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

先进治疗药物(ATMP)是一类新的生物治疗药物，它为预防和治疗危及生命的疾病铺平了道路。基因工程药物输送载体的多功能性也体现在预防保健方面，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；对病毒载体的前所未有的需求迫使制造商同时应对与工程产品和工艺相关的挑战，同时扩大生产。这突显了对复杂决策工具的需求，这些工具能够在整个产品生命周期内实现有效的制造和分销计划。流程系统工程(PSE)传统上帮助制药行业，尤其是流程工业开发此类工具。尽管缺乏解决新型病毒载体行业的工作，但迄今为止的文献回顾揭示了用于规划单站点和多站点制造和分销网络的可移植的PSE工具的类别；这些工具通常解决灵活的多产品和多用途制造的复杂性。计算挑战伴随着不确定性下的规划问题，这被考虑在制药行业的产能规划和投资组合管理的框架中。提出了一系列研究的目的和目标，并根据这些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，用于英国病毒载体供应链的设计和优化，结果表明了所开发的快照模型的能力和改进领域。该框架反过来又依赖于通过对成熟的病毒载体制造方案进行计算机辅助建模而获得的技术经济分析。局部敏感性分析强调，在确定模型产出的特征时，需要系统地考虑假定投入的不确定性。

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.