Parvo virus removal by filter membranes is regarded as a robust and efficient unit operation in downstream processing of biopharmaceuticals. The retention of viruses is predominantly based on size exclusion. However, recent results point to the fact, that virus particle retention can also significantly be impacted by adsorptive interactions between virus particles and membranes. Furthermore, the impact of flow rate and flow interruptions on virus retention has been identified and responsible mechanisms discussed. The goal of this investigation is to gain a holistic picture of the underlying mechanisms for virus particle retention in size exclusion membranes as a function of membrane structure and membrane surface properties, as well as flow- and solution conditions. Therefore, parvo virus retentive membranes with different pore sizes and different levels of surface hydrophilization were generated in order to systematically change the level of size exclusion and adsorptive action on particle retention. The respective membranes were characterized with regards to their permeability, non-specific protein adsorption, surface zeta potential and pore size distribution by using liquid-liquid displacement porometry (LLDP). Furthermore, an experimental space of solution conditions regarding pH, salt and protein concentration was chosen, that impacts the adsorptive interaction between virus model particles and membrane surface. Bacteriophages (like PP7) were chosen as model particles, due to the established correlation to parvo virus retentive behavior and the related ease of handling. Filtration runs to determine the respective levels of retention were complemented by flow stop conditions and a set of permeate fractions for titer determination was taken at different process stages. This study will introduce to the generated set of data and will draw first conclusions. Based on the DOE character of the experimental space and respective analysis, interactions between different factors can be determined. The results enable to differentiate size exclusion from adsorptive action with respect to virus particle retention within the given space of material, process and solution conditions, significantly sharpening our understanding of retention mechanisms in parvo virus filtration.

Investigation of virus retention mechanisms by size exclusion membranes: The role of membrane properies and solution conditions in different flow regimes

253rd National Meeting (2017)

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