The FDA recently shared information regarding its flexible approach to overseeing chemistry, manufacturing, and control (CMC) requirements for cell and gene therapies (CGT). Due to the unique nature of the characteristics of CGT, regulatory flexibility must be adapted in a way that encourages increased innovation while still maintaining the integrity of safety and efficacy.
Part of what makes CGTs unique is the inherent complexities of biologic products, which are often individualized to meet the specific needs of patient populations. For example, for patients with immune system issues, biologics can be precision targeted to the particular aspect of the patient’s immune system which is not functioning as it should. Due to their complexities, some CGTs require sophisticated manufacturing under certain time constraints.
To date, the FDA’s flexible approach has been constructive in expediting the development of biologics and the FDA’s evaluation process when reviewing Biologics License Applications (BLA). The FDA outlines three categories of areas of flexibility: (1) clinical development, (2) commercial specifications, and (3) process validation for CGT. For example, as part of its clinical development flexibilities, the FDA “reviews process and method validation consistent with a product lifecycle approach, understanding that process and method validations approaches are refined over time.” Commercial specifications flexibilities include, amongst others, the consideration of submissions “seeking to re-evaluate and revise product release acceptance criteria based on post-approval manufacturing experience, when manufacturers demonstrate consistent product quality.” Amongst the process validation flexibilities, the FDA cites the absence of a requirement to “supply three (3) [Process Performance Qualification] lots for process validation.” Process Performance Qualification lots are commercial-scale batches which are manufactured under normal conditions in order to prove that the manufacturing process is able to produce quality goods with consistency.
The excitement of product developers has resulted in an exponential increase of cell and gene therapy submissions, many of which address “serious or life-threatening conditions with an unmet medical need,” according to Dr. Vinay Prasad, M.P.H., Chief Medical and Scientific Officer and Director of the FDA’s Center for Biologics Evaluation and Research. Over the last ten years the FDA’s Center for Biologics Evaluation and Research (CBER) has green-lit nearly 50 CGTs, and CBER is hoping their increased communication regarding regulatory flexibility will continue to encourage creative development.
CBER stresses the importance of every sponsor being aware of the types of regulatory flexibility that are scientifically available, especially as the agency and administration work to remove barriers that previously existed and misconceptions that stood in the way of accelerated product development.
Information in this blog post was sourced from the FDA.gov articles “FDA Increases Flexibility on Requirements for Cell and Gene Therapies to Advance Innovation” and “Flexible Requirements for Cell and Gene Therapies to Advance Innovation.”
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