Technoeconomic comparison of optimised bioreactor-filtration systems for mAb production
Technoeconomic comparison of optimised bioreactor-filtration systems for mAb production
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DOI：
10.1016/j.compchemeng.2023.108438
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发表时间：
2023-11
期刊：
影响因子：
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通讯作者：
Wil Jones;Dimitrios I. Gerogiorgis
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文献类型：
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作者：
Wil Jones;Dimitrios I. Gerogiorgis
初级培养后生物量回收（从富含api的溶液中去除细胞培养）在生物制药制造中是必不可少的。离心和深度过滤是工业上主要的一次回收技术，但目前还缺乏适合于性能评价的机制动态模型。本文使用已建立的文献模型，以明确的旋转盘（动态横流）过滤模型（用于初级回收）为基础，提出并分析了补料批式或灌注式CHO生物反应器（用于通过CHO培养单克隆抗体）集成工艺设计的最佳操作策略。这里采用严格的DAE过滤模型（market等人，2020）来评估系统性能。生物反应器-过滤系统的动态优化已经完成了不同的生物反应器类型，过滤器安排和饲料操作，考虑到相同的单克隆抗体工厂的年度生产目标。优化设计的技术经济分析解决了工业可行性，确认了进料间歇反应器与堆叠膜微过滤器相结合的明显成本优势。
Primary post-cultivation biomass recovery (cell culture removal from API-rich solutions) is essential in biopharmaceutical manufacturing. Centrifugation and depth filtration are dominant industrial primary recovery technologies, but mechanistic dynamic models suitable for performance evaluation are scarce. This paper uses established literature models to present and analyse optimal operation strategies for integrated process designs of fed-batch or perfusion CHO bioreactors (for mAb cultivation via CHO cultures), with an explicit rotational disk (dynamic crossflow) filtration model (for primary recovery). A rigorous DAE filter model (Marke et al., 2020) is employed here, to evaluate system performance. Dynamic optimisation of bioreactor-filter systems has been completed for different bioreactor types, filter arrangements and feed manipulations, considering the same annual mAb plant production target. A technoeconomic analysis of optimal designs addresses industrial viability, confirming a clear cost advantage of fed-batch reactors combined with stacked membrane microfilters.