Scientific and regulatory approaches to demonstrating the bioequivalence of topical corticosteroids in the Brazilian and international contexts

Abstract

Introduction: Bioequivalence of topical corticosteroids is essential to ensure the efficacy and safety of generic drugs, but the evaluation of these products is challenging due to limited systemic action and the influence of the formulation on skin permeation. The vasoconstriction assay (VCA) is the most widely used method worldwide. Objective: To analyze the scientific and regulatory strategies for demonstrating the bioequivalence of topical corticosteroids in Brazilian and international scenarios. Methods: Integrative literature review (2016-2026) in the PubMed, Scielo, Scopus and LILACS databases, as well as official documents from ANVISA, FDA and EMA. Experimental in vivo, ex vivo and in vitro studies were also reviewed. Results: Ten experimental studies and ten regulatory documents were selected. The FDA presents the most consolidated model for the VCA, while the EMA adopts a phased approach (Q1/Q2/Q3). ANVISA aligns internationally, but requires a larger number of participants in the pilot study (24 vs. 12). Studies have shown interindividual variability and the influence of excipients (e.g., white paraffin mimics the placebo effect). Conclusion: Although VCA is the gold standard, the trend is towards the integration of complementary methods (IVRT, IVPT) into multiparametric models, with ANVISA (Brazilian Health Regulatory Agency) recently consolidating its regulations.