Notice2022-23787
S1B(R1) Addendum to S1B Testing for Carcinogenicity of Pharmaceuticals; International Council for Harmonisation; Guidance for Industry; Availability
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Published
November 2, 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 "S1B(R1) Addendum to S1B Testing for Carcinogenicity of Pharmaceuticals." The guidance was prepared under the auspices of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), formerly the International Conference on Harmonisation. The final guidance expands the testing scheme for assessing human carcinogenic risk of pharmaceuticals by introducing an additional approach that is not described in the original S1B Guideline. The final guidance is intended to offer an integrative approach that provides specific weight of evidence criteria that inform whether a 2-year rat study is likely to add value in completing a human carcinogenicity risk assessment. The Addendum also adds a plasma exposure ratio-based approach for setting the high dose in the rasH2-Tg mouse model, while all other aspects of the recommendations for high-dose selection in ICH guidance for industry "S1C(R2) Dose Selection for Carcinogenicity Studies of Pharmaceuticals" still apply.
Full Text
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<title>Federal Register, Volume 87 Issue 211 (Wednesday, November 2, 2022)</title>
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[Federal Register Volume 87, Number 211 (Wednesday, November 2, 2022)]
[Notices]
[Pages 66195-66197]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2022-23787]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2021-D-0669]
S1B(R1) Addendum to S1B Testing for Carcinogenicity of
Pharmaceuticals; 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 ``S1B(R1)
Addendum to S1B Testing for Carcinogenicity of Pharmaceuticals.'' The
guidance was prepared under the auspices of the International Council
for Harmonisation of Technical Requirements for Pharmaceuticals for
Human Use (ICH), formerly the International Conference on
Harmonisation. The final guidance expands the testing scheme for
assessing human carcinogenic risk of pharmaceuticals by introducing an
additional approach that is not described in the original S1B
Guideline. The final guidance is intended to offer an integrative
approach that provides specific weight of evidence criteria that inform
whether a 2-year rat study is
[[Page 66196]]
likely to add value in completing a human carcinogenicity risk
assessment. The Addendum also adds a plasma exposure ratio-based
approach for setting the high dose in the rasH2-Tg mouse model, while
all other aspects of the recommendations for high-dose selection in ICH
guidance for industry ``S1C(R2) Dose Selection for Carcinogenicity
Studies of Pharmaceuticals'' still apply.
DATES: The announcement of the guidance is published in the Federal
Register on November 2, 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-2021-D-0669 for ``S1B(R1) Addendum to S1B Testing for
Carcinogenicity of Pharmaceuticals.'' 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)).
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: Timothy McGovern, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, Rm. 6426, Silver Spring, MD 6426, 240-402-
0477 <a href="/cdn-cgi/l/email-protection#3d6954505249554413705e7a524b584f537d5b595c1355554e135a524b"><span class="__cf_email__" data-cfemail="db8fb2b6b4afb3a2f596b89cb4adbea9b59bbdbfbaf5b3b3a8f5bcb4ad">[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, <a href="/cdn-cgi/l/email-protection#7f2c0b1a0f171a11512d160f131a063f191b1e5117170c51181009"><span class="__cf_email__" data-cfemail="287b5c4d58404d46067a4158444d51684e4c490640405b064f475e">[email protected]</span></a>.
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#b6fcdfdada98f7d2dad3d4d3c4d1f6d0d2d798dedec598d1d9c0"><span class="__cf_email__" data-cfemail="89c3e0e5e5a7c8ede5ecebecfbeec9efede8a7e1e1faa7eee6ff">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a final guidance for industry
entitled ``S1B(R1) Addendum to S1B Testing for Carcinogenicity of
Pharmaceuticals.'' 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, 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.
The six Founding Members of the ICH are the 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;
[[Page 66197]]
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
(<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 October 5, 2021 (86 FR 54982), FDA
published a notice announcing the availability of a draft guidance
entitled ``S1B(R1) Addendum to S1B Testing for Carcinogenicity of
Pharmaceuticals.'' The notice gave interested persons an opportunity to
submit comments by December 6, 2021.
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 on August 4, 2022.
The final guidance provides guidance on expanding the testing
scheme for assessing human carcinogenic risk of pharmaceuticals by
introducing an additional approach that is not described in the
original S1B Guideline and also adds a plasma exposure ratio-based
approach for setting the high dose in the rasH2-Tg mouse model. This
guidance finalizes the draft guidance issued on October 5, 2021.
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. 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. 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 in 21 CFR part 312 have been approved under OMB control
number 0910-0014; the collections of information in 21 CFR part 314
have been approved under OMB control number 0910-0001.
III. Electronic Access
Persons with access to the internet may obtain the guidance at
<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>, <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.regulations.gov">https://www.regulations.gov</a>.
Dated: October 27, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-23787 Filed 11-1-22; 8:45 am]
BILLING CODE 4164-01-P
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