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.
Tag: <span>process intensification</span>
A perfusion approach at N-1, where cells stay in the exponential growth phase throughout the entire culture duration, is becoming more common as a strategy for process intensification. This is because the higher cell densities it generates allows manufacturers to skip seed stages and reduce process transfer time through multiple bioreactor sizes, thus providing more cost-effective biologics production in smaller facilities. However, this N-1 perfusion approach requires optimization. In this article, we describe the development and proof-of-concept studies with single-use rocking motion perfusion bioreactors in which we have achieved a ten-fold increase in viable cell count in N-1 seed stage, compared to the fed-batch control process, in just 6–8 days. We also mention in detail how we inoculated a 50 L bioreactor production run using this intensified seed train and show comparable growth kinetics and yield with a control process, also at 50 L scale. Using this intensification approach in the future will help our manufacturing facility, the Biopharma Division of Intas Pharmaceuticals Ltd., reach 4000 L production-scale volumes with fewer process transfer steps, and without changing the feeding strategy or production bioreactors of our biologics’ portfolio.