Viral Clearance in Antibody Purification Using Tentacle Ion Exchangers

anufacturers strive toward cost-effective purification of target molecules and a high level of confidence that their biologics are safe and not compromised by the presence of endogenous retrovirus-like particles or adventitious viruses (1). Reliable reduction of viral particles throughout downstream purification processes must be ensured through different techniques such as chemical treatment, filtration, and chromatography. Common monoclonal antibody (MAb) purification schemes use both cationand anion-exchange chromatography steps (CEX, AEX). Although CEX (to remove productand process-related impurities) is not generally considered robust enough for virus reduction, in some conditions it has made a significant contribution to virus removal. By contrast, AEX (a polishing step in MAb purification) is generally considered as a robust step for virus reduction. Tentacle ion exchangers are chromatography media comprising porous hydrophilic polymeric base beads with grafted functional polymers, which can be either AEX (e.g., trialkylammonium, dialkylammonium) or CEX groups (e.g., sulfonate, carboxyl) on particle surfaces. Those surface polymers (tentacles) interact with charged groups or patches on biomolecule surfaces and efficiently bind impurities or target molecules of interest under appropriate operating conditions. Tentacle ion exchangers have been shown to successfully remove viruses in different MAb purification applications. This article provides a comprehensive review of previously published applications of tentacle ion-exchange media for virus removal in the purification of MAbs. Different types of tentacle chromatography media (e.g., CEX, AEX), as well as various modes of operation (e.g., bind and elute, flow-through, weak partitioning) will be discussed.