Polishing of monoclonal antibodies streams through convective flow devices

Abstract

Monoclonal antibodies (mAbs) are the class of biopharmaceuticals showing the fastest growth in the pharmaceutical market. Therefore, an efficient manufacture process must be designed to meet the actual market needs. Diffusion-based devices such as packed-bed resins are traditionally used for polishing steps with some drawbacks, the most important of which is the low process throughput. A promising alternative is the use of convective flow devices, such as membranes and monoliths. In line with this, the performances of Sartobind® Q SingleStep Nano membrane and of CIM® QA monolithic column were evaluated for the polishing of mAbs from different cell fluids and their mimetics and compared with that of HiTrap Q XL packed-bed. Concerning recovery and purification, best working pH values were found in the range 7.5–8.0, and the best performing buffer was phosphate, opposed to HEPES and Tris–HCl. Two different polishing scenarios were evaluated, with and without a previous mAbs capture step, both studied with convective flow and diffusion-based devices. All three-used anion-exchange supports originated yields around 98% and purity higher than 99%. Monoliths outperformed the other two media, in both IgG recovery and impurities removal. However, data reported herein strengthens the choice of using both monoliths and membranes at higher flow rates to overcome the bottlenecks currently found in the purification of mAbs.