[Federal Register Volume 91, Number 37 (Wednesday, February 25, 2026)]
[Notices]
[Pages 9283-9285]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2026-03713]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2026-D-1256]
Considerations for the Use of the Plausible Mechanism Framework
To Develop Individualized Therapies That Target Specific Genetic
Conditions With Known Biological Cause; Draft Guidance for Industry;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 document entitled ``Considerations for the
use of the Plausible Mechanism Framework to Develop Individualized
Therapies that Target Specific Genetic Conditions with Known Biological
Cause.'' The draft guidance document describes considerations for
generating substantial evidence of effectiveness and evidence of safety
of individualized therapies based on a plausible mechanism framework.
DATES: Submit either electronic or written comments on the draft
guidance by April 27, 2026 to ensure that the Agency considers your
comment on this draft guidance before it begins work on the final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:
[[Page 9284]]
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-2026-D-1256 for ``Considerations for the use of the Plausible
Mechanism Framework to Develop Individualized Therapies that Target
Specific Genetic Conditions with Known Biological Cause.'' 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 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 Office of Communication, Outreach and Development, Center for
Biologics Evaluation and Research (CBER), Food and Drug Administration,
by emailing [email protected]. 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
draft guidance document.
FOR FURTHER INFORMATION CONTACT: Tami Belouin, Center for Biologics
Evaluation and Research, Food and Drug Administration, Food and Drug
Administration, 240-402-7911. Teresa Buracchio, Center for Drug
Evaluation and Research, Food and Drug Administration, Food and Drug
Administration, 240-402-4274.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft document entitled
``Considerations for the use of the Plausible Mechanism Framework to
Develop Individualized Therapies that Target Specific Genetic
Conditions with Known Biological Cause.'' The draft guidance describes
considerations for generating substantial evidence of effectiveness and
evidence of safety of individualized therapies based on a plausible
mechanism framework. The guidance specifically discusses genome editing
and RNA-based therapies; however, the general concepts may apply to
other types of individualized therapies. Specifically, the draft
guidance applies when clinical evidence from a limited number of
patients will be available to support the individualized product's
safety or efficacy in the intended patient population.
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
``Considerations for the use of the Plausible Mechanism Framework to
Develop Individualized Therapies that Target Specific Genetic
Conditions with Known Biological Cause.'' 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.
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 210 and 211 relating to current good manufacturing
practice have been approved under OMB control number 0910-0139. The
collections of information in 21 CFR part 312 related to the submission
of investigational new drug applications have been approved under 0910-
0014. The collections of information in 21 CFR part 314 for submission
of a new drug application have been approved under OMB control number
0910-0001. The collections of information in 21 CFR part 601 relating
to the submissions of biologic license applications have been approved
under OMB control number 0910-0338.
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III. Electronic Access
Persons with access to the internet may obtain the draft guidance
at https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or
https://www.regulations.gov.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-03713 Filed 2-23-26; 11:15 am]
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