Notice2022-07690
E8(R1) General Considerations for Clinical Studies; International Council for Harmonisation; Guidance for Industry; Availability
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Published
April 11, 2022
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 "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.
Full Text
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<title>Federal Register, Volume 87 Issue 69 (Monday, April 11, 2022)</title>
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[Federal Register Volume 87, Number 69 (Monday, April 11, 2022)]
[Notices]
[Pages 21127-21129]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[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:
<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-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 <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
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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: <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)).
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,
<a href="/cdn-cgi/l/email-protection#0e436f7c6520426b786b607d61604e686a6f2066667d20696178"><span class="__cf_email__" data-cfemail="c489a5b6afea88a1b2a1aab7abaa84a2a0a5eaacacb7eaa3abb2">[email protected]</span></a>; 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,
<a href="/cdn-cgi/l/email-protection#e6ac8f8a8ac8a7828a8384839481a6808287c88e8e95c8818990"><span class="__cf_email__" data-cfemail="3e74575252107f5a525b5c5b4c597e585a5f1056564d10595148">[email protected]</span></a>.
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 <a href="https://www.ich.org/">https://www.ich.org/</a>).
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
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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 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
<a href="https://www.regulations.gov">https://www.regulations.gov</a>, <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/regulatory-information/search-fda-guidance-documents">https://www.fda.gov/regulatory-information/search-fda-guidance-documents</a>, or <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>.
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
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