F基因型腮腺炎减毒活疫苗(人二倍体细胞)的质量稳定性分析

目的分析在细胞工厂上生产的F基因型腮腺炎减毒活疫苗(人二倍体细胞)的质量稳定性。方法将KMB17细胞在细胞工厂中传代,待细胞长为单层时,将腮腺炎病毒SP-A株按MOI 0.02接种于KMB17细胞,在细胞工厂上连续制备6批F基因型腮腺炎减毒活疫苗,对病毒收获液、原液、半成品和成品进行病毒滴度检测,其中成品还进行热稳定性试验及无菌检查、异常毒性检查、细菌内毒素、牛血清白蛋白残留量和抗生素残留量等检测。对检测数据进行统计学分析,对实验结果进行正态性检验,并绘制2倍标准差及3倍标准差质量控制图,进一步分析其质量稳定性。结果不同阶段产品的病毒滴度、牛血清白蛋白残留量、抗生素残留量检测值均符合正态分布,且在2倍标准差控制限范围内波动;无菌试验、异常毒性试验、细菌内毒素检测结果均符合《中国药典》三部(2015版)要求。结论利用细胞工厂在人二倍体细胞基质上制备F基因型腮腺炎减毒活疫苗的工艺,能持续稳定地获得有效性与安全性可靠的疫苗成品,且各项检测指标均符合《中国药典》三部(2015版)要求。本研究为F基因型腮腺炎减毒活疫苗的规模化生产提供了实验依据。

Quality stability of live attenuated mumps vaccine (human diploid cells) of genotype F

Objective To analyze the quality stability of live attenuated mumps vaccine(human diploid cells)of genotype F produced in cell factory.Methods KMB17 cells were subcultured in cell factory until a monolayer was formed,and inoculated with mumps virus SP-A strain at a MOI of 0.02 to prepare six consecutive batches of live attenuated mumps vaccine of genotype F.The virus harvest,bulk,final bulk and final product were determined for virus titer,while the final product were also tested for thermal stability,sterility,abnormal toxicity,bacterial endotoxin as well as contents of residual BSA and residual antibiotics.These data were statistically analyzed and tested for normal distribution.The quality control charts of 2 and 3 times of standard deviation were drawn to analyze the quality stability.Results The test data of virus titer as well as residual BSA and residual antibiotics contents of the products in different stages were in normal distribution and fluctuated within the control limit of 2 times of standard deviation.The test results of sterility,abnormal toxicity and bacterial endotoxin were in line with the requirements in Chinese Pharmacopoeia(VolumeⅢ,2015 edition).Conclusion By the procedure for production of live attenuated mumps vaccine of genotype F with human diploid cells in cell factory,the final product of vaccine with reliable effectiveness and safety was obtained persistently,of which all the indexes met the requirements in Chinese Pharmacopoeia(VolumeⅢ,2015 edition).This study provided an experimental basis for large-scale production of live attenuated mumps vaccine of genotype F.