Document ID: FDA-2021-D-0875-0009
Agency: fda
Document Type: Notice
Title: S12 Nonclinical Biodistribution Considerations for Gene Therapy Products; International Council for Harmonisation; Guidance for Industry; Availability
Posted Date: 2023-05-01T04:00Z

[Federal Register Volume 88, Number 83 (Monday, May 1, 2023)]
[Notices]
[Pages 26562-26563]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-09179]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2021-D-0875]

S12 Nonclinical Biodistribution Considerations for Gene Therapy 
Products; 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 ``S12 
Nonclinical Biodistribution Considerations for Gene Therapy Products.'' 
The guidance was prepared under the auspices of the International 
Council for Harmonisation of Technical Requirements for Pharmaceuticals 
for Human Use (ICH). The final guidance provides harmonized 
recommendations for the conduct and overall design of nonclinical 
biodistribution (BD) studies for gene therapy (GT) products. The 
recommendations in the guidance endeavor to facilitate the development 
of investigational GT products, while avoiding unnecessary use of 
animals, in accordance with the 3Rs (reduce/refine/replace) principles. 
The final guidance replaces the draft guidance entitled ``S12 
Nonclinical Biodistribution Considerations for Gene Therapy Products'' 
issued on September 9, 2021.

DATES: The announcement of the guidance is published in the Federal 
Register on May 1, 2023.

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-2021-D-0875 for ``S12 Nonclinical Biodistribution Considerations 
for Gene Therapy Products.'' 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

[[Page 26563]]

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: Alyssa Galaro, Center for Biologics 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 6260, Silver Spring, MD, 20993-0002, 301-
796-6589.
    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 guidance for industry 
entitled ``S12 Nonclinical Biodistribution Considerations for Gene 
Therapy Products.'' 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 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 September 9, 2021 (86 FR 50536), FDA 
published a notice announcing the availability of a draft guidance 
entitled ``S12 Nonclinical Biodistribution Considerations for Gene 
Therapy Products.'' The notice gave interested persons an opportunity 
to submit comments by November 8, 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 March 14, 2023.
    This guidance finalizes the draft guidance of the same title issued 
on September 9, 2021. The guidance is intended to promote harmonization 
of recommendations for the BD assessment for investigational GT 
products and facilitate a more efficient and timely nonclinical 
development program. The revisions to the draft guidance aimed to 
clarify key elements of the BD assessment by providing additional 
information on selecting dose levels and identifying a biologically 
relevant model. Additional details were provided on what product and 
study characteristics should be considered to determine if previous BD 
data can be leveraged.
    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 ``S12 Nonclinical Biodistribution 
Considerations for Gene Therapy Products.'' 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

    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 final 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: April 26, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-09179 Filed 4-28-23; 8:45 am]
BILLING CODE 4164-01-P