Suarez-Zuluaga Diego A, van der Pol Leo A, van 't Oever Aart G, Bakker Wilfried A M, Thomassen Yvonne E
Intravacc, P.O. Box 450, 3720 AL Bilthoven, the Netherlands.
Vaccine X. 2022 Sep 30;12:100223. doi: 10.1016/j.jvacx.2022.100223. eCollection 2022 Dec.
Inactivated polio vaccine production using attenuated Sabin strains (sIPV) instead of wild type polio viruses (cIPV) is an initiative encouraged by the World Health Organization. This use of attenuated viruses is preferred as it reduces risks related to potential outbreaks during IPV production. Previously, an sIPV production process was set up based on the cIPV production process. Optimizing this process while using only animal component free (ACF) substances allows reduction of operational costs and mitigates risks of adverse effects related with animal derived compounds. Here, development of a process for production of sIPV using only ACF compounds, is described. The upstream process required a change in cell growth medium from serum-containing medium to ACF medium, while virus production media remained the same as the already used M199 medium was free of animal components. In the downstream process multiple modifications in existing unit operations were made including addition of a diafiltration step prior to inactivation. After optimizing each unit operation, robustness of the whole process was demonstrated using design of experiments (DoE) methodology. By using DoE we were able to vary different process parameters across unit operations to assess the impact on our quality attributes. The developed process was robust as the observed variation for quality attributes due to differences in process parameters remained within specification. The resulting pilot process showed not only to be robust, but also to have a considerable higher product yield when compared to the serum containing sIPV process. Product yields are now comparable to the cIPV process based on using wild type polio viruses. Moreover, the potency of the produced vaccine was comparable that of cIPV vaccine. The developed ACF sIPV process can be transferred to vaccine manufacturers at the end-of pre-clinical development phase, at lab- or pilot scale, before production of clinical trial material.
使用减毒的萨宾株（sIPV）而非野生型脊髓灰质炎病毒（cIPV）生产灭活脊髓灰质炎疫苗是世界卫生组织鼓励的一项举措。使用减毒病毒更受青睐，因为它降低了脊髓灰质炎灭活疫苗（IPV）生产过程中潜在爆发相关的风险。此前，基于cIPV生产工艺建立了sIPV生产工艺。在仅使用无动物成分（ACF）物质的情况下优化该工艺，可降低运营成本并减轻与动物源化合物相关的不良反应风险。在此，描述了一种仅使用ACF化合物生产sIPV的工艺开发过程。上游工艺需要将细胞生长培养基从含血清培养基改为ACF培养基，而病毒生产培养基保持不变，因为已使用的M199培养基不含动物成分。在下游工艺中，对现有单元操作进行了多项改进，包括在灭活前增加一个渗滤步骤。在优化每个单元操作后，使用实验设计（DoE）方法证明了整个工艺的稳健性。通过使用DoE，我们能够在不同单元操作中改变不同的工艺参数，以评估对质量属性的影响。所开发的工艺很稳健，因为由于工艺参数差异导致的质量属性观察到的变化仍在规格范围内。与含血清的sIPV工艺相比，所得的中试工艺不仅稳健，而且产品收率相当高。基于使用野生型脊髓灰质炎病毒，现在产品收率与cIPV工艺相当。此外，所生产疫苗的效力与cIPV疫苗相当。所开发的ACF sIPV工艺可在临床前开发阶段结束时，在生产临床试验材料之前，以实验室或中试规模转移给疫苗制造商。
