Process considerations for Protein A affinity capture, virus inactivation, and linked polishing steps in multi-column continuous purification of monoclonal antibodies
September 17-21, 2017
Multi-column continuous chromatography (MCC) offers significant economic advantages over traditional batch methods for purification of monoclonal antibodies (mAbs), including increased resin capacity utilization, smaller columns, reduced buffer consumption, and faster process time. The Protein A capture step is a primary target to apply MCC due to its high cost, which is driven even higher as improvements in upstream processing have produced a steady increase in mAb titers. In this study we consider the key factors in designing an MCC process that optimizes productivity. Process design begins with determination of the feed duration, which is governed by the mAb titer, column dimensions, residence time, binding capacity, and flow properties of the resin. Use of 3 columns in the capture zone enables efficient utilization of the resin even at short residence times, thereby increasing productivity. Column number and resin volume are optimized to relieve scheduling constraints experienced at high mAb titer while maximizing cycling for single use columns. Productivities exceeding 100 g mAb/L resin/h were achieved loading concentrated CHO expressed feed stream using a Semba ProPD™ System and 8-column MCC Protein A affinity process. Flow-through and bind-elute polishing steps including ion exchange and mixed mode have been converted from batch to MCC toward realization of a completely continuous biomanufacturing platform.
Robert Mierendorf, Tom Van Oosbree, Anthony Grabski, William Wessel, and Emily Schirmer, "Process considerations for Protein A affinity capture, virus inactivation, and linked polishing steps in multi-column continuous purification of monoclonal antibodies" in "Integrated Continuous Biomanufacturing III", Suzanne Farid, University College London, United Kingdom Chetan Goudar, Amgen, USA Paula Alves, IBET, Portugal Veena Warikoo, Axcella Health, Inc., USA Eds, ECI Symposium Series, (2017). https://dc.engconfintl.org/biomanufact_iii/20