High throughput development of a non protein A monoclonal antibody purification process using mini‐columns and bio‐layer interferometry

Downstream purification process development for therapeutic mAbs is a critical step that must be accomplished under compressed timelines. High‐throughput sorbent screening has gained much attention for accelerating process development, based on the rapid acquisition of a large dataset. This study describes the development of a non protein A purification process for a mAb expressed in a CHO cell supernatant. Capture and intermediate steps were screened on three mixed‐mode and one cation exchange chromatography sorbents using 200 μL mini‐columns compatible with automation. Capacity and yield were evaluated using biolayer interferometry and mAb purity, using SEC‐HPLC. A scale‐up of the capture and intermediate steps using 2.5 cm id and 0.5 cm id lab‐scale columns packed with MEP HyperCel™ mixed‐mode sorbent and CM Ceramic HyperD® F cation exchange sorbent, respectively, led to an overall mAb recovery yield of 90% and an mAb purity close to 97%. The high‐throughput workflow applied here, both in terms of screening and analytics, was a key point to accelerate process development and achieve optimal mAb product purity and yield at minimized time and cost.