目的 探究不同供应商来源动物在同一生物制品异常毒性试验中的差异,并通过增加血常规分析探讨异常毒性试验的科学性与合理性。方法 参考中国药典2025年版三部通则1141异常毒性检查法,通过分析免疫不同疫苗后动物的体重及血常规结果,对不同供应商来源的动物进行差异性比对。结果 B供应商的NIH小鼠在疫苗组与对照组中的体重增长趋势均低于当前供应商(A供应商)且差异有统计学意义(t=2.64~7.07,均P<0.05);C供应商与A供应商差异不明显。血常规结果显示,B供应商NIH小鼠两种疫苗组的红细胞数均明显高于A供应商的(t=2.44~4.07,均P<0.05),且多项白细胞指标与A供应商有明显差异(t=2.31~5.96,均P<0.05);C供应商仅少数指标与A供应商有差异。将新增的D、E豚鼠供应商与现有评估合格的豚鼠供应商(B供应商)进行比较,3个供应商来源Hartley豚鼠对照组与疫苗组的体重生长趋势均一致,血常规结果也无明显差异。结论 B供应商的NIH小鼠与A、C供应商的小鼠存在明显差异,B、D、E供应商的Hartley豚鼠无明显差异。动物自身的差异可能影响异常毒性试验结果的判定,将异常毒性试验作为疫苗批次放行的检测手段,其合理性值得探讨。
Objective To screen differences in abnormal toxicity test (ATT) for same biological product using animals from different suppliers and to explore the scientific and rational nature of ATT by additional blood routine analysis.Methods With reference to Chinese pharmacopoeia 2025 edition (volume Ⅲ) general rule 1141 “Abnormal toxicity test method”, the differences between animals from different suppliers were compared by analyzing the weights and blood routine results of animals after immunization with different vaccines.Results The body weight growth trend of NIH mice from supplier B was statistically significantly lower than that of the current supplier (supplier A) in both control and vaccine groups (t=2.64-7.07, all P<0.05), and the difference between suppliers C and A was not significant. Using the blood routine results of NIH mice from supplier A as a reference, blood routine results of mice from supplier B had significantly more red blood cells in both vaccine groups (t=2.44-4.07, all P<0.05) and showed significant differences in many white blood cell indicators (t=2.31-5.96, all P<0.05), while that of supplier C only showed significant differences in a few indicators. The body weight growth trends of Hartley guinea pigs from 3 suppliers (B, D, E) remained the same in both control and vaccine groups, and there was no significant difference in blood routine results.Conclusions NIH mice from supplier B have significantly different quality from those from suppliers A and C, while the quality of Hartley guinea pigs from suppliers B, D, and E is similar. The difference in animal quality directly affects the determination of ATT results, and the rationality of using ATT as a testing method for vaccine batch release is worth exploring.