November 1-5, 2015
Monoclonal antibodies (mAbs) are a predominant modality for a broad range of clinical indications including oncology and inflammatory diseases. Increasing manufacturing capacity and decreasing cost per purification campaign are critical factors for making antibody therapies more affordable. Cell culture mAb expression levels have steadily increased over the past ten years with titers of five grams per liter frequently achieved. Higher titers reduce production costs and allow processing of kilogram quantities for clinical trials from single use cell culture vessels. Drawbacks of increased titers include higher levels of aggregates, fragments, variants, and process impurities. These combined titer and impurity burdens further stress downstream processing that already accounts for up to 70% of mAb production cost. Protein A and other batch chromatography methods are the primary contributors to this cost. Multi-column continuous chromatography (MCC), a form of simulated moving bed chromatography (SMBC), is a scalable technology previously demonstrated to improve productivity and lower the cost of Protein A affinity chromatography versus the standard single column batch process. This study incorporates another MCC process using hydroxyapatite for aggregate removal and concurrent depletion of impurities following Protein A purification of mAb. Results indicate that a completely continuous downstream process, including only two chromatographic steps, may be possible to increase efficiency and reduce cost in mAb biomanufacture.
Anthony Grabski, Tom Van Oosbree, Beth Hammer, Alla Zilberman, and Robert Mierendoff, "Toward complete continuity in antibody biomanufacture: Multi-column continuous chromatography for Protein A capture and mixed mode hydroxyapatite polishing" 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). http://dc.engconfintl.org/biomanufact_ii/137