Paula Salmikangas - Director of Biopharmaceuticals and ATMP, NDA Advisory Services Ltd., Finland
The approval of first Advanced Therapy Medicinal Products (ATMPs) both in EU and US have raised high expectations towards novel cell- and gene-based medicinal products, especially for indications with high unmet medical needs. On the other hand, clinical trials of first CAR-T cell products have shown the difficulties related to the substantial genetic modification of T-cells in the form of severe adverse reactions, cytokine release syndrome (CRS) and neurotoxicity. It is well known that for cell-based products the product composition, quality and control of product variability are critical for safety and efficacy. For CAR-Ts certain signaling domains seem to be related to better cell persistence, whereas impact of the T-cell composition / characteristics on the product safety has not yet been clarified. For many cell-based products long in vitro culture has been associated with higher safety risks (e.g. tumourigenicity) and lower efficacy e.g. due to dedifferentiation or apoptosis of cells, leading to restrictions in cell expansion and lower cell doses. This presentation will discuss importance of early product design and how the balance between quality, safety and efficacy could be achieved.