(156l) Development of a Harvest Small Scale Model to Simulate Continuous Centrifugation

Disk stack centrifugation is one of the main clarification steps used in large scale mammalian cell culture processes. During process development, pilot scale disc stack centrifuge is normally used to develop and characterize the harvest process for new cell culture processes due to the lack of smaller scale model for disc stack centrifugation. In order to increase speed of development, a small scale model (SSM) of a disk stack centrifuge is of high demand to enable harvest development in an earlier stage of process development. A small scale model can also improve throughput and reduce cost. In this study, we have developed a SSM for disc stack centrifugation using a capillary shear device combined with benchtop centrifugation. Capillary tube size, length, and flow rate were optimized to generate energy dissipation rates comparable to large scale disk stack centrifuges. Additionally, shear force from multiple centrifuges at different scales were standardized and compared. Mathematical correlations were established for energy dissipation, viable cell density, cell viability, and lactate dehydrogenase (LDH) activity. Our SSM offers an approach to understand how the separation process, such as centrifuge designs, sizes, and configurations affect filtration performance and product quality. This work can speed up harvest development during process scale-up in biopharmaceutical mammalian cell culture processes.