Flow distribution and scalability of depth filter capsules used in bioprocessing

• CFD and experimental work used to characterize depth filter flow distribution. • Data shows effective sealing of media edges to prevent fluid bypass in capsules. • Effective media sealing enables predictive performance across capsule scales. • Depth filter scalability data provided from bench- to commercial-scale. • Performance variability across scales can inform sizing and safety factor decisions. Depth filters are widely used in bioprocessing as a scalable, cost-effective approach to separating insoluble and soluble impurities from biologic products. They are typically used in single-use formats where filter media comes preassembled into capsules. These capsules often contain multiple layers of media with progressively tighter retention ratings. The design of these capsules largely dictates the distribution of flow through the media and is critical to performance. Non-uniform flow distribution can lead to premature breakthrough of impurities, thus lowering the filter capacity. Differences in flow distribution across capsule scales can make scale-up and tech transfer more challenging for drug manufacturers and can lead to larger required safety factors. In this work we evaluate flow distribution through a commonly used line of depth filter capsules, with a particular focus on edge seal integrity. CFD modeling was used to simulate the affect edge seal integrity can have on flow distribution. Simulations run on a capsule containing a non-integral edge seal showed the potential for fluid bypass of filter media, consistent with previous findings. However, experimental studies conducted on these capsules showed no indication of fluid bypass when loaded with common bioprocess solutions. Finally, a full scalability trial was run using bench-, pilot-, and commercial-scale capsules with a single feedstock to characterize how differences in capsule design translate to differences in performance across scales.