Bioequivalence studies: a new EMA guideline

In January 2010, a new guideline on bioequivalence studies appeared on the website of the European Medicines Agency (EMA, previously EMEA): Guideline on the investigation of bioequivalence (CPMP/QWP/EWP/1401/98 Rev.1). It is not only a revision of the previous version dated July 2001 completed by several announcements through specific guidelines or the Q & A document (CHMP/EWP/40326/06), it is a deeply modified review of the state of the art in the field so that all participants to a bioequivalence study could benefit from more precise rules. Looking at the dates of the discussion, from the beginning during May 2007 to the adoption by the CHMP on 20th January 2010, there is no doubt that numerous discussions were necessary to improve the Guideline.

Every part of such a study has been more or less challenged leading to precise recommendations for the comparison of absorption of immediate release formulations with systemic action of chemical entities. This includes the evaluation of different formulations used during the development of a new medicinal product containing a new chemical entity, generics, or comparative bioavailability studies included in extension or hybrid applications.

All parts of such a study are dealt with in detail, including the study design, tested compounds and strength to be investigated, subjects – including the calculation of the number of subjects necessary to come to a conclusion –, characteristics to be investigated, bioanalytical methodology and statistical evaluation of the results. Important points are also described such as the problems raised by narrow therapeutic index drugs, highly variable drugs or drug products. Finally, an appendix provides the basis for a BCS (Biopharmaceutics Classification System) based biowaiver.

Some particular points will be detailed below to show the completeness of the document: