Viral removal by column chromatography in downstream processing of monoclonal antibodies

Abstract

For monoclonal antibodies (mAbs) produced in mammalian cells, viral safety is a critical concern. The downstream process, in addition to removing other impurities, needs to ensure robust clearance (removal or inactivation) of potential endogenous and adventitious viruses. In general, Protein A and polishing chromatography steps all can provide certain level of virus removal. Chromatographic removal combined with virus inactivation and nanofiltration usually provides adequate virus clearance across the overall downstream process. This article reviews the virus clearance capability of commonly used column chromatography, with attention to possible interference of virus-mAb interaction on virus removal. In addition, the potential of using viral surrogate as a safe alternative to live virus for assessing viral clearance is briefly discussed.

Keywords: Anion exchange (AEX); Cation exchange (CEX); Mixed-mode; Monoclonal antibody (mAb); Protein A; Viral surrogate; Virus removal; Virus-mAb interaction.