Bioequivalence of topical corticosteroids: a regulatory perspective

After reviewing the history of generic drug substitution policy in the United States, this paper discusses issues of equivalence as they apply to topical drug products. Documentation of bioequivalence of topical products has been problematic, and current methods are being re-evaluated by the Food and Drug Administration. The FDA is currently evaluating various extensions of the basic methodology of the Stoughton-McKenzie vasoconstrictor assay, in order to develop a more comprehensive pharmacodynamic methodology for documenting topical drug bioequivalence. A modern pharmacodynamic model is described, based on nonlinear dose-response relationship, a baseline effect, and a maximum or plateau effect. The Agency's goal is a bioequivalent methodology that will be simple, readily performed, and based on more objective methods of measuring the vasoconstrictor response.