New EMA Guideline on the Investigation of Bioequivalence

Revision 1 of the "Guideline on the Investigation of Bioequivalence"  (CPMP/QWP/EWP/1401/98 Rev. 1/Corr) came into effect on 1 August 2010. It replaces the former "Note for Guidance on the Investigation of Bioavailability and Bioequivalence"  (CPMP/QWP/EWP/1401/98) and the related Q&A document (CHMP/EWP/40326/06).

This guideline applies to the design, conduct, and evaluation of bioequivalence studies for immediate release dosage forms with chemically defined substances and systemic action.

The possibility of using in vitro instead of in vivo studies is also addressed.

In applications for generic medicinal products, the concept of bioequivalence is fundamental. By this means, equivalence in biopharmaceutics quality is demonstrated between the generic medicinal product and a reference medicinal product.

The number of studies and study design depend on the physico-chemical characteristics of the substance, its pharmacokinetic properties and proportionality in composition, and should be justified accordingly.

The study should be designed in such a way that the formulation effect can be distinguished from other factors. If two formulations are compared, a randomised, two-period, two-sequence single dose crossover design is recommended as standard design.

Under certain circumstances, provided the study design and the statistical analyses are scientifically sound, alternative designs could be considered.

Furthermore, the appendices of this Guideline enlarge upon the following topics:

  • Dissolution testing and similarity of dissolution profiles
  • Bioequivalence study requirements for different dosage forms
  • BCS (Biopharmaceutics Classification System)-based biowaiver

For further information please see the complete Guideline on the Investigation of Bioequivalence.

Dr Günter Brendelberger

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