The Revised 2010 EMA Guideline for the Investigation of Bioequivalence for Immediate Release Oral Formulations with Systemic Action

On August 1, 2010, a revised guidance regarding bioequivalence (BE) assessment for the approval of innovator (bridging studies, variations, line extensions) and generic medicinal products in the EU came into effect (EMA Guideline on the Investigation of Bioequivalence, CPMP/EWP/QWP/1401/98 Rev. 1/Corr**, London, 20 January 2010). This guideline specifies the requirements for BE assessment for immediate release oral dosage forms with systemic action. Compared to the previous BE guideline of the EMA, clearer guidance is now given on several topics including BE assessment of highly variable drugs/drug products (HVDs/HVDPs), the use of metabolite data, acceptance criteria for narrow therapeutic index drugs (NTIDs), BCS-based biowaivers, and dose strength to be used in case of application for marketing authorization of several strengths. However, the health authorities of the various EU member states do not necessarily apply the same rules as far as substitution and switchability between medicinal products are concerned. Moreover, differences still exist between the BE guidelines of the major health authorities (FDA, EMA, NIHC, ... ) on topics such as HVDs/HVDPs, NTIDs and BCS-based biowaivers. Global harmonization should be the next logical step to guarantee accessibility to safe and efficacious drug products for patients in all parts of the world.