title: A control strategy to investigate the relationship between specific productivity and high-mannose glycoforms in CHO cells.
abstract: The integration of physiological knowledge into process control strategies is a cornerstone for the improvement of biopharmaceutical cell culture technologies. The present contribution investigates the applicability of specific productivity as a physiological control parameter in a cell culture process producing a monoclonal antibody (mAb) in CHO cells. In order to characterize cell physiology, the on-line oxygen uptake rate (OUR) was monitored and the time-resolved specific productivity was calculated as physiological parameters. This characterization enabled to identify the tight link between the deprivation of tyrosine and the decrease in cell respiration and in specific productivity. Subsequently, this link was used to control specific productivity by applying different feeding profiles. The maintenance of specific productivity at various levels enabled to identify a correlation between the rate of product formation and the relative abundance of high-mannose glycoforms. An increase in high mannose content was assumed to be the result of high specific productivity. Furthermore, the high mannose content as a function of cultivation pH and specific productivity was investigated in a design of experiment approach. This study demonstrated how physiological parameters could be used to understand interactions between process parameters, physiological parameters, and product quality attributes.
authors.affiliation: Department of Biotechnology, Gedeon Richter Plc., 19-21, Gyömrői út, Budapest, 1103, Hungary.|Institute of Chemical Engineering, Research Area Biochemical Engineering, Vienna University of Technology, Gumpendorfer Strasse 1a, 1060, Vienna, Austria.
authors.forename: Dénes
authors.initials: D
authors.lastname: Zalai
authors.affiliation: Spectroscopic Research Department, Gedeon Richter Plc., 19-21, Gyömrői út, Budapest, 1103, Hungary.
authors.forename: Helga
authors.initials: H
authors.lastname: Hevér
authors.affiliation: Department of Biotechnology, Gedeon Richter Plc., 19-21, Gyömrői út, Budapest, 1103, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Lovász
authors.affiliation: Department of Biotechnology, Gedeon Richter Plc., 19-21, Gyömrői út, Budapest, 1103, Hungary.
authors.forename: Dóra
authors.initials: D
authors.lastname: Molnár
authors.affiliation: Institute of Chemical Engineering, Research Area Biochemical Engineering, Vienna University of Technology, Gumpendorfer Strasse 1a, 1060, Vienna, Austria.|CD Laboratory for Mechanistic and Physiological Methods for Improved Bioprocesses, Vienna, Austria.
authors.forename: Patrick
authors.initials: P
authors.lastname: Wechselberger
authors.affiliation: Institute of Chemical Engineering, Research Area Biochemical Engineering, Vienna University of Technology, Gumpendorfer Strasse 1a, 1060, Vienna, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hofer
authors.affiliation: Department of Biotechnology, Gedeon Richter Plc., 19-21, Gyömrői út, Budapest, 1103, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Párta
authors.affiliation: Department of Biotechnology, Gedeon Richter Plc., 19-21, Gyömrői út, Budapest, 1103, Hungary.
authors.forename: Ákos
authors.initials: Á
authors.lastname: Putics
authors.affiliation: Institute of Chemical Engineering, Research Area Biochemical Engineering, Vienna University of Technology, Gumpendorfer Strasse 1a, 1060, Vienna, Austria. christoph.herwig@tuwien.ac.at.|CD Laboratory for Mechanistic and Physiological Methods for Improved Bioprocesses, Vienna, Austria. christoph.herwig@tuwien.ac.at.
authors.forename: Christoph
authors.initials: C
authors.lastname: Herwig
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism*; D019149:Bioreactors; D016466:CHO Cells; D018929:Cell Culture Techniques; D002460:Cell Line; D002468:Cell Physiological Phenomena / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D006031:Glycosylation; D008358:Mannose / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D008358:Mannose
keywords: CHO; Cell culture; Control of specific productivity; Glycosylation; Monoclonal antibody; Product quality attributes