The distinctive separation attributes of mixed-mode resins and their application in monoclonal antibody downstream purification process.

Increased upstream productivity and the continuous pressure to deliver high quality drug product have resulted in the development of new separation technologies and platform strategies for downstream purification processes of monoclonal antibodies (mAb). In this study, the separation attributes of three mixed-mode resins, Mercapto-Ethyl-Pyridine (MEP) hydrophobic charge induction resin, Capto adhere multi-modal anion exchange resin, and ceramic hydroxyapatite/fluoroapatite (CHT/CFT) resins, were investigated to define their roles in monoclonal antibody purification processes. We demonstrated that the multi-modal nature of ligands on mixed-mode resins allows the separation resolution to be honed, either through a single dominant mechanism or through mix-modal balanced purification strategies. In addition, the three mixed-mode resins present different purification powers for different types of impurities. We also demonstrated that besides enhancing chromatography separation and improve product quality, especially for high molecular weight (HMW) aggregate reduction, mixed-mode resins can also help to improve process efficiency in industrial-scale mAb drug manufacturing. Our results underscore the importance of selecting appropriate chromatography resins during DSP design to obtain the best overall process outcome. Copyright 2009 Elsevier B.V. All rights reserved.