Tangential flow filtration (TFF) has become a desirable choice for cell retention devices due to the ability to handle high cell concentration (>100 million CHO cells/mL) and large-scale bioreactors for an extended continuous bioprocess. The shift to TFF allows for a more scalable process utilizing Levitronix’s magnetically levitated centrifugal pump resulting in high sieving performance while maintaining relatively low mechanical stress on cells. However, there are still a myriad of difficulties when scaling TFF from bench to large scale.

Major considerations are hollow fiber membrane fouling, large facility footprint, increasing operational demand, and hollow fiber geometry limitations. In this discussion, we will explore methods for overcoming TFF limitations including: the reduction of Starling flow via high flux to maximize filter capacity, optimizing filter geometry, and modular operational approaches to reduce facility footprint at large scales. These mitigation techniques in combination result in a fraction of the filter area demand while maintaining maximized product yield.