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Notice2025-17311

E6(R3) Good Clinical Practice; International Council for Harmonisation; Guidance for Industry; Availability

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Published
September 9, 2025

Issuing agencies

Health and Human Services DepartmentFood and Drug Administration

Abstract

The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled "E6(R3) Good Clinical Practice." The guidance was prepared under the auspices of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). The guidance includes a principles document and annex 1 and is the precursory guidance to the draft guidance entitled "E6(R3) Good Clinical Practice: Annex 2." Once complete, the guidance will be composed of a principles document, annex 1, and annex 2. The guidance is intended to outline flexible and modern good clinical practices for conducting clinical trials. Notably, the guidance highlights the importance of quality-by-design, proportionality, and risk-based approaches in conducting clinical trials to ensure safety and reliability of results. The guidance also encourages use of innovative design elements and technology in clinical trials, while avoiding unnecessary complexities. The guidance finalizes the draft guidance of the same title issued on June 7, 2023.

Full Text

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<title>Federal Register, Volume 90 Issue 172 (Tuesday, September 9, 2025)</title>
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[Federal Register Volume 90, Number 172 (Tuesday, September 9, 2025)]
[Notices]
[Pages 43460-43462]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2025-17311]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2023-D-1955]


E6(R3) Good Clinical Practice; International Council for 
Harmonisation; 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 final guidance for industry entitled ``E6(R3) 
Good Clinical Practice.'' The guidance was prepared under the auspices 
of the International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use (ICH). The guidance 
includes a principles document and annex 1 and is the precursory 
guidance to the draft guidance entitled ``E6(R3) Good Clinical 
Practice: Annex 2.'' Once complete, the guidance will be composed of a 
principles document, annex 1, and annex 2. The guidance is intended to 
outline flexible and modern good clinical practices for conducting 
clinical trials. Notably, the guidance highlights the importance of 
quality-by-design, proportionality, and risk-based approaches in 
conducting clinical trials to ensure safety and reliability of results. 
The guidance also encourages use of innovative design elements and 
technology in clinical trials, while avoiding unnecessary complexities. 
The guidance finalizes the draft guidance of the same title issued on 
June 7, 2023.

DATES: The announcement of the guidance is published in the Federal 
Register on September 9, 2025.

ADDRESSES: You may submit either electronic or written comments on 
Agency guidances at any time as follows:

Electronic Submissions

    Submit electronic comments in the following way:
    <bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a> 
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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
    <bullet> 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:
    <bullet> 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.
    <bullet> 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-2023-D-1955 for ``E6(R3) Good Clinical Practice.'' Received 
comments will be placed in the docket and, except for those submitted 
as ``Confidential Submissions,'' publicly viewable at <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets Management Staff between 9 a.m. 
and 4 p.m., Monday through Friday, 240-402-7500.
    <bullet> 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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>. 
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: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> 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)).

[[Page 43461]]

    Submit written requests for single copies of this 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. Send one self-
addressed adhesive label to assist that office in processing your 
requests. The guidance may also be obtained by mail by calling Center 
for Biologics Evaluation and Research at 1-800-835-4709 or 240-402-
8010. See the SUPPLEMENTARY INFORMATION section for electronic access 
to the 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, 240-402-0992, 
<a href="/cdn-cgi/l/email-protection#8dece0f4a3eee5e4cdebe9eca3e5e5fea3eae2fb"><span class="__cf_email__" data-cfemail="d4b5b9adfab7bcbd94b2b0b5fabcbca7fab3bba2">[email&#160;protected]</span></a>; Phillip Kurs, Center for Biologics Evaluation and 
Research, Food and Drug Administration, 240-402-7911.
    Regarding the ICH: Brooke Dal Santo, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 
51, Rm. 6304, Silver Spring, MD 20993-0002, 301-348-1967, 
<a href="/cdn-cgi/l/email-protection#1456667b7b7f713a50757847757a607b547270753a7c7c673a737b62"><span class="__cf_email__" data-cfemail="3270405d5d59571c76535e61535c465d725456531c5a5a411c555d44">[email&#160;protected]</span></a>.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``E6(R3) Good Clinical Practice.'' The guidance was prepared 
under the auspices of ICH. ICH seeks to achieve greater regulatory 
harmonization worldwide to ensure that safe, effective, 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 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 <a href="https://www.ich.org/">https://www.ich.org/</a>).
    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 the Federal Register of June 7, 2023 (88 FR 37257), FDA 
published a notice announcing the availability of a draft guidance 
entitled ``E6(R3) Good Clinical Practice.'' The notice gave interested 
persons an opportunity to submit comments by September 5, 2023.
    After consideration of the comments received and revisions to the 
guideline, a final draft of the guideline was submitted to the ICH 
Assembly and endorsed by the regulatory agencies in December 2024.
    This guidance finalizes the draft guidance issued on June 7, 2023. 
The guidance offers modernized and agile recommendations for designing 
and conducting trials efficiently, safely, and innovatively. In 
response to public comments, the guidance clarifies that technology and 
design elements are likely to evolve and that the principles of E6(R3) 
are developed to remain relevant as such advances occur. The guidance 
stresses proportionality and a focus on the risk to participants and 
the reliability of the results. Furthermore, the guidance adds clarity 
to enable different modalities of informed consent (including remote 
and eConsent) as well as refining language on consent and assent. The 
guidance also clarifies the responsibilities of the investigators and 
sponsors regarding delegating clinical trial conduct responsibilities 
to service providers to reflect the practical application of E6(R3). 
Lastly, the guidance significantly streamlines and adds clarity to the 
section on data governance and simplifies the table in appendix C by 
providing clarity on the considerations for determining what records 
are considered essential.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
current thinking of FDA on ``E6(R3) Good Clinical Practice.'' 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.
    FDA considered the applicability of Executive Order 14192, per OMB 
guidance in M-25-20, and finds this action to be deregulatory in 
nature.

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 found in 21 CFR part 312 for investigational new drug 
applications have been approved under OMB control number 0910-0014. The 
collections of information under 21 CFR part 312.145 pertaining to good 
clinical practice have been approved under OMB control number 0910-
0843. The collections of information found 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 found in 21 CFR part 314 relating 
to the review of new drug applications have been approved under OMB 
control number 0910-0001. The collections of information found in 21 
CFR part 601 relating to the review of biologic licensing applications 
have been approved under OMB control number 0910-0338. The collections 
of information found in 21 CFR part 11 pertaining to electronic records 
and electronic signatures have been approved under OMB control number 
0910-0303. The collections of information found in 21 CFR parts 210 and 
211 pertaining to current good manufacturing practice have been 
approved under OMB control number 0910-0139.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
https://

[[Page 43462]]

www.regulations.gov, <a href="https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs">https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs</a>, <a href="https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances">https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances</a>, or <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents">https://www.fda.gov/regulatory-information/search-fda-guidance-documents</a>.

Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2025-17311 Filed 9-8-25; 8:45 am]
BILLING CODE 4164-01-P


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