Modeling the effect of monoclonal antibody on the performance of small virus filters using an advanced multilayer membrane model

Virus filters are designed to achieve high log reduction value (LRV) while maintaining high permeability and high target protein recovery. Performance arises from carefully controlled asymmetry in both porosity and pore size distribution. In this study, the unique multilayer membrane model that accounts for both these effects was applied to quantify and compare the structural characteristics—porosity and pore size distribution—of three small virus filters (Planova 20N, Planova S20N, and Planova BioEX; Asahi Kasei Life Science). Experimental data were obtained from constant flux filtration (75 LMH) of PBS solutions spiked with minute virus of mice (MVM). The model successfully reproduced MVM retention profiles within the membranes, revealing structural differences among the filters. Additionally, PBS containing 5 g/L monoclonal antibody (mAb) and MVM was filtered under identical conditions. By modeling transmembrane pressure (TMP) profiles, the composition of mAb aggregates was determined by fitting, indicating trace levels of trimers or higher-order aggregates below the size exclusion chromatography (SEC) detection limit (0.01%). Filtrations with 5 g/L monoclonal antibody (mAb) showed a MVM retention distribution peak shifted toward the permeate side. Model analysis suggests that this shift results from displacement of initially trapped MVM by reversible mAb aggregates within the pores. Variation in filtration behavior among the filters reflects differences in membrane structure. Experimental observations indicate that the presence of mAb can lead to a change in virus capture profile. To our knowledge, this is the first time the multilayer model has been used to predict this effect, providing insights into optimizing virus filtration in biopharmaceutical processes. • Advanced multilayer model quantifies asymmetric virus filter structures. • Model reproduces MVM retention distributions under constant flux filtration. • mAb causes permeate-side shift of virus retention peak via aggregate displacement. • TMP profiles reveal trace high-order aggregates below SEC detection limits. • Higher shear stress in the virus filter generates more self-association of mAb.