Effect of operating pressure on protein fouling during constant-pressure virus removal filtration

Joshua Peles, Fatemeh Fallahianbijan, Benjamin Cacace, Christina Carbrello, Sal Giglia, Andrew L. Zydney

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Virus removal filtration provides a robust size-based removal of enveloped and non-enveloped viruses in the production of monoclonal antibodies and serum-derived products. The filtrate flux in virus removal filtration is typically dominated by membrane fouling associated with the therapeutic protein product, but very few studies have examined the effect of operating pressure on the fouling rate/mechanisms or the virus filter capacity. Filtration experiments were performed using Viresolve® Pro virus removal filters with human serum Immunoglobulin G (hIgG) as a model protein over a range of operating pressures from 10 to 60 psi. The extent of fouling (evaluated in terms of the overall resistance at a given throughput) decreased with increasing operating pressure up to about 30 psi, while the filter capacity (evaluated using the Vmax model) increased with increasing pressure. The flux decline behavior was shown to be in good agreement with the combined complete pore blockage and cake filtration model, with the pore blockage parameter decreasing with increasing pressure, while the cake filtration parameter increased with increasing pressure. Confocal microscopy was used to identify the location and extent of protein deposition within the membrane cross-section, providing further support for the effects of pressure on both pore blockage and cake resistance. These results provide important insights into the factors controlling protein fouling during virus removal filtration and the influence of operating pressure on the flux decline and filter capacity.

Original languageEnglish (US)
Article number120351
JournalJournal of Membrane Science
Volume648
DOIs
StatePublished - Apr 15 2022

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • General Materials Science
  • Physical and Theoretical Chemistry
  • Filtration and Separation

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