摘要
目的研究在特定的储存条件下,细胞工厂工艺生产的麻疹病毒原液和含麻疹成分疫苗中麻疹病毒滴度随温度、时间的变化规律。方法按照细胞工厂工艺分别制备3批麻疹、腮腺炎和风疹病毒原液,将麻疹病毒原液置于2~8℃保存21 d和–60℃以下保存15个月进行稳定性分析,并将同批次原液分别用于配制6批麻疹减毒活疫苗(measles attenuated live vaccine,MV)、麻疹-腮腺炎联合减毒活疫苗(measles and mumps combined attenuated live vaccine,MM)和麻疹-腮腺炎-风疹联合减毒活疫苗(measles,mumps and rubella combined attenuated live vaccine,MMR),对上述18批疫苗进行(25±2)℃保存6个月加速稳定性试验及2~8℃保存30个月长期稳定性试验。检测原液以及成品的麻疹病毒滴度,分析不同产品中的麻疹病毒在不同储存温度下的稳定性,并应用Minitab 17分析软件预估原液和成品稳定期。结果3批麻疹病毒原液于2~8℃保存21 d和–60℃以下保存15个月,麻疹病毒滴度最低值分别为5.5和5.8 lgCCID_(50)/ml,均符合≥5.3 lgCCID_(50)/ml的质量标准。18批疫苗于(25±2)℃保存6个月,MV、MM和MMR的麻疹病毒滴度最低值分别为4.0、4.7和3.4 lgCCID_(50)/ml;2~8℃保存30个月,MV、MM和MMR的麻疹病毒滴度最低值分别为4.4、4.5和3.8 lgCCID_(50)/ml。上述成品稳定性试验中的麻疹病毒滴度均符合各产品的质量标准;应用分析软件预估的原液和成品稳定期均远超各产品批准效期。结论细胞工厂工艺的麻疹病毒原液以及3种含麻疹成分疫苗中的麻疹病毒的稳定性良好。
Objective To study the variation of measles virus titer with temperature and time under specific storage conditions of measles virus bulk and measles-containing vaccines made by cell factory process.Methods Three batches each of measles virus,mumps virus and rubella virus bulks were prepared according to cell factory process.The measles virus bulks were stored at 2-8℃for 21 d and below-60℃for 15 months for stability analysis.The same batchs of measles virus bulk were used to prepare six batches each of measles attenuated live vaccine(MV),measles and mumps combined attenuated live vaccine(MM)and measles,mumps and rubella combined attenuated live vaccine(MMR).Accelerated stability test at(25±2)℃for 6 months and long-term stability test at 2-8℃for 30 months were carried out on 18 batches of vaccines.Measles virus titers of bulk and final products were detected,and the stability of measles virus in different samples at different storage temperatures was analyzed.Minitab 17 analysis software was used to predict the stability period of bulk and final products.Results In 3 batches of measles virus bulks stored at 2-8℃for 21 d and below-60℃for 15 months,the lowest titers of measles virus were 5.5 and 5.8 lgCCID_(50)/ml,respectively,and met the quality standard of≥5.3 lgCCID_(50)/ml.The lowest measles virus titers of MV,MM and MMR were 4.0,4.7 and 3.4 lgCCID_(50)/ml,respectively,when 18 batches of vaccines were stored at(25±2)℃for 6 months,and were 4.4,4.5 and 3.8 lgCCID_(50)/ml,respectively,when stored at 2-8℃for 30 months.The measles virus titer in the stability test of final products all met the product quality standards.The stability period of bulk and final products predicted by analysis software was far beyond the corresponding approved effective period.Conclusion In measles virus bulk and three measles-containing vaccines made by cell factory process,measles virus has good stability.
作者
沈谊清
杨文震
马雷钧
郁佳俊
周锋
张芹
许乐燕
Shen Yiqing;Yang Wenzhen;Ma Leijun;Yu Jiajun;Zhou Feng;Zhang Qin;Xu Leyan(Vaccine DivisionⅡ,Shanghai Institute of Biological Products Co.,Ltd.,Shanghai 201403,China;Shanghai Institute of Biological Products Co.,Ltd.,Shanghai 201403,China;Quality Control Department,Shanghai Institute of Biological Products Co.,Ltd.,Shanghai 201403,China;Quality Assurance Department,Shanghai Institute of Biological Products Co.,Ltd.,Shanghai 201403,China)
出处
《国际生物制品学杂志》
CAS
2024年第4期197-202,共6页
International Journal of Biologicals
基金
国家科技重大专项(2018ZX09738003-005)。
