水痘减毒活疫苗生产场地变更质量可比性研究

Investigation quality comparability on change of manufacturing site for varicella vaccine live

目的通过可比性研究证明水痘减毒活疫苗生产场地变更后质量的产品一致性。方法从生产用原材料、生产工艺、产品质量和稳定性等几个方面进行可比性分析,比较水痘减毒活疫苗生产场地变更前后产品质量特性。结果确认水痘疫苗生产车间场地变更前后原材料未发生改变;生产工艺未发生变化,部分工艺参数由于设备更新进行了调整但未对工艺控制造成影响;对工艺用水、疫苗质量、疫苗稳定性的关键质量指标进行统计分析,其中新车间生产的原液病毒滴度为5.0 lgPFU/mL、半成品病毒滴度为4.6 lgPFU/mL,成品中水分含量为1.0%~1.4%、病毒滴度为7.8~8.0 lgPFU/mL、热稳定性试验为6.8 lgPFU/mL与老车间同步生产的成品结果(原液病毒滴度为4.9~5.0 lgPFU/mL,半成品病毒滴度为4.5~4.6 lgPFU/mL,成品中水分含量为1.1%~1.3%、病毒滴度为7.8~8.0 lgPFU/mL、热稳定性试验为6.8 lgPFU/mL)相似,且均在2014年老车间相对应检测项目均值±3 SD范围内,新老车间成品中的牛血清白蛋白残留量和乳糖酸红霉素残留量差异均无统计学意义(t=1.50,P>0.05;t=1.00,P>0.05);加速稳定性试验和长期稳定性试验结果显示,新老车间同步生产的各3批水痘疫苗成品的数据稳定性一致,各项检测指标均符合相关规定要求;疫苗安全性均符合相关要求,新老车间同步生产的疫苗试验结果一致。结论水痘减毒活疫苗生产场地变更前后产品质量特性高度相似,场地变更未对产品的安全性和有效性产生不良影响。

Objective To prove the quality consistency of the product before and after the change of the manufacturing lo- cation for varicella vaccine, live by a comparative investigation. Methods Comparability practice were carried out on raw materials for production, manufacturing technique, product quality and stability, etc. The quality characteristics for product were compared before and after the change of the manufacture site. Results The investigation showed that the raw materi- als had not changed before and after the site change. The manufacture technique had not changed, and some process param- eters had been adjusted because of the equipment renewal without influencing the process. The key quality indexes for the process including water, vaccine quality and vaccine stability were statistically analyzed, virus titers of the bulk was 5.0 lg- PFU/mL and that of the final bulk was 4.6 lgPFU/mL, the moisture contents of the final products were 1.0%--1.4%, the virus titers were 7.8--8.0 lgPFU/mL, and thermal stability test were 6.8 lgPFU/mL, the test results were similar to those produced by the old workshop（ virus titers of the bulk were 4.9--5.0 lgPFU/mL and those of the final bulk product were 4.5--4.6 lgPFU/mL, the moisture contents of the final products were 1.1%--1.3%, virus titers were 7.8--8.0 lgPFU/mL, and thermal stability test were 6.8 lgPFU/mL） , and these were also in the range of the average value ±3 SD in relative test items for old workshop. There was no a statistical difference between the bovine serum albumin residue and erythromycin residues produced in new and old workshop （t = 1.50, P〉0.05; t = 1.00, P〉0.05）. Three batches of the vaccines by syn- chronized production revealed that data stability was consistent by accelerated stability test and stability test, and the detec-tion indicators were in line with the relevant requirements. The vaccine safety was qualified according to the relevant require- ments. Conclusion The quality characteristics for product were similar before and after change of the manufacture site for vari- cella vaccine,live, by which the safety and efficacy for product were not effected.