[Federal Register Volume 91, Number 72 (Wednesday, April 15, 2026)]
[Notices]
[Pages 20173-20174]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2026-07285]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2026-D-1255]
Safety Assessment of Genome Editing in Human Gene Therapy
Products Using Next-Generation Sequencing; Draft Guidance for Industry;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 ``Safety Assessment of
Genome Editing in Human Gene Therapy Products Using Next-Generation
Sequencing; Draft Guidance for Industry.'' The draft document provides
recommendations for next-generation sequencing (NGS)-based methods used
in nonclinical studies that will likely be needed to support initiation
of clinical trials of investigational human genome editing (GE)
products.
DATES: Submit either electronic or written comments on the draft
guidance by July 14, 2026 to ensure that the Agency considers your
comment on this draft guidance before it begins work on the final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:
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-1255 for ``Safety Assessment of Genome Editing in Human Gene
Therapy Products Using Next-Generation Sequencing; Draft Guidance for
Industry.'' 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 industry@[email protected]. The draft guidance may also
be obtained by mail by calling CBER at 800-835-4709 or 240-402-8010.
See the SUPPLEMENTARY INFORMATION section for electronic access to the
draft guidance document.
FOR FURTHER INFORMATION CONTACT: Andrew C. Harvan, 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
``Safety Assessment of Genome Editing in Human Gene Therapy Products
Using Next-Generation Sequencing; Draft Guidance for Industry.''
This draft guidance is intended for sponsors developing human gene
therapy products involving GE technologies. Clinical development
programs of human GE products should address both the risks associated
with the gene therapy product itself as well as the additional risks
associated with GE, including off-target editing and
[[Page 20174]]
unintended consequences. The recommendations in this draft guidance may
guide stakeholders on designing nonclinical studies that uses NGS
methods and bioinformatics to evaluate the potential safety risks
associated with off-target editing and loss of genome integrity in
human GE products submitted in support of Investigational New Drug
applications and Biologics License Applications.
The recommendations provided in this draft guidance are in addition
to the nonclinical, clinical, and CMC considerations discussed in the
``Guidance for Industry: Human Gene Therapy Products Incorporating
Human Gene Editing'' dated January 2024.
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 ``Safety
Assessment of Genome Editing in Human Gene Therapy Products Using Next-
Generation Sequencing.'' 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 any 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 part 312 relating to the submission of Investigational New
Drug Applications, including clinical trials, have been approved under
OMB control number 0910-0014. The collections of information contained
in 21 CFR part 601 relating to the submission of biologics license
applications have been approved under OMB control number 0910-0338. The
collections of information in 21 CFR part 1271 relating to human gene
therapy products have been approved under OMB control number 0910-0543.
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. 2026-07285 Filed 4-14-26; 8:45 am]
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