The European Union's dependence on imports of active pharmaceutical ingredients from third countries – challenges and EU initiatives

The European Union‘s dependence on imports of active pharmaceutical ingredients from third countries – challenges and EU initiatives Atanas Toshev1, Anna A. Mihaylova2, Vasil Madzharov3, Elina Petkova-Gueorguieva4, Bogdan Kirilov5, Dimitar Mirchev6, Stanislav Gueorguiev3 1 Ministry of Health, Sofia, Bulgaria 2 Department of Health Care Management, Faculty of Public Health, Medical University of Plovdiv, Plovdiv, Bulgaria 3 Department of Organisation and Economics of Pharmacy, Faculty of Pharmacy, Medical University of Plovdiv, Plovdiv, Bulgaria 4 Department of Health Policy and Management, Faculty of Public Health, Medical University of Sofia, Sofia, Bulgaria 5 Bulgarian Drug Agency, Sofia, Bulgaria 6 Department of languages and specialized training, Medical University of Plovdiv, Plovdiv, Bulgaria Corresponding author: Anna A. Mihaylova ([email protected]) Received 17 September 2025♦ Accepted 22 September 2025♦ Published 14 October 2025 Citation: Toshev A, Mihaylova AA, Madzharov V, Petkova-Gueorguieva E, Kirilov B, Mirchev D, Gueorguiev S (2025) The European Union‘s dependence on imports of active pharmaceutical ingredients from third countries – challenges and EU initiatives. Pharmacia 72: 1–6. https://doi.org/10.3897/pharmacia.72.e172383 Abstract The European Union’s dependence on imports of active pharmaceutical ingredients (API) from third countries has emerged as a critical challenge to the resilience of pharmaceutical supply chains and public health. Over recent decades, the production of API for generic medicines has progressively shifted outside the EU, primarily to China and India, leading to risk concentration and heightened vulnerability during global disruptions. The COVID-19 pandemic and the war in Ukraine further exacerbated the problem, illustrating how geopolitical and health crises can interrupt access to essential medicinal products. This study examines the existing regulatory frameworks and policy initiatives of the European Union aimed at diversifying supply sources, promoting domestic production, and strengthening strategic autonomy. It identifies the root causes of medicine shortages as well as potential risks to the Union’s health systems and economic security. The article underscores the need for a comprehensive and coordinated EU-level approach to ensure the security of medicine supply and to achieve greater resilience in the European pharmaceutical sector. Keywords active pharmaceutical ingredients, API, critical medicinal products, diversification, strategic autonomy, supply chains Introduction The European Union has a strong and competitive pharmaceutical sector, which occupies a leading position globally in the production of medicinal products and plays a significant role in the Union’s economy, providing employment for approximately 800,000 people (European Commission 2023). Traditionally, the EU pharmaceutical industry has been characterized by intensive research and development activities focused on innovative medicinal products, a trend that was clearly reaffirmed during the COVID-19 crisis. Copyright Toshev A et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Pharmacia 72: 1–6 DOI 10.3897/pharmacia.72.e172383 Review Article Toshev A et al.: EU Dependence on Imported APIs2 In recent decades, however, the structure of pharmaceutical production in the EU has undergone substantial transformations. While production within the Union remains primarily focused on innovative medicines requiring advanced technological capacity, highly skilled personnel, and complex manufacturing processes, a significant share of the production of active pharmaceutical ingredients (API) for generic medicines has progressively shifted outside Europe. This trend is particularly concerning given that nearly 70% of prescribed medicines in Europe are generics (Troein et al. 2024). As a result, the resilience and security of supply chains for critical medicinal products, essential for ensuring continuous patient access to treatment across the EU, are placed under serious strain. Recent global events, including the COVID-19 pandemic and armed conflict, further exacerbated existing weaknesses in European pharmaceutical supply chains. Shortages of essential medicines pose a serious threat to public health and hinder the effective functioning of healthcare systems, thereby jeopardizing timely and adequate treatment for patients (Sabogal De La Pava and Tucker 2025). An analysis of the underlying causes of medicine shortages reveals a highly complex picture that spans the entire pharmaceutical value chain – from manufacturing and quality issues to business decisions and logistical challenges to factors linked to competitiveness. Supply chain disruptions are often rooted in insufficient diversification of suppliers and the existence of vulnerable links that compromise the availability of essential ingredients and components (Shukar et al. 2021). When examining shortages of critical medicinal products – those without suitable alternatives, whose absence could cause serious harm to patients – it is essential to distinguish between generic (non-patented) and innovative (patented) medicines. Market dynamics affecting generics do not always apply to innovative products. Moreover, cost-containment policies implemented in most EU health systems, including public tenders, are frequently based on the selection of the lowest price (Grumiller et al. 2021). The COVID-19 crisis further highlighted strategic weaknesses in the EU’s capacity to secure domestic production of certain medicines. Temporary export bans imposed by third countries during the pandemic clearly illustrated the EU’s vulnerability stemming from its reliance on external suppliers of active substances (Vogler 2024; Fortune et al. 2025). This situation underscored the urgent need to prioritize economic security and supply chain resilience, as global disruptions – whether driven by health crises, geopolitical tensions, or other risk factors – can have profound consequences for the functioning of healthcare systems as well as for the social and economic stability and security of the EU. Methodology This article employs a systematic review method to examine the challenges and opportunities associated with the European Union’s dependence on imports