Simplified strategy for developing purification processes for antibody-drug conjugates using cation-exchange...

The development of manufacturing processes for antibody-drug conjugates (ADCs) presents many challenges compared to a standard monoclonal antibody. Conjugation processes typically start with an antibody intermediate that was purified to have very low levels of aggregates. The additional processing required for ADCs, including a hydrophobic small molecule and co-solvents, contributes to unacceptable levels of protein aggregate species. A post-conjugation purification step could be necessary to ensure that the process robustly delivers a product that achieves the desired product quality specifications. This paper describes a methodology for developing chromatographic purification steps to remove very high molecular weight species (vHMWS) in ADCs and was applied to three products, decreasing the vHMWS by ≥ 85% to ≤ 0.1%. Leveraging the antibody intermediate purification conditions to streamline development, we efficiently developed robust flow-through cation-exchange chromatography steps for ADC products.