The US Food and Drug Administration (FDA) has finalised its industry guidance for chimeric antigen receptor (CAR)-T cell products and gene therapies, while also acknowledging a lack of precedent in the space.
The new guidance, Considerations for the Development of CAR-T Cell Products: Guidance for Industry, follows a March 2022 draft release that received feedback from industry players, including the Biotech Innovation Organization (BIO).
They urged the agency to take a closer look at the role of manufacturing processes, refine early-stage trial guidelines and define how guidelines apply to other therapies beyond CAR-T.
The new guidance not only focuses on CAR-T cell products, but can also be applied to other genetically modified lymphocyte products, including CAR natural killer (NK) cells or T cell receptor (TCR) modified T cells.
Additionally, the FDA also indicates differing specifications for allogenic versus autologous therapies, underscoring the importance of characterisation data during early studies.
The agency considered the challenging nature of developing, manufacturing and testing CAR-T cells by acknowledging that the process involves “complex multi-step procedures, which are potential sources of variability among product lots”.
“Appropriate in-process testing at relevant time points is vital to achieve and maintain control of the manufacturing process,” wrote the FDA.
The agency’s recommendations also include nonclinical testing of CAR-T cells, which “can be challenging due to the inherent biological complexity and variability of this product type and the limited availability of suitable animal models to test safety and activity,” the FDA said.
With this in mind, the agency recommends a case-by-case strategy and available nonclinical and clinical knowledge from related products to support the use of CAR-T cells in a proposed trial.
The new safety recommendations follow a month-long agency investigation into the risk of patients developing secondary T-cell cancers after receiving a CAR-T drug.
In total, the FDA recorded 22 cases of T-cell cancer following treatment with a CAR-T product by the end of 2023.
In addition, the agency has also released a final gene editing guideline that specifically targets the best safety and quality processes when undergoing the Investigational New Drug application for investigational gene therapy products.