of active pharmaceutical ingredients (API) and medicinal products from third countries. A systematic review was conducted of regulatory, institutional, and scientific literature related to the EU’s reliance on imported API. The data reviewed were extracted from various information sources and European and national regulations, including articles and official communications of the European Commission, the European Parliament, the European Medicines Agency, and the Critical Medicines Alliance, as well as publications from the scientific databases Medline, PubMed, Scopus, and Google Scholar. The review was conducted using the following keywords: active pharmaceutical ingredients, API, critical medicinal products, diversification, strategic autonomy, and supply chains. Inclusion criteria for the sources were based on their timeliness (no older than 5 years from the date of publication), relevance to the topic of shortages and the EU’s dependence on API, and the robustness of the data presented (Fig. 1). Within this framework, European and national regulatory measures aimed at strengthening supply security and achieving strategic autonomy in the pharmaceutical sector were analyzed. Figure 1. Study design. Pharmacia 72: 1–6 3 Particular attention was devoted to identifying the root causes of this dependence and its consequences, manifested in shortages of critical medicines. In addition, the review explored potential risks to public health and economic security stemming from external reliance. The analysis encompassed both existing policies and newly proposed legislative initiatives at the EU level, focusing on diversifying supply sources, stimulating domestic production, and enhancing the resilience of pharmaceutical supply chains. Results and discussion According to data from a study carried out within the framework of a joint initiative of EU Member States, funded under the “EU4Health” program, more than half of the reported cases of medicine shortages are attributable to difficulties related to the manufacturing process. This category also includes shortages arising from problems in the supply of active pharmaceutical ingredients (Fig. 2) (AEMPS and WP5 beneficiaries 2024). The issue of medicine shortages has been on the European Union’s policy agenda for nearly a decade. The Pharmaceutical Strategy for Europe, adopted in 2020, emphasized the need to establish a resilient regulatory framework for medicinal products as well as to provide additional support for the pharmaceutical industry in order to stimulate research, innovation, and technological development that respond to real therapeutic needs of patients while ensuring access to affordable and effective medicines (European Commission 2020). As part of its measures, the Strategy also envisaged the initiation of a structured dialogue addressing the industrial aspects of supply security. Launched in 2021, this initiative brought together a broad range of stakeholders, including representatives of the pharmaceutical industry (notably manufacturers of active pharmaceutical ingredients), wholesale distributors, healthcare professionals, patient organizations, and national regulatory authorities (European Commission 2021). In 2023, the European Commission presented a communication outlining specific measures to improve the prevention and mitigation of shortages of critical medicines within the EU. The document highlighted that the responsibility for ensuring sufficient quantities of medicines to meet patients’ needs lies with pharmaceutical companies, while national authorities are expected to maintain effective oversight of availability and distribution in their territories. Most cases of shortages are managed and resolved at the national level. However, in critical situations where no therapeutic alternatives exist and sustainable solutions cannot be found nationally, joint and coordinated action at the European level becomes necessary. The aim is to address supply-related challenges and to strengthen the long-term resilience of pharmaceutical supply chains across the EU. In this context, the European Commission’s 2022 communication placed particular emphasis on the need to safeguard the security of supply for essential critical medicines (European Parliament 2022). The document stressed the Figure 2. Root causes of medicine shortages in 2022 and 2023 in EU/EEA countries, grouped according to the classification of the Working Group of Single Points of Contact (Joint Action CHESSMEN). Toshev A et al.: EU Dependence on Imported APIs4 importance of compiling and publishing an EU-level list of such medicinal products prior to the final adoption of the revised pharmaceutical legislation. The first such list, developed using criteria relating to disease severity and the availability of therapeutic alternatives, was published in December 2023 by the European Commission in cooperation with the European Medicines Agency and the network of national regulatory authorities (EMA 2024). The list includes more than 270 active substances used in the treatment of a wide range of conditions, including infectious diseases, cardiovascular disorders, mental health conditions, and cancers. It serves as a starting point for an in-depth analysis of vulnerabilities in the supply chain and for identifying areas where targeted measures are required to enhance resilience and ensure supply security. The European Union’s dependence on imports of active pharmaceutical ingredients from third countries: challenges to supply security The dependence of EU Member States on imports of active pharmaceutical ingredients (API) and medicinal products from third countries represents a significant challenge to the resilience of supply chains and the safeguarding of public health within the Union. The issue has attracted growing attention in both the scientific literature and reports of European and international institutions, which analyze its scope, underlying causes, and potential policy responses. The study “International trade of pharmaceutical products and issues of national security” highlights the high degree of concentration of API production in Asia. According to the authors, up to 80% of the chemical substances required for pharmaceutical production in the EU are sourced or synthesized outside its territory, primarily in China and India (Salikova 2024). This geographical concentration creates structural