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首页> 外文期刊>Bioprocess and Biosystems Engineering >Investigation of the interactions of critical scale-up parameters (pH, pO(2) and pCO(2)) on CHO batch performance and critical quality attributes
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Investigation of the interactions of critical scale-up parameters (pH, pO(2) and pCO(2)) on CHO batch performance and critical quality attributes

机译：关键放大参数（pH，pO（2）和pCO（2））对CHO批处理性能和关键质量属性的相互作用的研究

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摘要

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, pO(2) and pCO(2) 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 pCO(2) 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 pCO(2) 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.
机译：了解过程参数的相互作用及其对哺乳动物细胞培养的影响，是鲁棒的过程放大的基本要求。此外，必须具备工艺参数与产品关键质量属性（CQA）之间关系的知识，才能通过设计准则来满足质量要求。到目前为止，主要研究了单个参数对CQA的影响。在这里，我们基于实验设计和扩展的产品质量，提供了一项综合研究，以研究按比例放大相关参数（如pH，pO（2）和pCO（2））对CHO细胞生理学，过程性能和CQA的相互作用。分析。该研究使用了一种新颖的控制策略，在该策略中，过程参数彼此分离，因此可以在定义的设定点对它们进行单独控制。除了已经确定了单个参数对过程性能和产品质量的影响之外，使用此方法还可以得出过程参数对特定细胞生长，特定生产率和氨基酸代谢的进一步显着相互作用。关于单参数影响，几个单克隆抗体（mAb）电荷变异体受到过程pCO（2）和pH的影响。 N-糖基化分析显示mAb唾液酸化和高pH值之间呈正相关，以及高甘露糖变体与过程pH之间存在关系。这项研究还揭示了几个相互作用的影响，如过程pH和pCO（2）相互作用对mAb电荷变体和N-糖基化模式的影响。因此，通过我们的过程控制策略和多变量研究，发现了新的重要过程参数交互作用和单一影响，尤其是过程放大时，必须考虑这些影响。

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  • 来源
    《Bioprocess and Biosystems Engineering》 |2017年第2期|251-263|共13页
  • 作者

    Brunner Matthias; Fricke Jens; Kroll Paul; Herwig Christoph;

  • 作者单位

    Vienna Univ Technol, Res Div Biochem Engn, Gumpendorferstr 1a, A-1060 Vienna, Austria|Vienna Univ Technol, CD Lab Mechanist & Physiol Methods Improved Biopr, Gumpendorferstr 1a-166, A-1060 Vienna, Austria;

    Vienna Univ Technol, Res Div Biochem Engn, Gumpendorferstr 1a, A-1060 Vienna, Austria|Vienna Univ Technol, CD Lab Mechanist & Physiol Methods Improved Biopr, Gumpendorferstr 1a-166, A-1060 Vienna, Austria;

    Vienna Univ Technol, Res Div Biochem Engn, Gumpendorferstr 1a, A-1060 Vienna, Austria|Vienna Univ Technol, CD Lab Mechanist & Physiol Methods Improved Biopr, Gumpendorferstr 1a-166, A-1060 Vienna, Austria;

    Vienna Univ Technol, Res Div Biochem Engn, Gumpendorferstr 1a, A-1060 Vienna, Austria|Vienna Univ Technol, CD Lab Mechanist & Physiol Methods Improved Biopr, Gumpendorferstr 1a-166, A-1060 Vienna, Austria;

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  • 正文语种 eng
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  • 关键词

    CHO cell culture; Process parameter; Scale-up; Monoclonal antibody CQA; Design of experiments;

    机译：CHO细胞培养;工艺参数;放大;单克隆抗体CQA;实验设计;

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