Deciphering Virus Removal With Ultrafiltration Membrane: Effects of Membrane Properties, Operating Conditions, and Antibody Characteristics

ABSTRACT Virus filtration is a critical step to ensure the safety of antibody‐based therapeutics. Due to the stringent performance requirements, commercially available virus filtration membranes are limited, and studies on virus retention behavior across different antibodies remain scarce, partly due to the high cost of these biologics. Herein, we comprehensively evaluated a newly developed virus filtration membrane, UF‐Viremoval‐Plus, by benchmarking it against leading commercial virus filters. The results demonstrate that UF‐Viremoval‐Plus exhibits superior antifouling properties and virus retention performance, which are attributed to its less negative charge, higher hydrophilicity, gradient pore structure and funnel‐shaped geometry. We further investigated the effects of key process parameters, including pH, ionic strength, antibody type, and concentration, on membrane flux and virus removal efficiency. The membrane maintained stable operation under varying pressures and process disturbances, consistently achieving virus removal levels above 4 log reduction value, with no evidence of virus breakthrough. However, significant shifts in feed solution pH or ionic strength, as well as membrane fouling caused by high protein concentrations, affected virus removal. These observations are governed by complex membrane‐protein‐virus interactions. This work provides theoretical insights for the rational design of virus filtration membrane microstructures and the optimization of viral clearance processes in biopharmaceutical manufacturing.