(131f) Flow Distribution in Commercial Depth Filter Capsules for Clarification of Cell Culture Fluid – Effects on Performance and Scale-up

Significant improvements in cell density and product titer have led to renewed interest in the application of depth filtration for initial clarification of cell culture fluid in antibody production. The performance of these depth filters will depend on the local pressure and velocity distribution within the filter capsule, but these are very difficult to probe experimentally, leading to challenges in both process design and scale-up. We have used a combination of carefully designed experimental studies and computational fluid dynamics (CFD) to examine these issues in a series of Pall depth filter capsules (Supracap^TM 50 and Stax^TM), both with PDH4 media containing diatomaceous earth. CFD calculations were used to identify multiple flow paths through the capsules, with the predicted flow distribution validated by comparison with the measured residence time distribution in both the lab-scale and pilot-plant modules. The impact of the flow distribution on protein binding was evaluated using a series of model proteins with different charge, molecular weight, and hydrophobicity. Furthermore, cell deposition and filter capacity were examined using suspensions of CHO and HEK 293 cells over a range of cell density and viability. The results provide important insights into the factors controlling the performance and scale-up of these commercially important depth filters as well as a framework that can be broadly applied to develop more effective depth filters and depth filtration processes.