Polishing approach with fully connected flow-through purification for therapeutic monoclonal antibody.

Abstract

The biopharmaceutical industry is evolving toward process intensification that can offer increased productivity and improved economics without sacrificing process robustness. A semi-continuous downstream process linking purification/polishing unit operations in series can reduce or eliminate intermediate holding tanks and reduce overall processing time. Accordingly, we have developed a therapeutic monoclonal antibody polishing template comprised of a connected flow-through polishing technologies that include activated carbon, cation exchange, and anion-exchange chromatography. In this report, we evaluated fully-connected pool-less polishing with three flow-through technologies, operating as a single skid to streamline and improve an mAb purification platform. Laboratory-scale pool-less processing was achieved without utilizing in-line pH adjustment and conductivity dilution based on the previously optimized single process parameter. Two connected flow-through configurations of polishing steps were evaluated: a two-step process using anion exchange and cation exchange and a three step process using activated carbon, anion exchange and cation exchange chromatography. Laboratory-scale proof of concept studies showed comparable performance between the batch purification process and the pool-less process configuration. Three step polishing highly intensified the processes and provided higher process loading and achieved bulk drug specification with higher impurity clearance (>95%) and high overall mAb yield (>95%).