[Federal Register Volume 87, Number 69 (Monday, April 11, 2022)]
[Notices]
[Pages 21127-21129]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-07690]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2019-D-3049]


E8(R1) General Considerations for Clinical Studies; 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 ``E8(R1) 
General Considerations for Clinical Studies.'' The guidance was 
prepared under the auspices of the International Council for 
Harmonisation (ICH), formerly the International Conference on 
Harmonisation. The guidance describes internationally accepted 
principles and practices for the design and conduct of clinical studies 
of drug and biological products. In addition, the guidance provides an 
overview of the types of clinical studies that may be performed and 
data sources used during the product's life cycle. The guidance is 
intended to promote the quality of the studies submitted to regulatory 
authorities, while allowing for flexibility. This guidance revises the 
guidance for industry ``E8 General Considerations for Clinical Trials'' 
issued in December 1997.

DATES: The announcement of the guidance is published in the Federal 
Register on April 11, 2022.

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:
     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-2019-D-3049 for ``E8(R1) General Considerations for Clinical 
Studies.'' 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

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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 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, 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 mail by calling 
CBER 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: Mark Levenson, 
Center for Drug Evaluation and Research, Food and Drug Administration, 
Bldg. 21, Rm. 4626, Silver Spring, MD 20993-0002, 301-796-2097, 
[email protected]; 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.
    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 final guidance for industry 
entitled ``E8(R1) General Considerations for Clinical Studies''. The 
guidance was prepared under the auspices of ICH. ICH has the mission of 
achieving 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 have substantially reduced duplicative clinical 
studies, prevented unnecessary animal studies,\1\ standardized the 
reporting of important safety information, standardized marketing 
application submissions, and made many other improvements in the 
quality of global drug development and manufacturing and the products 
available to patients.
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    \1\ We support the principles of the ``3Rs,'' to reduce, refine, 
and replace animal use in testing when feasible. We encourage 
sponsors to consult with us if it they wish to use a non-animal 
testing method they believe is suitable, adequate, validated, and 
feasible. We will consider if such an alternative method could be 
assessed for equivalency to an animal test method.
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    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. Additionally, the 
Membership of ICH has expanded to include other regulatory authorities 
and industry associations from around the world (refer to https://www.ich.org/).
    ICH works by involving technical experts from both regulators and 
industry parties in detailed technical harmonization work and the 
application of a science-based approach to harmonization through a 
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 August 1, 2019 (84 FR 37649), FDA 
published a notice announcing the availability of a draft guidance 
entitled ``E8(R1) General Considerations for Clinical Studies.'' The 
notice gave interested persons an opportunity to submit comments by 
September 30, 2019. 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 October 2021.
    This guidance finalizes the draft guidance issued on August 1, 
2019. The revised final guidance describes internationally accepted 
principles and practices in the design and conduct of clinical studies 
of drug and biological products. Changes from the 2019 draft guidance 
to the final guidance include a reduced emphasis on distinct phases of 
clinical development, the addition of examples of novel studies, and 
amendments to appendices. The original ICH guidance ``E8 General 
Considerations for Clinical Trials,'' that was issued in 1997 has not 
undergone revision previously. Since the 1997 guidance was issued, 
clinical trial design and conduct have become more complex, impacting 
the time and feasibility of developing drugs. In response, the revised 
guidance directly addresses study quality to ensure the protection of 
study participants and the generation of reliable and meaningful 
results, while promoting study efficiency. The ICH E8(R1) guidance 
focuses on the identification of factors that are critical to the study 
quality and the management of risks to those factors. Additionally, a 
wider range of study designs and data sources play an increasingly 
important role in drug development and are not adequately addressed in 
the original ICH E8 guidance. Hence, the revised final guidance 
addresses a broad range of study designs and data sources. The revised 
final guidance also provides updated cross-referencing to other 
relevant ICH guidances that inform the design, planning, and conduct of 
clinical research, without reproducing the detailed material found in 
those guidances.
    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 ``E8(R1) General Considerations for Clinical 
Studies.'' It does not establish any rights for any person and is not 
binding on FDA or the

[[Page 21129]]

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 for investigational new drug applications under have 
been approved under OMB control number 0910-0014; the collections of 
information for review of new drug applications in have been approved 
under OMB control number 0910-0001; and the collections of information 
for review of biologic licensing applications in have been approved 
under OMB control number 0910-0338.

III. Electronic Access

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

    Dated: April 5, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-07690 Filed 4-8-22; 8:45 am]
BILLING CODE 4164-01-P


