Title: Investigation of the interactions of critical scale-up parameters (pH, pO2 and pCO2) on CHO batch performance and critical quality attributes
Language: English
Authors: Brunner, Matthias 
Fricke, Jens 
Kroll, Paul 
Herwig, Christoph 
Category: Original Research Article
Issue Date: 2017
Journal: Bioprocess and Biosystems Engineering 
ISSN: 1615-7591
Abstract: 
Understanding process parameter interactions and their effects on mammalian cell cultivations is an essential requirement for robust process scale-up. Furthermore, knowledge of the relationship between the process parameters and the product critical quality attributes (CQAs) is necessary to satisfy quality by design guidelines. So far, mainly the effect of single parameters on CQAs was investigated. Here, we present a comprehensive study to investigate the interactions of scale-up relevant parameters as pH, pO2 and pCO2 on CHO cell physiology, process performance and CQAs, which was based on design of experiments and extended product quality analytics. The study used a novel control strategy in which process parameters were decoupled from each other, and thus allowed their individual control at defined set points. Besides having identified the impact of single parameters on process performance and product quality, further significant interaction effects of process parameters on specific cell growth, specific productivity and amino acid metabolism could be derived using this method. Concerning single parameter effects, several monoclonal antibody (mAb) charge variants were affected by process pCO2 and pH. N-glycosylation analysis showed positive correlations between mAb sialylation and high pH values as well as a relationship between high mannose variants and process pH. This study additionally revealed several interaction effects as process pH and pCO2 interactions on mAb charge variants and N-glycosylation pattern. Hence, through our process control strategy and multivariate investigation, novel significant process parameter interactions and single effects were identified which have to be taken into account especially for process scale-up.
Keywords: CHO cell culture; Process parameter; Scale-up; Monoclonal antibody CQA; Design of experiments
DOI: 10.1007/s00449-016-1693-7
Library ID: AC15187464
URN: urn:nbn:at:at-ubtuw:3-3928
Organisation: E166 - Institut für Verfahrenstechnik, Umwelttechnik und technische Biowissenschaften 
Publication Type: Article
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