[Federal Register Volume 88, Number 21 (Wednesday, February 1, 2023)]
[Notices]
[Pages 6748-6750]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-02094]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2022-D-2983]


Considerations for the Design and Conduct of Externally 
Controlled Trials for Drug and Biological Products; Draft Guidance for 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the availability of a draft guidance for industry entitled 
``Considerations for the Design and Conduct of Externally Controlled 
Trials for Drug and Biological Products.'' FDA is issuing this draft 
guidance as part of a series of guidance documents under its Real-World 
Evidence (RWE) Program and to satisfy, in part, a mandate under the 
Federal Food, Drug, and Cosmetic Act (FD&C Act) to issue guidance about 
the use of RWE in regulatory decision-making. This draft guidance 
includes recommendations to sponsors and investigators considering the 
use of externally controlled trials to provide evidence of the safety 
and effectiveness of a drug product. The draft guidance also describes 
considerations related to communicating with FDA and ensuring access by 
the Agency to data from an externally controlled trial.

DATES: Submit either electronic or written comments on the draft 
guidance by May 2, 2023 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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:

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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-2022-D-2983 for ``Considerations for the Design and Conduct of 
Externally Controlled Trials for Drug and Biological Products.'' 
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, 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.
    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 to 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: John Concato, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6346, Silver Spring, MD 20993-0002, 301-
796-2500, [email protected]; or Diane Maloney, 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 ``Considerations for the Design and Conduct of Externally 
Controlled Trials for Drug and Biological Products.'' This draft 
guidance provides recommendations to sponsors and investigators 
considering the use of externally controlled trials to provide evidence 
of the safety and effectiveness of a drug product. In an externally 
controlled trial, outcomes in participants receiving the test treatment 
according to a protocol are compared to outcomes in a group of people 
external to the trial who had not received the same treatment.
    The draft guidance addresses considerations for the design and 
analysis of externally controlled trials to study the effectiveness and 
safety of drugs, including discussion of threats to the validity of 
trial results from potential bias. Although various sources of data can 
serve as the control arm in an externally controlled trial, this draft 
guidance focuses on the use of patient-level data from other clinical 
trials or from real-world data (RWD) sources, such as registries as 
well as electronic health records and medical claims. The draft 
guidance also describes considerations related to communicating with 
FDA and ensuring access by the Agency to data from an externally 
controlled trial.
    This draft guidance does not address other types of external 
controls, such as using summary-level estimates instead of patient-
level data. This draft guidance does not discuss details of the design 
and analysis of a natural history study, nor the reliability and 
relevance of various sources of RWD that could be used in an externally 
controlled trial. Finally, this draft guidance also does not discuss 
considerations for using external control data to supplement a control 
arm in a traditional randomized controlled clinical trial.
    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 
``Considerations for the Design and Conduct of Externally Controlled 
Trials for Drug and Biological Products.'' It does not establish any 
rights for any person and is not binding on FDA or the

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public. You can use an alternative approach if it satisfies the 
requirements of the applicable statutes and regulations.

II. Paperwork Reduction Act of 1995

    While this guidance contains no collection of information, it does 
refer to previously approved FDA collections of information. Therefore, 
clearance by the Office of Management and Budget (OMB) under the 
Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not 
required for this guidance. The previously approved collections of 
information are subject to review by OMB under the PRA. The collections 
of information in 21 CFR part 312 have been approved under OMB control 
number 0910-0014; the collections of information in 21 CFR part 314 
have been approved under OMB control number 0910-0001; and the 
collections of information in 21 CFR part 601 have been approved under 
OMB control number 0910-0338.

III. Electronic Access

    Persons with access to the internet may obtain an electronic 
version of the draft guidance at https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.

    Dated: January 27, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-02094 Filed 1-31-23; 8:45 am]
BILLING CODE 4164-01-P


