WHO Working Document on Bioequivalence open for Public Consultation

On 24 April 2026, the WHO posted a new draft working document entitled “Bioequivalence for Immediate Release Oral Dosage Forms” (QAS/25.990) on the WHO Medicines website under “Working documents in public consultation”. The document is issued as a draft for comments and is intended to update WHO’s recommendations for demonstrating bioequivalence (BE) for orally administered immediate-release (IR) products such as tablets, capsules and oral suspensions

Background

In the Background section, WHO explains that the update was recommended by the 58th Expert Committee on Specifications for Pharmaceutical Preparations (ECSPP) in 2024, informed by outcomes of the 2024 Joint Meeting on Regulatory Guidance for Multisource Products. The revision is positioned as part of a broader effort to modernise WHO guidance related to bioequivalence and interchangeability for multisource (generic) products and to align with relevant ICH guidance (including ICH M9, M10 and M13).

WHO notes that, when reviewing ICH M13A (bioequivalence for immediate-release solid oral dosage forms), the Expert Committee considered the scientific principles and core requirements largely aligned with existing WHO guidance, but identified differences in specific areas—explicitly including dose proportionality, endogenous compounds, pH-dependent considerations and certain product categories. 

As a consequence, the ECSPP recommended a structured update of WHO BE guidance, including a dedicated revision for IR products informed by ICH M13A, while remaining responsive to the needs and capacities of WHO Member States and emphasising appropriate sequencing of related updates.

Document Structure and Key Content Areas

The draft is structured into five main chapters:

• Introduction – Objective, Background (Bioequivalence; Data integrity) and Scope 
• General principles in establishing bioequivalence – covering study design and data analysis for PK endpoint BE studies 
• Specific topics – including endogenous compounds, other IR dosage forms (e.g., orally disintegrating tablets, chewable tablets, oral suspensions, oral solutions), fixed dose combinations, and pH-dependency 
• Documentation
• Glossary

From a technical perspective, WHO reiterates that BE for IR oral dosage forms is typically established via clinical pharmacokinetic BE studies (or, where appropriate, comparative in vitro dissolution) and references the possibility of Biopharmaceutics Classification System-based biowaivers in line with separate WHO guidance. The guideline also includes a dedicated Data Integrity section, pointing to WHO GCP principles and emphasising that the applicant retains ultimate responsibility for submitted data integrity.

Commenting Process and Further Steps

Comments should be submitted through the online PleaseReview™ platform by 23 June 2026. Further information on the commenting process is described in the draft document.

The draft also provides a schedule indicating that the working document is planned for discussion and possible adoption by the ECSPP at its fifty-ninth meeting (12–16 October 2026).