Safety Assessment of Genome Editing Human Gene Therapy Products Using Next-Generation Sequencing
Summary
FDA's Center for Biologics Evaluation and Research has issued draft guidance recommending next-generation sequencing (NGS)-based methods for assessing safety of human genome editing gene therapy products in nonclinical studies. The guidance addresses evaluation of off-target editing risks and genome integrity for products supporting IND and BLA applications. Comments are being accepted via regulations.gov under docket FDA-2026-D-1255.
What changed
FDA's Office of Therapeutic Products has published draft guidance providing specific recommendations for using next-generation sequencing and bioinformatics methods to evaluate safety risks associated with human genome editing products in nonclinical studies. The guidance supplements the January 2024 Genome Editing Guidance and focuses on detecting off-target editing events and unintended genomic changes that may arise from gene therapy products.
Manufacturers and sponsors developing human genome editing gene therapy products should consider these recommendations when preparing nonclinical safety data packages for IND and BLA submissions. The guidance is particularly relevant for clinical development programs targeting genetic diseases, including individualized therapies, where both gene therapy and genome editing-specific risks must be addressed.
What to do next
- Review the draft guidance and submit comments via regulations.gov or mail
- Consider NGS-based methods when designing nonclinical studies for genome editing products
- Ensure off-target editing and genome integrity evaluations are addressed in regulatory submissions
Archived snapshot
Apr 15, 2026GovPing captured this document from the original source. If the source has since changed or been removed, this is the text as it existed at that time.
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Guidance Documents
Docket Number: FDA-2026-D-1255 Issued by: Guidance Issuing Office Center for Biologics Evaluation and Research, Office of Therapeutic Products This guidance 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. These recommendations are in addition to the nonclinical, clinical, and CMC considerations discussed in the “Guidance for Industry: Human Gene Therapy Products Incorporating Human Genome Editing” dated January 2024 (January 2024 GE Guidance) (Ref. 1). 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 changes to the genome for therapies targeting genetic diseases, including individualized therapies. For more information on clinical study design considerations and our science-based approach weighing the benefits and risks for human GE products, please refer to the January 2024 GE Guidance (Ref. 1). The recommendations in this guidance may guide stakeholders on designing nonclinical studies that use 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 (IND) applications and Biologics License Applications (BLAs).
Submit Comments
Submit Comments Online You can submit online or written comments on any guidance at any time (see 21 CFR 10.115(g)(5))
If unable to submit comments online, please mail written comments to:
Dockets Management
Food and Drug Administration
5630 Fishers Lane, Rm 1061
Rockville, MD 20852
All written comments should be identified with this document's docket number: FDA-2026-D-1255.
Questions?
Contact Point Office of Communication, Outreach and Development (OCOD) Center for Biologics Evaluation and Research
Food and Drug Administration
10903 New Hampshire Ave WO71-3128
Silver Spring, MD 20993-0002 ocod@fda.hhs.gov (800) 835-4709 (240) 402-8010
- ## Content current as of:
04/14/2026
Regulated Product(s)
- Biologics
- Gene Therapy
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