[Federal Register Volume 89, Number 149 (Friday, August 2, 2024)]
[Notices]
[Pages 63205-63207]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-17103]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2022-D-1527]


M12 Drug Interaction Studies; M12 Drug Interaction Studies: 
Questions and Answers; International Council for Harmonisation; 
Guidances 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 the final guidance for industry entitled ``M12 Drug 
Interaction Studies'' and the supplemental document entitled ``M12 Drug 
Interaction Studies: Questions and Answers.'' The guidance and 
supplemental questions and answers document were prepared under the 
auspices of the International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use (ICH). The guidance 
provides general recommendations on evaluating the enzyme and 
transporter-mediated pharmacokinetic drug-drug interaction potential 
for investigational drugs. The supplemental questions and answers 
document provides clarity to some concepts related to evaluation of 
drug interactions covered in the guidance. The guidance is intended to 
harmonize the regional recommendations for designing, conducting, and 
interpreting in vitro and clinical evaluations of drug-drug 
interactions while developing investigational drugs. The guidance 
replaces the draft guidance ``M12 Drug Interaction Studies'' issued on 
August 29, 2022.

DATES: The announcement of the guidance is published in the Federal 
Register on August 2, 2024.

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-2022-D-1527 for ``M12 Drug Interaction Studies'' and ``M12 Drug 
Interaction Studies: Questions and Answers.'' 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

[[Page 63206]]

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: Kellie Reynolds, Center for Drug Evaluation 
and Research, Food and Drug Administration, 10903 New Hampshire Ave., 
Bldg. 51, Rm. 2134, Silver Spring, MD 20993-0002, 301-796-1594, 
[email protected]; or James Myers, 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 the guidance for industry 
entitled ``M12 Drug Interaction Studies'' and the supplemental document 
entitled ``M12 Drug Interaction Studies: Questions and Answers.'' The 
guidance and supplemental questions and answers document were 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 August 29, 2022 (87 FR 52801), FDA 
published a notice announcing the availability of the draft guidance 
entitled ``M12 Drug Interaction Studies.'' The notice gave interested 
persons an opportunity to submit comments by September 28, 2022.
    After consideration of the comments received and revisions to the 
guideline, the final draft of the guideline and supplemental questions 
and answers were submitted to the ICH Assembly and endorsed by the 
regulatory agencies in May 2024.
    This guidance finalizes the draft guidance issued on August 29, 
2022. The guidance entitled ``M12 Drug Interaction Studies'' introduces 
minor formatting refinements and new key concepts to improve 
navigability and clarity of recommendations. Based on significant 
comments received and additional analysis, the final guidance refines 
descriptions of in vitro evaluation, clinical evaluation, reporting and 
interpretation, risk management, and predictive modeling. In addition 
to adding a glossary, the final guidance includes new sections on 
endogenous biomarkers and protein binding. Lastly, the supplemental 
questions and answers document, ``M12 Drug Interaction Studies: 
Questions and Answers,'' clarifies questions received during public 
consultation of the draft guidance ``M12 Drug Interaction Studies'' 
related to the evaluation of drug interactions.
    The guidances are being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
current thinking of FDA on ``M12 Drug Interaction Studies.'' The 
guidance and supplemental questions and answers document do not 
establish any rights for any person and are 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

    This guidance contains no collection of information. Therefore, 
clearance by the Office of Management and Budget under the Paperwork 
Reduction Act of 1995 is not required.

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/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances, or https://www.fda.gov/regulatory-information/search-fda-guidance-documents.


[[Page 63207]]


    Dated: July 30, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-17103 Filed 8-1-24; 8:45 am]
BILLING CODE 4164-01-P