Protein A chromatography is very effective in separating impurities from monoclonal antibodies (mAbs) and continues to be used as the capture step in the majority of mAb purification process. The performance of Protein A chromatography, as indicated by capacity, operational flow rate, and productivity, has improved over the past few decades, and has played a significant role in the growth of therapeutic mAb industry. However, the high cost of Protein A resins has required better utilization of its capacity or the use of cheaper and comparable alternatives to improve the downstream process economics. While the improvements in capacities have been limited, achieving higher operational flow rates has led to dramatic improvements in the productivity of the Protein A capture step. Protein A in membrane formats, rather than packed beds, is an emerging technology that enables significantly higher productivity through substantially reduced cycle times. Rapid cycling time enables this technology to be applied in a single column multi-cycle mode, whereby the lifetime of the unit is exhausted over a single batch process, thereby; significantly improving the resin utilization and reducing the resin requirements compared to a conventional single column process, without compromising the throughput of the capture step. The shorter residence time and smaller formats enable acceleration of process development, optimization and characterization activities and reduce load material requirements, and thereby serve as an instrumental tool to accommodate ever-shrinking CMC (Chemistry, Manufacturing and Controls) timelines. In a short time frame, we developed and optimized the Protein A membrane capture step for therapeutic proteins, and demonstrated robust performance. The Protein A membranes delivered consistent product quality, impurity profiles, and chromatograms over a number of cycles, and performed consistently across different scales (scale varied by at least 10-fold). The disposable format of this technology and the ability to perform multiple cycles in a very short time makes Protein A membranes a highly economical, and offers a productive alternative to the conventional packed resin format.<br/>

Advances in affinity purification technologies for monoclonal antibody capture

255th National Meeting (2018)

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