Cell Therapy Drug Product Development: Technical Considerations and Challenges

Abstract

Cell therapy uses living cells as a drug to treat diseases. To develop a cell therapy drug product (DP), cryopreservation plays a central role in extending the shelf life of these living medicines by pausing their biological activities, especially preventing degradation, at a temperature as low as liquid nitrogen. This helps overcome the temporal and geographical gaps between centralized manufacturing and clinical administration, as well as allowing sufficient time for full release testing and flexibility in scheduling patients for administration. Cryopreservation determines or influences several key manufacturing, logistical, or clinical in-use processes, including formulation, filling, controlled rate freezing, cryogenic storage and transportation, thawing, and dose preparation. This article overviews the key technical aspects of cell therapy DP development and elucidates fundamental principles of cryobiology that should be considered when we design and optimize the relevant processes. This article also discusses the challenges that motivate continued innovation for cell therapy drug product development.

Keywords: CAR T; Controlled-rate freezer; Cryopreservation; Cryoprotectant; Dose preparation; Fill and finish; Formulation; Stability.