vulnerabilities, raising concerns about national security and health autonomy. A 2023 report by the European Parliament reviews current API production within the EU, analyzing initiatives for reshoring manufacturing back to the Union and measures to facilitate local production of API (Fischer et al. 2023). Similarly, a factual analysis published by EFPIA in 2021 provides detailed data on production, trade, dependencies, and vulnerabilities of the pharmaceutical sector in the EU-27. Although the report stresses that the causes of medicine shortages are multifactorial, it indirectly supports the thesis that increased reliance on a small number of countries for strategically important products contributes to supply chain disruptions (Guinea and Espés 2021). In this regard, the European Commission’s report “Strategic dependencies and capacities” (2021) officially identified dependence on API as a strategic risk for the EU. The document underscores China’s critical role as a key supplier and highlights the need for diversification and reinforcement of internal production capacity for essential raw materials. A more in-depth analysis is offered in the study by Stiftung Wissenschaft und Politik (SWP) – “The EU’s open strategic autonomy in the field of pharmaceuticals” (2023), which examines dependence on Chinese imports with a particular focus on antibiotics. Given their crucial role in healthcare, potential supply disruptions could have serious consequences for public health (Bayerlein 2023). The report “Safer together: strengthening Europe’s civilian and military preparedness and readiness” by Sauli Niinistö further sheds light on critical aspects of supply chain resilience. It emphasizes the substantial vulnerabilities inherent in the global distribution of medicines, pointing out that excessive reliance on a limited number of producers or geographic regions for key API and finished medicinal products creates serious risks of shortages. The analysis also highlights how geopolitical events, natural disasters, or pandemics can rapidly disrupt these highly interconnected networks, leading to acute shortages of vital medicines. The report proposes measures such as diversifying supply sources, increasing strategic stockpiles at both national and EU levels, and improving transparency within supply chains. Such mechanisms could ensure more continuous access to critical medicines while minimizing risks to public health and security (Niinistö 2024). To address these vulnerabilities in pharmaceutical supply chains, the European Commission established the Critical Medicines Alliance (CMA) in October 2023 (HERA 2023). Designed as a consultative mechanism, the Alliance brings together a wide range of stakeholders, including representatives of EU Member States, key industries, civil society, and the scientific community. Its primary objective was to identify priority areas for action and propose solutions to strengthen the supply of critical medicines in the EU, thereby enhancing efforts to prevent and effectively manage shortages. Among its main goals are providing an inclusive and transparent platform for consultation with the European Commission and other EU decision-makers, with a focus on medicines facing the greatest vulnerabilities. In 2024, the CMA held a series of meetings, producing recommendations based on the shared expertise of Member States. On 28 February 2025, the Alliance published its strategic report, which outlined a set of proposals subsequently considered by the European Commission in drafting the Critical Medicines Act (Critical Medicines Alliance 2025). Conclusion The shortage of critical medicines and the EU’s dependence on imports of active pharmaceutical ingredients represent a serious challenge requiring supranational efforts to address what is inherently a global problem. EU initiatives, led by the European Commission, must take into account the national specificities and contexts of Member States with lower gross domestic product levels as well as the presence or absence of local pharmaceutical manufacturing capacity. Failure to do so risks concentrating financial Pharmacia 72: 1–6 5 resources primarily in Western Europe, where the pharmaceutical industry is traditionally stronger. Future mechanisms and initiatives aimed at fostering European pharmaceutical autonomy must create conditions that enable technology transfer and capacity building across different regions of the Union – for instance, between Western and Eastern Europe. Only through such an inclusive and balanced approach can the EU strengthen its resilience and ensure equitable access to medicines across all Member States. Additional information Conflict of interest The authors have declared that no competing interests exist. Ethical statements The authors declared that no clinical trials were used in the present study. The authors declared that no experiments on humans or human tissues were performed for the present study. The authors declared that no informed consent was obtained from the humans, donors or donors’ representatives participating in the study. The authors declared that no experiments on animals were performed for the present study. The authors declared that no commercially available immortalised human and animal cell lines were used in the present study. Use of AI No use of AI was reported. Funding No funding was reported. Author contributions A.T.: conceptualization of the study, patient management, manuscript drafting, and critical revisions; D.M.: literature review, data collection, and interpretation of clinical findings; V.M.: preparation of figures and discussion section; E.P.G. and B.K.: diagnostic data analysis, cardiological evaluation, and clinical correlation; A.M.: pharmacological review and contribution to manuscript editing; S.G.: supervision, final approval of the manuscript, and overall coordination of the study. All authors have read and agreed to the published version of the manuscript. Author ORCIDs Atanas Toshev https://orcid.org/0009-0001-2379-3141 Anna A. Mihaylova https://orcid.org/0000-0002-7674-6074 Elina Petkova-Gueorguieva https://orcid.org/0000-0003-14883863 Dimitar Mirchev https://orcid.org/0000-0003-2813-9787 Stanislav Gueorguiev https://orcid.org/0000-0003-0498-6172 Data availability All of the data that support the findings of this study are available in the main text. 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