TY - JOUR
T1 - Antibody retention by virus filtration membranes
T2 - Polarization and sieving effects
AU - Billups, Matthew
AU - Minervini, Mirko
AU - Holstein, Melissa
AU - Feroz, Hasin
AU - Ranjan, Swarnim
AU - Hung, Jessica
AU - Bao, Haiying
AU - Ghose, Sanchayita
AU - Li, Zheng Jian
AU - Zydney, Andrew L.
N1 - Funding Information:
The authors would like to acknowledge Bristol Myers Squibb for funding of this project. The Viresolve® Pro and Pegasus™ SV4 virus filters were generously donated by MilliporeSigma and Pall, respectively.
Funding Information:
The authors would like to acknowledge Bristol Myers Squibb for funding of this project. The Viresolve? Pro and Pegasus? SV4 virus filters were generously donated by MilliporeSigma and Pall, respectively.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2021/2/15
Y1 - 2021/2/15
N2 - 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.
AB - 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.
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U2 - 10.1016/j.memsci.2020.118884
DO - 10.1016/j.memsci.2020.118884
M3 - Article
AN - SCOPUS:85096574612
VL - 620
JO - Journal of Membrane Science
JF - Journal of Membrane Science
SN - 0376-7388
M1 - 118884
ER -