Statistical Methods for Quality Equivalence of Topical Products. 0.5 mg/g Betamethasone Ointment as a Case-Study

Abstract

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.

Keywords

• Fieller’s confidence interval
• equivalence test
• batch effect
• multiple quality variables
• principal component analysis