Chhatre S, Francis R, O'Donovan K, Titchener-Hooker N J, Newcombe A R, Keshavarz-Moore E
The Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, UK.
Bioprocess Biosyst Eng. 2007 Jan;30(1):1-11. doi: 10.1007/s00449-006-0086-8. Epub 2006 Nov 9.
A simulation is described that evaluates the impacts of altering bio-manufacturing processes. Modifications designed to improve production levels, times and costs were assessed, including increasing feed volumes/titres, replacing initial downstream stages with packed or expanded bed affinity steps and removing ion exchange steps. Options were evaluated for manufactured product mass, COG, batch times and development costs and timescales. Metrics were combined using multi-attribute-decision-making techniques generating a single assessment metric for each option. The utility of this approach was illustrated by application to an FDA-approved process manufacturing rattlesnake anti-venom (Protherics U.K.). Currently, ovine serum containing anti-venom IgG is purified by precipitation/centrifugation, prior to antibody proteolysis by papain. An ion exchanger removes F(C), before affinity chromatography yields the final anti-venom. An expanded bed affinity column operating with an 80% higher IgG titre, 66% higher feed volume and without the ion exchanger delivered the best multi-attribute-decision-making value, potentially providing the most desirable alternative.
本文描述了一种评估生物制造工艺变更影响的模拟方法。对旨在提高产量、缩短生产时间和降低成本的改进措施进行了评估，包括增加进料体积/滴度、用填充床或扩张床亲和步骤取代初始下游阶段以及去除离子交换步骤。对制成产品的质量、生产成本、批次时间以及研发成本和时间尺度等选项进行了评估。使用多属性决策技术对各项指标进行综合，为每个选项生成单一评估指标。通过将该方法应用于美国食品药品监督管理局（FDA）批准的响尾蛇抗蛇毒血清（英国普罗泰克斯公司生产）生产工艺，展示了该方法的实用性。目前，含有抗蛇毒IgG的羊血清在通过木瓜蛋白酶进行抗体蛋白水解之前，先通过沉淀/离心进行纯化。在亲和色谱法得到最终抗蛇毒血清之前，离子交换器去除F(C)。使用IgG滴度高80%、进料体积高66%且无需离子交换器的扩张床亲和柱，获得了最佳多属性决策值，可能提供了最理想的替代方案。
