Gene Therapy Chemistry, Manufacturing, and Controls

Recently, FDA CBER Office of Tissues and Advanced Therapies (OTAT) organized a Town Hall to address industry questions regarding gene therapy CMC information. For IND submissions, phase-appropriate CMC expectations are published in the 2020 gene therapy CMC guidance. Qualified assays, including a potency assay, should be in place prior to initiating studies that are intended to provide the primary efficacy data for licensure. In general, variability and risk in the manufacturing process should be assessed and controls should be in place to reduce variability of the product. It is recommended to move to the expected commercial configuration prior to conducting the pivotal study.This includes the intended commercial manufacturing process at the intended manufacturing facility and the expected lot release testing strategy. It should be noted that significant changes late in development introduce uncertainty, as analytical comparability is not always sufficient. OTAT is developing a guidance regarding comparability assessments. Major recommendation is to implement changes in the manufacturing process as early as possible to reduce risk. While developers may have considerations, including costs, FDA recommends that product quality should be top priority at all phases of development.

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