An Integrated Approach to Viral Vector Manufacturing and Supply Chain Network Development

先进治疗药物产品（atmp）形成了一类新的生物治疗药物，为预防和治疗危及生命的疾病铺平了道路。基因工程药物传递载体的多功能性也出现在预防性医疗保健中，最近批准了基于载体的疫苗平台。病毒载体目前处于下一代疫苗和疗法的前沿；对病毒载体的空前需求迫使制造商在扩大生产的同时，解决工程产品和工艺相关的挑战。这突出了对复杂决策工具的需求，这些工具可以在整个产品生命周期内实现有效的制造和分销计划。过程系统工程（PSE）传统上帮助制药，更一般地说，过程工业开发这样的工具。尽管缺乏解决新型病毒载体行业的工作，但迄今为止的文献综述揭示了用于规划单点和多点制造和分销网络的可转移PSE工具的类别；这些通常解决灵活的多产品和多用途制造的复杂性。计算挑战与不确定性下的规划问题一起出现，这在制药行业的能力规划和投资组合管理框架中得到了考虑。成熟方法的局限性显现出来，应用驱动的工具为病毒载体行业的运筹学带来了机会。提出了一系列的研究目的和目标，然后根据上述目标概述了迄今为止的进展。提出了一个初步的混合整数线性规划（MILP）模型，用于设计和优化英国病毒载体供应链，结果说明了开发的快照模型的能力和改进领域。该框架的回报依赖于从计算机辅助建模中获得的技术经济分析，这些建模是对成熟的病毒载体制造协议进行的。局部敏感性分析强调，在描述模型输出时，需要系统地考虑假设输入的不确定性。

Advanced Therapy Medicinal Products (ATMPs) form a novel class of biologic therapeutics whichpave the way to prevention and treatment of life-threatening diseases. The versatility ofgenetically-engineered drug delivery vehicles is also seen in preventive healthcare, with recentapprovals of vector-based vaccine platforms. Viral vectors are currently at the forefront of bothnext-generation vaccines and therapeutics; the unprecedented demand for viral vectors forcesmanufacturers to simultaneously tackle engineering product and process-related challenges, whilescaling up their production. This is highlighting the need for sophisticated decision-making tools,which enable effective manufacturing and distribution planning throughout product lifetimes.Process systems engineering (PSE) has traditionally assisted the pharmaceutical, and moregenerally, process industries in the development of such tools. Despite the absence of worksaddressing the novel viral vector industry, a review of literature to date reveals classes oftransferable PSE tools for planning of single- and multi-site manufacturing and distribution networks;these often address complexities of flexible multi-product and multi-purpose manufacture.Computational challenges emerge alongside the problem of planning under uncertainty, which isconsidered in frameworks for capacity planning and portfolio management for the pharmaceuticalindustry. Limitations in well-established approaches emerge and the opportunity brought byapplication-driven tools for the viral vector industry to operations research is highlighted.A series of research aims and objectives is proposed, followed by an overview of the progressto date in light of said objectives. A preliminary mixed-integer linear programming (MILP) modelfor the design and optimisation of UK viral vector supply chains is presented and results illustratethe capabilities and areas of improvement of the developed snapshot model. The framework inturn relies on techno-economic analyses obtained from computer-aided modelling of well-establishedviral vector manufacturing protocols. A local sensitivity analysis highlights a need to systematicallyaccount for uncertainty of the assumed inputs when characterising model outputs.