TY - JOUR
T1 - The role of intermolecular interactions on monoclonal antibody filtration through virus removal membranes
AU - Billups, Matthew
AU - Minervini, Mirko
AU - Holstein, Melissa
AU - Feroz, Hasin
AU - Ranjan, Swarnim
AU - Hung, Jessica
AU - Zydney, Andrew L.
N1 - Publisher Copyright:
© 2023 The Authors. Biotechnology Journal published by Wiley-VCH GmbH.
PY - 2023/12
Y1 - 2023/12
N2 - The removal of viruses by filtration is a critical unit operation to ensure the overall safety of monoclonal antibody (mAb) products. Many mAbs show very low filtrate flux during virus removal filtration, although there are still significant uncertainties regarding both the mechanisms and antibody properties that determine the filtration behavior. Experiments were performed with three highly purified mAbs through three different commercial virus filters (Viresolve Pro, Viresolve NFP, and Pegasus SV4) with different pore structures and chemistries. The flux decline observed during mAb filtration was largely reversible, even under conditions where the filtrate flux with the mAb was more than 100-fold smaller than the corresponding buffer flux. The extent of flux decline was highly correlated with the hydrodynamic diameter of the mAb as determined by dynamic light scattering (DLS). The mAb with the lowest filtrate flux for all three membranes showed the largest attractive intermolecular interactions and the greatest hydrophobicity, with the latter determined by binding to a butyl resin in an analytical hydrophobic interaction chromatography (HIC) column. These results strongly suggest that the flux behavior is dominated by reversible self-association of the mAbs, providing important insights into the design of more effective virus filtration processes and in the early identification of problematic mAbs/solution conditions.
AB - The removal of viruses by filtration is a critical unit operation to ensure the overall safety of monoclonal antibody (mAb) products. Many mAbs show very low filtrate flux during virus removal filtration, although there are still significant uncertainties regarding both the mechanisms and antibody properties that determine the filtration behavior. Experiments were performed with three highly purified mAbs through three different commercial virus filters (Viresolve Pro, Viresolve NFP, and Pegasus SV4) with different pore structures and chemistries. The flux decline observed during mAb filtration was largely reversible, even under conditions where the filtrate flux with the mAb was more than 100-fold smaller than the corresponding buffer flux. The extent of flux decline was highly correlated with the hydrodynamic diameter of the mAb as determined by dynamic light scattering (DLS). The mAb with the lowest filtrate flux for all three membranes showed the largest attractive intermolecular interactions and the greatest hydrophobicity, with the latter determined by binding to a butyl resin in an analytical hydrophobic interaction chromatography (HIC) column. These results strongly suggest that the flux behavior is dominated by reversible self-association of the mAbs, providing important insights into the design of more effective virus filtration processes and in the early identification of problematic mAbs/solution conditions.
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U2 - 10.1002/biot.202300265
DO - 10.1002/biot.202300265
M3 - Article
C2 - 37641433
AN - SCOPUS:85170359764
SN - 1860-6768
VL - 18
JO - Biotechnology Journal
JF - Biotechnology Journal
IS - 12
M1 - 2300265
ER -