EMA publishes Draft of ICH M13B Guideline on Bioequivalence

As recently reported, the European Medicines Agency (EMA) published a new document entitled "Considerations regarding the implementation of ICH M13A on bioequivalence for immediate-release solid oral dosage forms" at the end of February 2025. In this context, it has already been pointed out that ICH M13A is the first part of a planned three-part series of guidance documents (M13A, M13B, M13C).

On 9 April, the EMA published the "ICH Guideline M13B on bioequivalence for immediate release solid oral dosage forms - additional strengths - Step 2b" on its website for public consultation.

Content of the Guideline

As mentioned in the objective section, the "guideline is intended to provide recommendations on obtaining waivers of bioequivalence (BE) studies for one or more additional strengths of a drug product in an application where in vivo BE has been demonstrated for at least one of the strengths. The guideline is applicable during both development and post-approval phases of orally administered immediate release (IR) solid dosage forms designed to deliver drugs to the systemic circulation, such as tablets, capsules, and granules/powders for oral suspension."

The document is structured into the following sections:

• 1. Introduction
• 2. Criteria for biowaiver of additional strengths
• 3. Specific topics
• 4. Documentation
• 5. Glossary
• Annex I: Considerations for deviation from direct compositional proportionality
• Annex II: Decision tree to determine the possibility of an additional strength biowaiver for non-high-risk drug products

A biowaiver may be accepted if, among others, the following criteria are fulfilled:

• Pharmacokinetic dose proportionality of the drug
• Qualitative and quantitative composition among different strengths
• Similarity of in vitro dissolution

The guideline also provides specific considerations for:

• Fixed dose combination (FDC)
• Deviation from direct proportionality (Annex I)
• Bracketing approaches

A decision tree (Annex II) is included to assist applicants in determining whether a biowaiver for an additional strength is appropriate, particularly for non-high-risk drug products.

Download and Commenting Process

The draft guideline is available for download as a PDF document. The public consultation period is open until 9 July 2025. Comments should be submitted using the template linked in the guideline document.

Further information can be found on the EMA website and on the ICH homepage.