Application of the Food and Drug Administration

Application of the Food and Drug Administration
(FDA) bioequivalent guidance of topical dermatological
corticosteroid in yellow-skinned Japanese population:
Validation study using a chromameter

Tomoko KEIDA, Nobukazu HAYASHI, Makoto KAWASHIMA
Department of Dermatology, Tokyo Women's Medical University, Skin clinic Daikanyama,Tokyo, Japan

The American Food and Drug Administration (FDA) bioequivalent guidance of topical dermatological corticosteroids in 1995 (the Guidance) requires measurement of the skin blanching response with a chromameter for evaluation of cutaneously applied corticosteroid formulations. The Japanese government decided to apply the same guide-lines in 2003, despite there having been no reported trial for the yellow-skinned races.
The purpose of this study was to obtain basic data of corticosteroid-induced skin blanching response measured with a chromameter on yellow-skinned races. Four studies were performed according to the Japanese version of the Guidance for lndustry using a chromameter the forearms of healthy Japanese volunteers. This involved: (i) a validation study of proper duration of treatment exposure (dose duration); (ii) a comparison study of two dermatological corticosteroid products that represented different potency classes; (iii) inspection of reproducibility using right and left forearms; and (iv) study of seasonal difference. We showed that : (i) the same medication can give different values of ED50 (the dose duration required to achieve 50% of the fitted areas under the affect curves [AUEC]max value) under different dose durations; (ii)ED50 do not always represent the potency of the corticosteroid; (iii) the results of AUEC at the maximum duration were similar, but AUEC at an approximate ED50 duration time varied widely; and (iv) the results of AUEC were different according to season. In conclusion the dose duration relationships, determination of the AUECmax, and the ED50 could be obtained on yellow-skinned races using the FDA method. However, negligible differences were found in our study regarding dose duration, reproducibility and seasonal change.

Key word: bioavailability, chromameter, Food and Drug Administratin (FDA) Guidance for Industry, skin blanching assay, topical corticosteroid, vasoconstricting activity, yellow-skinned races.