November 1-5, 2015
Background and Novelty: Glycosylation is one of the major post-translational modifications of biotherapeutics important for bioactivity, bioavailability, immunogenicity and patient coverage. By establishment of the GlycoExpress™ toolbox (GEX™) we have generated a set of glycoengineered human cell lines for the high yield production of fully human glycoproteins to optimize the glycosylation of antibodies and non-antibody biotherapeutics for improvement of the clinical efficacy and side effects. The system is biotechnologically superior in quality, reproducibility and yield compared to other including conventional production systems. All four clinical products derived from GlycoExpress cells are produced using a perfusion bioreactor system in order to assure highest possible product quality and reproducibility combined with high yield production. Methods: GlycoExpress cells producing mAb are cultivated with perfusion bioreactor systems applying different cell retention mechanisms such as centrifugation (centritech) or alternating tangential flow (ATF) filtration at different scales. A 10 mL based down-scale perfusion system with good comparability to larger scale cultivations was also established. Growth, product yield and product quality, especially glycosylation, are evaluated during the cultivation. Conclusion: Perfusion culture helps to keep cells in the optimal growing and production phase over the production process which leads to highly stable product quality allowing a flexible duration of the run in one batch size in combination with stable high productivity of the cells over time. Furthermore the product qualities produced in different scales ranging from 10 mL to 1000 L cultivation vessels are highly comparable.
Steffen Kreye, "GlycoExpress: A toolbox for the high yield production of glycooptimized fully human biopharmaceuticals in perfusion bioreactors at different scales" 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/110