Visualizing protein fouling and its impact on parvovirus retention within distinct filter membrane morphologies

Abstract

Virus filtration is considered an effective and robust method to remove viral contaminants that may enter the manufacturing process of biotherapeutics. However, insights into the retention mechanism of viruses under the influence of different operating conditions have been limited so far. In this work, we visualize the impact of filter fouling and flow decay on the retention of fluorescently labeled minute virus of mice (MVM) in asymmetric Planova 20N and nearly homogeneous Pegasus SV4 filter membranes. Filtration of feedstreams containing polyclonal human immunoglobulin G (IgG) revealed a complex interplay of different fouling mechanisms depending on high- or low-fouling solution properties, and characteristic for the distinct filter types. The asymmetric filter morphology – which allowed gradual foulant deposition across membrane zones with different pore sizes – provided a larger capacity for capture of fouling particulates as well as robust virus retention under challenging feedstream conditions. Taken together, our results demonstrate that different filtration conditions can lead to a combination of various, even opposing effects on virus retention depending on the membrane structure and pore size characteristics. The phenomena visualized in this work contribute to a better understanding of the underlying molecular mechanisms and provide cues for specific optimization of virus filtration processes.