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[1] This post and the paper it links to were prepared at the instruction of Novartis; it reflects the views of the authors.
Radiopharmaceuticals are a special type of medicinal products. Where they are prepared industrially or by a method involving an industrial process and are intended to be placed on the market in the European Union ('EU'), they are subject to the rules of Directive 2001/83/EC on medicinal products for human use (the 'Medicines Directive'). In addition, if patients are treated with radiopharmaceuticals, account should be taken of Directive 2013/59/EURATOM (the 'Euratom Directive') which lays down basic standards for the protection of individuals against radiation exposure.
On 17 November 2025 the European Medicines Agency ("EMA") is organising a multi-stakeholder workshop on the clinical evaluation of therapeutic radiopharmaceuticals in oncology. This workshop complements a recent consultation, in October 2024, on a concept paper on the clinical evaluation of ready-to-use therapeutic radiopharmaceuticals in oncology (the 'Concept Paper'). In the Concept Paper, the EMA has proposed key items to be included in a future guideline about the clinical development of radiopharmaceuticals.
According to the Concept Paper, the scope of this new guideline is to provide specific guidance on how the key concepts of the two areas of legislation should be applied to the clinical development of therapeutic radiopharmaceuticals for marketing authorisation applications. In this respect the Concept Paper notes that the Euratom Directive requires that all medical exposures of patients for radiotherapeutic purposes, which include treatment with therapeutic radiopharmaceuticals is to be optimised and individually planned in terms of radiation exposure of target volumes vs non-target volumes. As one of the key points that needs to be addressed in the future guideline, the Concept Paper identifies the incorporation of systematic evaluation of dosimetry in the clinical development of therapeutic radiopharmaceuticals and a specification of the data requirements allowing definition of posology for individualised planning of the absorbed radiation dose.
In a paper we discuss the different scope and objectives of the Medicines Directive and the Euratom Directive and also where they meet in ensuring (i) the safety and efficacy of radiopharmaceuticals when they are placed on the market and (ii) that they are used in a manner that limits the radiation risks for patients and what this means for the nature and scope of a new EMA guideline.
In particular it discusses that while the Euratom Directive provides for safety standards to protect individuals and thus requires that medical exposure must be individually justified, optimised and planned, the Medicines Directive provides for a regulatory framework for the placing on the market of standardised medicinal products for the treatment of identified patient populations. Accordingly, the Medicines Directive requires clinical research to be conducted in a defined study population in accordance with a specific study design based on an assessment of the risk / benefit ratio of a medicinal product at a population level, i.e. the level of the target population for which the medicinal product is indicated. The results of these studies are reflected in the Summary of Product Characteristics ("SmPC") of the authorised medicinal product where these results are translated into a standardised posology which contains a recommended treatment regime for the patient population for which the product is intended. It usually provides for an initial standard dose and allows for dose modifications for subsequent doses based e.g. on adverse reactions but it does not and cannot regulate the prescription and use of these medicinal products for each and every individual patient in clinical practice.
It is ultimately for the clinician to decide whether a medicinal product, taking into account the information provided in the SmPC on the one hand and the individual patient characteristics on the other, is suitable for treatment of that individual patient.
The differences in scope and objectives do not mean, however, that there is no relationship at all between the two sets of rules. These sets of rules meet where the Medicines Directive provides for specific requirements that need to be considered in the clinical development of radiopharmaceuticals in order to gather specific data for regulatory assessment and approval, such as dosimetry data, which is then reflected in the product information to serve as a basis for the clinician to make decisions about the treatment of patients with radiopharmaceuticals in clinical practice. As such, the requirements of the Medicines Directive contribute to the objective of the Euratom Directive that where radiopharmaceuticals are used in clinical practice, information is available for the clinician as a basis to apply the principles of the Euratom Directive that medical exposure of patients for radiotherapeutic purposes needs to be individually justified (i.e. taking into account individual patient characteristics), optimised and planned.
A future guideline that is adopted by the EMA on the clinical development of therapeutic radiopharmaceuticals has to fit within this context. As for every other scientific guideline, a new guideline on the clinical development of radiopharmaceuticals cannot introduce requirements that go beyond the legal and regulatory system of which they are part. This means that it has to fit within the system of the Medicine Directive which system aims to regulate the placing on the market of standardised products with information targeted towards the relevant patient population and not tailor-made medicinal products for individual patients and which specifically does not regulate the use of medicinal products in clinical practice. Therefore, the objective of a new guideline on the clinical development of radiopharmaceuticals should be to provide more detailed guidance on the data that are to be gathered during the clinical development of the product, e.g. dosimetry data in the study population, and other data such as data on anti-tumour effect and radiation-induced toxicity in the studied population, that can be reflected in the SmPC and provided to the clinician to inform his or her decision on the treatment of the individual patient.
In this way the Medicines Directive and the Euratom Directive work together in, on the one hand, ensuring the placing on the market of new radiopharmaceutical medicinal products, and, on the other hand, ensuring that their use in clinical practice complies with the principles of the Euratom Directive that all medical exposures for radiotherapeutic purposes be optimised and individually planned.
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