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<p>Understanding the impact of critical process parameters on CHO cell cultivation and critical quality attributes (CQAs) of monoclonal antibody is an essential requirement for robust process scale-up and technology transfer. The effect of process parameters on lactate metabolism is of particular interest as it has been shown to be associated with cell growth and productivity. Here, a comprehensive study is presented to investigate the impact of potentially critical process parameters (aeration rate, agitation speed, dissolved oxygen level and copper concentration) on process performance and CQAs. Results demonstrated that dissolved oxygen level has a dominate positive effect on lactate consumption. Scale-relevant parameters (aeration rate and agitation speed) and copper concentration have smaller but also significant positive influence on lactate consumption. Based on these results, it can be summarized that low dissolved oxygen, agitation and aeration rates plus low copper concentration, would lead to insufficient oxygen availability for cell respiration (hypoxia). Under this condition, cells would rely on anaerobic glycolysis to generate energy and hence promote lactate production. This study also revealed a linkage between hypoxic condition and antibody purity and charge heterogeneity. This work provides critical insights for lactate metabolic and product quality control through optimizing critical process parameters and medium component.</p>

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Impact of DO, agitation, aeration and copper concentration on lactate metabolism and charge heterogeneity for monoclonal antibody production by CHO cells in fed-batch culture

  • 期刊论文

  • 发表日期：

    2025年7月14日

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  • Pei Yin,
  • Huizhi Lin,
  • Qian Zhou,
  • Jing Tong,
  • Meijin Guo

摘要

Understanding the impact of critical process parameters on CHO cell cultivation and critical quality attributes (CQAs) of monoclonal antibody is an essential requirement for robust process scale-up and technology transfer. The effect of process parameters on lactate metabolism is of particular interest as it has been shown to be associated with cell growth and productivity. Here, a comprehensive study is presented to investigate the impact of potentially critical process parameters (aeration rate, agitation speed, dissolved oxygen level and copper concentration) on process performance and CQAs. Results demonstrated that dissolved oxygen level has a dominate positive effect on lactate consumption. Scale-relevant parameters (aeration rate and agitation speed) and copper concentration have smaller but also significant positive influence on lactate consumption. Based on these results, it can be summarized that low dissolved oxygen, agitation and aeration rates plus low copper concentration, would lead to insufficient oxygen availability for cell respiration (hypoxia). Under this condition, cells would rely on anaerobic glycolysis to generate energy and hence promote lactate production. This study also revealed a linkage between hypoxic condition and antibody purity and charge heterogeneity. This work provides critical insights for lactate metabolic and product quality control through optimizing critical process parameters and medium component.