EMA Is Tackling Vulnerabilities in the Supply Chain of Radiopharmaceuticals

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On 14 Apr. 2025, the European Medicines Agency (EMA) published strategic recommendations designed to strengthen the supply chain of radiopharmaceuticals (1). In the recommendations, the Executive Steering Group on Shortages and Safety of Medicinal Products (MSSG) highlighted key areas of vulnerability and proposed measures to mitigate the impact of shortages in the European Union (EU).

EU radiopharmaceutical regulations

Radiopharmaceuticals are specialised drugs that contain radioactive isotopes and are used primarily in nuclear medicine. The production and distribution of radiopharmaceuticals involves several critical processes that must adhere to stringent regulatory guidelines to ensure the safety and efficacy of these products (2). As of 2024, all radiopharmaceutical products are considered medicines in the EU, and industrially prepared products must be authorized as pharmaceuticals (3). However, country-level regulation is diverse, and the different regulatory and Health Technology Assessment (HTA) systems have led to significant differences in the use and availability of radiopharmaceuticals across the EU (4–5).

Demand for radiopharmaceuticals increasing

Radiopharmaceuticals play important roles in medical imaging, diagnosis, and treatment. Several radiopharmaceuticals have received regulatory approval for therapeutic use, and many more are in clinical development (Table I). The global radiopharmaceutical market is estimated to be worth US$6.97 billion in 2024 and is forecast to reach US$11.06 billion by 2034, as market demand increases and innovative agents reach the market (6).

Table I. Regulatory-approved radiopharmaceuticals for therapeutic use. Modified from KPMG. Leveraging Opportunities in Radiopharmaceuticals. Kpmg.com. 21 Mar. 2025.

Whilst the demand for radiopharmaceuticals is steadily increasing, the manufacturing capacity in Europe is limited, and many research reactors are ageing (8).

Manufacture of radiopharmaceuticals is complex

The production of radiopharmaceuticals relies on stable isotopes and other materials, which are mainly sourced from China, Russia, and other geopolitically sensitive areas (9). Importantly, high-assay-low-enriched uranium (HALEU), used as fuel for research reactors, is currently not produced in the EU and can only be imported from Russia or the United States. Additionally, the supply chain of these medicines, including how to transport them safely, is complex (1).

Most radiopharmaceuticals used for diagnostic purposes are produced at the time of use because they begin to decay the moment they are made (10). Manufacturers are unable to stockpile radioisotopes, which means that small fluctuations in the global supply of some isotopes can have a significant impact on manufacturing. As a result, strong supplier relationships and risk-based plans for transporting raw materials and finished radiopharmaceuticals are essential (10).

Large pharma companies, such as Bayer AG, Bracco Imaging, Cardinal Health, Curium Pharma, Eli Lilly, Lantheus Holdings, Novartis AG, and Nordion, provide radiopharmaceuticals to healthcare facilities that include hospitals, ambulatory surgical centres, clinics, and specialty hospitals (6). Companies are forming partnerships with contract development and manufacturing organisations (CDMOs) and other manufacturers to expand their reach and ensure a reliable supply chain.

MSSG recommendations for radiopharmaceuticals

To mitigate supply chain issues, the MSSG recommends:

• enhancing domestic production capabilities, including the development of EU-based HALEU enrichment and metallization facilities
• continuation and expansion of the European Radioisotope Valley Initiative (ERVI), alongside optimizing existing production installations
• harmonization of transport procedures and extended monitoring to additional radioisotopes, ensuring preparedness for rising demand
• diversifying sources of key materials to reduce geopolitical risks
• investing in modernizing and expanding EU-based production facilities
• enhancing collaborative efforts among Member States for coordinated responses (1, 11).

Recommendations to Member States and EMA

The MSSG has provided specific recommendations and invited EU Member States to assess national supply chains, address transport issues, include new radiopharmaceuticals in horizon scanning activities, and provide regulatory support (12). The recommendations also encourage EMA to offer regulatory support, assist Member States with horizon scanning, and coordinate related activities to ensure efficiency and avoid duplication of efforts (12). All stakeholders are invited to cooperate and share relevant information to help secure the EU supply of medical radioisotopes.

