[New guidelines for the assessment of bioavailability and bioequivalence]

Bioavailability and bioequivalence studies are essential in the clinical development of medicinal products and the optimization of pharmaceutical forms. Bioavailability means the rate and extent to which the active substance or active moiety is absorbed from a pharmaceutical form and becomes available at the site of action. In practice, drug concentration-time courses are measured in the systemic circulation, and the area under the curve (AUC) as well as the observed maximum concentration (C(max)) are determined. Products are considered bioequivalent if their bioavailabilities after administration of the same molar doses are similar to such a degree that their effects, with respect to both efficacy and safety, will be essentially the same and thus, there are no relevant differences in terms of AUC and C(max). In 2002 a revised version of the 'Note for Guidance on the Investigation of Bioavailability and Bioequivalence' came into effect (CPMP/EWP/QWP/1401/98). Relevant changes in comparison to the previous version are: request for GLP-compliant bioanalytical measurements; for long half-life drugs a truncated AUC is acceptable; acceptance criteria for bioequivalence assessment and requirements for a waiver of bioequivalence studies were further specified. In this context the Biopharmaceutics Classification System (BCS) seems appropriate to decide whether in special cases of rapidly dissolving solid oral dosage forms a biowaiver may be granted or not. Products not considered critical in this matter are medicinal products for which the formulation does not affect the rate and extent of absorption, i. e. bioavailability, of the active moiety. Highly soluble (and highly permeable) drugs (BCS class I) are such candidates. Comprehensive state-of-the-art guidance on the design, conduct and analysis of bioavailability and bioequivalence studies is given in the current European guideline.