Antibody retention by virus filtration membranes: Polarization and sieving effects

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 PegasusTM 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.

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Work Title Antibody retention by virus filtration membranes: Polarization and sieving effects
Access
Open Access
Creators
  1. Andrew Zydney
  2. Matthew Billups
  3. Melissa Holstein
  4. Hasin Feroz
  5. Swarnim Ranjan
  6. Jessica Hung
  7. Haiying Bao
  8. Sanchayita Ghose
  9. Zheng Jian Li
Keyword
  1. Virus filtration, Ultrafiltration, Antibody, Retention, Membrane
License CC BY-ND 4.0 (Attribution-NoDerivatives)
Work Type Article
Acknowledgments
  1. Bristol Myers Squibb
Publisher
  1. Elsevier
Publication Date November 1, 2020
Subject
  1. Virus Filtration
Language
  1. English
Publisher Identifier (DOI)
  1. 10.1016/j.memsci.2020.118884
Geographic Area
  1. United States
Deposited March 02, 2021

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Version 1
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  • Created
  • Updated Acknowledgments Show Changes
    Acknowledgments
    • Bristol Myers Squibb
  • Added Creator Andrew Zydney
  • Added Creator Matthew Billups
  • Added Virus Filter-mAb sieving-unmarked.docx
  • Updated License Show Changes
    License
    • https://creativecommons.org/licenses/by-nd/4.0/
  • Added Creator Melissa Holstein
  • Added Creator Hasin Feroz
  • Added Creator Swarnim Ranjan
  • Added Creator Jessica Hung
  • Added Creator Haiying Bao
  • Added Creator Sanchayita Ghose
  • Added Creator Zheng Jian Li
  • Published
  • Updated