(296b) The Effects of Filtration Flux on the Clearance of Minute Virus of Mice during Viral Filtration

Viral safety is one of the major concerns in the production of mammalian cell and plasma derived biotherapeutic products. Demonstration of virus clearance is required by the regulatory agencies. Virus filtration is a size exclusion-based virus clearance method and is conducted industrially in dead-end mode. It is often operated in a batch mode under constant pressure. Membrane performance is shown to be affected by feed condition (pH, ionic strength and feed buffer components) as well as the operation condition (flux, pressure, time). During continuous bioprocessing, constant flux is a more desirable operation mode. Here the effects of flux operated under constant flux filtration mode and the solution condition on virus retention are systematically investigated for the filtration of monoclonal antibodies spiked with minute virus of mice (MVM) using three commercially available virus filters. Surprisingly, virus breakthrough was observed for two of the three filters when low constant flux operation was performed for a relatively longer periods of time. The interplay between virus loading on the filter, flux, membrane fouling and filtration time on virus retention will be discussed.