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USFDA Guidance: Human Gene Therapy Products Incorporating Human Genome Editing & Development of Chimeric Antigen Receptor (CAR) T Cell Products

On Monday (29 January 2024) the U.S. Food and Drug Administration (FDA) Center for Biologics Evaluation released two final guidance "Human Gene Therapy Products Incorporating Human Genome Editing" and "Considerations for the Development of Chimeric Antigen Receptor (CAR) T Cell Products".



Human Genome Editing (GE) is a process by which DNA sequences are added, deleted, altered or replaced at the specified location(s) in the genome of human somatic cells, ex vivo or in vivo, using nuclease-dependent or nuclease-independent GE technologies.


Each product's benefit-risk profile is determined by the indication and patient population, the extent and duration of the therapeutic benefit, as well as the availability of alternative therapeutic options. In addition to off-target editing, unintended consequences of on-target editing, and unknown long-term effects of on-target and off-target editing, GE approaches have specific risks.


To assist sponsors in developing human gene therapy products incorporating genome editing (GE) of human somatic cells, the FDA is providing recommendations. This guidance specifies the information that needs to be included in an Investigational New Drug (IND) application to assess the safety and quality of an investigational genetically modified organism product, as stated in 21 CFR 312.23. This includes information on product design, product manufacturing and testing, nonclinical safety assessment, and clinical trial design. 



A chimeric antigen receptor (CAR) T cell product is a therapeutic gene therapy product that changes the specificity of a T cell to enable it to recognize a desired target antigen.


This guidance is intended to assist sponsors, including industry and academic sponsors, in developing ex vivo-manufactured CAR T cell products. Specifically, FDA provides recommendations regarding chemistry, manufacturing, and control (CMC), pharmacology and toxicology, and the design of clinical studies for oncology indications.


CAR T cell products that are either autologous or allogeneic are addressed in this guidance as well as recommendations for CAR T cell product analytical comparability studies. Although this guidance focuses on CAR T cell products, many of its recommendations and information will also apply to other genetically modified lymphocyte products such as CAR Natural Killer (NK) cells and T cell receptor (TCR) modified T cells.


To know more about the CMC, Clinical & Nonclinical recommendations click this LINK.

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