November 1-5, 2015
Development of Protein A based purification platforms have simplified the downstream processing of monoclonal antibodies (mAb), the largest component of biopharmaceuticals. The ever increasing titer of the cell culture process is putting more pressure on the downstream process to further increase its productivity. The classical Protein A based mAb purification platform consists of two polishing steps, bind and elute cation-exchanger and flowthrough anion-exchanger. Cation-exchange chromatography is very efficient at the separation of HCP, leached Protein A and product-related impurities such as aggregates and fragments in bind and elute mode. However, anion-exchange chromatography is a proven technology to remove DNA, viruses, endotoxins and HCP in flowthrough mode. This study compares bind and elute mAb purification performance with that in flowthrough mode for the Natrix HD-Sb hydrogel membrane. Natrix HD-Sb is a salt-tolerant strong cation-exchange membrane augmented with hydrophobic butyl groups. This study demonstrates the effectiveness of Natrix HD-Sb chemistry in removing aggregates and HCP from challenging feed at high load with significant improvement in productivity and simplicity. The flowthrough separation performance of Natrix HD-Sb at neutral pH will be highlighted to show the potential of having tandem polishing steps (cation-exchange → anion-exchange) without needing any pH or conductivity adjustment. This tandem membrane approach has the potential for streamlining the downstream process for increased productivity & process efficiency.
Dharmesh Kanani, Daniel Luo, Nirali Paghdal, Navneet Sidhu, Annabel Shang, and Jim Stout, "Salt-tolerant cation exchange HD-Sb hydrogel membrane: mAb purification performance in flowthrough mode" in "Integrated Continuous Biomanufacturing II", Chetan Goudar, Amgen Inc. Suzanne Farid, University College London Christopher Hwang, Genzyme-Sanofi Karol Lacki, Novo Nordisk Eds, ECI Symposium Series, (2015). https://dc.engconfintl.org/biomanufact_ii/136