Comparability assessments for cell-based therapies are challenging due to complex manufacturing processes, inherent variability of cell starting materials, and evolving understanding of product quality attributes and analytical technologies. Many of these products are made-to-order for a specific patient, and materials are limited for any type of analytical evaluation. Early generation of the first autologous cell therapy products applied fast-to-market CMC approaches to expedite the delivery of life-saving treatments to patients.
As the focus of the field shifts towards optimized manufacturing, better understanding of CQAs, and superior product performance, well designed comparability strategies can streamline cell therapy product development, reduce the costs of manufacturing, and provide faster access to these important medicines. Limited characterization and understanding of the relationship between the product and its function further complicate the ability to rigorously compare pre- and post-change product.
In this session, comparability strategies used with commercial and investigational cellular therapy products will be presented as case studies. In addition, industry stakeholders and regulators will engage in discussions to address uncertainties in comparability including planning comparability studies during early and late stages of drug development, and challenges involved in showing clinical relevance. The relevance of the lessons learned to newer generations of autologous and allogeneic CAR-T cell products will be discussed. Discussions will also include gene editing and healthy donor considerations to maximize product and process consistency while ensuring product quality, safety, and efficacy.
Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products
Elizabeth Lessey-Morillon, CBER, FDA
Statistical Perspectives on Analytical Comparability Studies for Autologous Cell-based Therapies
Kedar Dave, Bristol-Myers Squibb Company
Challenges and Considerations for Allogeneic CAR T Therapy Comparability Studies