口服三价重配轮状病毒减毒活疫苗(Vero细胞)运输稳定性研究

Transport stability of an oral trivalent reassortant live-attenuated rotavirus vaccine (Vero cell)

目的 评价口服三价重配轮状病毒减毒活疫苗(Vero细胞)的运输稳定性。方法 通过非温度因素研究及温度偏移研究考察疫苗的运输稳定性。以兰州市至广西壮族自治区公路运输路线来模拟疫苗运输过程的最差条件,进行一次往返运输,用以考察非温度因素条件下的疫苗稳定性。极端温度及温度循环等破坏性试验来模拟疫苗脱冷链后在极端条件下的情况,通过检测外观、pH、渗透压、装量、不溶性微粒、重金属、病毒滴度、异常毒性等项目来考察疫苗温度偏移稳定性。结果 9批次疫苗往返运输后外观均合格,内包材破损率均为0%,运输前后病毒滴度差异均无统计学意义(P>0.05),各质量指标均符合可接受标准。疫苗在(37±2)℃放置7 d病毒滴度平均下降1.1 lgCCID;/mL,与2~8℃及(-20±5)℃差异均有统计学意义(P均<0.05),(-20±5)℃放置7 d病毒滴度与2~8℃差异无统计学意义(P>0.05)。3次温度循环后,疫苗病毒滴度略有下降,不溶性微粒、重金属检测、异常毒性等质量指标均符合药典要求。结论 长距离公路运输后疫苗的安全性、有效性不受非温度因素影响,稳定性良好,且疫苗在特定温度偏移范围内及一定时间段内仍安全、有效。

Objective To evaluate the stability of an oral trivalent live-attenuated reassortant rotavirus vaccine(Vero cell) during transportation. Methods Non-temperature factors and temperature deviation were used to study the transport stability of the vaccine. The road transportation route from Lanzhou to Guangxi was used to simulate the worst conditions of vaccine transport process, and a round trip transport was carried out to investigate the stability of vaccine under non-temperature factors. Destructive tests such as extremely temperature and temperature cycle were used to simulate the extreme conditions of the vaccine after cold chain was removed. The stability of vaccine temperature deviation was investigated by detecting the items such as appearance, pH, osmotic pressure, loading, insoluble particles, heavy metals, virus titer, abnormal toxicity and so on. Results The appearance of the 9 batches of vaccine was qualified and the damage rate of inner packaging materials was 0%. There was no difference in the virus titer before and after transportation(P>0.05), and all quality indexes met the acceptable standards. When the vaccine was placed at(37±2) ℃ for 7 days, the virus titer decreased 1.1 lgCCID;/mL on average, which was statistically significant compared with that at 2~8 ℃ and(-20±5) ℃(P<0.05).There was no significant difference between the virus titer placed at(-20 ± 5) ℃ for 7 days and that at 2 ~ 8 ℃(P > 0.05). After three temperature cycles, the virus titer decreased slightly. The quality indexes such as insoluble particles, heavy metal and abnormal toxicity met the requirements of the pharmacopoeia. Conclusion The safety and effectiveness of the vaccine after long-distance road transportation were not affected by non-temperature factors, the stability was well, and the vaccine was still safe and effective in a specific temperature offset range and a certain period of time.