A Survey of the Quality of Generic???Clarithromycin Products from???18 Countries

Abstract

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.