Drug Permeability Studies in Regulatory Biowaiver Applications

The Biopharmaceutics Classification System is a drug development tool that estimates the contributions of solubility, dissolution, and intestinal permeability affecting drug absorption from solid oral products. A regulatory guidance proposes human, animal, and in vitro methods to determine the permeability class membership of a drug substance. Method suitability is a process to establish and validate cellular or tissue permeability assays for classification of drug substances. It consists of establishing an assay with comparison of experimental permeability to in vivo extent of absorption, defining reference standards and acceptance criteria, and classifying new drug substances. Literature examples with cells, intestinal tissue, and artificial membranes demonstrate the applicability and feasibility of method suitability for evaluating permeability models. An assay with established method suitability, standard compounds, and criteria for classifying drugs improves the reliability for such assays for regulatory applications.

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