2019年国产口服轮状病毒活疫苗质量控制中病毒滴度趋势分析

Trend analysis of virus titer in quality control of a domestic oral rotavirus vaccine in 2019

目的对口服轮状病毒活疫苗(oral rotavirus vaccine, ORV)质量控制中的病毒滴度进行趋势分析。方法利用CCID50+ELISA检测国内企业2019年生产的ORV的关键控制指标(病毒滴度),根据检测结果计算均值,建立警戒限(均值■和行动限(均值■,绘制趋势分析图,进行连续性和周期性趋势分析;并将中国食品药品检定研究院(National Institutes for Food and Drug Control, NIFDC)病毒滴度结果与企业病毒滴度结果进行比较。结果病毒滴度趋势分析显示NIFDC检测结果未见超趋势(out of trend, OOT),企业检测结果有1次连续10批以上结果高于平均值,经偏差调查证实生产、质控和检测环节均未发现异常情况,分析原因可能是其中有多批成品来自同一批原液。2019年度和2018年度比较结果显示年度间具有较好的一致性。NIFDC与企业病毒滴度结果显示均检测结果差异没有统计学意义(P=0.082 7,P>0.05);Bland-Altman法统计显示97%批次的检测结果的差值位于2倍标准差(2s)以内。结论对2019年国产ORV病毒滴度的趋势分析反映出该制品的批间一致性以及生产工艺的稳定性良好。

Objective To analyze the trend of virus titer in quality control of a domestic oral rotavirus vaccine(ORV). Methods The key parameter(virus titer) of ORV was measured by CCID50 and ELISA assays, and the virus titer was calculated by the Spearman-Karber method. The warning limit ■ and action limit ■ were defined according to the determination results from National Institutes for Food and Drug Control(NIFDC)and those from the quality control laboratory of the manufacturer in 2019. Based on the determination results of the virus titer, a trend graph was plotted, and the consistency and periodic trend of virus titer of ORV were analyzed. Results Trend analysis of virus titers from NIFDC in 2019 showed that no out of trend(OOT) was observed. The results from the manufacturer showed that the test values of more than 10 consecutive batches of products were above average. Deviation analysis showed that there was no abnormal situation in production and quality control. OOTs were considered to be caused by many lots of final products from the same bulk and it was determined that there was no effect on the quality of the ORV. Comparison of the virus titer of ORV between 2018 and 2019 showed a good consistency in manufacturing process. There was no significant difference between the results from NIFDC and those from the manufacturer(P=0.082 7, P>0.05). Bland-Altman difference analysis showed that 97% of the determination results fell within ■. Conclusion The trend analysis of virus titer of a domestic ORV revealed the batch-to-batch consistency and production process stability were good.