Ongoing initiatives

The ERVI is reviewing the EU's production capacity for metallic HALEU. It is also looking at ways to enhance the production of enriched stable isotopes, strengthen medical radionuclide production, expand the European medical radionuclide programme, and develop more reliable monitoring of supply and demand (1).

The Euratom Supply Agency (ESA) is responsible for securing the supply of source materials for radioisotopes production and is involved in theStrategic Agenda for Medical Ionising Radiation Applications, or SAMIRA. This is a comprehensive action plan to support safe, high-quality, and reliable use of radiological and nuclear technology in healthcare (13). ESA also monitors the production chain of medical radioisotopes through the European Observatory on the Supply of Medical Radioisotopes.

Radiopharmaceutical security

Given the increasing demand for isotopes and the geopolitical uncertainties surrounding supply, diversification is essential (9). The European Association of Nuclear Medicine welcomed the EMA's recommendations and was “pleased to see such a political commitment to the supply of medical radioisotopes at the highest level. As the demand for radiopharmaceuticals grows, ensuring their consistent availability is paramount for patient care across Europe” (12).

The European Parliament has already been proactive in addressing supply chain issues associated with the production of APIs and finished medicines (14), and it is now up to the MSSG to align radiopharmaceutical supplies with the EU demands through the Medicine Shortages Single Point of Contact Working Party (15).

Efforts are underway in Europe to expand stable isotope enrichment capabilities outside of Russia to help reduce dependency and enhance long-term security. In addition, new technologies are emerging that may provide alternative approaches to reactor-based production, and the construction of new research reactors, such as the PALLAS reactor in the Netherlands, will expand capacity for medical isotope production (9). However, legislative changes, such as the implementation of the Critical Medicines Act, are essential to minimize the risk of medicine shortages and safeguard the health of EU citizens moving forward (16).

References

1. EMA.Tackling Vulnerabilities in the Supply Chain of Radiopharmaceuticals in the EU.EC.europa.eu.14 Apr. 2025.
2. Open Medscience. Regulatory Radiopharmaceutical Production. 25 Sept. 2024.
3. Alira Health. Radiopharmaceuticals Landscape in Europe: Commercial and In-House Production. Alirahealth.com. (accessed May 2025).
4. Moya, E., Cerrato, C., Bedoya, L.M. et al. Radiopharmaceutical Small-scale Preparation in Europe: Will We Be Able to Harmonize the Situation?. EJNMMI Radiopharm. Chem. 2024 9, 64.
5. Regulink. The Regulatory Landscape of Radiopharmaceuticals: Ensuring Safety and Effectiveness. Regulink.com. 16 Feb. 2024
6. Future Market Insights. Radiopharmaceuticals Market. Futuremarketinsights.com. March 2024.
7. KPMG. Leveraging Opportunities in Radiopharmaceuticals. Kpmg.com. 21 Mar. 2025.
8. Walderwyss. EMA: Recommendations Regarding Vulnerabilities in the Supply Chain of Radiopharmaceuticals. Walderwyss.com. 14 Apr. 2025.
9. Nuclidx. The Geopolitical Tightrope of Medical Isotope Supply: Risks and Opportunities. LinkedIn Post. LinkedIn.com. 19 Feb. 2025
10. Bauers, J. Radiopharmaceuticals: A Guide for Manufacturers. CRBgroup.com (accessed May 2025).
11. Market Access Today. EU Takes Action to Secure Radiopharmaceutical Supply Chains. Marketaccesstoday.com. 15 Apr. 2025.
12. EANM. EMA’s Recommendations to Address Vulnerabilities in the Supply Chain of Radiopharmaceuticals. Eanm.org. April 2025.
13. EC. Supply of Medical Radioisotopes. ESA. euratom-supply.ec.europa.eu/ (accessed May 2025).
14. EP. Overreliance on Imports of Active Pharmaceutical Ingredients. Committee of Public Health. 29 Jan. 2025.
15. EMA. Medicine Shortages Single Point of Contact (SPOC) Working Party. EC.europa.eu. 11 May 2022.
16. EC. Proposal for a Critical Medicines Act. EC.europa.eu. 11 Mar. 2025.

About the author

Cheryl Barton is founder and director of PharmaVision, Pharmavision.co.uk.