Comparative Analyses of Bioequivalence Assessment Methods for In Vitro Permeation Test Data

Area of Science:

• Dermatology
• Pharmacokinetics
• Biostatistics

Background:

• In vitro permeation test (IVPT) is crucial for topical dermatological drug bioequivalence (BE) assessment.
• The FDA's 2022 draft guidance proposes a reference-scaled approach for IVPT data analysis.
• Accurate statistical methods are vital for reliable BE determination.

Purpose of the Study:

• To comprehensively evaluate various methodologies for estimating critical parameters in IVPT bioequivalence assessment.
• To compare the FDA draft IVPT guidance approach with alternative empirical and model-based methods.
• To investigate the performance of these methods using simulated and real-world IVPT data.

Main Methods:

• Analysis of simulated and real-world in vitro permeation test (IVPT) data.
• Evaluation of the FDA draft IVPT guidance statistical methods.
• Comparison with alternative empirical formulas and model-based methods using mixed-effects models.

Main Results:

• Empirical formulas demonstrated robustness in approximating true models and handling treatment-donor interactions in simulated scenarios.
• Model-based approaches showed performance heavily dependent on accurate model selection.
• Empirical formulas exhibited greater reliability compared to model-based approaches in IVPT data analysis.

Conclusions:

• Accurate model selection is paramount for the success of model-based bioequivalence assessment methodologies.
• Empirical formulas offer a reliable and robust alternative for IVPT data analysis, particularly in addressing variability.
• This research provides valuable insights for advancing the understanding and application of robust methodologies in dermatological drug bioequivalence assessment.