Analytical Sciences, Vaccine CMC Development and Supply, Sanofi, Toronto, ON, M2R 3T4, Canada.
Manufacturing Sciences, Analytics and Technology, Sanofi, Toronto, Canada.
Pharm Res. 2024 Feb;41(2):375-385. doi: 10.1007/s11095-023-03642-6. Epub 2023 Dec 19.
This study is focused on monitoring process parameters and quality attributes of aluminum phosphate (AlPO) using multiple in-line probes incorporated into an industrial-scale adjuvant suspension manufacturing unit.
The manufacturing of aluminum adjuvant suspension was monitored at manufacturing scale using conductivity, turbidity, infrared, and particle sizing and count probes to follow the continuous evolution of particle formation and size distribution, and the reaction kinetics during the synthesis of AlPO.
The data showed that AlPO forms large particles at the early stages of mixing, followed by a decrease in size and then stabilization towards the later stages of mixing and pH adjustment. The results provided a complementary view of process events and assisted in optimizing several parameters, e.g., flow rate of reactants AlCl and NaPO solutions, mixing rate, pH, and conductivity of AlPO, as well as adjuvant quality attribute such as particle size, thus streamlining and shortening the process development stage.
The results of this study showed the usefulness of the in-line probes to automate continuous assessment of AlPO batch-to-batch consistency during in-house adjuvant production at the industrial scale.
本研究采用多个在线探头对磷酸铝（AlPO）的过程参数和质量特性进行监测，这些探头被整合到工业规模的佐剂混悬剂生产单元中。
在生产规模下使用电导率、浊度、红外、颗粒尺寸和计数探头对铝佐剂混悬剂的制造进行监测，以跟踪颗粒形成和粒径分布的连续演变，以及在 AlPO 合成过程中的反应动力学。
数据表明，AlPO 在混合的早期形成大颗粒，然后在混合和 pH 值调节的后期阶段粒径减小并稳定下来。结果提供了对工艺事件的补充性看法，并有助于优化多个参数，例如反应物 AlCl 和 NaPO 溶液的流速、混合速度、pH 值和 AlPO 的电导率，以及佐剂质量属性，如粒径，从而简化和缩短工艺开发阶段。
本研究结果表明，在工业规模的内部佐剂生产中，在线探头可用于自动连续评估 AlPO 批间一致性，具有实用性。
