The evolution of down-scale virus filtration equipment for virus clearance studies.

The role of virus filtration in assuring the safety of biopharmaceutical products has gained importance in recent years. This is due to the fundamental advantages of virus filtration, which conceptually can remove all pathogens as long as their size is larger than the biomolecule of commercial interest, while at the same time being neutral to the biological activity of biopharmaceutical compound(s). Major progress has been made in the development of adequate filtration membranes that can remove even smaller viruses, or possibly even all. Establishing down-scaled models for virus clearance studies that are fully equivalent with respect to operating parameters at manufacturing scale is a continuing challenge. This is especially true for virus filtration procedures where virus clearance studies at small-scale determine the operating parameters, which can be used at manufacturing scale. This has limited volume-to-filter-area-ratios, with significant impact on process economics. An advanced small-scale model of virus filtration, which allows the investigation of the full complexity of these processes, is described here. It includes the automated monitoring and control of all process parameters, as well as an electronic data acquisition system, which is fully compliant with current regulatory requirements for electronic records in a pharmaceutical environment.