Investigation of bioequivalence - Scientific guideline

This guidance specifies the requirements for the design, conduct, and evaluation of bioequivalence studies for immediate release dosage forms with systemic action. 

On 25 January 2025, the date of coming into effect, ICH Guideline M13A on bioequivalence for immediate-release solid oral dosage forms supersedes applicable parts of this EMA guideline related to bioequivalence study considerations and data analysis for a non-replicate study design (see Tier 1 in the ICH M13 Concept_Paper - ich.org).

On 17 March 2027, the date of coming into effect, ICH Guideline M13B on bioequivalence for immediate-release solid oral dosage forms - additional strengths biowaiver supersedes applicable parts of the EMA guideline related to obtaining waivers of bioequivalence studies for one or more additional strengths of a drug product in an application where in vivo bioequivalence has been demonstrated for at least one of the strengths.

Note: Appendix III of the EMA guideline is already superseded by the ICH M9 Guideline on biopharmaceutics classification system-based biowaivers.

Specific considerations to enable the practical application of ICH Guideline M13A in the European Union and the transition from the current EMA Guideline on the investigation of bioequivalence have been published and are available in the section below. 

Keywords: Bioequivalence, pharmacokinetics, biowaiver, BCS-based biowaiver, in vitro dissolution, generics

Current effective version

Guideline on the investigation of bioequivalence (Rev.1)

Adopted Reference Number: CPMP/EWP/QWP/1401/98 Rev. 1 Legal effective date: 01/08/2010

Considerations regarding the implementation of ICH M13A on bioequivalence for immediate-release solid oral dosage forms

Adopted Reference Number: EMA/531548/2024

Document history - Revision 1 (current version)

Guideline on the investigation of bioequivalence (Rev.1)

Adopted Reference Number: CPMP/EWP/QWP/1401/98 Rev. 1 Legal effective date: 01/08/2010

Overview of comments received on draft guideline on the investigation of bioequivalence CPMP/EWP/QWP/1401/98 Rev. 1

Reference Number: EMA/CHMP/EWP/26817/2010

Draft guideline on the investigation of bioequivalence

Draft: consultation closed Reference Number: CPMP/EWP/QWP/1401/98 Rev. 1

Concept paper on BCS-based biowaiver

Reference Number: EMEA/CHMP/EWP/213035/2007

Recommendation on the need for revision of (CHMP) (note for guidance on the investigation of bioavailability and bioequivalence)

Reference Number: EMEA/CHMP/EWP/200943/2007

Document history - First version

Note for guidance on the investigation of bioavailability and bioequivalence

Adopted Reference Number: CPMP/EWP/QWP/1401/98 Legal effective date: 01/01/2002