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Titel
A control strategy to investigate the relationship between specific productivity and high-mannose glycoforms in CHO cells
VerfasserZalai, Dénes ; Hevér, Helga ; Lovász, Krisztina ; Molnár, Dóra ; Wechselberger, Patrick ; Hofer, Alexandra ; Párta, László ; Putics, Ákos ; Herwig, Christoph In der Gemeinsamen Normdatei der DNB nachschlagen
Erschienen in
Applied Microbiology and Biotechnology, Berlin; Heidelberg, 2016, Jg. 100, H. 16, S. 7011-7024
ErschienenSpringer, 2016
Ausgabe
Published version
SpracheEnglisch
DokumenttypAufsatz in einer Zeitschrift
Schlagwörter (EN)Cell culture / CHO / Product quality attributes / Monoclonal antibody / Control of specific productivity / Glycosylation
ISSN1432-0614
URNurn:nbn:at:at-ubtuw:3-1559 Persistent Identifier (URN)
DOI10.1007/s00253-016-7380-4 
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A control strategy to investigate the relationship between specific productivity and high-mannose glycoforms in CHO cells [1.89 mb]
Supplementary Material [0.59 mb]
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Zusammenfassung (Englisch)

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.

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CC-BY-Lizenz (4.0)Creative Commons Namensnennung 4.0 International Lizenz