Statistical Methods for Quality Equivalence of Topical Products. 0.5 mg/g Betamethasone Ointment as a Case-Study
Jordi Ocaña,
Toni Monleón-Getino,
Virginia Merino,
Daniel Peris,
Lluís Soler
Affiliations
Jordi Ocaña
Department of Genetics, Microbiology and Statistics, Section of Statistics, University of Barcelona, Av. Diagonal, 643, 08028 Barcelona, Spain
Toni Monleón-Getino
Department of Genetics, Microbiology and Statistics, Section of Statistics, University of Barcelona, Av. Diagonal, 643, 08028 Barcelona, Spain
Virginia Merino
Departamento de Farmacia y Tecnología Farmacéutica y Parasitología, Facultad de Farmacia, Universitat de València, Av. Vicente Andrés Estellés s/n, Burjassot, 46100 Valencia, Spain
Daniel Peris
Department of Clinical Affairs & Development. Uriach, Pol. Ind. Riera de Caldes, Avda. Camí Reïal 51-57, 08184 Palau-Solitá i Plegamans, Spain
Lluís Soler
Department of Formulation and Late Scale Development, Kern Pharma. Av Venus 72, Pol. Ind Colon II, 08228 Terrassa, Spain
This study examines the statistical implications, and their possible implementation, of the “Draft guideline on quality and equivalence of topical products” issued by the European Medicines Agency in 2018, with particular focus on the section devoted to quality equivalence of physical properties. A new confidence interval to conduct the quality equivalence test and a way to cope with the multiplicity of quality parameters are presented and discussed. As an example, the results and the statistical analysis of a study on betamethasone 0.5 mg/g ointment are presented. It is suggested that the equivalence limits proposed in the draft guideline are overly strict: It is as difficult to declare quality equivalence between two packaging formats of the same reference product as to declare quality equivalence between the reference and the test product.
