Notice2021-19410
S12 Nonclinical Biodistribution Considerations for Gene Therapy Products; International Council for Harmonisation; Draft Guidance for Industry; Availability
Primary source
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Published
September 9, 2021
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled "S12 Nonclinical Biodistribution Considerations for Gene Therapy Products." The draft guidance was prepared under the auspices of the International Council for Harmonisation (ICH), formerly the International Conference on Harmonisation. The draft guidance provides harmonized recommendations for the conduct and overall design of nonclinical biodistribution (BD) studies for gene therapy (GT) products.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 The draft guidance is intended to promote harmonization of recommendations for BD studies for investigational GT products and facilitate a more efficient and timely nonclinical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.
Full Text
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<title>Federal Register, Volume 86 Issue 172 (Thursday, September 9, 2021)</title>
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[Federal Register Volume 86, Number 172 (Thursday, September 9, 2021)]
[Notices]
[Pages 50536-50538]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[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Products; International Council for Harmonisation; Draft Guidance for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the availability of a draft guidance for industry entitled ``S12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:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<bullet> 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:
<bullet> 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.
<bullet> 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 <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets
Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-
402-7500.
<bullet> 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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>. 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: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> 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,
<a href="/cdn-cgi/l/email-protection#692300050547280d050c0b0c1b0e290f0d084701011a470e061f"><span class="__cf_email__" data-cfemail="e0aa898c8ccea1848c8582859287a0868481ce888893ce878f96">[email protected]</span></a>.
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 <a href="https://www.ich.org/">https://www.ich.org/</a>).
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
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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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>, <a href="https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs">https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs</a>, <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents">https://www.fda.gov/regulatory-information/search-fda-guidance-documents</a>, or <a href="https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances">https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances</a>.
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
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