[Federal Register Volume 89, Number 129 (Friday, July 5, 2024)]
[Notices]
[Pages 55613-55615]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-14717]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2024-D-2754]


M14 General Principles on Plan, Design, and Analysis of 
Pharmacoepidemiological Studies That Utilize Real-World Data for Safety 
Assessment of Medicines; International Council for Harmonisation; Draft 
Guidance for Industry; Availability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the availability of a draft guidance for industry entitled ``M14 
General Principles on Plan, Design, and Analysis of 
Pharmacoepidemiological Studies That Utilize Real-World Data for Safety 
Assessment of Medicines.'' The draft guidance was prepared under the 
auspices of the International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use (ICH). The draft 
guidance outlines general principles on planning, designing, and 
analyzing observational (noninterventional) pharmacoepidemiological 
studies that utilize fit-for-purpose data for safety assessment of 
medicines (drugs, vaccines, and other biological products). The draft 
guidance includes recommendations and high-level best practices for the 
conduct of these studies. The draft guidance is intended to streamline 
the development and regulatory assessment of postmarketing 
pharmacoepidemiological safety studies that include Real-World Data. 
This guidance also seeks to improve the ability of the study protocol 
and/or results to be accepted across health authorities and support 
decision making in response to study results.

DATES: Submit either electronic or written comments on the draft 
guidance by September 3, 2024 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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-2024-D-2754 for ``M14 General Principles on Plan, Design, and 
Analysis of Pharmacoepidemiological Studies That Utilize Real-World 
Data for Safety Assessment of Medicines.'' 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

[[Page 55614]]

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 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 draft guidance 
document.

FOR FURTHER INFORMATION CONTACT: 
    Regarding the guidance: Wei Hua, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10903 New Hampshire Ave. Bldg. 
22, Rm. 2414, Silver Spring, MD 20993-0002, 240-402-8658, 
[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 a draft guidance for industry 
entitled ``M14 General Principles on Plan, Design, and Analysis of 
Pharmacoepidemiological Studies That Utilize Real-World Data for Safety 
Assessment of Medicines.'' The draft guidance was 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 May 2024, the ICH Assembly endorsed the draft guideline entitled 
``M14 General Principles on Plan, Design, and Analysis of 
Pharmacoepidemiological Studies That Utilize Real-World Data for Safety 
Assessment of Medicines'' and agreed that the guideline should be made 
available for public comment. The draft guideline is the product of the 
Quality Expert Working Group of the ICH. Comments about this draft will 
be considered by FDA and the Quality Expert Working Group.
    This draft guidance provides general considerations and 
recommendations for use of real-world data for drug, vaccine, and other 
biologic product safety assessments. The draft guidance seeks to 
harmonize regional recommendations for the design, analysis, and 
reporting of postmarketing pharmacoepidemiologic studies that use real-
world data as the number of pharmacoepidemiological studies utilizing 
real-world data in a regulatory context have increased globally.
    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 ``M14 General Principles on Plan, Design, 
and Analysis of Pharmacoepidemiologic Studies That Utilize Real-World 
Data for Safety Assessment of Medicines.'' 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. The 
previously approved collections of information are subject to review by 
the Office of Management and Budget (OMB) under the Paperwork Reduction 
Act of 1995 (44 U.S.C. 3501-3521). The collections of information 
supporting investigational new drug regulations in 21 CFR part 312 have 
been approved under OMB control number 0910-0014. The collections of 
information supporting FDA approval of new drugs in part 314 (21 CFR 
part 314) have been approved under OMB control number 0910-0001. The 
collections of information supporting general licensing provisions of 
biological products in 21 CFR part 601 have been approved under OMB 
control number 0910-0338. The collections of information supporting 
adverse experience reporting in 21 CFR 310.305 and 329.100, and 
Sec. Sec.  314.80, 314.81, and 314.98, have been approved under OMB 
control number 0910-0230. The collections of information supporting 
MedWatch safety and adverse event reporting have been approved under 
OMB control number 0910-0291. The collections of information supporting 
biological products postmarket adverse experience reporting in 21 CFR 
part 600 have been approved under OMB control number 0910-0308 and the 
collections of information supporting medical device reporting have 
been approved under OMB control number 0910-0437.

[[Page 55615]]

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

    Dated: July 1, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-14717 Filed 7-3-24; 8:45 am]
BILLING CODE 4164-01-P