仿制药的生物不等效风险与质量一致性评价

Bioinequivalence risk and quality consistency assessment of generic drugs

我国仿制药占上市化学药品的绝大部分,由于仿制药的质量参差不齐,直接影响到人民群众用药安全性和有效性。现阶段,我国提出要全面提高仿制药质量,将仿制药分期分批与被仿制药进行质量一致性评价。而仿制药数量众多,如何开展质量一致性评价工作成为关键环节。本文基于生物药剂学分类系统(BCS)、生物豁免等理论,以及本实验室曾开展的盐酸二甲双胍片和盐酸二甲双胍肠溶片上市后人体生物等效性再评价的实践,提出生物不等效风险的概念。建议在进行口服固体制剂仿制药质量一致性评价前,可先根据其生物不等效风险程度进行分级,生物不等效风险低的品种主要进行体外溶出试验,一般情况下不必进行人体生物等效性试验;生物不等效风险高的品种应主要进行人体生物等效性试验。本文旨在促进我国对药品生物不等效风险的重视,为仿制药质量一致性评价提供有益的参考,以切实提高我国仿制药质量。

Generic drugs are the main body of the marketed chemical drugs in China. However,the variable quality of generic drugs directly influence the medication safety and efficacy of the masses. At present,our country proposed to comprehensively improve the quality of generic drugs through assessing the consistency between generic drugs and the original drugs. But generic drugs are numerous,how can we carry out this significant work？In this paper,based on the theory of biopharmaceutical classification system（BCS） and biowaiver,and also the data of the post-marketing reevaluations of bioequivalence of metformin hydrochloride tablets and metformin hydrochloride enteric-coated tablets in our lab,we proposed a conception of bioinequivalence risk and suggested that generic drug should be classified according to their bioinequivalence risk levels before the quality consistency assessments. For generic drugs with low bioinequivalence risk,in vitro dissolution or release test should be carried out to evaluate the quality consistency,while in vivo bioequivalence test is not commonly necessary. For those with high bioinequivalence risk,in vivo bioequivalence test is primarily necessary. The purpose of this article is to bring more attention to bioinequivalence risk of pharmaceutical products and to provide useful information for the quality consistency assessment of generic drugs in China,thus to effectively improve the quality of drugs.