Pressure Impacts
Operating conditions that are considered worst-case for viral filtration are those that lead to break-through of the filter by a non-catastrophic failure such that the filter integrity test still shows that the filter is intact. The presumed failure mechanism for non-catastrophic failures is particle diffusion, where it is hypothesized that virus migrates through the membrane structure during flow disruptions by diffusion. Operating conditions that are considered worst-case (e.g. increase particle diffusion) include is low transmembrane pressure, transitions in pressure, low flux, or pausing of pressure/flow (Fan, Namila et al. , Brorson, Miesegaes et al. 2014, LaCasse, Lute et al. 2016, Strauss, Goldstein et al. 2017).”Virus movement within the membrane (e.g. particle diffusion) structure during flow disruptions was visualized using fluorescently labeled phi X-174 bacteriophage and polystyrene nanospheres.”(Dishari, Micklin et al. 2015, Fallahianbijan, Giglia et al. 2017). In general, previous generation viral filters suffered a decline in viral retention at lower pressures or with flow pauses (Fan, Namila et al. , LaCasse, Lute et al. 2016), and log reduction values (LRVs) of MMV varied depending on the product and feed solution conditions (Strauss, Goldstein et al. 2017). In newer generation viral filters, clearance appeared to be robust despite variations in pressure and extended flow pauses (Mattila, Clark et al. 2016, Strauss, Goldstein et al. 2017). High pressure limits are typically set based on the structural integrity limits provided by the filter manufacturer or by system capabilities. High differential pressure operation within the filter limit is not known to lead to filter breakthrough by a non-catastrophic mechanism and, thus, high differential pressures across a membrane alone are unlikely to pose a risk to viral retention.