The BCS, BDDCS, and Regulatory Guidances

Abstract

The BCS (Biopharmaceutics Classification System), based on aqueous solubility and intestinal permeability, has been widely used since 1995 to predict drug absorption during the course of pharmaceutical development (1). However, as will be discussed subsequently in more detail, when the BCS concepts were initiated, now more than 15 years ago, the term “intestinal permeability” was used interchangeably with both measures of rate and extent of absorption, believing from the data available at that time that permeability/absorption rate and extent are correlated. The BCS has also been utilized by regulatory authorities to determine whether in vivo bioequivalence studies may be waived for drug products in immediate release solid oral dosage forms (2,3). For example, the U.S. FDA currently grants waiver of in vivo bioequivalence studies for BCS Class 1 (highly soluble and highly permeable) drugs that are formulated in rapidly dissolving, immediate release products (2). In 2005, the BDDCS (Biopharmaceutical Drug Disposition Classification System), based on solubility and metabolism, was developed to predict drug disposition and potential drug-drug interactions in the intestine and/or liver (4). In view of the apparent correlation between drug metabolism and intestinal permeability rate, it was further suggested that extensive drug metabolism may provide an alternate (or additional) tool for characterizing high intestinal permeability under BCS (4,5). However, discrepancies between the two systems have been noted over the years. For instance, assignment of a drug class using BDDCS was not in accordance with that using BCS, and vice versa (4–6). In addition, it was found that some highly permeable drugs (as measured by the extent of absorption)