title: Scientific considerations concerning the EMA change in the definition of "dose" of the BCS-based biowaiver guideline and implications for bioequivalence.
abstract: This work discusses the scientific aspects of the definition of dose as the 'highest single oral IR dose' recommended for administration in the SmPC (summary of product characteristics) in the current European Medicines Agency (EMA) 2010 Guideline, for the purpose of biopharmaceutics classification system (BCS)-based biowaiver decision making. Analysis of theoretical and experimental data dealing with drug dissolution and biopharmaceutic drug classification reveals that the drug dose is an important parameter for both drug dissolution and biopharmaceutic classification. The relevant implications for the dose considerations in bioequivalence studies are also discussed briefly. It is suggested that the concept of "the highest single dose oral IR dose recommended for administration in the SmPC" of the EMA 2010 Guideline be abolished. It is advisable, each dose strength be considered separately i.e., whether or not it meets the solubility-dissolution regulatory criteria.
authors.affiliation: Laboratory of Biopharmaceutics & Pharmacokinetics, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens 15771, Greece.
authors.forename: Chrysa
authors.initials: C
authors.lastname: Daousani
authors.affiliation: Laboratory of Biopharmaceutics & Pharmacokinetics, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens 15771, Greece. Electronic address: macheras@pharm.uoa.gr.
authors.forename: Panos
authors.initials: P
authors.lastname: Macheras
mesh_terms: D001702:Biopharmaceutics / Q000145:classification*; D005060:Europe; D006077:Government Agencies; D017408:Guidelines as Topic; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000145:classification; D010599:Pharmacokinetics; D012995:Solubility; D009626:Terminology as Topic; D013810:Therapeutic Equivalency
chemical_list: D004364:Pharmaceutical Preparations
keywords: BCS; Bioequivalence; Dose; EMA; Guideline