Fed-batch and perfusion culture processes: Economic, environmental, and operational feasibility under uncertainty
Fed-batch and perfusion culture processes: Economic, environmental, and operational feasibility under uncertainty
复制标题
DOI：
10.1002/bit.24608
复制
发表时间：
2013-01-01
影响因子：
3.8
通讯作者：
Farid, Suzanne S.
中科院分区：
文献类型：
--
作者：
Pollock, James;Ho, Sa V.;Farid, Suzanne S.
本文通过基于单克隆抗体商业化生产的案例研究，评估了批量和连续细胞培养技术的当前和未来潜力。该案例研究比较了补料分批培养与两种灌注技术：旋转过滤器灌注和利用交替切向流（ATF）灌注的新兴灌注技术。基于这些系统的整个生物过程的操作，经济和环境的可行性进行了评估，使用原型动态决策支持工具建立在UCL包括过程经济学，离散事件模拟和不确定性分析，并结合多属性决策技术，使一个整体的评估。这些策略在一系列规模和滴度上进行了比较，以便可视化它们在不同行业场景中的排名变化。确定性分析表明，当假设最大活细胞密度增加五倍时，与传统补料分批生产工艺相比，ATF灌注策略有可能节省20%的商品成本。对于大多数滴度和生产规模的组合，当ATF细胞密度下降到比补料分批策略增加三倍时，也可以看到节省。相比之下，补料分批策略在环境可持续性方面表现更好，水和消耗品的使用量更低。利用蒙特卡罗模拟的不确定性和故障率的影响的可行性的战略进行了探讨。风险分析结果证明了补料分批工艺的耐用性增强，但也强调了即使在不确定性下，ATF工艺仍然是最具成本效益的选择。多属性决策分析提供了深入了解自旋过滤器灌注策略在工业中的有限使用。由此产生的灵敏度蜘蛛图能够识别影响ATF灌注和补料分批策略之间的选择的经济和操作效益的权重的临界比率。Biotechnol. Bioeng. 2013; 110：206219. (C)2012 Wiley Periodicals，Inc.
This article evaluates the current and future potential of batch and continuous cell culture technologies via a case study based on the commercial manufacture of monoclonal antibodies. The case study compares fed-batch culture to two perfusion technologies: spin-filter perfusion and an emerging perfusion technology utilizing alternating tangential flow (ATF) perfusion. The operational, economic, and environmental feasibility of whole bioprocesses based on these systems was evaluated using a prototype dynamic decision-support tool built at UCL encompassing process economics, discrete-event simulation and uncertainty analysis, and combined with a multi-attribute decision-making technique so as to enable a holistic assessment. The strategies were compared across a range of scales and titres so as to visualize how their ranking changes in different industry scenarios. The deterministic analysis indicated that the ATF perfusion strategy has the potential to offer cost of goods savings of 20% when compared to conventional fed-batch manufacturing processes when a fivefold increase in maximum viable cell densities was assumed. Savings were also seen when the ATF cell density dropped to a threefold increase over the fed-batch strategy for most combinations of titres and production scales. In contrast, the fed-batch strategy performed better in terms of environmental sustainability with a lower water and consumable usage profile. The impact of uncertainty and failure rates on the feasibility of the strategies was explored using Monte Carlo simulation. The risk analysis results demonstrated the enhanced robustness of the fed-batch process but also highlighted that the ATF process was still the most cost-effective option even under uncertainty. The multi-attribute decision-making analysis provided insight into the limited use of spin-filter perfusion strategies in industry. The resulting sensitivity spider plots enabled identification of the critical ratio of weightings of economic and operational benefits that affect the choice between ATF perfusion and fed-batch strategies. Biotechnol. Bioeng. 2013; 110: 206219. (C) 2012 Wiley Periodicals, Inc.