BIOPROCESSING ISSUES FOR MANUFACTURING OF CELL THERAPY PRODUCTS

Human immune cells have been produced using Advanced Therapy Medicinal Products (ATMP) guidelines and have been tested in clinical studies for a number of diseases, for which still no or only inadequate alternative therapies are available. Examples include several cancer entities, stroke, myocardial infarction, severe autoimmune disorders and chronic infections. Despite many in vitro or in animal studies report positive outcomes after immune cell therapy, convincing results showing the benefits of ATMP in clinical studies are rare. Part of this discrepancy in the outcome of the clinical studies in comparison to the in vitro and in animal studies may be caused by the manufacturing of immune cells for clinical trials. Cells prepared for clinical trials were mostly manufactured using archaic, scarcely controlled and incomparable production processes and stringent analytical methods for assessing proliferation and differentiation of the immune cells during the manufacturing process were not applied. The production of ATMPs is first of all dependent on the donor specific biology, which significantly varies from one donor or patient, respectively, to another (biological heterogeneity). In case of immune cell therapy, the manufacturing process is key for cytotoxic function and is the basis for the biological activity of the cells after injection into the patient. The challenge for future clinical trials therefore is to reproducibly provide a sufficient number of biologically active cells of appropriate quality preferably in accordance with quality manufacturing guidelines (e. g. Good Manufacturing Practice, ICH etc.). Only using cells which have been produced under these rigorous quality control regimes will allow the conduction of clinically meaningful trials. The talk presents a survey and discusses consequences on future requirements for manufacturing processes of products for immune cell therapies.