Centre for Biological Engineering, Holywell Park, Loughborough University, Loughborough, United Kingdom; Wolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM), School of Medicine, Nottingham, United Kingdom.
Department of Biochemical Engineering, Faculty of Engineering Science, University College London, Gower Street, London, United Kingdom.
Cytotherapy. 2018 Jun;20(6):873-890. doi: 10.1016/j.jcyt.2018.05.003. Epub 2018 May 25.
The cell and gene therapy (CGT) field is at a critical juncture. Clinical successes have underpinned the requirement for developing manufacturing capacity suited to patient-specific therapies that can satisfy the eventual demand post-launch. Decentralised or 'redistributed' manufacturing divides manufacturing capacity across geographic regions, promising local, responsive manufacturing, customised to the end user, and is an attractive solution to overcome challenges facing the CGT manufacturing chain.
A study was undertaken building on previous, so far unpublished, semi-structured interviews with key opinion leaders in advanced therapy research, manufacturing and clinical practice. The qualitative findings were applied to construct a cost of goods model that permitted the cost impact of regional siting to be combined with variable and fixed costs of manufacture of a mesenchymal stromal cell product.
Using the United Kingdom as an exemplar, cost disparities between regions were examined. Per patient dose costs of ~£1,800 per 75,000,000 cells were observed. Financial savings from situating the facility outside of London allow 25-41 additional staff or 24-35 extra manufacturing vessels to be employed. Decentralised quality control to mitigate site-to-site variation was examined. Partial decentralisation of quality control was observed to be financially possible and an attractive option for facilitating release 'at risk'.
There are important challenges that obstruct the easy adoption of decentralised manufacturing that have the potential to undermine the market success of otherwise promising products. By using the United Kingdom as an exemplar, the modelled data provide a framework to inform similar regional policy considerations across other global territories.
细胞和基因治疗（CGT）领域正处于关键时刻。临床成功为开发适合满足上市后最终需求的患者特异性疗法的制造能力提供了依据。分散或“分布式”制造将制造能力分散在各个地理区域，有望实现本地化、响应式制造，针对最终用户进行定制，是克服 CGT 制造链面临的挑战的一种有吸引力的解决方案。
本研究是在先前未发表的与先进治疗研究、制造和临床实践的主要意见领袖进行的半结构化访谈的基础上进行的。定性研究结果被应用于构建一个商品成本模型，该模型允许将区域选址的成本影响与间充质基质细胞产品的制造可变成本和固定成本结合起来。
以英国为例，研究了各地区之间的成本差异。每 7500 万细胞的单个患者剂量成本约为 1800 英镑。将设施设在伦敦以外的地方可以节省资金，允许额外雇佣 25-41 名员工或额外使用 24-35 个制造容器。还研究了分散质量控制以减轻站点间差异的情况。观察到部分分散质量控制在财务上是可行的，并且是促进“有风险”放行的有吸引力的选择。
有一些重要的挑战阻碍了分散制造的轻易采用，这些挑战有可能破坏有前途的产品的市场成功。通过以英国为例，模型数据为在其他全球地区制定类似的区域政策考虑提供了框架。
