Variations in novel cellular therapy products manufacturing

Background aims: At the frontier of transfusion medicine and transplantation, the field of cellular therapy is emerging. Most novel cellular therapy products are produced under investigational protocols with no clear standardization across cell processing centers. Thus, the purpose of this study was to uncover any variations in manufacturing practices for similar cellular therapy products across different cell processing laboratories worldwide. Methods: An exploratory survey that was designed to identify variations in manufacturing practices in novel cellular therapy products was sent to cell processing laboratory directors worldwide. The questionnaire focused on the manufacturing life cycle of different cell therapies (i.e., collection, purification, in vitro expansion, freezing and storage, and thawing and washing), as well as the level of regulations followed to process each product type. Results: The majority of the centers processed hematopoietic progenitor cells (HPCs) from peripheral blood (n = 18), bone marrow (n = 16) or cord blood (n = 19), making HPCs the most commonly processed cells. The next most commonly produced cellular therapies were lymphocytes (n = 19) followed by mesenchymal stromal cells (n = 14), dendritic cells (n = 9) and natural killer (NK) cells (n = 9). A minority of centers (<5) processed pancreatic islet cells (n = 4), neural cells (n = 3) and induced-pluripotent stem cells (n = 3). Thirty-two laboratories processed products under an investigational status, for either phase I/II (n = 27) or phase III (n = 17) clinical trials. If purification methods were used, these varied for the type of product processed and by institution. Environmental monitoring methods also varied by product type and institution. Conclusion: This exploratory survey shows a wide variation in cellular therapy manufacturing practices across different cell processing laboratories. A better understanding of the effect of these variations on the quality of these cell-based therapies will be important to assess for further process evaluation and development.