Notice2025-18651
Innovative Designs for Clinical Trials of Cellular and Gene Therapy Products in Small Populations; Draft Guidance for Industry; Availability
Primary source
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Published
September 25, 2025
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA, the Agency, or we) is announcing the availability of a draft document entitled "Innovative Designs for Clinical Trials of Cellular and Gene Therapy Products in Small Populations." The draft guidance document provides recommendations to sponsors who are planning clinical trials of cell and gene therapy (CGT) products intended for use in a disease or condition that affects a small population, generally one that meets the definition of a rare disease or condition under section 526(a)(2) of the FD&C Act (21 U.S.C. 360bb(a)(2)). It describes FDA requirements and provides considerations for the use of various clinical trial designs and endpoints to generate clinical evidence to support product licensure. The recommendations are intended for sponsors developing CGTs intended for use in small populations to leverage the use of innovative trial designs to simultaneously expedite drug development and generate data necessary to demonstrate substantial evidence of effectiveness.
Full Text
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<title>Federal Register, Volume 90 Issue 184 (Thursday, September 25, 2025)</title>
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[Federal Register Volume 90, Number 184 (Thursday, September 25, 2025)]
[Notices]
[Pages 46220-46222]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2025-18651]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2025-D-3403]
Innovative Designs for Clinical Trials of Cellular and Gene
Therapy Products in Small Populations; Draft Guidance for Industry;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, the Agency, or we) is
announcing the availability of a draft document entitled ``Innovative
Designs for Clinical Trials of Cellular and Gene Therapy Products in
Small Populations.'' The draft guidance document provides
recommendations to sponsors who are planning clinical trials of cell
and gene therapy (CGT) products intended for use in a disease or
condition that affects a small population, generally one that meets the
definition of a rare disease or condition under section 526(a)(2) of
the FD&C Act (21 U.S.C. 360bb(a)(2)). It describes FDA requirements and
provides considerations for the use of various
[[Page 46221]]
clinical trial designs and endpoints to generate clinical evidence to
support product licensure. The recommendations are intended for
sponsors developing CGTs intended for use in small populations to
leverage the use of innovative trial designs to simultaneously expedite
drug development and generate data necessary to demonstrate substantial
evidence of effectiveness.
DATES: Submit either electronic or written comments on the draft
guidance by November 24, 2025 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-2025-D-3403] for ``Innovative Designs for Clinical Trials of
Cellular and Gene Therapy Products in Small Populations; Draft Guidance
for Industry.'' Received comments will be placed in the docket and,
except for those submitted as ``Confidential Submissions,'' 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 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 the 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. 3103, Silver Spring, MD 20993-
0002. Send one self-addressed adhesive label to assist the 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 or emailing
<a href="/cdn-cgi/l/email-protection#234a4d47565057515a0d414a4c4f4c444a4050634547420d4b4b500d444c55"><span class="__cf_email__" data-cfemail="a1c8cfc5d4d2d5d3d88fc3c8cecdcec6c8c2d2e1c7c5c08fc9c9d28fc6ced7">[email protected]</span></a>. See the SUPPLEMENTARY INFORMATION
section for electronic access to the draft guidance document.
FOR FURTHER INFORMATION CONTACT: Janet Goldberg, Center for Biologics
Evaluation and Research, Food and Drug Administration, 240-402-7911.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft document entitled
``Innovative Designs for Clinical Trials of Cellular and Gene Therapy
Products in Small Populations; Draft Guidance for Industry.'' The draft
guidance document provides recommendations to sponsors who are planning
clinical trials of CGT products intended for use in a disease or
condition that affects a small population, generally one that meets the
definition of a rare disease or condition under section 526(a)(2) of
the FD&C Act (21 U.S.C. 360bb(a)(2)). It describes FDA requirements and
provides considerations for the use of various clinical trial designs
and endpoints to generate clinical evidence to support product
licensure. The guidance expands on principles described in FDA's
existing guidance documents related to this topic, by providing
additional recommendations for the planning, design, conduct, and
analysis of cell and gene therapy trials to facilitate FDA's assessment
of product effectiveness. The recommendations are intended for sponsors
developing CGTs intended for use in small populations to leverage the
use of innovative trial designs to simultaneously expedite drug
development and generate data necessary to demonstrate substantial
evidence of effectiveness.
FDA is issuing this draft guidance in accordance with a commitment
outlined in the reauthorization of the Prescription Drug User Fee Act
(PDUFA VII) under the 2022 FDA User Fee Reauthorization Act.
This draft guidance is being issued consistent with FDA's good
guidance practices regulation (21 CFR 10.115). The draft guidance, when
finalized, will represent the current thinking of FDA on ``Innovative
Designs for Clinical Trials of Cellular and Gene Therapy Products in
Small Populations.'' 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
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it satisfies the requirements of the applicable statutes and
regulations.
As we develop final guidance on this topic, FDA will consider
comments on costs or cost savings the guidance may generate, relevant
for Executive Order 14192.
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 (PRA) (44 U.S.C. 3501-3521). The collections of information
in 21 CFR parts 50 and 56 pertaining to institutional review boards and
the protection of human subjects, respectively, have been approved
under OMB control number 0910-0130. The collections of information
under 21 CFR part 312 pertaining to Investigational New Drug
Applications, including clinical trials and formal meetings, have been
approved under OMB control number 0910-0014. The collections of
information in 21 CFR part 601 pertaining to the submissions of
biologics license application product for development have been
approved under OMB control number 0910-0338. The collections of
information described in FDA's guidance entitled ``Formal Meetings
Between the FDA and Sponsors or Applicants of PDUFA Products'' have
been approved under OMB control number 0910-0297.
III. Electronic Access
Persons with access to the internet may obtain the draft guidance
at <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>, <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.regulations.gov">https://www.regulations.gov</a>.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2025-18651 Filed 9-24-25; 8:45 am]
BILLING CODE 4164-01-P
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