Raut S, Costanzo A, Daniels S, Heath A, Buchheit K-H
National Institute for Biological Standards and Control (NIBSC), Health Protection Agency, Potters Bar, EN6 3QG, Hertfordshire, UK.
Pharmeur Bio Sci Notes. 2010 Oct;2010(2):1-29.
The European Pharmacopoeia Biological Reference Preparation (Ph. Eur. BRP) Batch 4 was established as an international common working standard for potency determination of human coagulation factor VIII (FVIII) preparations to replace the dwindling stocks of the BRP Batch 3, the current European standard. Similarly, stocks of the current World Health Organisation 7th International Standard (WHO 7th IS) were also running low. Therefore a project was jointly organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM, Council of Europe) and the National Institute for Biological Standards and Control (NIBSC, UK) in order to replace both standards concomitantly. The potency of the BRP Batch 4 was assigned during an international collaborative study involving 38 laboratories with reference to the WHO 7th IS and the BRP Batch 3. Four candidate materials, 2 plasma-derived (samples A and C) and 2 recombinant (samples B and D) have been evaluated, sample C being the specific candidate for the replacement of the BRP Batch 3. Participants were instructed to perform 8 independent assays following their own routine validated methods, by either the one-stage clotting assay or the chromogenic assay, or both. Laboratories returned 22 data sets for the clotting assay and 30 data sets for the chromogenic assay. This publication reports the results obtained with both assays but only the results of the chromogenic assay are highlighted in the conclusions, as it is the assay prescribed by the European Pharmacopoeia. Data were analysed separately for both assays. The consensus potency value was calculated as the unweighted geometric mean of the unweighted geometric means of each individual laboratory. For sample C, there was a significant difference in potency estimate between the chromogenic and the clotting assay. It was therefore not possible to reconcile both results. The chromogenic potencies however were in very good agreement being 10.4 IU/ampoule (n = 30), when assessed against both standards. The inter-laboratory geometric coefficient of variation (GCV) was 4.8 % and 7.1 % against the WHO 7th IS and the BRP Batch 3 respectively. The Ph. Eur. BRP Batch 4 is a freeze-dried, plasma-derived concentrate. The material was filled in approximately 20,000 ampoules and lyophilised. The final residual water content is 0.33 %. Based on accelerated degradation studies, the stability of the material is suitable for a reference preparation. The candidate Ph. Eur. BRP Batch 4 was adopted at the 136th session of the European Pharmacopoeia Commission in March 2010. The standard will be available from the EDQM with the catalogue number H0920000 upon exhaustion of the current batch.
欧洲药典生物参考制剂（欧洲药典生物参考品）第4批被确立为用于人凝血因子VIII（FVIII）制剂效价测定的国际通用工作标准，以替代日渐减少的第3批生物参考品库存，即现行欧洲标准。同样，世界卫生组织第7国际标准品（WHO第7国际标准品）的库存也在减少。因此，欧洲药品质量管理局（欧洲委员会）和英国国家生物制品标准与控制研究所（NIBSC）联合组织了一个项目，以便同时替换这两种标准品。第4批生物参考品的效价是在一项国际协作研究中确定的，该研究涉及38个实验室，参照了WHO第7国际标准品和第3批生物参考品。对4种候选材料进行了评估，其中2种源自血浆（样品A和C），2种为重组材料（样品B和D），样品C是替代第3批生物参考品的特定候选材料。要求参与者按照各自经验证的常规方法，通过单阶段凝血试验或发色底物法或两种方法同时进行8次独立检测。各实验室返回了22个凝血试验数据集和30个发色底物法数据集。本出版物报告了两种检测方法获得的结果，但结论中仅突出显示了发色底物法的结果，因为这是欧洲药典规定的检测方法。对两种检测方法的数据分别进行了分析。共识效价值计算为每个实验室未加权几何平均值的未加权几何平均值。对于样品C，发色底物法和凝血试验的效价估计值存在显著差异。因此，无法使两种结果达成一致。然而，当对照两种标准品评估时，发色底物法效价非常一致，为10.4 IU/安瓿（n = 30）。针对WHO第7国际标准品和第3批生物参考品，实验室间几何变异系数（GCV）分别为4.8%和7.1%。欧洲药典生物参考品第4批是一种冻干的、源自血浆的浓缩物。该材料灌装于约20,000支安瓿中并进行冻干。最终残余水分含量为0.33%。基于加速降解研究，该材料的稳定性适合作为参考制剂。候选的欧洲药典生物参考品第4批于2010年3月在欧洲药典委员会第136届会议上被采用。当前批次耗尽后，该标准品将可从欧洲药品质量管理局获得，目录编号为H0920000。
