S1B(R1) Addendum to S1B Testing for Carcinogenicity of Pharmaceuticals; International Council for Harmonisation; Draft Guidance for Industry; Availability, 54982-54983 [2021-21692]

Download as PDF 54982 Federal Register / Vol. 86, No. 190 / Tuesday, October 5, 2021 / Notices Maryanne Dingman (see FOR FURTHER INFORMATION CONTACT) no later than November 9, 2021. Streaming Webcast of the Public Workshop: This public workshop will be webcast. A live webcast of this workshop will be available at https:// go.usa.gov/xMxPZ on the day of the workshop. If you have never attended a Connect Pro event before, test your connection at https://collaboration.fda.gov/common/ help/en/support/meeting_test.htm. To get a quick overview of the Connect Pro program, visit https://www.adobe.com/ go/connectpro_overview. FDA has verified the website addresses in this document, as of the date this document publishes in the Federal Register, but websites are subject to change over time. Transcripts: Please be advised that as soon as a transcript of the public meeting is available, it will be accessible at https://www.regulations.gov. It may be viewed at the Dockets Management Staff (HFA–305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. It will also be accessible at https://go.usa.gov/ xMxPZ. Dated: September 28, 2021. Lauren K. Roth, Acting Principal Associate Commissioner for Policy. [FR Doc. 2021–21758 Filed 10–4–21; 8:45 am] BILLING CODE 4164–01–P 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S1B(R1) Addendum to S1B Testing for Carcinogenicity of Pharmaceuticals; International Council for Harmonisation; Draft Guidance for Industry; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice of availability. The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled ‘‘S1B(R1) Addendum to S1B Testing for Carcinogenicity of Pharmaceuticals’’. The draft guidance was prepared under the auspices of the International Council for Harmonisation (ICH), formerly the International Conference on Harmonisation. The draft guidance expands the testing scheme for assessing human carcinogenic risk of small molecule pharmaceuticals by introducing an additional approach that lotter on DSK11XQN23PROD with NOTICES1 SUMMARY: VerDate Sep<11>2014 18:56 Oct 04, 2021 Jkt 256001 is not described in the original S1B Guideline. The draft guidance is intended to offer an integrative approach that provides specific weight of evidence (WoE) criteria that inform whether or not a 2-year rat study adds value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 S1C(R2) Guideline would still apply. DATES: Submit either electronic or written comments on the draft guidance by December 6, 2021 to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance. ADDRESSES: You may submit comments on any guidance 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 PO 00000 Frm 00067 Fmt 4703 Sfmt 4703 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 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 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-201509-18/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 the draft guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food E:\FR\FM\05OCN1.SGM 05OCN1 Federal Register / Vol. 86, No. 190 / Tuesday, October 5, 2021 / Notices 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 draft 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 20993–0002, 240–402–0477, Timothy.McGovern@fda.hhs.gov; 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, Jill.Adleberg@fda.hhs.gov. SUPPLEMENTARY INFORMATION: lotter on DSK11XQN23PROD with NOTICES1 I. Background FDA is announcing the availability of a draft 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 resourceefficient 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 FDA; the Pharmaceutical Research VerDate Sep<11>2014 18:56 Oct 04, 2021 Jkt 256001 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 consensusdriven 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 May 2021, the ICH Assembly endorsed the draft guideline entitled ‘‘S1B(R1) Addendum to S1B Testing for Carcinogenicity of Pharmaceuticals’’ and agreed that the guideline should be made available for public comment. The draft guideline is the product of the Safety Expert Working Group of the ICH. Comments about this draft will be considered by FDA and the Safety Expert Working Group. The draft guidance provides guidance on expanding the testing scheme for assessing human carcinogenic risk of small molecule 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 draft guidance has been left in the original ICH format. The final guidance will be reformatted and edited to conform with FDA’s good guidance practices regulation (21 CFR 10.115) and style before publication. The draft guidance, when finalized, will represent the current thinking of FDA on ‘‘S1B(R1) Addendum to S1B Testing for Carcinogenicity of Pharmaceuticals’’. It PO 00000 Frm 00068 Fmt 4703 Sfmt 4703 54983 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 draft guidance at https://www.regulations.gov, https:// www.fda.gov/drugs/guidancecompliance-regulatory-information/ guidances-drugs, https://www.fda.gov/ regulatory-information/search-fdaguidance-documents, or https:// www.fda.gov/vaccines-blood-biologics/ guidance-compliance-regulatoryinformation-biologics/biologicsguidances. Dated: September 30, 2021. Lauren K. Roth, Acting Principal Associate Commissioner for Policy. [FR Doc. 2021–21692 Filed 10–4–21; 8:45 am] BILLING CODE 4164–01–P DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration Meeting of the National Advisory Committee on Rural Health and Human Services Health Resources and Services Administration (HRSA), Department of Health and Human Services (HHS). ACTION: Notice. AGENCY: In accordance with the Federal Advisory Committee Act, this notice announces the Secretary’s National Advisory Committee on Rural Health and Human Services (NACRHHS) has scheduled a public meeting. Information about NACRHHS SUMMARY: E:\FR\FM\05OCN1.SGM 05OCN1

Agencies

[Federal Register Volume 86, Number 190 (Tuesday, October 5, 2021)]
[Notices]
[Pages 54982-54983]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-21692]


-----------------------------------------------------------------------

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; Draft 
Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a draft guidance for industry entitled ``S1B(R1) 
Addendum to S1B Testing for Carcinogenicity of Pharmaceuticals''. The 
draft guidance was prepared under the auspices of the International 
Council for Harmonisation (ICH), formerly the International Conference 
on Harmonisation. The draft guidance expands the testing scheme for 
assessing human carcinogenic risk of small molecule pharmaceuticals by 
introducing an additional approach that is not described in the 
original S1B Guideline. The draft guidance is intended to offer an 
integrative approach that provides specific weight of evidence (WoE) 
criteria that inform whether or not a 2-year rat study adds 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 S1C(R2) Guideline would 
still apply.

DATES: Submit either electronic or written comments on the draft 
guidance by December 6, 2021 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 
version of the guidance.

ADDRESSES: You may submit comments on any guidance 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-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 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 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 the draft guidance to 
the Division of Drug Information, Center for Drug Evaluation and 
Research, Food

[[Page 54983]]

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 draft 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 20993-0002, 240-402-0477, [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 draft 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 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 May 2021, the ICH Assembly endorsed the draft guideline entitled 
``S1B(R1) Addendum to S1B Testing for Carcinogenicity of 
Pharmaceuticals'' and agreed that the guideline should be made 
available for public comment. The draft guideline is the product of the 
Safety Expert Working Group of the ICH. Comments about this draft will 
be considered by FDA and the Safety Expert Working Group.
    The draft guidance provides guidance on expanding the testing 
scheme for assessing human carcinogenic risk of small molecule 
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 draft guidance has been left in the original ICH format. The 
final guidance will be reformatted and edited to conform with FDA's 
good guidance practices regulation (21 CFR 10.115) and style before 
publication. The draft guidance, when finalized, will represent the 
current thinking of FDA on ``S1B(R1) Addendum to S1B Testing for 
Carcinogenicity of Pharmaceuticals''. 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 draft 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: September 30, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-21692 Filed 10-4-21; 8:45 am]
BILLING CODE 4164-01-P

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