title: Global Harmonization of Comparator Products for Bioequivalence Studies.
abstract: Comparator products should be the products that were shown to be safe and efficacious in pivotal clinical trials to ensure prescribability of generics. The use of a common comparator ensures switchability between generics. The selection of the comparator is a national responsibility and may be different between countries. This paper discusses the current recommendations on selection of comparators, the associated problems, and the possibility of harmonization. Most countries follow the World Health Organization (WHO) recommendations for selecting comparator products and require the comparator product to be obtained from their national markets to ensure switchability between the local comparator and their generics. These recommendations are only feasible in the few countries where the repetition of the bioequivalence study is economically feasible, but they are impracticable in all other countries. Furthermore, the exclusive use of the local comparator to ensure switchability is ethically and scientifically questionable. The innovator product from well-regulated markets should be the global comparator. This harmonization is feasible as the concept already applies in the WHO prequalification program. It is ineffectual to harmonize only the requirements for performing bioequivalence studies, if such a study has to be repeated for every single country simply because of the different comparator products.
authors.affiliation: Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht, The Netherlands.|Medicines Control Authority of Zimbabwe, Harare, Zimbabwe.
authors.forename: Luther
authors.initials: L
authors.lastname: Gwaza
authors.affiliation: Division of Biopharmaceutics Evaluation, Bureau of Pharmaceutical Sciences, Therapeutic Products Directorate, Health Canada, Ottawa, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Gordon
authors.affiliation: Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht, The Netherlands.
authors.forename: Hubert
authors.initials: H
authors.lastname: Leufkens
authors.affiliation: The Prequalification Team, Regulation of Medicines and other Health Technologies, Essential Medicines and Health Products, World Health Organization, Geneva, Switzerland.
authors.forename: Matthias
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. agarciaa@aemps.es.
authors.forename: Alfredo
authors.initials: A
authors.lastname: García-Arieta
mesh_terms: D004335:Drug and Narcotic Control; D016568:Drugs, Generic / Q000592:standards*; D000074099:Equivalence Trials as Topic; D038622:Internationality; D013810:Therapeutic Equivalency
chemical_list: D016568:Drugs, Generic
keywords: bioequivalence study; comparator product; generic drug development; generic drug product; generic medicines; harmonization; interchangeability; reference product