Feasibility of using continuous chromatography in downstream processing: Comparison of costs and product quality for a hybrid process vs. a conventional batch process

•Product quality is comparable between continuous and batch protein A chromatography.•Use of continuous chromatography allows for 420% productivity increase.•Buffer amounts can be reduced by 30-40% for continuous protein A chromatography.•Continuous chromatography reduces cost of goods by 300% for the protein A step.

The protein A capture step is the main cost-driver in downstream processing, with high attrition costs especially when using protein A resin not until end of resin lifetime. Here we describe a feasibility study, transferring a batch downstream process to a hybrid process, aimed at replacing batch protein A capture chromatography with a continuous capture step, while leaving the polishing steps unchanged to minimize required process adaptations compared to a batch process. 35 g of antibody were purified using the hybrid approach, resulting in comparable product quality and step yield compared to the batch process. Productivity for the protein A step could be increased up to 420%, reducing buffer amounts by 30-40% and showing robustness for at least 48 h continuous run time. Additionally, to enable its potential application in a clinical trial manufacturing environment cost of goods were compared for the protein A step between hybrid process and batch process, showing a 300% cost reduction, depending on processed volumes and batch cycles.