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Optimizing virus filtration for continuous processing using serial filtration at high area ratio
  • +4
  • Sal Giglia,
  • Benjamin Cacace,
  • Jacob McCoskey,
  • Matthew Johnson,
  • Christina Carbrello,
  • Corine Miller,
  • Joseph Hersey
Sal Giglia
MilliporeSigma

Corresponding Author:[email protected]

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Benjamin Cacace
MilliporeSigma
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Jacob McCoskey
MilliporeSigma
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Matthew Johnson
MilliporeSigma
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Christina Carbrello
MilliporeSigma
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Corine Miller
MilliporeSigma
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Joseph Hersey
MilliporeSigma
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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.
Submitted to Biotechnology and Bioengineering
10 May 2024Reviewer(s) Assigned
29 May 2024Review(s) Completed, Editorial Evaluation Pending
13 Jul 20241st Revision Received
16 Jul 2024Submission Checks Completed
16 Jul 2024Assigned to Editor
16 Jul 2024Review(s) Completed, Editorial Evaluation Pending
17 Jul 2024Reviewer(s) Assigned
23 Jul 2024Editorial Decision: Accept