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[Federal Register Volume 89, Number 249 (Monday, December 30, 2024)]
[Notices]
[Pages 106519-106521]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-31275]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2024-D-5601]

E6(R3) Good Clinical Practice: Annex 2; International Council for 
Harmonisation; Draft Guidance for Industry; Availability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the availability of a draft guidance for industry entitled ``E6(R3) 
Good Clinical Practice: Annex 2.'' The draft guidance was prepared 
under the auspices of the International Council for Harmonisation of 
Technical Requirements for Pharmaceuticals for Human Use (ICH). The 
draft guidance is the second annex to ``E6(R3) Good Clinical Practice'' 
published June of 2023. This annex provides additional considerations 
for the application of good clinical practices to a variety of trial 
designs and data sources.

[[Page 106520]]

Specifically, this draft guidance discusses trials with decentralized 
and pragmatic elements and real-world data sources. This draft guidance 
highlights the importance of quality by design and focusing efforts and 
resources on critical aspects of the trials that might impact the 
safety of participants and the reliability of results. The draft 
guidance is intended to encourage innovation in trial design and 
provides flexible, modern, and clear good clinical practices for 
conducting trials, while avoiding unnecessary complexities.

DATES: Submit either electronic or written comments on the draft 
guidance by February 28, 2025 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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-2024-D-5601 for ``E6(R3) Good Clinical Practice: Annex 2.'' 
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 the 
Office of Communication, Outreach and Development, Center for Biologics 
Evaluation and Research (CBER), 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. The guidance may also be obtained by calling CBER at 1-
800-835-4709 or 240-402-8010. See the SUPPLEMENTARY INFORMATION section 
for electronic access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT: Regarding the guidance: Amy Chi, 
Center for Drug Evaluation and Research, Food and Drug Administration, 
10903 New Hampshire Ave., Bldg. 51, Rm. 6334, Silver Spring, MD 20993-
0002, [email protected]; or James Myers, 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.
    Regarding the ICH: Jill Adleberg, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 
51, Rm. 6364, Silver Spring, MD 20993-0002, 301-796-5259, 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``E6(R3) Good Clinical Practice: Annex 2.'' The draft guidance 
was prepared under the auspices of ICH. ICH seeks to achieve greater 
regulatory harmonization worldwide to ensure that safe, effective, and 
high-quality medicines are developed, registered, and maintained in the 
most resource-efficient manner.
    By harmonizing the regulatory requirements in regions around the 
world, ICH guidelines enhance global drug development, improve 
manufacturing standards, and increase the availability of medications. 
For example, ICH guidelines have substantially reduced duplicative 
clinical studies, prevented unnecessary animal studies, standardized 
the reporting of important safety information, and standardized 
marketing application submissions.
    The six Founding Members of the ICH are FDA; the Pharmaceutical 
Research and Manufacturers of America; the European Commission; the 
European Federation of Pharmaceutical Industries Associations; the 
Japanese Ministry of

[[Page 106521]]

Health, Labour, and Welfare; and the Japanese Pharmaceutical 
Manufacturers Association. The Standing Members of the ICH Association 
include Health Canada and Swissmedic. ICH membership continues to 
expand to include other regulatory authorities and industry 
associations from around the world (refer to https://www.ich.org).
    ICH works by engaging global regulatory and industry experts in a 
detailed, science-based, and consensus-driven process that results in 
the development of ICH guidelines. The regulators around the world are 
committed to consistently adopting these consensus-based guidelines, 
realizing the benefits for patients and for industry.
    As a Founding Regulatory Member of ICH, FDA plays a major role in 
the development of each of the ICH guidelines, which FDA then adopts 
and issues as guidance for industry. FDA's guidance documents do not 
establish legally enforceable responsibilities. Instead, they describe 
the Agency's current thinking on a topic and should be viewed only as 
recommendations, unless specific regulatory or statutory requirements 
are cited.
    In November 2024, the ICH Assembly endorsed the draft guideline 
entitled ``E6(R3) Good Clinical Practice: Annex 2'' and agreed that the 
guideline should be made available for public comment. The draft 
guideline is the product of the Efficacy Expert Working Group of the 
ICH. FDA and the Efficacy Expert Working Group will consider comments 
on this draft.
    The draft guidance provides guidance on good clinical practices for 
trial design and conduct, with a focus on trials with decentralized and 
pragmatic elements as well as trials that utilize real-world data. 
Since the original E6 guidance was published in 1996, clinical trials 
have evolved significantly with new designs and technological 
innovations. Annex 2 provides additional considerations to the 
previously published draft guidance entitled ``E6(R3) Good Clinical 
Practice (GCP),'' which includes a Principles document and Annex 1. 
This draft guidance, entitled ``E6(R3) Good Clinical Practice: Annex 
2,'' is intended to be read and implemented with E6(R3) Principles and 
Annex 1.
    This draft guidance has been left in the original ICH format. The 
final guidance will be reformatted and edited to conform with FDA's 
good guidance practices regulation (21 CFR 10.115) and style before 
publication. The draft guidance, when finalized, will represent the 
current thinking of FDA on ``E6(R3) Good Clinical Practice: Annex 2.'' 
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

    While this guidance contains no collection of information, it does 
refer to previously approved FDA collections of information. The 
previously approved 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. 3501-3502). The collections of information in 21 
CFR part 312.145 pertaining to good clinical practices have been 
approved under OMB control number 0910-0014. The collections of 
information in 21 CFR parts 50 and 56 pertaining to protection of human 
subjects, institutional review boards, and informed consent have been 
approved under OMB control number 0910-0130. The collections of 
information in 21 CFR part 11 pertaining to electronic records and 
electronic signatures have been approved under OMB control number 0910-
0303.

III. Electronic Access

    Persons with access to the internet may obtain the draft guidance 
at https://www.regulations.gov, 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.fda.gov/regulatory-information/search-fda-guidance-documents.

    Dated: December 20, 2024.
P. Ritu Nalubola,
Associate Commissioner for Policy.
[FR Doc. 2024-31275 Filed 12-27-24; 8:45 am]
BILLING CODE 4164-01-P
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