Simulation of periodic counter-current chromatography purification of monoclonal antibodies with column degradation

Sammanfattning: The purification process of monoclonal antibodies (mAbs) for therapeutic drugs is expensive, especially the chromatography step in which the mAbs are separated from other proteins and cells present in the feed. The antibodies are separated from the feed using affinity chromatography, where only the antibodies interact with active sites within the column, whereas the rest passes through the column without stopping. The antibodies leave the column when their chemical environment is changed, and the column is cleaned thoroughly with strong chemicals. The chemicals are essential in the cleaning process to ensure that there is no contamination between cycles or that there are any antibodies left. The chemicals are however slightly damaging the column, and after many cycles of loading with mAbs, eluting the mAbs and then cleaning, the capacity of the column is reduced. In this master thesis, periodic counter-current chromatography is modelled and simulated in python with columns that exhibit degradation. Two different controllers and a flow trajectory method is applied, to varying degrees, in different cases to investigate if they can counteract some of the problems that emerge due to the column degradation. To evaluate the effectiveness of the controllers and the flow trajectory, the performance process variables productivity, yield, and resin utilization were used. The best case used both controllers, the flow trajectory and had a productivity at 0.18 mg mAb per ml resin and minute, a minimum yield of 94.7% and a maximum resin utilization of 62.5 mg mAb per maximum amount adsorbed mAb at feed concentration.