C-41: Pre-cryopreservation processing and storage: A biologist’s perspective on the balance between manufacturing efficiency and post-thaw quality

Abstract

The ex vivo storage of cells at low temperatures for extended periods of time has been one of the most important advances that led to the creation of biobanks and the widespread therapeutic use of cellular products. Most cellular products used today spend a large portion of their product lifecycle at hypothermic temperatures or cryopreserved and stored frozen in freezers. As it is generally understood in the biobanking industry that the length and temperature of pre-cryopreservation storage can influence the post-thaw recovery of cells, biobankers have empirically established thresholds for the “optimal” conditions for the: shipment of raw material to centralized manufacturing sites, cell selection, donor testing and processing. Unfortunately, there is a general lack of appreciation of the impact that pre-cryopreservation processing and storage has on critical cell properties that are crucial to post-thaw recovery of viable cells. This presentation will provide a biologist’s perspective on the impact that cell manufacturing conditions can have on the quality of cellular therapeutics. Emerging data on the hypothermic storage lesion and cryoinjury of red blood cells and hematopoietic progenitor cells will be discussed with a focus on changes to cell metabolism, oxidative injury and membrane remodeling. The impact of the biological changes on the ability for cells to respond to the physical and chemical stresses encountered during cryopreservation will be introduced. Current quality control methods and international regulations will be briefly described. Recent clinical data on the effects of hypothermic storage and cryopreservation on recipient outcomes will be reviewed. While there is a practical / commercial need to optimize the pre-cryopreservation manufacturing efficiency of cellular products, consideration must be given to the impact and dependency that each manufacturing step has on the quality and potency of the final product.