Virus Filtration and Flow Variation: An Approach To Evaluate Any Potential Impact on Virus Retention.
Virus removal by filtration has been an important improvement for the safety margins of plasma-derived medicinal products and has become a standard manufacturing process step for recombinant proteins. While the mechanism of action was initially considered to be strictly size-based, it has recently been recognized that a more complex interaction of the specific filter membrane and its pore architecture with filtrate flow rates may potentially influence the level of virus removal. Based on this improved understanding, parameters beyond the traditional state-of-the-art may need to be included into the design and control of these processes, and the validity of virus removal data generated in small-scale models for the manufacturing scale processes may need to be reevaluated. This article presents a tool for the analysis of flow rate during manufacturing or virus-spiked small-scale runs with a focus on the effects of low or no flow (stop) situations on the robustness of virus removal. Virus removal by filtration has improved safety margins of plasma-derived medicinal products and recombinant proteins. However, low or no flow (stop) situations during virus filtration may potentially affect virus removal. Transforming filtrate flow versus time data into histograms generates intuitively understandable visuals that provide a powerful tool to investigate the equivalence of manufacturing scale processes and down-scaled virus-spiked study runs, and thus to understand the robustness of virus removal for this parameter. With this tool at hand, lower mean flow rates during small-scale experiments are an elegant approach to support the robustness of virus filtration with respect to this parameter at manufacturing scale.