Computational fluid particle dynamics modeling of tangential flow filtration in perfusion cell culture

Membrane fouling is a common and complex challenge with cell culture perfusion process in biopharmaceutical manufacturing that can have detrimental effects on the process performance. In this study, we evaluated a method to calculate the hollow fiber membrane resistance at different time points for water and supernatant. In addition, the number of subvisible particles of 50% when the feed flow rate was increased from 35 ml/min to 300 ml/min. Our findings suggest that the total number of subvisible particles has a significant impact on TMP and membrane resistance and, thus, could play a major role in the mechanism of membrane fouling. CFD modeling can be a useful tool to predict the behavior of a process in a specific membrane. CFD simulations could also be used to optimize process parameters to improve membrane cleanability, reduce particle deposition, and reduce the risk of membrane fouling.