The role of intermolecular interactions on monoclonal antibody filtration through virus removal membranes

Author:

Billups Matthew1,Minervini Mirko1,Holstein Melissa2,Feroz Hasin2ORCID,Ranjan Swarnim2,Hung Jessica2,Zydney Andrew L.1ORCID

Affiliation:

1. Department of Chemical Engineering The Pennsylvania State University University Park Pennsylvania USA

2. Bristol Myers Squibb Biologics Process Development Global Product Development and Supply Devens Massachusetts USA

Abstract

AbstractThe 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.

Publisher

Wiley

Subject

Molecular Medicine,Applied Microbiology and Biotechnology,General Medicine

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