ABSTRACT
INTRODUCTION The Biopharmaceutics Classification System (BCS) is an approach to justify a waiver for in vivo bioequivalence (BE) of immediate-release (IR) oral solid dosage forms (1,2). According to the BCS, a drug product is characterized in terms of the solubility and permeability of the drug substance and in terms of its in vitro drug product dissolution characteristics. Solubility, permeability, and dissolution are the major determinants of the rate and extent of drug absorption from IR oral solid dosage forms. The Food and Drug Administration (FDA) and European Medicines Evaluation Agency (EMEA) implemented the BCS about 10 years ago to address the regulatory question of BE. While maintaining high standards for product assessment, the BCS enables biowaivers, which allow BE assessment through the in vitro BCS guidance tests (i.e., solubility, permeability, in vitro dissolution) rather than through a human in vivo BE study. The BCS allows sponsors to request biowaivers for highly soluble and highly permeable drug substances (class I) in IR solid oral dosage forms that show rapid in vitro dissolution. Restrictions to its application include poor stability of the drug in the gastrointestinal tract, significant effects of excipients on the rate and extent of oral drug absorption, classification as a narrow therapeutic index drug, and products designed to be absorbed from the oral cavity.
