Resolving the Conflict between BCS and BDDCS for the Advancement of the Drug Discovery, Development, and Regulatory Processes

Drug permeability is accepted as a screening tool for determining intestinal absorption via the Biopharmaceutics Classification System (BCS) during the drug development and regulatory approval processes. Currently, predicting clinically significant drug interactions during drug development is a known challenge for the pharmaceutical industry and regulatory agencies. The Biopharmaceutics Drug Disposition Classification System (BDDCS), a modification of BCS utilizing drug metabolism instead of intestinal permeability, predicts drug disposition and potential drug-drug interactions in the intestine, the liver, and most recently the brain. While correlations between BCS and BDDCS have been observed with drug permeability, discrepancies in drug classification between the two systems using different permeability models, accepted as surrogate models for demonstrating human intestinal permeability by the FDA, have been noted. This project examines the role of drug permeability in drug absorption and drug metabolism and recommends the suitability of these models for predicting BDDCS and BCS classifications. This project evaluates methodologies that can lead to recommendations for facilitating the drug discovery, development, and regulatory approval processes.