Bayer P, Daas A, Milne C
AGES Pharmed, Vienna, Austria.
Pharmeur Bio Sci Notes. 2011 Nov;2011(2):16-25.
A human plasma reference preparation in International Units (IU) must be used in each potency assay of the human coagulation factors V, VIII and XI in human plasma pooled and treated for virus inactivation, according to the European Pharmacopoeia (Ph. Eur.) monograph 1646 and general chapters 2.7.4 and 2.7.22 respectively, and in the potency assay of human coagulation factor XIII in fibrin sealant kits, according to Ph. Eur. monograph 0903. International reference standards for all of these factors are now established, however, regional reference standards were not available for the required routine use. It was therefore proposed by European OMCLs and manufacturers to establish a European reference preparation, and it was the goal of this study to accomplish that. Two candidate biological reference preparations (BRPs), separate lyophilisation lots of the same normal human plasma bulk material, were calibrated against the International Standards (ISs) for human coagulation factors V, VIII, XI and XIII. Twelve European laboratories including OMCLs and manufacturers participated. The candidate material was tested against the ISs in 4 separate assays for each factor using the methods described in the relevant Ph. Eur. monographs and general chapters. No discernable difference was noted between the activities of the 2 candidates. They were shown to be suitable for their intended use and it was recommended to assign to both batches a potency of 0.73 IU/mL for factor V, 0.74 IU/mL for factor VIII, 0.59 IU/mL for factor XI and 0.79 IU/mL for factor XIII. Candidate batch B is proposed to be used first as lot 1, followed upon its depletion by candidate batch A (lot 2). The BRP batches will be monitored regularly for potency throughout their lifetime. EDQM BRP batches 1 and 2 of coagulation factors V, VIII, XI and XIII plasma were formally adopted by the Ph. Eur. Commission at their session in June 2011.
根据欧洲药典（Ph. Eur.）专论1646以及通则2.7.4和2.7.22，在对用于病毒灭活的人血浆进行汇集和处理后，人血浆中凝血因子V、VIII和XI的每一次效价测定，以及根据Ph. Eur.专论0903在纤维蛋白密封剂试剂盒中进行人凝血因子XIII的效价测定时，都必须使用以国际单位（IU）表示的人血浆参考制剂。目前已经建立了所有这些因子的国际参考标准，然而，所需的常规使用没有区域参考标准。因此，欧洲药品质量控制实验室（OMCLs）和制造商提议建立一种欧洲参考制剂，本研究的目标就是实现这一点。两种候选生物参考制剂（BRPs），即同一正常人血浆原料的不同冻干批次，针对人凝血因子V、VIII、XI和XIII的国际标准（ISs）进行了校准。包括OMCLs和制造商在内的12个欧洲实验室参与了此项工作。使用相关Ph. Eur.专论和通则中描述的方法，针对每种因子在4次单独的测定中，将候选材料与ISs进行了测试。在2种候选制剂的活性之间未观察到明显差异。结果表明它们适用于其预期用途，并建议为两个批次的因子V指定效价为0.73 IU/mL，因子VIII为0.74 IU/mL，因子XI为0.59 IU/mL，因子XIII为0.79 IU/mL。建议首先使用候选批次B作为批次1，在其耗尽后使用候选批次A（批次2）。在BRP批次的整个有效期内，将定期监测其效价。凝血因子V、VIII、XI和XIII血浆的欧洲药品质量管理局（EDQM）BRP批次1和2于2011年6月在其会议上被Ph. Eur.委员会正式采用。
