(235c) Multi-Column Continuous Chromatography for Process Intensified Capture and Polishing of Monoclonal Antibodies

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. Scheduling constraints experienced at high titer with MCC approaches using only 2–4 columns are relieved by including additional columns to perform all process operations simultaneously. Productivities exceeding 100 g mAb/L resin/h were achieved with 10.8 g/L titers using a Semba ProPD™ System and 8-column MCC Protein A affinity process. Downstream 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.