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Continuous chromatography, Continuous Capture, Process Design, Protein A, Modelling

Abstract

Continuous capture chromatography using twin columns, also called Capture Simulated Moving Bed (CaptureSMB, or “cSMB”) is a chromatographic technique promising higher resin utilization, higher productivity and lower buffer consumption than traditional single column capture processes. The design of cSMB processes is more challenging than the design of batch processes because each “switch” of a given column is influenced by the load from the previous switch and it is in turn influencing the subsequent switch. An iterative approach is necessary to identify optimal loading conditions.

Currently, process design of cSMB processes is based on a single column breakthrough curve and feeding the breakthrough data into a model. However, this concept leads to a sub-optimal process as it is based on a single loading flow rate, while effectively, the cSMB process uses two different loading flow rates in the interconnected and the parallel load phases and the chosen flow rate is not necessarily optimal.

We are presenting an approach where different flow rates and different breakthrough curves are used as model inputs together with pressure-flow dependencies for the resin of interest. Using the improved design procedure of cSMB, significantly higher productivities were achieved than with the regular procedure. The effect was confirmed for a given in-house model process (mAb purification using Protein A affinity chromatography) where productivities could be increased by approximately 50% which has been confirmed at laboratory scale. The presented approach was also evaluated using mechanistic modelling. Finally, Implications of the new cSMB design approach for large-scale manufacturing are discussed.