Assessment of the interchangeability between generics

Abstract

Generic medicines are approved by regulatory authorities based on demonstration of bioequivalence with the innovator, however, direct comparison between all available generics of the same innovator to ensure interchangeability between them is not feasible. With this in mind, the recent use of indirect comparison in investigating the differences in bioavailability between generics was reviewed. Among the available methods for performing indirect comparisons, the adjusted indirect comparison is the simplest and most suitable method for bioequivalence studies, because it uses publicly available data, and partly preserves the power of randomized controlled trials. The homoscedastic method is the most conservative approach, thus recommended for calculating the width of the confidence intervals for adjusted indirect comparisons. In the present review, the majority of adjusted indirect comparisons of the generic antimalarial artemether/lumefantrine, first-line antituberculosis, and the first-line antiretroviral medicines prequalified by World Health Organization (WHO), and generics approved in the European Union were within the typical acceptance limits of ±20%, and none exceeded the ±30% range, despite the reduced precision of indirect estimates. To ensure interchangeability between generics, the original studies should be sufficiently powered, i.e. >80%, and the point estimate ratios should not exceed the 7% difference. Thus, a point estimate constraint in the original studies is recommended where it is important to ensure generic drug interchangeability, e.g. narrow therapeutic index drugs. In conclusion, adjusted indirect comparison is a useful tool to compare relative bioavailabilities between generics that have been compared with a common reference in direct comparison to ensure interchangeability between the generics.