Automation preserves product consistency and quality for the formulation, fill, and finish of T cell-based therapies

Abstract

Scaling up the manufacture of cell therapies can be complex and challenging. Maintaining critical quality attributes of the cell product during its final formulation and fill-finish into multiple containers can be especially difficult and laborious. Here, we tested the automated Finia™ Fill and Finish System to efficiently scale up the formulation and fill-finish of a T cell product, and then assessed cell quality and product consistency across different sub-lots filled during this expanded process. We found that this automated system could be effectively scaled to 4 times its singular capacity in a 2-h time interval, with variation in cell number and product volume less than 12% across all containers. Analysis of the different sub-lots of the final product revealed high cell viability and consistent T cell phenotype, with a high proportion of effector memory and central memory T cells and low expression of T cell senescence and exhaustion markers. The functionality of the T cell product was compared by measuring cytokine response after restimulation, with secreted levels of effector cytokines like IFN-γ and TNF-α being similar across the different sub-lots. Collectively, these results show that automation can scale up the formulation and fill-finish of a cell manufacturing process while maintaining the phenotype and functionality of the cell product. Better understanding of how to maintain product uniformity and quality during final manufacturing is important to the further scale-up and development of successful cell therapies.