(255a) Constant Flux Viral Reduction Filtration: Effect of Flux on the Retention of Minute Virus of Mice

Virus reduction filtration is a key component of downstream processing platform in modern biologics production processes. In a typical batch process, it is operated at constant pressure whereby flux decreases with time as filter gets fouled. The main objective of this study is to understand the impact of flux on virus breakthrough and gain some understanding of process design flexibility in the context of continuous manufacturing. In this study, the effect of filtration flux on the Minute Virus of Mice (MVM) retention capability of commercially available virus filters were evaluated in constant flux
filtration mode, with and without the presence of protein product. Fluxes chosen were guided by the Peclet number and the processing logistics as well as based on the filter characteristics.

At the low flux condition of 5 LMH when diffusive force dominates, a significant breakthrough was observed for all the filtrate fractions for the filtration of a low fouling monoclonal antibody for three of the four filters. When both diffusive and convective forces are equally important at 40 LMH, virus
breakthrough in buffer chase was observed only in one of the four filters investigated. When convective force dominates at 60 LMH or above, a high degree of virus clearance was observed for all parvovirus filters investigated. This study shed light on virus clearance during constant flux virus
filtration for future continuous biomanufacturing.