Document ID: FDA-2021-D-0875-0001
Agency: fda
Document Type: Notice
Title: S12 Nonclinical Biodistribution Considerations for Gene Therapy Products; International Council for Harmonisation; Draft Guidance for Industry; Availability
Posted Date: 2021-09-09T04:00Z

[Federal Register Volume 86, Number 172 (Thursday, September 9, 2021)]
[Notices]
[Pages 50536-50538]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-19410]

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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Products; International Council for Harmonisation; Draft Guidance for 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the availability of a draft guidance for industry entitled ``S12 
Nonclinical Biodistribution Considerations for Gene Therapy Products.'' 
The draft guidance was prepared under the auspices of the International 
Council for Harmonisation (ICH), formerly the International Conference 
on Harmonisation. The draft guidance provides harmonized 
recommendations for the conduct and overall design of nonclinical 
biodistribution (BD) studies for gene therapy (GT) products. 
Considerations for interpretation and application of the BD data to 
support a nonclinical development program and inform the design of 
clinical trials are also provided. The recommendations in the guidance 
endeavour to facilitate the development of investigational GT products, 
while avoiding unnecessary use of animals, in accordance with the 3Rs 
(reduce/refine/replace) principles. The draft guidance is intended to 
promote harmonization of recommendations for BD studies for 
investigational GT products and facilitate a more efficient and timely 
nonclinical development program.

DATES: Submit either electronic or written comments on the draft 
guidance by November 8, 2021 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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-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,'' 
are 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

[[Page 50537]]

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 this draft guidance to 
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, or 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. 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: 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:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``S12 Nonclinical Biodistribution Considerations for Gene 
Therapy Products.'' The draft 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 June 2021, the ICH Assembly endorsed the draft guideline 
entitled ``S12 Nonclinical Biodistribution Considerations for Gene 
Therapy Products'' and agreed that the guidance should be made 
available for public comment. The draft guidance is the product of the 
Safety Expert Working Group of the ICH. Comments about this draft 
guidance will be considered by FDA and the Safety Expert Working Group.
    FDA is thus announcing the availability of a draft guidance for 
industry entitled ``S12 Nonclinical Biodistribution Considerations for 
Gene Therapy Products.'' The draft guidance discusses the definition of 
BD and gives examples of GT products that are within the scope of the 
document. The guidance also provides recommendations for the design of 
nonclinical BD studies, such as the test article and dose level(s) 
administered, the animal species tested, route of administration, 
biofluid and tissue collection procedure, and other design elements. In 
addition, specific considerations, such as BD assay methods, GT 
expression product levels, and product immunogenicity are provided. The 
recommendations in the draft guidance are intended to promote 
harmonization in the development of a nonclinical development program 
for GT products to support clinical trial design, and reduce the use of 
animals, in accordance with the 3Rs (reduce/refine/replace) principles.
    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 ``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

    While this guidance contains no collection of information, it does 
refer to

[[Page 50538]]

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 314 have been approved under OMB control 
number 0910-0001 and in 21 CFR part 601 under OMB control number 0910-
0338.

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 2, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-19410 Filed 9-8-21; 8:45 am]
BILLING CODE 4164-01-P