(160b) Are Membranes Finally Ready to Compete with Chromatography in the Purification of High Value Biopharmaceuticals?

There has been long-standing interest in trying to develop membrane systems for purification of proteins and other biologically-derived products, dating all the way back to the pioneering work of Alan Michaels. Despite these efforts, nearly all of the key purification steps in biomanufacturing are currently performed using column chromatography. Although chromatographic systems can provide very high resolution separations, many chromatography resins are quite expensive, scale-up can be challenging, and it is difficult to apply column chromatography in the development of continuous downstream processes. Recent work in our lab has demonstrated the potential of High Performance Countercurrent Membrane Purification (HPCMP) for protein separations based on selective diffusive transport across low-cost hollow fiber membranes. This talk will examine the principles underlying HPCMP technology and the application of HPCMP for removal of Host Cell Proteins (HCP) in the purification of a monoclonal antibody (mAb) produced in Chinese Hamster Ovary (CHO) cells. HPCMP was able to provide more than 95% mAb yield with more than 100-fold reduction in HCP. Stable operation could be maintained for 48 hr, without any membrane regeneration or cleaning, for feeds that were first pre-filtered through the 3Mâ„¢ Harvest RC chromatographic clarifier to remove DNA and other foulants. In addition, the Process Mass Intensity (PMI) for HPCMP can be much less than that for alternative HCP separation processes. These results highlight the potential of using membrane systems instead of chromatography for the development of fully continuous mAb purification processes, reducing the overall manufacturing cost and potentially enabling the broader application of these life-saving biopharmaceuticals.