title: Adjusted indirect treatment comparison of the bioavailability of WHO-prequalified first-line generic antituberculosis medicines.
abstract: 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.
authors.affiliation: 1] Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands [2] Evaluations and Registration Division, Medicines Control Authority of Zimbabwe, Harare, Zimbabwe.
authors.forename: L
authors.initials: L
authors.lastname: Gwaza
authors.affiliation: Division of Biopharmaceutics Evaluation, Bureau of Pharmaceutical Sciences, Therapeutic Products Directorate, Health Canada, Ottawa, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Gordon
authors.affiliation: Medicines Evaluation Board, Utrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Welink
authors.affiliation: Subdepartment of Biostatistics and Pharmacokinetics, Federal Institute for Drugs and Medical Devices, Bonn, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Potthast
authors.affiliation: 1] Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands [2] Medicines Evaluation Board, Utrecht, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Leufkens
authors.affiliation: The Prequalification of Medicines Programme Quality Assurance and Safety: Medicines, Essential Medicines and Health Products, World Health Organization, Geneva, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Stahl
authors.affiliation: División de Farmacología y Evaluación Clínica, Departamento de Medicamentos de Uso Humano, Agencia Española de Medicamentos y Productos Sanitarios, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: García-Arieta
mesh_terms: D000995:Antitubercular Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D016001:Confidence Intervals; D016568:Drugs, Generic / Q000493:pharmacokinetics*; D006801:Humans; D014944:World Health Organization
chemical_list: D000995:Antitubercular Agents; D016568:Drugs, Generic