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首页> 美国卫生研究院文献>Wiley-Blackwell Online Open >Integrated economic and experimental framework for screening of primary recovery technologies for high cell density CHO cultures
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Integrated economic and experimental framework for screening of primary recovery technologies for high cell density CHO cultures

机译：综合的经济和实验框架用于筛选高细胞密度CHO培养物的主要回收技术

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摘要

Increases in mammalian cell culture titres and densities have placed significant demands on primary recovery operation performance. This article presents a methodology which aims to screen rapidly and evaluate primary recovery technologies for their scope for technically feasible and cost‐effective operation in the context of high cell density mammalian cell cultures. It was applied to assess the performance of current (centrifugation and depth filtration options) and alternative (tangential flow filtration (TFF)) primary recovery strategies. Cell culture test materials (CCTM) were generated to simulate the most demanding cell culture conditions selected as a screening challenge for the technologies. The performance of these technology options was assessed using lab scale and ultra scale‐down (USD) mimics requiring 25–110mL volumes for centrifugation and depth filtration and TFF screening experiments respectively. A centrifugation and depth filtration combination as well as both of the alternative technologies met the performance selection criteria. A detailed process economics evaluation was carried out at three scales of manufacturing (2,000L, 10,000L, 20,000L), where alternative primary recovery options were shown to potentially provide a more cost‐effective primary recovery process in the future. This assessment process and the study results can aid technology selection to identify the most effective option for a specific scenario.
机译：哺乳动物细胞培养滴度和密度的增加对初级恢复操作性能提出了重大要求。本文介绍了一种方法，旨在快速筛选并评估主要回收技术的范围，以便在高细胞密度哺乳动物细胞培养的背景下在技术上可行且具有成本效益的操作。它用于评估当前（离心和深度过滤选项）和替代（切向流过滤（TFF））一级回收策略的性能。生成了细胞培养测试材料（CCTM），以模拟最苛刻的细胞培养条件，这些条件被选为该技术的筛选挑战。这些技术选项的性能是通过实验室规模和需要25–110mL体积的超规模缩减（USD）模拟物进行评估的，分别用于离心和深度过滤以及TFF筛选实验。离心和深度过滤的组合以及两种替代技术均符合性能选择标准。在三个制造规模（2,000L，10,000L，20,000L）上进行了详细的过程经济学评估，其中显示了替代的一级回收选择方案，这些方案将来可能会提供更具成本效益的一级回收过程。评估过程和研究结果可以帮助技术选择，以针对特定情况确定最有效的选择。

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