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首页> 外文期刊>Biotechnology Progress >Fluctuations in dissolved oxygen concentration during a CHO cell culture process affects monoclonal antibody productivity and the sulfhydryl-drug conjugation process
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Fluctuations in dissolved oxygen concentration during a CHO cell culture process affects monoclonal antibody productivity and the sulfhydryl-drug conjugation process

机译：CHO细胞培养过程中溶解氧浓度的波动影响单克隆抗体生产率和巯基 - 药物缀合过程

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During a CHO cell culture production process, important parameters are generally well controlled by a feedback mechanism (PID loop) in order to ensure consistency in both productivity and product quality. These parameters typically include pH, dissolved oxygen (DO), and temperature. While most of these parameters are very well controlled within their specific deadband, stable DO control can be challenging. Oscillations in DO concentration are not uncommon and these fluctuations can be exacerbated with an efficient mass transfer aeration strategy. In this study, where an IgG(2) producing cell line was used, we observed increased lactate accumulation accompanied by decreased titer production in lots with fluctuations in DO concentration (DOF) when compared with lots with stable DO control (DOS). We demonstrate that DOF had a greater impact on performance with respect to titer production and lactate accumulation than DO setpoint. Furthermore, we report that estimated specific oxygen uptake rates (qOURs) were lower in DOF lots when compared with DOS lots. We also report that purified mAb sourced from DOF lots yielded lower drug-to-antibody ratio (DAR) after the sulfhydryl-targeted maleimide conjugation process when equivalent reducing agent was used. All mAb lots were within the analytical specifications for release, though a slight increase in measureable trisulfides were observed in DOF mAb lots. DO control aimed to minimize fluctuations around DO setpoint was essential for us to produce consistent DAR without adjusting the conjugation process. (c) 2018 American Institute of Chemical Engineers
机译：在CHO细胞培养生产过程中，重要的参数通常由反馈机制（PID环）控制，以确保生产力和产品质量的一致性。这些参数通常包括pH，溶解氧（DO）和温度。虽然大多数这些参数在其特定死区内非常良好地控制，但稳定的控制可能具有挑战性。浓度的振荡并不少见，并且这些波动可以通过高效的传质曝气策略加剧。在该研究中，在使用IgG（2）产生的细胞系中，我们观察到增加乳酸乳液积累，伴随着浓度（DOF）的批量的批量产生的批量产生的较低，与稳定进行控制（DOS）相比。我们证明，DOF对滴度产生和乳酸积累的性能产生了更大的影响，而不是设定点。此外，与DOS批次相比，我们报告说，估计的特定氧气摄取率（QUARS）在DOF批次中较低。我们还报告，当使用等效还原剂时，从DOF批量中，来自DOF批量的纯化的mAb来自DOF批量的药物 - 抗体比（DAR）较低，得到较低的药物 - 抗体比（DAR）。所有MAB批次都在分析规范内进行释放，但在DOF MAB批次中观察到可测量的三硫醚的略微增加。控制旨在最大限度地减少Do SetPoint周围的波动对我们来说是必不可少的，而不是在不调节缀合过程的情况下生产一致的粉末。 （c）2018美国化学工程研究所

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