Intensified Chromatography for more sustainable protein purification

Abstract

This thesis investigates how process intensification and sustainability improvements can be achieved in plasma manufacturing by optimizing an ion-exchange chromatography step. The work focuses on systematic modification of the key parameters influencing resin utilization, recovery, and resource efficiency and transferring an existing batch process to a periodic counter-current chromatography (PCC) operation.Increasing the feed protein concentration proved to be the most effective lever for intensification. Higher feed titers enhanced mass transfer toward the resin, enabling increased loading and slightly higher recovery while reducing process time and water consumption. Building on these findings, a four-column PCC configuration was designed in which two columns operated in series during loading and a short wash phase, minimizing product loss.Under optimized conditions, the PCC process achieved higher recovery and drastically increased productivity compared with the batch reference, while reducing resin and water requirements. Overall, the intensified setup demonstrated significant economic and environmental benefits, cutting resource consumption like resin volume and water as well as operational costs.These results highlight that process intensification and sustainability are not opposing objectives but can be realized simultaneously through intelligent process design. The implementation of PCC thus represents a viable step toward greener and more efficient plasma-derived biopharmaceutical manufacturing.