Virus retention filtration is a common step in modern biopharmaceutical manufacturing as it enables efficient removal of potential adventitious and endogenous viruses via size exclusion. Modern parvovirus retention filters have significantly improved fluxes and parvovirus retention in comparison to earlier versions of these filters. However, these filters may be more susceptible to premature fouling and require more effort for process optimization. Here, we demonstrate that polyamide‐6,6 (nylon‐6,6) membranes when used as prefilters can increase the capacity of these Parvovirus retentive filters that are less susceptible to premature fouling. We found that the mechanism of polyamide‐mediated filtration improvement can be explained by the binding of monoclonal antibody (mAb) aggregates with a diameter of 20–100 nm, and we show that this mechanism is shared by other types of adsorptive prefilters. Finally, by the combination of mobile phase screening, additive spiking, and molecular dynamics simulations, we show that polyamide‐6,6 removes mAb aggregates through hydrophobic interactions making its design space potentially complementary to other available prefilters. Our studies support the aggregate‐mediated mechanism of flux decay during viral filtration and suggest that polyamide‐6,6 could be considered as an alternative cost‐effective option to extend the capacity of viral filters.
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