Single-use centrifugation solution for volume reduction and cell washing process in cell therapy manufacturing

Abstract

Current bioprocessing technologies have limited applications in cell therapy manufacturing as they are optimized for the manufacture of recombinant proteins. For example, most cell harvest technologies are efficient in removing cells but not in maximizing viable cell density, viability, washing, and recovery; parameters that are most important for cell therapy manufacturing. Most commonly cells are retained by either centrifugation or filtration based devices. These approaches are often problematic. Conventional centrifugation based devices cause stress and nutrient deprivation to the cells in the pellet which results in low viability, while filtration based devices often suffer from issues such as clogging, retention of cell debris, and shear stress on cells. We have developed the first single-use fluidized-bed centrifugation systems that are completely closed. Our results show that kSep systems can concentrate diverse types of cells with high recovery while maintaining high viability. Additionally, kSep systems can remove cell debris, light particulate impurities, all while significantly reducing aggregation of cells. We have designed these systems without any rotary seals (providing reduced sterility risk) or filters (for reduced issues from clogging). Once captured and concentrated, the cells can efficiently be washed, manipulated, and harvested. This technology is a breakthrough for applications requiring maintenance of cellular integrity during processing. Results show >90% recovery of cells with unchanged viability and 99.9% removal of contaminants. Our automated systems are currently being used for cell therapy, recombinant proteins, and vaccine manufacturing processes.