EMA publishes final ICH M13B Guideline and Q&A on Bioequivalence

The EMA has published the final ICH M13B guideline together with an accompanying Questions and Answers document:

• ICH M13B guideline on bioequivalence for immediate-release solid oral dosage forms - additional strengths biowaiver - Step 5; Reference Number: EMA/CHMP/ICH/85092/2025
• ICH M13B guideline on bioequivalence for immediate-release solid oral dosage forms - additional strengths biowaiver: Questions and Answers - Step 5; Reference Number: EMA/CHMP/ICH/192826/2026

This publication follows the earlier release of the draft guideline and the overview of comments received during the consultation.

Both new documents were first published by the EMA on 21 September 2026. The final guideline will enter into force on 17 March 2027 and will supersede the applicable provisions of the current EMA bioequivalence guideline relating to additional-strength biowaivers.

ICH M13B Guideline

In the Introduction, the guideline states that it "is intended to provide recommendations on obtaining waivers of bioequivalence (BE) studies (biowaivers) for one or more additional strengths of a drug product in an application where in vivo pharmacokinetic (PK) BE or efficacy/safety has been demonstrated for at least one of the strengths, thereby reducing the need for additional in vivo PK BE studies."

The guideline applies to immediate-release solid oral dosage forms, such as tablets, capsules and granules or powders for oral suspension, both during development and in the post-approval phase.

The criteria for an additional-strength biowaiver include the proportionality of the drug substance dose, the qualitative and quantitative composition of the formulations, the similarity of the manufacturing process and comparative dissolution profiles. The guideline also introduces a risk-based approach for justified deviations from direct compositional proportionality and includes decision trees and practical examples.

Q&A Document

The accompanying Q&A document clarifies several aspects discussed during the consultation. The scope and organization of the document follow that of ICH M13B.

It explains that an additional-strength biowaiver under ICH M13B is distinct from a BCS-based biowaiver under ICH M9. Since the M13B approach is based on an existing in vivo bioequivalence demonstration, as well as formulation and dissolution data, it is not restricted to BCS Class I or III drug substances.

The Q&A also confirms that a “waiver on a waiver” is not acceptable where the strength serving as the basis for the waiver was itself approved solely on the basis of a BCS-based biowaiver.

For further information and to download the documents, please visit the EMA website.