reasonably likely to predict clinical benefit or on a 
clinical endpoint that can be measured earlier than irreversible 
morbidity or mortality or other clinical benefit.

III. Electronic Access

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

    Dated: October 21, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-23312 Filed 10-24-19; 8:45 am]
BILLING CODE 4164-01-P