Non-protein A purification platform for continuous processing of monoclonal antibody therapeutics

Protein A capture chromatography, the core of a mAb purification platform, is known to account for more than 50% of downstream processing costs along with other limitations including lack of complete stability to alkaline cleaning solutions, relatively lower binding capacity, and ligand leaching. Researchers have explored alternatives to protein A chromatography, both chromatographic and non-chromatographic, but with limited success. In this paper, we propose a non-protein A purification platform for continuous processing of monoclonal antibodies (mAbs). The proposed platform consists of precipitation in coiled flow inverter reactor, cation exchange chromatography for capture, multimodal chromatography and a salt tolerant anion exchange membrane as polishing steps. The versatility of the proposed platform has been successfully demonstrated for three different mAbs. In all cases, acceptable process yield was obtained (70-80 %) and the product quality attributes of the final unformulated drug substance were consistent and well within accepted limits (HCP < 100 ppm, DNA < 10 ppb, % aggregate content < 1%) along with desired charge variant composition.