人凝血因子Ⅸ制剂效价检测影响因素研究  

Influencing factors on the titer detection of human coagulation factorⅨpreparations

作　　者：庾昌文 肖雅芳 刘郴 郑炎 Yu Changwen;Xiao Yafang;Liu Chen;Zheng Yan(Research Development Center,Guang Dong Shuanglin Bio-Pharmacy Co.,Ltd,Zhanjiang 524076,China)

机构地区：[1]广东双林生物制药有限公司研发中心,湛江524076

出　　处：《国际生物制品学杂志》2024年第1期33-38,共6页International Journal of Biologicals

摘　　要：目的探讨不同标准品、样品预处理方式、稀释液对人凝血因子Ⅸ(human coagulation factorⅨ,FⅨ)制剂中FⅨ效价检测的影响,建立最优的FⅨ效价检测方法,并对该方法进行验证.方法选用人凝血酶原复合物(human prothrombin complex,PCC)标准品和欧洲药典FⅨ标准品,分别采用生理盐水和乏FⅨ血浆预处理方式稀释标准品和FⅨ制剂,以及分别采用Owren-Koller稀释液和药典稀释液作为上机稀释液对FⅨ制剂效价进行检测,比较得出最优FⅨ效价检测方法,并对该方法的初步应用、专属性、准确度、中间精密度和线性进行检测.结果采用PCC标准品和欧洲药典FⅨ标准品定标检测FⅨ效价时,FⅨ效价检测值与标示量的比值范围分别为0.94~1.14、0.96~1.03;乏FⅨ血浆预处理方式的FⅨ效价检测值相比生理盐水预处理方式更接近于标准值;Owren-Koller稀释液相比药典稀释液作为上机稀释液的检测结果更接近标示量,因此选用PCC标准品、乏FⅨ血浆预处理方式及Owren-Koller稀释液建立FⅨ效价检测方法.该方法对于广东双林生物制药有限公司FⅨ制剂样品和FⅨ上市产品同样适用,灭活后与未经灭活FⅨ制剂稀释的标准品溶液测得的效价比值为0.96,4组不同相对效价水平的FⅨ制剂效价检测值的相对偏倚均在±20%范围内,检测值的几何变异系数均≤20%,线性回归方程的相关系数均≥0.98,以上检测值均在可接受范围内.结论采用PCC标准品、乏FⅨ血浆预处理方式及Owren-Koller稀释液建立了最优的FⅨ效价检测方法,该方法具有良好的专属性、准确度、中间精密度和线性.Objective To explore the effects of different standards,sample pretreatment methods,and diluents on the detection of human coagulation factorⅨ(FⅨ)titer in FⅨformulations,establish the optimal FⅨtiter detection method,and validate the method.Methods The human prothrombin complex(PCC)standard substance and the European Pharmacopeia FⅨstandard substance were selected.The standard substance and FⅨpreparation were diluted with normal saline and FⅨdeficient plasma pretreatment,respectively.FⅨtiter in FⅨpreparation was detected using Owren-Koller diluent and Pharmacopoeia diluent as on-machine diluent,the optimal FⅨtiter detection method was selected,and the preliminary application,specificity,accuracy,intermediate precision and linearity of the method were detected.Results When FⅨtiter was detected by PCC standard substance and European Pharmacopeia FⅨstandard substance,the ratio of FⅨtiter detected to labeled amount ranged from 0.94-1.14 and 0.96-1.03,respectively.Compared with normal saline,the FⅨtiter value of pretreatment with FⅨdeficient plasma was much closer to the standard value.The result of Owren-Koller diluent was closer to the labeled amount than that of pharmacopeial diluent used as on-machine diluent,so the FⅨtiter detection method was established by using PCC standard substance,FⅨdeficient plasma pretreatment and Owren-Koller diluent.This method was applicable to FⅨpreparation samples of Guangdong Shuanglin Bio-Pharmacy Co.,Ltd.and FⅨlisted products.The ratio of titer measured between the inactivated and uninactivated FⅨpreparation diluted standard solution was 0.96,and the relative bias of FⅨtiter detected values of FⅨpreparations with relative titer levels in the 4 groups was all within the range of±20%.The geometric variation coefficients of the detected values were all≤20%,and the correlation coefficient of the linear regression equation was≥0.98.All the above detected values were within the acceptable range.Conclusion The optimal FⅨtiter detection m

关 键 词：人凝血因子Ⅸ 标准品 方法学验证 

分 类 号：R457.1[医药卫生—治疗学]