Optimizing virus filtration for continuous processing using serial
filtration at high area ratio
Abstract
Compared to batch operation, continuous bioprocessing can offer numerous
advantages, including increased productivity, improved process control,
reduced footprint, and increased flexibility. However, integration of
traditional batch operations into a connected process can be
challenging. In contrast to batch operations run at constant pressure or
high flux, virus filtration in continuous processes may be operated at
very low flux. This change in operating conditions may reduce the viral
retention performance of the filter which has inhibited adoption of
truly continuous virus filtration. To overcome this limitation, a novel
approach is described that utilizes serial virus filtration, with a high
area ratio between first to second stage filters, to achieve virus
retention targets. In this study, virus filters were operated
continuously (except for planned process interruptions) for 200 hours in
a serial configuration at a first to second stage filter area ratio of
13:1 and at a first stage flux of 5 L/m 2/hr. While
the minute virus of mice (MVM) retention performance of the first stage
filter was about 4 log reduction value (LRV), there was no virus
detected in the second stage filtrate, translating to an MVM LRV across
the filtration train of ≥6.7. The second stage filter was the dominant
flow resistance at the start of the run but, as it was protected from
foulants by the first stage filter, it suffered minimal fouling and the
life of the filter train was controlled by the first stage. A
theoretical case study projected that continuous virus filtration using
serial configuration at high area ratio would have about 30% longer
filter changeout time, 14% higher productivity, and virus retention
nearly 6 LRV greater than single stage operation. The findings of this
research are expected to provide valuable insights into optimizing virus
filtration in continuous bioprocessing.