Virus filtration is one of the key unit operations to demonstrate adequate virus clearance during downstream processing of mammalian host-derived therapeutic proteins. Virus filter throughput can be limited by the filter fouling. This study describes the membrane fouling characterization of industry-leading Viresolve® Pro virus filter. Previous investigations on this filter suggest that a very small fraction of large size aggregates in the load material could result in the premature plugging of the virus filter. Such investigations were primarily focused on the removal of higher order aggregates using pre-filters to improve the filtration capacity. However, there is limited information on the underlying mechanism of Viresolve Pro membrane fouling and characteristics of these aggregates. The objective of this study was to isolate and characterize the higher order aggregates using SEC-HPLC, SEC-MALS, analytical ultracentrifugation, ELISA, quantitative PCR, analytical hydrophobic interaction and ion-exchange chromatography methods. The final goal of this investigation was to understand the biophysical properties (e.g., size, charge, hydrophobicity) of these aggregates and correlate it to the premature plugging and adsorptive fouling of the Viresolve Pro membrane. Key words: membrane fouling, surface interactions, aggregates, membrane resistance, protein purification

Parvovirus filter robustness investigation: The characterization of higher order aggregates and membrane fouling

249th National Meeting (2015)

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