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.