Guidance: Safety Assessment of Genome Editing in Human Gene Therapy Products Using Next-Generation Sequencing

Safety Assessment of Genome Editing in Human Gene Therapy Products Using Next-Generation Sequencing; Draft Guidance for Industry; Availability

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Submit either electronic or written comments on the draft guidance by July 14, 2026 to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance.

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for "Safety Assessment of Genome Editing in Human Gene Therapy Products Using Next-Generation Sequencing; Draft Guidance for Industry."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.

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 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 .