The European Medicines Agency (EMA) and the Heads of Medicines Agencies (HMA) have issued recommendations through the Executive Steering Group on Shortages and Safety of Medicinal Products (MSSG) for securing the supply of anti-D immunoglobulins used to prevent RhD immunization during pregnancy in the European Union. The supply is in trouble because the number of plasma donors has declined. Donors with anti-D immunoglobulins are the only source for manufacturing these drugs, according to EMA, and these treatments are the only option to prevent RhD immunization during pregnancy.
Key Takeaways
- Supply of anti-D immunoglobulins used to prevent RhD immunization during pregnancy is at risk in the EU. The number of immunized donors is limited and there is a decline in existing donors.
- EMA’s drug shortages steering group recommends EU Member States to create plans to secure the supply of anti-D immunoglobulins in the EU that include safety, legal, ethical, and regulatory considerations.
- Industry is encouraged to invest in manufacturing capacity and development of alternatives to plasma-derived anti-D immunoglobulins.
PhD immunization occurs, according to EMA, when a pregnant person with RhD-negative blood is exposed to RhD-positive blood from the fetus growing in their body. A potentially fatal immune reaction may result from the exposure and impact the health of the fetus as well as after the baby is born (1).
Vulnerabilities in the supply chain
During their assessment, MMSG identified the following key vulnerabilities in the supply chain (2):
- The number of immunized donors was limited and there was a decline in existing donors.
- There were challenges in the collection, manufacturing, and pooling of small plasma batches.
- Global capacity was constrained by a limited number of marketing authorization holders and centers collecting plasma for anti-D immunoglobulins.
- There was a dependency on countries outside of the EU for supply of plasma for these products.
Recommendations for regulators, industry, and other stakeholders
MMSG issued recommendations to national regulators, the European Commission, the plasma industry, and research organizations. The new recommendations are for EU Member States to create plans to secure the supply of anti-D immunoglobulins in the EU that include safety, legal, ethical, and regulatory considerations. Reducing unnecessary use through procedures such as non-invasive prenatal screening should be focused on. Alternative treatments should also be researched and developed. Communication campaigns about plasma-derived medicinal products should also be implemented.
The recommendations also state, “Member States, in collaboration with experts, including learned societies, patient organizations, and other relevant stakeholders should develop national guidelines to facilitate prioritization of patients who require these medicines during shortage situations, where necessary. The MSSG may coordinate the development of a Union level prioritization plan to manage critical shortages, coordinated at Union level” (2).
EMA stated in the press release that the EC should identify measures to ensure the supply of these treatments and coordinate with EU Member States (1). “Policy measures set out in the proposed Critical Medicines Act could be leveraged, such as joint procurement of manufacturing services to establish or increase supply of these medicines to the EU,” the agency stated in the release. The recommendations document says the EC should also “facilitate cooperation between key stakeholders, including national competent blood authorities and national competent medicines authorities to ensure coherence across relevant legislative frameworks.”
Industry is also being encouraged to ensure the supply of these treatments in Europe by investing in manufacturing capacity and development of alternatives to plasma-derived anti-D immunoglobulins.
The recommendations (2) state that the plasma industry and research organizations should “collaborate with Member States and the European Commission to identify effective mechanisms to support plasma collection and use. Consider initiatives and tools implemented by regulatory authorities to secure the supply of anti-D immunoglobulins and where needed, provide relevant data necessary for identifying and developing these mechanisms.”
References
- EMA. Strengthening Supply Chain of Anti-D Immunoglobulins. Press Release. July 4, 2025. https://www.ema.europa.eu/en/news/strengthening-supply-chain-anti-d-immunoglobulins
- EMA. Recommendations of the Executive Steering Group on Shortages and Safety of Medicinal Products to Address Anti-D Immunoglobulin Supply Chain Vulnerabilities. EMA/135603/2025. June 23, 2025. https://www.ema.europa.eu/en/documents/other/recommendations-executive-steering-group-shortages-safety-medicinal-products-address-anti-d-immunoglobulin-supply-chain-vulnerabilities_en.pdf
