November 1-5, 2015
We have evaluated novel cation exchange resin and membrane which is potentially suited for continuous process in biologics manufacturing.
Typically cation exchange chromatography (CEX) is used in a bind/elute (B/E) mode for the MAb process since MAb act as cation at the buffer condition used for CEX due to the pI from neutral to weak basic. Generally, purpose of CEX chromatography is to remove aggregates and other impurities like HCP and DNA. Especially, aggregate removal is of interest to the industries. A continuous process in MAb downstream process can solve several bottlenecks in typical batch process. However its capability cannot be fully utilized if some step of chromatography is used in a B/E mode since it will take a longer process time due to the posing of product stream for binding and washing and it will take a more cost due to the requirement of large amount of resins as we use at the batch process. In such a case, chromatography in flowthrough mode has a potential to overcome those issues for both cost and time and enables us to develop more streamlined continuous process.
We will present the result of our study to evaluate novel CEX resin developed by Merck Millipore by comparing with the existing process of Mab A and we obtained a conclusion that this resin is fitted to the continuous processing very much. The novel resin showed a better impurity clearance than our existing process. For example, over 65% removal of aggregate by the novel resin was obtained in contrast to no removal by the existing process. A 20-fold better clearance for DNA was confirmed for the novel resin than the existing process. This indicates an additional polishing step can be omitted and this new chromatography can be a strong option if we need to reduce such impurities further. Also the resin cost is expected to be reduced down to 1/10 in maximum since those impurity clearance results were obtained about 10-times larger load than the typical B/E mode operation of CEX. Considering those aspects, we conclude that this resin showed a better fit for a continuous process. We will also discuss an expected effect of the novel CEX resin on cost and process time savings by a continuous process
Takuya Muramoto, Satoshi Murakami, Shinsuke Higuchi, and Keiji Iwamoto, "Evaluation of novel CEX resin for continous processing of MAb purification" 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/129