Adjusted indirect treatment comparison of the bioavailability of WHO-prequalified first-line generic antituberculosis...

Approval of generic medicines is based on bioequivalence with the innovator product, but it is not unusual for generics to be interchanged with each other. This study investigated the differences in bioavailability between World Health Organization-prequalified antituberculosis generics by means of indirect comparisons to ensure interchangeability between these diverse generics. Data on 22 products containing isoniazid, rifampicin, pyrazinamide, or ethambutol in single- or fixed-dose combination were included. The indirect comparison between generics shows that the differences, expressed as 90% confidence intervals, are always less than 30%. Furthermore, assurances regarding interchangeability of two generic products are reduced when either the point estimate ratios in the original studies are shifted from unity by more than 5% or when the width of the 90% confidence interval is large. From a bioequivalence perspective, not only are the generics bioequivalent with the reference but also all these generics can be interchanged without safety/efficacy concerns.