Individualized Human Genome Editing Products: Considerations for BLA Submission and Postapproval Management; Draft Guidance for Industry; Availability

Issuing agencies

Abstract

The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft document titled "Individualized Human Genome Editing Products: Considerations for BLA Submission and Postapproval Management." The draft guidance document provides recommendations for how an individualized human genome editing (GE) product that includes multiple product variants can be submitted in a single Biologics License Application (BLA). When finalized, this guidance will describe the FDA's current thinking on individualized GE products with respect to how to specify the extent of GE component variation in a BLA, how to add new product variants to the BLA after licensure, and related topics.

Full Text

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<title>Federal Register, Volume 91 Issue 207 (Wednesday, October 28, 2026)</title>
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[Federal Register Volume 91, Number 207 (Wednesday, October 28, 2026)]
[Notices]
[Pages 67838-67839]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-21954]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2026-D-11783]


Individualized Human Genome Editing Products: Considerations for 
BLA Submission and Postapproval Management; Draft Guidance for 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 titled ``Individualized Human 
Genome Editing Products: Considerations for BLA Submission and 
Postapproval Management.'' The draft guidance document provides 
recommendations for how an individualized human genome editing (GE) 
product that includes multiple product variants can be submitted in a 
single Biologics License Application (BLA). When finalized, this 
guidance will describe the FDA's current thinking on individualized GE 
products with respect to how to specify the extent of GE component 
variation in a BLA, how to add new product variants to the BLA after 
licensure, and related topics.

DATES: Submit either electronic or written comments on the draft 
guidance by November 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:
    <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-2026-D-11783 for ``Individualized Human Genome Editing Products: 
Considerations for BLA Submission and Postapproval Management.'' 
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

[[Page 67839]]

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 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. 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 titled 
``Individualized Human Genome Editing Products: Considerations for BLA 
Submission and Postapproval Management.'' The draft guidance document, 
intended for sponsors and applicants developing individualized GE 
products, provides recommendations for how an individualized GE product 
that includes multiple product variants can be submitted in a single 
BLA under section 351(a) of the Public Health Service Act (PHS Act) (42 
U.S.C. 262(a)). When finalized, this guidance will describe FDA's 
current thinking regarding how to specify the extent of GE component 
variation in a BLA and how to add new product variants to the BLA after 
licensure. This guidance also addresses related topics, including 
potency and safety evaluation of product variants, manufacturing 
process validation, labeling and indication statements, and drug naming 
and identification. This guidance is intended to complement existing 
FDA guidances on GE products addressing investigational new drug (IND)-
stage chemistry, manufacturing, and controls (CMC); nonclinical and 
clinical trial design; evidentiary standards for approval of 
individualized therapies; and leveraging of CMC, nonclinical, and 
clinical knowledge across GE programs <SUP>1 2 3</SUP> with additional 
advice and considerations on how to prepare and submit BLAs and BLA 
supplements for individualized GE products.
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    \1\ See Guidance for Industry ``Human Gene Therapy Products 
Incorporating Human Genome Editing,'' January 2024, <a href="https://www.fda.gov/media/156894/download">https://www.fda.gov/media/156894/download</a>.
    \2\ See Draft Guidance for Industry ``Considerations for the Use 
of the Plausible Mechanism Framework to Develop Individualized 
Therapies that Target Specific Genetic Conditions with Known 
Biological Cause,'' February 2026, <a href="https://www.fda.gov/media/191247/download">https://www.fda.gov/media/191247/download</a>. When finalized, this guidance will represent FDA's current 
thinking on this topic.
    \3\ See Draft Guidance for Industry ``Leveraging Prior Knowledge 
in the Development of Human Gene Therapy Products Incorporating 
Genome Editing,'' June 2026, <a href="https://www.fda.gov/media/192810/download">https://www.fda.gov/media/192810/download</a>. When finalized, this guidance will represent FDA's current 
thinking on this topic.
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    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 
``Individualized Human Genome Editing Products: Considerations for BLA 
Submission and Postapproval Management.'' 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 pertaining to manufacturing, processing, 
packing, and holding of finished pharmaceuticals and biological 
products for human use (CGMP regulations) have been approved under OMB 
control number 0910-0139. The collections of information in 21 CFR 
312.23(a)(7)(i) pertaining to submission of proper identification, 
quality, purity, and strength of an investigational drug in an IND 
application have been approved under OMB control number 0910-0014. The 
collections of information in 21 CFR 600.14(b) pertaining to biological 
product deviation reporting is included in OMB control number 0910-
0458. The collections of information in 21 CFR part 601 pertaining to 
biological license applications have been approved 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.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. 2026-21954 Filed 10-27-26; 8:45 am]
BILLING CODE 4164-01-P


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