新建主细胞库对水痘减毒活疫苗质量影响的分析

目的 基于细胞基质分析新建人二倍体细胞MRC-5主细胞库，并通过主细胞库变更前后所制的水痘减毒活疫苗（水痘疫苗）可比性研究，分析新建主细胞库对水痘疫苗质量和稳定性的影响。方法 对新建MRC-5主细胞库、工作细胞库和生产终末代细胞按照中国药典2015年版和企业质量标准进行抽样检定，并传代至超高代次细胞进行传代稳定性研究，对比细胞生长与细胞计数。用新建主细胞库连续试生产3批水痘疫苗并进行工艺验证，分析疫苗原液及成品的质量结果，并考察水痘病毒基因序列和产品稳定性。结果 新建主细胞库、工作细胞库及其他各代次细胞在传代过程中生长良好，细胞计数正常，检定结果均符合质量标准。试生产的水痘疫苗工艺合格，变更前后生产的疫苗水痘病毒基因序列无差异；病毒滴度均为4.0 lg噬斑形成单位（plaque-forming unit，PFU）/0.5 ml，热稳定性试验结果均为3.4 lgPFU/0.5 ml，水分含量均不高于1.5%，符合企业注册标准；质量稳定性趋势基本一致。结论  建立的人二倍体细胞MRC-5主细胞库各项检定结果合格。用新细胞库试生产的水痘疫苗质量和稳定性与变更前的一致。

Analysis of the effect of new master cell bank on attenuated varicella vaccine quality

Objective  To analyze the new master cell bank of human diploid cells (MRC-5 cell line) based on cell matrix, and to analyze the effect of new master cell bank on the quality and stability of attenuated varicella vaccine (varicella vaccine) using comparative study. Methods  The new MRC-5 master cell bank, working cell bank and end of production cell (EOPC) were sampled and tested according to Chinese pharmacopoeia 2015 edition and the enterprise quality standard. The stability of post production cell (PPC) was studied by comparing the cell growth and cell count. Three consecutive batches of varicella vaccine were produced using cells from new master cell bank and subjected to process validation. The quality of bulk and final products were analyzed. The varicella virus gene sequencing and product stability test were performed. Results  The new master cell bank, working cell bank, EOPC and PPC presented good cell growth and normal cell counts during passaging, and test results all met quality standards. Vaccine process validation was qualified without abnormality. There was no difference in virus gene sequence of varicella vaccines produced with new and old master cell banks. The virus titers were both 4.0 lg plaque-forming unit (PFU)/0.5 ml, the thermal stability results were both 3.4 lgPFU/0.5 ml, and the water contents were both ≤1.5%. All key quality items met the enterprise registration standard. The quality stability trends of vaccines were similar. Conclusions  The established master cell bank of MRC-5 human diploid cell is qualified in all tests. Trial production of varicella vaccine with new master cell bank has consistent quality and stability as with old bank.