Junker B H, Seamans T C, Ramasubramanyan K, Aunins J, Paul E, Buckland B C
Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Biotechnol Bioeng. 1994 Dec;44(11):1315-24. doi: 10.1002/bit.260441107.
The titanium static mixer reactor, demonstrated for a variety of vaccine processes during the late 197s, was investigated for the production of attenuated hepatitis A virus antigen from anchorage-dependent MRC-5 cells. This reactor system used Charles River Biotechnological Services cabinets for monitoring and process control. Cell inoculation protocols, using 6000-10,000 cells/cm(2), resulted on over 95% attachment at both the laboratory and pilot scales. Indirect monitoring techniques using oxygen, glucose, L-serine, and L-glutamine uptake rates were indicative of cell growth prior to virus inoculation as well as environmental and/or nutrient limitations. Seven laboratory-scale (3900 cm(2)) runs and one pilotscale (265,000 cm(2)) run were conducted to investigate refeeding regiments, parallel versus perpendicular element orientation, increased element surface area per unit volume, and scale-up performance. In general, lysate antigen yields achieved were similar to those of parallel T-flasks cultivated under similar conditions.
钛静态混合器反应器在20世纪70年代末被用于多种疫苗生产工艺的展示，该反应器被用于研究从依赖贴壁生长的MRC - 5细胞生产减毒甲型肝炎病毒抗原。这个反应器系统使用查尔斯河生物技术服务公司的柜体进行监测和过程控制。细胞接种方案采用每平方厘米6000 - 10000个细胞，在实验室和中试规模下细胞贴壁率均超过95%。使用氧气、葡萄糖、L - 丝氨酸和L - 谷氨酰胺摄取率的间接监测技术可在病毒接种前指示细胞生长情况以及环境和/或营养限制。进行了七次实验室规模（3900平方厘米）的运行和一次中试规模（265000平方厘米）的运行，以研究补料方案、元件平行与垂直排列方向、单位体积内元件表面积增加以及放大性能。总体而言，所获得的裂解物抗原产量与在类似条件下平行培养的T型烧瓶所获产量相似。
