Safety Assessment of GE in Human Gene Therapy Products Using NGS

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).

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• Content current as of:

  04/14/2026

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