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>downstream purification</span>
In biopharmaceutical manufacturing, buffer preparation is traditionally performed manually by dissolving solid salts in water for injection (WFI) followed by offline mixing and specification testing. This method requires large buffer volumes, extensive infrastructure, and significant labor, often creating bottlenecks in production. To address these limitations and support process intensification, inline buffer preparation technologies have emerged…
Process optimization is a key development step that precedes scale-up and tech-transfer in a manufacturing environment. New England Biolabs (NEB) and GE Healthcare (GEHC) set the objective of improving filtration clarification and concentration process steps with the target of improving overall efficiency, and reducing the labor time and expense associated with these unit operations…
Tangential flow filtration (TFF) microfiltration has been used as one of the choices for clarification of mammalian cell or microbial cell culture in the biopharmaceutical industry. Unlike the ultrafiltration process for protein concentration and the diafiltration application where the feed solution is relatively clean (free of colloids or larger particles after the clarification/purification process), the microfiltration process needs to handle a rather high-fouling feed stream such as cells, cell debris, colloids, etc. In a previously published article, we discussed that a TFF microfiltration step is limited by a maximum throughput or capacity obtainable under a given set of operating conditions. Some distinct microfiltration characteristics, such as critical permeate flux, permeate flux control, and maximum throughput were explained in that article…