REGULATORY UPDATE: FDA Releases New Gene, Cellular Therapy Guidances

January 30, 2024

The Food and Drug Administration released two final guidance documents related to the biotherapies community on Monday. These guidance documents finalize the draft guidances of the same titles dated March 2022.

Gene Therapy Products

The first, “Human Gene Therapy Products Incorporating Human Genome Editing,” provides recommendations to sponsors of human gene therapy products that incorporate genome editing (GE) of human somatic cells. Specifically, the guidance provides recommendations related to information that sponsors should provide in an investigational new drug (IND) application to assess the safety and quality of the investigational GE product, as required by federal regulations. This includes information on product design, product manufacturing and testing, nonclinical safety assessment and clinical trial design.

In a Jan. 30 Federal Register notice, FDA noted that the agency received numerous comments on the draft guidance, which were considered as the guidance was finalized. Changes to the guidance include clarifying the recommendations for GE components used only once, expectations for potency assays, considerations for nonclinical studies with respect to potential for off-target toxicity and applicability of accelerated approval to GE products.

Considerations for Development of CAR T-Cell Products

In the second guidance, “Considerations for the Development of Chimeric Antigen Receptor (CAR) T-Cell Products,” FDA provides sponsors developing CAR T-cell products with CAR T-cell-specific recommendations regarding chemistry, manufacturing and control; pharmacology and toxicology; and design of clinical studies for oncology indications (including hematologic malignancies and solid tumors). The guidance also includes recommendations specific to autologous or allogeneic CAR T-cell products and recommendations for analytical comparability studies for CAR T-cell products. 

FDA made several changes to the final guidance as noted in the Jan. 30 Federal Register notice. These include clarifying the scope, focusing on treatment for oncology indications and including recommendations for CAR T cells manufactured using cellular starting material from patients who have previously received CAR T cells previously. The final guidance also addresses potency for CAR T cells that express multiple transgene elements, stability studies and clinical monitoring.

While this guidance specifically focuses on CAR T-cell products, FDA noted that much of the information and recommendations provided also apply to other genetically modified lymphocyte products, such as CAR natural killer (NK) cells or T-cell receptor (TCR)-modified T cells. To discuss considerations specific to these related products, FDA recommends that sponsors communicate with the CBER’s Office of Therapeutic Products before submitting an IND application by requesting a pre-IND meeting.

Interested individuals may submit comments on the gene therapy and CAR T-cell guidance may submit comments online.