(444f) Characterising the Fouling of An Industrial Anion Exchange Polishing Step During the Manufacturing Process of a Commercial Therapeutic Protein

There is an increasing desire within industry to develop and operate processes following a Quality by Design (QbD) strategy, where quality is built into the product and process based on a high level of product knowledge and process understanding. When considering chromatographic separations, the irreversible fouling of resin during its operational lifetime can significantly reduce its binding capacity and alter the process kinetics, thus severely decreasing the assurance of product quality and also potentially necessitating costly column replacement. From a QbD perspective, being able to characterise and predict the level of fouling is therefore of great importance.

Previous studies have been limited to fouling from simplified feed streams which are not fully representative of those seen in industry. In this work, adsorption experiments, scanning electron microscopy and confocal laser scanning microscopy were used to investigate the fouling of an anion exchange polishing step from an industrial purification process during the manufacture of a commercial therapeutic protein. The proposed methodology determines the spatial location of the foulant and its effect on intra-particle phenomena during protein uptake. The results can enable the optimal selection of appropriate operating and control strategies of commercial processes, in order to maintain product quality and thus significantly increase process robustness and performance over the operational lifetime of the resin.