Role of membrane structure on the filtrate flux during monoclonal antibody filtration through virus retentive membranes

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

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Virus removal filtration is a critical step in the manufacture of monoclonal antibody products, providing a robust size-based removal of both enveloped and non-enveloped viruses. Many monoclonal antibodies show very large reductions in filtrate flux during virus filtration, with the mechanisms governing this behavior and its dependence on the properties of the virus filter and antibody remaining largely unknown. Experiments were performed using the highly asymmetric Viresolve® Pro and the relatively homogeneous Pegasus™ SV4 virus filters using a highly purified monoclonal antibody. The filtrate flux for a 4 g/L antibody solution through the Viresolve® Pro decreased by about 10-fold when the filter was oriented with the skin side down but by more than 1000-fold when the asymmetric filter orientation was reversed and used with the skin side up. The very large flux decline observed with the skin side up could be eliminated by placing a large pore size prefilter directly on top of the virus filter; this improvement in filtrate flux was not seen when the prefilter was used inline or as a batch prefiltration step. The increase in flux due to the prefilter was not related to the removal of large protein aggregates or to an alteration in the extent of concentration polarization. Instead, the prefilter appears to transiently disrupt reversible associations of the antibodies caused by strong intermolecular attractions. These results provide important insights into the role of membrane morphology and antibody properties on the filtrate flux during virus filtration.

Original languageEnglish (US)
Article numbere3231
JournalBiotechnology progress
Volume38
Issue number2
DOIs
StatePublished - Mar 1 2022

All Science Journal Classification (ASJC) codes

  • Biotechnology

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