A Model-based Approach to Evaluating Chromatography Capture Steps

Abstract: Recent advances in upstream production of biopharmaceuticals have not yet been matched by equivalent advances in the downstream processing. As chromatography is currently the primary downstream processing method in production of biopharmaceuticals new methods for multicolumn processes are being developed. This paper investigates one such method, the three-column periodic counter-current (3C-PCC) process, through computer models and laboratory experiments. The process is optimized with respect to scheduling and the effect of feed concentration is studied. 3C-PCC is shown to have limited to no benefit from decreased flowrates, and the effects of the feed concentration shows clear signs of the internal scheduling limitations that arise when the feed concentration rises above a certain value. The results show an increase in resin utilization but a lower productivity for the multicolumn process compared to the base case batch process.