Anion exchange (AEX) chromatography is the core unit operation responsible for process related contaminant reduction in a recombinant protein purification process. Together with Protein A affinity capture, AEX chromatography step removes the bulk of host cell protein (HCP) from the bioprocess stream. As the manufacturing process have become more productive through intensification of cell culture, so has the concentration of host cell proteins in the cell culture fluid containing the biopharmaceutical product. Of particular importance are specific HCPs that catalyze target product degradation and bulk drug substance (DS) destabilization reactions. With the simplification of purification processes, clearance of the these HCPs has become more challenging and the development of specific strategies to address these challenges have come into focus.<br/>Here we present an evaluation of clearance of several problematic HCPs using new anion exchange technology, based on a combination of solid supports and AEX ligand chemistries. We combine quaternary ammonium (Q) functional fibrous media with a guanidinium (Gu) functionalized membrane to demonstrate reduction of problematic HCPs that cause product degradation and BDS destabilization from the process stream during the polishing stage of the purification process. We look at a variety of process conditions in terms of operating pH and conductivity to understand whether certain process conditions are particularly well suited for reduction of these host cell proteins. This analysis enables the ability to build more robust, simple, and platformable purification processes that accelerate discovery-to-clinic-to-commercial manufacturing timelines.

Evaluation of problematic HCP clearance by novel single use anion exchange technology

ACS Spring 2022

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