The impact of cell retention devices in the industrialisation of perfusion processes for recombinant protein manufacture

随着他们的兴趣日益增加，了解灌注工艺的工艺发展和工业化要求是很重要的。迄今为止，文献中的大多数研究都集中在减少媒体消耗和提高生产力的优化上。很少有研究关注细胞保留装置的影响以及泵在生物反应器和细胞保留装置之间流体传递的作用。该项目旨在建立细胞保留装置在灌注过程工业化中的影响。特别是，该项目旨在确定不同策略（如使用pluronic F68作为细胞剪切保护剂）或不同细胞保留装置操作或不同规模下灌注培养的特点。将调查所得灌注液的产品质量和杂质概况，并评估其对下游工艺步骤的影响，例如，在亲和色谱操作的整个生命周期内，它们对树脂性能的影响。该项目将解决以下生物工艺挑战：-在不同灌注策略或目标下优化细胞保留装置的操作-为稳健的下游处理获得一致的产品概况和灌注液质量的方法。-以不同的开发规模（例如250 mL和1L）进行灌注工艺操作，以生产相同质量的生物工艺材料用于下游加工。

With their increasing interest, it is important to understand the process development and industrialisation requirements of perfusion processes. Most studies in literature have so far focused on optimisation to reduce media consumption and increase productivity. Few studies have looked at the impact of cell retention devices and the action of pumps for fluid transfer between bioreactor and the cell retention devices. This project aims to establish the impact of cell retention devices in the industrialisation of perfusion processes. In particular, the project aims to determine the characteristics of perfusion culture when using different strategies (e.g. using pluronic F68 as shear-protectant for cells) or different cell retention device operation or when running at different scales. The product quality and impurity profile of the resulting perfusate will be investigated and their impact on downstream process steps will be assessed, e.g., their impact on resin properties during the lifetime of the affinity chromatography operation.The project will address the following bioprocess challenges:- the optimised operation of cell retention devices under different perfusion strategies or targets- the method of obtaining a consistent product profile and quality of perfusates for robust downstream processing.- the operation of perfusion processes at different development scale (e.g., 250 mL and 1L) to produce the same quality of bioprocess material for downstream processing.