EU-M4all is a procedure of the European Medicines Agency for medicines and vaccines intended exclusively for markets outside the European Union. It is based on Article 58 of Regulation (EC) No. 726/2004 and results in a scientific opinion from the EMA, rather than an EU marketing authorization. The goal is to support national or regional registrations in low- and middle-income countries as well as WHO prequalification.
Purpose and Scope
EU-M4all stands for “EU Medicines for all” and was formerly known as the Article 58 procedure. It is aimed at medicines and vaccines for the prevention or treatment of diseases that are of high priority from a public health perspective. This can include innovative therapies, new chemical or biological medicines, vaccines, biosimilars, and generics. New formulations, pharmaceutical forms, or routes of administration for already known medicines may also be considered.
The scope is focused on use outside the European Union. Products for diseases such as HIV/AIDS, malaria, or tuberculosis, as well as for maternal and newborn care, are particularly relevant. Before the actual application, the developer applies for eligibility for assessment. The CHMP assesses this eligibility in cooperation with the World Health Organization. This clarifies at an early stage whether the product and the intended target population fit within the framework of the procedure.
Scientific Assessment and Outcome
The CHMP evaluates the submitted products according to the same high scientific standards that apply to medicines for use in Europe. The WHO, as well as experts and national regulatory authorities from the target countries, participate in the assessment. This allows local epidemiological and disease-specific knowledge to be incorporated into the benefit-risk assessment alongside the EMA’s scientific review capacity. The involvement of the target regions is essential because the reality of care, disease burden, and context of use can differ from the EU market.
The process concludes with a scientific opinion from the EMA on the benefit-risk balance. The decision on whether a product is authorized or registered in the respective country lies with the national or regional regulatory authorities. The opinion can facilitate their decisions and WHO prequalification but does not replace them. Following an opinion, the sponsor is also subject to risk management obligations; in the event of new safety data, the EMA may re-examine the benefit-risk assessment.
Distinction from the Centralized Procedure and Compassionate Use
EU-M4all must be clearly distinguished from the centralized procedure. Following a CHMP opinion, the centralized procedure leads to a decision by the European Commission that is valid in the European Union. In contrast, EU-M4all only leads to a scientific opinion for the intended use outside the EU. It does not grant marketing authorization for the EU market, even if the same high assessment standards are applied.
EU-M4all is also not a compassionate use or hardship program. Compassionate use concerns access for specific patient groups to medicines that have not yet been authorized under special conditions. EU-M4all, on the other hand, systematically evaluates a product with the aim of supporting subsequent national or regional registration outside the EU. A developer can submit an EU-M4all application in parallel with a centralized marketing authorization application, provided the common requirements are met.
The scientific opinion is published and is intended to support regulatory decisions outside the EU. The procedure thus combines a European quality standard with the participation of the bodies that assess the application in the target context. It is particularly significant when a product is developed for a public health priority, but its primary market access is not in the European Union. The early eligibility check prevents an unsuitable product from dropping out of the process only after extensive dossier work.
Relevance for clinical trials
Clinical development for EU-M4all must convincingly take into account the target populations and the environment of the intended markets. In addition to the general quality of the evidence, differences in epidemiology, care pathways, concomitant treatment, and feasibility may be relevant. Study planning and benefit-risk argumentation should therefore make it transparent how the data can be extrapolated to the intended use outside the EU. The involvement of WHO and target region expertise can highlight questions regarding local relevance at an early stage.
Full-service CROs like Mediconomics provide support through study strategy, project management, data management, pharmacovigilance, medical writing, and regulatory affairs. Specific services include the planning of evidence relevant to the target population, the coordination of safety and risk management documentation, the preparation of clinical data for scientific assessment, and the alignment of dossier content with the requirements of parallel EU-M4all and centralized procedures.
Frequently Asked Questions (FAQ)
Does EU-M4all grant authorization in the European Union?
No. The procedure ends with a scientific opinion from the EMA for markets outside the European Union.
Who decides on registration in a target country?
The competent national or regional regulatory authorities decide on the basis of their respective legal systems.
Can EU-M4all run in parallel with the centralized procedure?
Yes. The EMA allows parallel applications if the requirements described for this purpose are met.
Regulatory References
- Regulation (EC) No. 726/2004, Article 58 – establishes the basis for scientific opinions on products for third-country markets.
- Regulation (EC) No. 726/2004, Articles 5 to 10 – regulates the centralized procedure, which is distinct from this.
- Regulation (EC) No. 726/2004, Article 83 – concerns the compassionate use procedure, which is different from this.
- EMA procedural guidance on EU-M4all – explains eligibility testing, assessment, and opinion.
