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目的验证终端干热法灭活凝血因子类制品中细小病毒的灭活工艺,并对其灭活效果进行评价。方法以猪细小病毒(Porcine parvovirus,PPV)为指示病毒,模拟凝血因子类制品生产工艺中病毒灭活的工艺,采用96孔板微量细胞病变法检测残余病毒滴度,验证终端干热法灭活病毒的效果。结果 3家企业生产的人凝血因子Ⅷ制品经100℃加热30min灭活,病毒滴度分别下降2.01～2.31、≥3.92和3.13～3.50LgTCID50/0.1ml;冻干与加热联合作用,病毒滴度分别下降2.82～3.00、≥4.24和4.00～4.12LgTCID50/0.1ml;5家企业生产的人纤维蛋白原经100℃加热30min灭活,病毒滴度分别下降3.50～3.63、2.56～2.70、3.06～3.57、3.00～3.25和≥3.75LgTCID50/0.1ml;冻干与加热联合作用,病毒滴度分别下降4.00～4.12、3.12～3.46、4.04～4.56、3.50～3.75和≥4.63LgTCID50/0.1ml。结论终端干热法对凝血因子类制品中的细小病毒具有一定的灭活作用,但由于工艺复杂、影响因素较多,不同企业生产的同类制品的病毒灭活效果不尽相同。
Objective To verify the inactivation process of parvovirus in inactivated clotting factor products by terminal dry-heat method and to evaluate the inactivation effect. Methods Porcine parvovirus (Porcine parvovirus) was used as the indicator virus to simulate virus inactivation in the production process of clotting factor products. The residual virus titer was detected by 96-well microplate method, and the terminal dry-heat inactivation The effect of the virus. Results The products of human coagulation factor Ⅷ produced by three companies were inactivated by heating at 100 ℃ for 30min and the virus titer decreased by 2.01 ~ 2.31, ≥3.92 and 3.13 ~ 3.50Lg TCID50 / 0.1ml, respectively. The combined effect of lyophilization and heating, Decreased 2.82 ~ 3.00, ≥4.24 and 4.00 ~ 4.12LgTCID50 / 0.1ml; The human fibrinogen produced by 5 enterprises was inactivated by heating at 100 ℃ for 30min, the virus titer decreased by 3.50 ~ 3.63, 2.56 ~ 2.70 and 3.06 ~ 3.57 respectively, 3.00 ~ 3.25 and ≥ 3.75LgTCID50 / 0.1ml; freeze-drying combined with heating, the virus titer decreased 4.00 ~ 4.12,3.12 ~ 3.46,4.04 ~ 4.56,3.50 ~ 3.75 and ≥4.63LgTCID50 / 0.1ml. Conclusion Terminal dry-heat method has some inactivation effect on parvovirus in coagulation factor products, but due to complex technology and many influencing factors, the inactivation effects of different products produced by different enterprises are different.