José Morais, iMed, Research Institute for Medicines and Pharmaceutical Sciences, Faculdade de Farmácia, Universidade de Lisboa, Portugal

A new revision of the former guidelines on the Investigation of Bioavailability (BA) and Bioequivalence (BE), first published in 1992 and revised in 2000, is now in force since 2010.

The focus of this new version is on BE only, leaving BA concepts and applications to more fundamental, PK oriented guidelines. Other features of this new version derive from the need to more prescriptive precepts in order to avoid frequent referrals due to ambiguous wording, during Mutual Recognition (MRP) and Decentralised (DCP) procedures to obtain Marketing Authorisations (MA) mainly for Generic Medicinal Products (GMP) in the European Union (EU).

Novelties include, e.g., (1) the specification of conditions under which the classical 0.800 – 0.125 acceptance interval for the 90% Confidence Interval (CI) of the geometric mean ratio (GMR) can be widened or narrowed; (2) the bracketing approach and other statements to the waiver of BE studies for different strengths; (3) the full application of the Biopharmaceutics Classification System (BCS) as a basis for biowaiver for BCS class I as well as for BCS class III; and (4) the acceptance of the 2-stage design in BE studies.

Not withstanding these and other new features, applications keep being referred to the CMDh and CHMP itself prompting the update of the Q&A document that deal with particularly complex cases of application of the guideline. A brief account of the new features and case studies will be presented.

26Oct