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Food and Drug Administration, HHS.
Notice of availability.
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 The guidance includes a principles document and annex 1 and is the precursory guidance to the draft guidance entitled “E6(R3) Good Clinical Practice: Annex 2.”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 The guidance finalizes the draft guidance of the same title issued on June 7, 2023.
The announcement of the guidance is published in the Federal Register on September 9, 2025.
You may submit either electronic or written comments on Agency guidances at any time as follows:
Submit electronic comments in the following way:
Submit written/paper submissions as follows:
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 https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.
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)). ( printed 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.
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, amy.chi@fda.hhs.gov; 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, Brooke.DalSanto@fda.hhs.gov.
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 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 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.
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.
Persons with access to the internet may obtain the guidance at https:// ( printed page 43462) ,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.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2025-17311 Filed 9-8-25; 8:45 am]
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