By Sayali Kulkarni and Anupama Kante, Jericho Coquilla, Sammy Samaha, Martin Hoang, Hayley Hua, Haiou Yang
Volume 25, Open Access (January 2026)
With growing interest in process intensification in the biopharmaceutical industry, implementing cost-effective purification strategies has become increasingly important, particularly for the expensive protein A affinity capture step in monoclonal antibody production. This study compares traditional resin-based batch chromatography (rbBC), multi-column chromatography (MCC), and membrane chromatography (MC) using small-scale experiments with commercially available formats. Performance metrics including yield, elution volume, and impurity reduction were evaluated. The best-performing conditions for MC and MCC were used to project cost and productivity for mAb purification at the 1,000 L bioreactor scale. Both MC and MCC demonstrated significant advantages over rbBC. MC achieved the highest productivity (234–236 g/L/h, 19–20-fold higher than rbBC) and the lowest media costs, resulting in up to 91% reduction in cost-of-goods (CoG) per batch. MCC also showed notable improvements, with 4.6–5.1-fold higher productivity than rbBC, and up to 72% CoG savings. Due to its operational similarity to rbBC and compatibility with existing infrastructure, MC was selected for further evaluation. Optimization was performed using a 3.5 mL membrane over 50 cycles, followed by scale-up to a 58 mL membrane tested on a pilot-scale skid representative of clinical or commercial manufacturing. The process was successfully run for 55 cycles, demonstrating comparable yield, impurity reduction, and elution profiles to rbBC. These results support the feasibility of membrane chromatography as a scalable and economical alternative for protein A capture in intensified downstream processing…
Citation: Kulkarni, S., and Kante, A.; Coquilla, J.; Samaha, S.; Hoang, M.; Hua, H.; Yang, H. Process intensification of protein A affinity step for monoclonal antibody purification using membrane and multi-column chromatography. BioProcessing Journal 2026, 25. https://doi.org/10.12665/bioprocess.j.260224
Posted online February 24, 2026