Fuchs F, Poirier B, Leparc-Goffart I, Buchheit K H
Agence Française de Sécurité Sanitaire des Produits de Santé (AFSSAPS), Site de Lyon, 321 avenue Jean Jaurès, F-69007 Lyon, France.
Pharmeuropa Bio. 2005 Sep;2005(1):13-8.
Upon suggestion of the French Official Medicines Control Laboratory, a collaborative study was initiated by the European Directorate for the Quality of Medicines with the goal of calibrating the candidate European Pharmacopoeia biological reference preparation (Ph. Eur. BRP) for anti-vaccinia immunoglobulin batch 1 in International Units (IU) against the 1(st) British standard (anti-smallpox serum). The candidate BRP batch 1 was obtained by lyophilising a pool of four plasma samples obtained from one donor who was multi-vaccinated with smallpox vaccine (Lister strain) and who had relatively high titres of neutralising anti-vaccinia antibodies. The plasma complied with the requirements of the Ph. Eur. monograph Human plasma for fractionation. For the candidate BRP the precision of fill and the residual moisture after lyophilisation comply with the requirements for biological reference preparations. The stability of the material was shown to be satisfactory for the intended purpose in an accelerated degradation test. Eight laboratories participated in the study. Two samples had to be assayed (candidate BRP batch 1 and 1(st) British standard). All participants were requested to test the samples using a common method (plaque reduction neutralisation) that had been validated beforehand, and their own in-house anti-vaccinia immunoglobulin titration method. From the raw data returned, the potency of the candidate BRP was calculated in IU/ml using the parallel lines method. The precision (intra-assay variation), repeatability (intra-laboratory variation) and reproducibility (inter-laboratory variation) were assessed. All laboratories used the Lister strain of vaccinia virus for the plaque reduction neutralisation assay. For laboratories using cell-adapted vaccinia virus, the results were satisfactory regarding intra-assay variability, intra-laboratory variability and inter-laboratory variability. For laboratories using vaccinia virus produced on animals, results were less satisfactory. The study suggests that the candidate BRP batch 1 is suitable as a reference preparation for the potency assay of vaccinia immunoglobulin by the plaque reduction neutralisation method, using cell-adapted vaccinia virus. For this purpose, a potency of 23 IU/vial could be assigned to the candidate BRP. Based on the results of the stability testing, storage of the reference material at -20 degrees C and shipment on ice is recommended. Furthermore, it is recommended to monitor the potency of the reference material once per year. The candidate material was adopted as Ph. Eur. BRP at the Ph. Eur. Commission session in March 2005.
应法国官方药品控制实验室的建议，欧洲药品质量理事会发起了一项合作研究，目的是将抗牛痘免疫球蛋白第1批欧洲药典生物参考制剂（Ph. Eur. BRP）以国际单位（IU）校准，使其与第1个英国标准（抗天花血清）对标。候选BRP第1批是通过冻干从一名多次接种天花疫苗（李斯特株）且具有较高中和抗牛痘抗体效价的供体采集的四份血浆样本混合液获得的。该血浆符合欧洲药典“用于分馏的人血浆”专论的要求。对于候选BRP，冻干后的装量精度和残留水分符合生物参考制剂的要求。在加速降解试验中，该物质的稳定性对预期用途而言表现令人满意。八个实验室参与了该研究。需要对两个样本进行检测（候选BRP第1批和第1个英国标准）。要求所有参与者使用预先验证的通用方法（蚀斑减少中和法）以及各自实验室内部的抗牛痘免疫球蛋白滴定法对样本进行检测。根据返回的原始数据，使用平行线法计算候选BRP的效价，单位为IU/ml。评估了精密度（批内变异）、重复性（实验室内变异）和再现性（实验室间变异）。所有实验室在蚀斑减少中和试验中均使用牛痘病毒李斯特株。对于使用细胞适应型牛痘病毒的实验室，批内变异性、实验室内变异性和实验室间变异性的结果令人满意。对于使用动物源牛痘病毒的实验室，结果不太令人满意。该研究表明，候选BRP第1批适合作为使用细胞适应型牛痘病毒通过蚀斑减少中和法进行牛痘免疫球蛋白效价测定的参考制剂。为此，可将候选BRP的效价指定为每瓶23 IU。根据稳定性测试结果，建议将参考物质储存在-20℃并在冰上运输。此外，建议每年监测一次参考物质的效价。该候选物质在2005年3月的欧洲药典委员会会议上被采纳为Ph. Eur. BRP。
