Supporting Design and Control of a Reversed-Phase Chromatography Step by Mechanistic Modeling



There is a need to design and understand control strategies for biopharmaceutical processes. The control strategy will influence the design space and process performance and should be chosen together with the operating point and design space. Mechanistic modeling is used to design and evaluate control strategies for product pooling in preparative chromatography. A kinetic dispersive model was calibrated to reversed-phase chromatography experiments. Uncorrelated process disturbances were introduced to optimized operating points, and the effects of disturbances were evaluated and reduced by control strategies. Pooling control was implemented at a fixed UV absorbance or as a function of retention volume and UV peak height. The higher flexibility of the second control strategy decreased the loss of yield and productivity caused by the disturbances.