A typical process for monoclonal antibody purification usually includes a capture affinity chromatography step followed by polishing chromatography steps (AEX, CEX, HIC) to achieve the desired product quality. The number and type of polishing steps can vary based upon the level and type of impurities that are present. Due to increasingly aggressive timelines for drug development, it is desirable to minimize the number of purification steps in the process to help reduce development time and enter the clinic sooner. As chromatography resin technology and upstream capabilities continues to evolve to provide increased capacity to remove impurities and generate high quality material, 2-column purification processes are becoming more prevalent in the bio-process industry. Pre-clinical development for a novel monoclonal antibody (mAb A) compared a 2-column process to a more traditional 3-column process. While the product quality for the 3-column process was higher, as expected, the 2-column process easily met the Phase I specifications. Yield was 10% higher in a 2 column process vs. 3 column. Aggregate clearance increased by 45% along with a clearance of &gt;90% in HCP, DNA, and ProA. Two column process easily meets phase I specifications and results in reduced development time, higher yield, lower cycle time, and lower production cost. Hence, a 2-column process was chosen for Safety Assessment and Phase I production. To improve process robustness for Phase III and commercial manufacturing, there is a potential for an addition of a third column however, the production cost and productivity will be evaluated as the antibody progresses in the pipeline.

Improvements in downstream processing: minimization in chromatographic steps for early milestones

249th National Meeting (2015)

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