Kis Zoltán, Kontoravdi Cleo, Shattock Robin, Shah Nilay
Centre for Process Systems Engineering, Department of Chemical Engineering, Faculty of Engineering, Imperial College London, London SW7 2AZ, UK.
Department of Infectious Disease, Faculty of Medicine, Imperial College London, London W2 1PG, UK.
Vaccines (Basel). 2020 Dec 23;9(1):3. doi: 10.3390/vaccines9010003.
To overcome pandemics, such as COVID-19, vaccines are urgently needed at very high volumes. Here we assess the techno-economic feasibility of producing RNA vaccines for the demand associated with a global vaccination campaign. Production process performance is assessed for three messenger RNA (mRNA) and one self-amplifying RNA (saRNA) vaccines, all currently under clinical development, as well as for a hypothetical next-generation saRNA vaccine. The impact of key process design and operation uncertainties on the performance of the production process was assessed. The RNA vaccine drug substance (DS) production rates, volumes and costs are mostly impacted by the RNA amount per vaccine dose and to a lesser extent by the scale and titre in the production process. The resources, production scale and speed required to meet global demand vary substantially in function of the RNA amount per dose. For lower dose saRNA vaccines, global demand can be met using a production process at a scale of below 10 L bioreactor working volume. Consequently, these small-scale processes require a low amount of resources to set up and operate. RNA DS production can be faster than fill-to-finish into multidose vials; hence the latter may constitute a bottleneck.
为了战胜大流行疾病，如新冠病毒肺炎（COVID-19），迫切需要大量的疫苗。在此，我们评估了为全球疫苗接种运动相关需求生产RNA疫苗的技术经济可行性。对三种信使核糖核酸（mRNA）疫苗和一种自扩增核糖核酸（saRNA）疫苗（均处于临床开发阶段）以及一种假设的下一代saRNA疫苗的生产过程性能进行了评估。评估了关键工艺设计和操作不确定性对生产过程性能的影响。RNA疫苗原料药（DS）的生产率、产量和成本主要受每剂疫苗的RNA量影响，在较小程度上受生产过程中的规模和滴度影响。满足全球需求所需的资源、生产规模和速度因每剂RNA量的不同而有很大差异。对于低剂量saRNA疫苗，使用工作体积低于10 L的生物反应器规模的生产过程即可满足全球需求。因此，这些小规模工艺的建立和运营所需资源较少。RNA DS的生产速度可能比灌装到多剂量小瓶的速度快；因此，后者可能成为瓶颈。
