Abstract：
The level of anti-D antibodies in human immunoglobulin products for intravenous administration (IVIG) is controlled by the direct haemagglutination method prescribed by the European Pharmacopoeia (Ph. Eur.) that requires 2 control reference reagents. The World Health Organization (WHO) positive control International Reference Reagent (IRR; 02/228) with a nominal titre of 8 defines the highest acceptable titre, while the negative control preparation (02/226) has a nominal titre of <2. Working reference preparations (04/132 and 04/140) were subsequently established as Biological Reference Preparations (BRPs) for the Ph. Eur., and for distribution by the United States Food and Drug Administration (US FDA) and the National Institute for Biological Standards and Control (NIBSC). Due to diminishing stocks of these working reference preparations across the 3 institutions, a joint international study was organised to establish harmonised replacement batches. Sixteen laboratories contributed data to the study to evaluate positive and negative candidate replacement batches (13/148 and 12/300, respectively) against the WHO positive and negative control IRRs and the current working reference preparations (BRPs). The results show that the candidate reference preparations (13/148 and 12/300) are indistinguishable from the corresponding IRRs and current BRPs. The candidate preparations 13/148 and 12/300 were adopted by the Ph. Eur. Commission as Immunoglobulin (anti-D antibodies test) BRP batch 2 and Immunoglobulin (anti-D antibodies test negative control) BRP batch 2 with nominal haemagglutination titres of 8 and <2, respectively. The same materials were also adopted as NIBSC and US FDA reference preparations, thus ensuring full harmonisation.
摘要：
静脉内给药的人免疫球蛋白产品（IVIG）中抗D抗体的水平由欧洲药典规定的直接血凝方法控制（Ph。欧尔.)需要2种对照参考试剂。世界卫生组织（WHO）阳性对照国际参考试剂（IRR;02/228）的标称滴度为8，定义了最高可接受滴度，而阴性对照制剂(02/226)的标称滴度<2。工作参考制剂(04/132和04/140)随后被确立为用于Ph的生物参考制剂(BRP)。欧尔.,并由美国食品和药物管理局（USFDA）和国家生物标准与控制研究所（NIBSC）分发。由于3家机构的这些工作参考准备工作的库存减少，组织了一项联合国际研究，以建立统一的替代批次。16个实验室为研究提供了数据，以评估阳性和阴性候选替代批次（分别为13/148和12/300）与WHO阳性和阴性对照IRR以及当前的工作参考制剂（BRP）。结果表明，候选参考制剂（13/148和12/300）与相应的IRR和当前的BRP没有区别。候选制剂13/148和12/300由博士通过。欧尔.作为免疫球蛋白（抗D抗体测试）BRP批次2和免疫球蛋白（抗D抗体测试阴性对照）BRP批次2，标称血凝滴度分别为8和<2。同样的材料也被采用作为NIBSC和美国FDA的参考制剂，从而确保全面协调。
