(T1230-02-10) Revisiting Potency Classification of Topical Corticosteroids Using a Standardized Approach Involving Vasoconstrictor Assay (VCA)

Purpose: Potency assessment and classification of topical corticosteroids (TCs) is important because the clinical choice of a TC depends on various physiological and pathological factors which are taken into account by the dermatologists when prescribing such products to achieve optimum safety and efficacy. The potencies of TCs have been classified based on clinical data or Vasoconstrictor Assay (VCA) data. However, several discrepancies exist in the potency ranking of TCs resulting in a lot of confusion. Therefore, we propose classification of several TC active pharmaceutical ingredients (APIs) based on their inherent potencies using the Food and Drug Administration’s (FDA’s) VCA.

Methods: The inherent potencies of TCs were assessed in accordance with the FDA’s VCA guidance using ten healthy human participants in each study. Standardized solutions (0.0025M) of the TC APIs in a common vehicle (i.e., propylene glycol) were used and skin blanching in human participants (Figure 1) measured with a chromameter. Eight TC APIs were assessed for their relative potencies in two sets of clinical studies – Part A involved 4 APIs, Part B involved 6 APIs. Two APIs were common between the clinical studies. The E_max model was used to fit VCA data obtained following application of the respective TCs, and the parameters, E_max and ED₅₀, were derived. The E_max values were used as a metric to assess the potencies of the TCs and rank them.

Results: Table 1 summarizes the results from the clinical studies. Part A of the table shows that the inherent potency of mometasone furoate was greater than fluocinolone acetonide which was similar to clobetasol propionate. Halcinonide had the lowest potency. Whereas Part B depicts that inherent potencies of fluticasone propionate, mometasone furoate, and hydrocortisone butyrate were similar. There were no significant differences between hydrocortisone butyrate and clobetasol propionate, while there was a significant difference between clobetasol propionate, fluticasone propionate, and mometasone furoate. The potency of hydrocortisone butyrate appears to overlap two potency classes and the potencies of betamethasone valerate and methylprednisolone aceponate were similar but lower than the other APIs.

Conclusion: Application of the VCA to classify inherent potency provides a reliable method to establish a classification system for TCs based on E_max values. Furthermore, it provides information that would aid choosing a suitable TC for incorporation into an appropriate vehicle for a specific clinical indication.

References: US Food and Drug Administration. Guidance for Industry: Topical Dermatologic Corticosteroids—In Vivo Bioequivalence; FDA: Silver Spring, MD, USA, 1995. Available at: https://www.fda.gov/media/70931/download (accessed on Apr 29, 2024).


Table 1. Summary of population model results

>br>Figure 1. Skin blanching response in humans