欧洲药典(Ph.欧尔.)专著0828规定了两种体外测定法来评估低分子质量肝素产品的生物活性。这些评估了低分子量肝素加速抗凝血酶抑制因子Xa和因子IIa的能力。以国际单位(IU)校准的参考标准,如肝素低分子量测定生物参考制剂(BRP),需要表达结果。由于库存不足,欧洲委员会和欧盟的生物标准化计划(BSP)启动了一项国际合作研究,以建立当前肝素低分子质量BRP(BRP10)的替代批次。13个官方药物控制实验室和制造商提供了数据,以根据世界卫生组织(WHO)第3号肝素国际标准校准候选批次。低分子量(11/176;第三IS)使用显色测定。根据参与者的计算和欧洲药品和医疗保健质量局(EDQM)的中央计算,候选BRP对第3IS的总体反Xa和IIa活动非常接近。两种测定的实验室间差异在2.8%和7.5%之间。研究数据证实了BRP10的指定活性。根据这项合作研究的结果,2019年12月,Ph。欧尔.委员会采用候选BRP作为肝素低分子质量,用于测定BRP第11批,其指定的抗Xa活性为110IU/mL,抗IIa活性为37IU/mL。
European Pharmacopoeia (Ph. Eur.) monograph 0828 prescribes two in vitro assays to evaluate the biological activity of low-molecular-mass heparin products. These assess the capacity of low-molecular-mass heparins to accelerate the inhibition of factor Xa and factor IIa by antithrombin. A reference standard calibrated in International Units (IU) such as the Heparin low-molecular-mass for assay Biological Reference Preparation (BRP), is required to express results. Due to low stocks, the Biological Standardisation Programme (BSP) of the Council of Europe and the European Union launched an international collaborative
study to establish a replacement batch for the current Heparin low-molecular-mass BRP (BRP10). Thirteen Official Medicines Control Laboratories and manufacturers contributed data to calibrate a candidate batch against the World Health Organization (WHO) 3rd International Standard for Heparin, low molecular weight (11/176; 3rd IS) using chromogenic assays. The overall anti-Xa and IIa activities of the candidate BRP against the 3rd IS based on the participants\' calculations and on central calculation at the European Directorate for the Quality of Medicines & HealthCare (EDQM) were very close. The inter-laboratory variation for both assays was between 2.8 % and 7.5 %. The
study data confirmed the assigned activities of BRP10. Based on the results of this collaborative
study, in December 2019 the Ph. Eur. Commission adopted the candidate BRP as Heparin low-molecular-mass for assay BRP batch 11 with assigned anti-Xa activity of 110 IU/mL and anti-IIa activity of 37 IU/mL.