国内外皮肤局部外用仿制药等效性评价对比

Comparison of BE Evaluation of Cutaneous Topical Preparations at Home and Abroad

皮肤局部外用制剂的给药部位为皮肤表面,药物通过皮肤吸收发挥疗效,剂型繁多,其仿制药等效性评价方法也与口服制剂不同。通常,体内药代动力学研究是各监管机构最为认可的等效性评价方法,但大部分外用制剂难以通过此方法证明其等效性;以临床终点为指标的等效性研究是应用最广泛的等效性评价方法,然而此类研究成本高,周期长,且准确性、灵敏度和重现性均较差;针对特定的外用制剂品种,研究人员开发了血管收缩试验、体外BE研究等方法进行等效性评价,被各国监管机构广泛接受;对于外用水溶液制剂,通过理化性质等药学研究方法即可证明生物等效性。本文总结了中国、美国、日本、欧洲关于皮肤局部外用制剂仿制药生物等效性研究的相关法规及指导原则,对比四个国家或地区等效性评价的常规方法,为国内外用制剂仿制药的开发提供参考。

The application site of topical skin preparations is the skin surface,the drug exerts its efficacy through skin absorption,there are many dosage forms,and its generic drug equivalence evaluation method is also different from that of oral preparations.Generally,in vivo pharmacokinetics study is the most recognized equivalence evaluation method by regulatory authorities,but it is difficult to prove the equivalence of most external preparations by this method;the equivalence study with clinical endpoints as indicators is the most widely used equivalent evaluation method,however,such study has high cost,long cycle,poor accuracy,sensitivity and reproducibility;for specific types of topical preparations,researchers have developed methods such as vasoconstriction test and in vitro BE study for equivalence evaluation,which have been widely accepted by regulatory authorities in various countries;for topical aqueous solution varieties,pharmaceutical research methods such as physical and chemical properties can prove bioequivalence.This article summarizes the relevant regulations and guidelines on the bioequivalence study of generic drugs of topical skin preparations in China,the United States,Japan,and Europe,and compares the conventional methods for equivalence evaluation in the four countries or regions to provide a reference for the development of generic drugs of preparations for domestic and foreign use.