Medicines for use outside the European Union
The European Medicines Agency (EMA), in cooperation with the World Health Organization (WHO), can provide scientific opinions on high priority human medicines, including vaccines, that are intended for markets outside of the European Union (EU).
The aim is to facilitate patient access to essential medicines in low- and middle-income countries, including new or improved therapies for unmet medical needs, which are intended to prevent or treat diseases of major public health interest.
The procedure combines EMA's scientific review capabilities with the local epidemiology and disease expertise of WHO and national regulators in the target countries, to provide a unique development and assessment pathway. It is targeted both at innovative medicines and new developments of already authorised medicines.
Following the evaluation, EMA publishes its scientific opinion of the benefit-risk balance of the product, which aims to facilitate prequalification of the medicine by WHO and registration in the target countries.
The procedure is called EU-Medicines for all or 'EU-M4all'. It was previously known as the Article 58 procedure, as the legal basis is Article 58 of Regulation (EC) No 726/2004. It has been in place since 2004.
For guidance on procedural and regulatory steps involved, see Obtaining and maintaining a scientific opinion on a medicine for use outside the European Union.
Medicine developers who obtain a scientific opinion from EMA for markets exclusively outside of the EU benefit from:
- rigorous scientific assessment by European experts to the same high standards as for medicines intended for use in Europe;
- involvement of experts from WHO and national regulatory authorities in target countries;
- benefit-risk assessment tailored to intended non-EU population;
- a streamlined assessment under the WHO prequalification programme;
- facilitated registration in target countries.
Medicines and vaccines eligible for this procedure are used to prevent or treat public health priority diseases. These include:
- used in the WHO Expanded Program on Immunization;
- for protection against a WHO public health priority disease;
- that are part of a WHO-managed stockpile for emergency response;
- other medicines:
- for WHO target diseases such as human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), malaria and tuberculosis.
- for maternal and newborn healthcare.
Applicants need to request eligibility for evaluation under Article 58 for a medicinal product before submitting an application. This request will be evaluated by the EMA's CHMP in collaboration with the WHO.
EMA has in place a range of regulatory tools to support medicine developers which are valid for developers of medicines for use exclusively outside the EU, including:
For further details, see:
Draft guidance on applying for the two procedures in parallel was available for public consultation until 15 February 2021:
EMA plans to finalise the guidance document in the first quarter of 2021. In the meantime, applicants may use the draft guidance for submitting parallel applications.
EMA applies the same fees as for the centralised marketing authorisation procedure.
In exceptional cases, applicants can request a total or partial fee waiver from EMA's Executive Director. They should submit a request as early as possible, and not later than 3 months before applying for scientic advice or submitting an application.
Based on ten years of experience, EMA, the European Commission and the Bill & Melinda Gates Foundation carried out a study in 2015 to look at stakeholder awareness, experience and views on the procedure. A slide presentation and a summary document present the study's findings and recommendations:
- Defining the strategic vision for the EMA 'Article 58' process
- Summary of Article 58 strategic review
EMA has included a number of activities relating to Article 58 in its work programme and future activities will take into account the global regulatory aspects of the EU Medicines Agencies Network Strategy to 2020.