Antibody retention by virus filtration membranes: Polarization and sieving effects

Matthew Billups, Mirko Minervini, Melissa Holstein, Hasin Feroz, Swarnim Ranjan, Jessica Hung, Haiying Bao, Sanchayita Ghose, Zheng Jian Li, Andrew L. Zydney

Research output: Contribution to journalArticlepeer-review

Abstract

Virus filtration is a key component of the overall virus clearance strategy in the production of monoclonal antibodies. These virus filtration membranes also provide one of the most selective membrane separations ever demonstrated, with more than 95% recovery of the antibody product in the filtrate with more than 99.99% retention of even small parvovirus, despite the less than 2-fold difference in size between the virus and antibody. However, there is currently no quantitative data on the intrinsic sieving characteristics of commercially available virus filters. Experiments were performed with the Viresolve® Pro and Pegasus™ SV4 virus filters both with and without stirring to control the effects of concentration polarization. The actual sieving coefficient of a highly purified monoclonal antibody was less than 0.05 for both membranes, demonstrating that the high antibody recovery during typical virus filtration processes is a direct result of the high degree of concentration polarization in these systems. The intrinsic selectivity of the virus filter was in good agreement with predictions of available hydrodynamic models accounting for a log-normal pore size distribution. The actual sieving coefficient also decreased with increasing antibody concentration, consistent with available models for proteins with attractive interactions (negative values of the interaction parameter). These results provide important insights into the transport characteristics of virus filters and their effect on the performance of these virus filters in bioprocessing.

Original languageEnglish (US)
Article number118884
JournalJournal of Membrane Science
Volume620
DOIs
StatePublished - Feb 15 2021

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Materials Science(all)
  • Physical and Theoretical Chemistry
  • Filtration and Separation

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