Safety population size and duration of exposure prior to approval of new medicines: A database analysis of medicines centralised approved in the European Union between 2011 and 2023
Luísa Bouwman, Hubert Leufkens, Bruno Sepodes, Carla Torre
Abstract
Background
This study aims to analyse the number of patients who had been exposed to a new medicine before the approval by the European Commission (EC), as well as the number of patients studied long-term for chronic medication use. The results were compared with the International Council for Harmonisation’s (ICH) E1 guideline recommendations.
Introduction
Safety evaluation is a central component in all stages of the drug development lifecycle. Prior to the marketing authorisation of a medicine, rigorous safety monitoring and evaluations from both preclinical and clinical development phases are required. The safety profile of the product should be adequately characterized in order to obtain regulatory approval [1].
Methods
The publicly available search-database of the European Medicines Agency (EMA) was used to identify all products approved in the EU through the centralised procedure between 1 January 2011 and 31 December 2023, including those that were subsequently withdrawn or suspended [7]. We included all unique, new active substances that were approved in this period. Duplicate products were excluded.
Results
We identified 498 newly approved medicines in the period 2011–2023, of which 322 (65%) were standard (non-orphan) medicines and 176 (35%) were orphan medicines. The specific medicines and number of subjects studied are listed in Dataset S1 File.
Discussion
In our study, which included 498 medicines approved in the European Union between 2011 and 2023, the median of the total number of patients studied prior to approval was 1,787 (IQR 781–3,351) for non-orphan medicines and 333 (IQR 139–648) for orphan medicines. In the study of Duijnhoven R. et al. [6], which included 200 medicines approved between 2000 and 2010, the median of the total number of patients studied prior to approval was 1,708 (IQR 968–3,195) for non-orphan medicines and 438 (IQR 132–915) for orphan medicines.
Conclusion
The percentage of medicines approved, intended to be used chronically and for which the number of patients exposed was under the recommended threshold has risen (from 20% to 46%), compared with the previous decennium. Over the period studied, one medicine was withdrawn due to safety reasons.
Citation: Bouwman L, Leufkens H, Sepodes B, Torre C (2026) Safety population size and duration of exposure prior to approval of new medicines: A database analysis of medicines centralised approved in the European Union between 2011 and 2023. PLoS One 21(2): e0342698. https://doi.org/10.1371/journal.pone.0342698
Editor: Eshetie Melese Birru, The kids Research Institute Australia, AUSTRALIA
Received: January 21, 2025; Accepted: January 26, 2026; Published: February 9, 2026
Copyright: © 2026 Bouwman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript and its Supporting Information files.
Funding: The author(s) received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
