Evaluating downstream processing options at the bioprocess-business interface

近年来，在重组哺乳动物细胞中产生的治疗性抗体已成为新生物制药领域增长最快的部分。随着这种增长，在细胞培养过程中，滴度也显著增加，因此，所有公司现在都面临着在下游加工过程中处理所得材料的巨大挑战。这一挑战与生物工艺开发的主要时间压力相结合，意味着现在的决策取决于大量的工艺和业务问题，并且变得极其复杂。探索所有这些选项的实验成本令人望而却步，因此建模工具对于不同的工艺序列和操作条件进行廉价检查至关重要，从而节省时间并减少昂贵的中试/规模试验。拟议中的项目将把CAT在抗体生产方面的领导地位、阿斯利康的制造专业知识和伦敦大学学院在生物工艺决策支持系统方面的领导地位联系起来，以解决这些复杂的工艺业务决策。由此产生的决策支持算法将确定未来最具成本效益的下游制造策略。这将通过开发组合优化技术并将其与多目标决策分析和详细的过程经济和物流模型相结合来实现，从而允许对替代净化策略的运营和财务指标之间的相互作用进行全面评估。

In recent years, therapeutic antibodies produced in recombinant mammalian cells have become the fastest growing part of the new biopharmaceuticals sector. Along with this growth there have been significant increases in titres during the cell culture, such that all companies now face great challenges in handling the resulting materials during downstream processing. This challenge combined with the major time pressures on bioprocess development means that the decisions now rest on a multitude of process and business issues and have become extremely complex. The cost of experimentation to explore all these options is prohibitive and hence modelling tools are vital for different process sequences and operating conditions to be examined inexpensively, thus saving time and reducing costly pilot/scale trials. The proposed programme will link the leadership in antibody production of CAT, the manufacturing expertise of AstraZeneca and the leadership in bioprocess decisional support systems of UCL to tackle some of these intricate process-business decisions. The resulting decision-support algorithms will identify the most cost-effective downstream manufacturing strategies for the future. This will be achieved by developing combinatorial optimisation techniques and integrating them with multi-objective decision analysis and detailed process economic and logistical models to allow for a holistic assessment of the interactions between operational and financial indicators for alternative purification strategies.