Center for Anti-Infective Research and Development, Hartford Hospital and University of Connecticut School of Pharmacy, Hartford, Connecticut, USA.
Clin Drug Investig. 2005;25(2):135-52. doi: 10.2165/00044011-200525020-00006.
This study compared the quality of 65 generic clarithromycin products manufactured in 18 countries with that of the innovator product.
To assess quality, the generic products were examined visually, assayed by high-pressure liquid chromatography for clarithromycin content and impurities, tested for dissolution properties, and compared with the innovator product manufactured by Abbott Laboratories.
This survey found that many generic clarithromycin products were not equivalent to the innovator product and many of these generic products fell short of the approved specifications developed for the innovator product. Overall, 9% (6 of 65) of all generic tablets tested failed to contain between 95% and 105% of the clarithromycin claimed in the label, thus falling short of the approved registered specification for the innovator product. Seventeen percent (1 of 6) of tablets from Latin America (LA), 8% (3 of 38) of tablets from the Asia, Africa, Pacific (AAP) region, and 10% (2 of 21) of tablets from Europe did not contain the amount of clarithromycin drug content claimed in the label. A total of 34% (17 of 50) of the generic products tested released less drug in 30 minutes than did the innovator tablets. Although the majority of these generic products met the dissolution specification requiring that 80% of the drug must dissolve in 30 minutes, one generic product failed to meet this specification with 68% of drug dissolving in 30 minutes. Moreover, 19% (12 of 65) of all the generic products tested exceeded the Abbott Laboratories' 3% limit for total impurities in bulk drug, and 30% (20 of 65) exceeded the Abbott Laboratories' 0.8% limit for the known impurity 6,11 di-O-methyl erythromycin A.
These results demonstrated that generic tablets are often not comparable in vitro to the innovator product. These findings suggest that results achieved with branded clarithromycin (Abbott Laboratories) should not be extrapolated to generic products. In vivo studies would be needed to determine the clinical relevance of these findings.
本研究比较了 18 个国家生产的 65 种通用克拉霉素产品与原研产品的质量。
为了评估质量，对通用产品进行了外观检查，用高压液相色谱法对克拉霉素含量和杂质进行了测定，对溶出性质进行了测试，并与雅培实验室生产的原研产品进行了比较。
本调查发现，许多通用克拉霉素产品与原研产品不等效，其中许多通用产品不符合为原研产品制定的批准规格。总体而言，在测试的 65 种通用片剂中，有 9%（6 种）未能包含标签中声称的克拉霉素的 95%至 105%，因此不符合原研产品的批准注册规格。来自拉丁美洲（LA）的 17%（1/6）片剂、来自亚洲、非洲、太平洋（AAP）地区的 8%（3/38）片剂和来自欧洲的 10%（2/21）片剂未包含标签中声称的克拉霉素药物含量。在测试的 50 种通用产品中，共有 34%（17/50）在 30 分钟内释放的药物少于原研片剂。尽管大多数通用产品符合要求 80%药物必须在 30 分钟内溶解的溶出度规格，但一种通用产品在 30 分钟内仅溶解 68%的药物，未能达到该规格。此外，在测试的所有通用产品中，有 19%（12/65）超过了雅培实验室对原料药中总杂质的 3%限制，有 30%（20/65）超过了雅培实验室对已知杂质 6,11-二-O-甲基红霉素 A 的 0.8%限制。
这些结果表明，通用片剂在体外通常与原研产品不可比。这些发现表明，不应该将使用品牌克拉霉素（雅培实验室）获得的结果推断到通用产品。需要进行体内研究来确定这些发现的临床意义。
