国内外质控差异可能对多组分抗生素注射剂一致性评价产生的影响

Possible impact on consistency evaluation of multi-component antibiotic injections by domestic and international differences in the quality control

目的探讨不同国家药典在多组分抗生素质控中存在的差异,特别是参比制剂所遵从标准与我国药典限度间的差异,可能对我国此类品种注射剂仿制药质量和疗效一致性评价产生的影响。方法选择替考拉宁作为典型品种,在市场流通环节获取参比制剂和国内不同厂家仿制药的注射剂产品,按不同国家药典标准开展检测,对关键质控差异项进行比较。结果参比制剂和各仿制药在组分/有关物质构成及其相对比例上存在显著性差异,若按参比制剂所遵从的现行版欧洲药典标准进行合格判定,则全部国产仿制药各批次产品均无法满足其限度规定。结论多组分抗生素在组分构成上的差异客观存在,故对此类品种开展一致性评价过程中:应尽量明确各组分的毒/活性特点,并关注各组分对临床耐药菌的有效性,更为全面、客观地对仿制药和参比制剂在实际临床疗效/安全性间的差异进行评价;同时,需明确关键原辅料属性、关键工艺参数与关键质量属性间的相互关系,通过精准控制最终实现产品质量持续一致的目标。

Objective To explore the possible impact on the quality and efficacy consistency evaluation of a multi-component antibiotic generic injection or for injection by the differences of the quality control concepts from different national pharmacopoeias,especially the differences between the limit requirements of a certain national pharmacopoeia which the reference preparation complies with and those of the Chinese Pharmacopoeia.Methods Teicoplanin was selected as the typical research object,the generic teicoplanin for injection of different domestic manufacturers and the reference preparation were collected from market circulation,and were tested according to different national pharmacopoeias.The results of the critical testing items with significant differences in quality control concepts were compared.Results There are significant differences in the component composition,related substances,and the relative proportions of main composition between the reference preparation and each generic teicoplanin for injection.All batches of domestic generic teicoplanin for injection cannot meet the limit requirements of the critical items according to the current edition of European Pharmacopoeia.Conclusion As a multi-component antibiotic,the difference of its component composition,especially the relative proportions,is inevitable.We suggest that the following points should be considered in the process of quality and efficacy consistency evaluation for a multi-component antibiotic.Firstly,for evaluating the differences in actual clinical efficacy and safety between the generic drugs and the reference preparations more comprehensively and objectively,the toxicity and activity characteristics and the effectiveness against clinically drug-resistant bacteria of each component should be clarified as clearly as possible.Secondly,in order to guarantee the consistency of product qualities through precisely controlling a certain productive process,the relationships among the critical material attributes,the critical process parameters,and the critical quality attributes should be clarified,especially the differences of those between the generic drugs and the reference preparations.