Real-World Data Included in Post-authorisation Measures: A Case Study of Approved Advanced Therapy Medicinal Products in the European Union between 2013 and 2024

BioDrugs (2025) 39:927–941 https://doi.org/10.1007/s40259-025-00737-x ORIGINAL RESEARCH ARTICLE Real‑World Data Included in Post‑authorisation Measures: A Case Study of Approved Advanced Therapy Medicinal Products in the European Union between 2013 and 2024 Diogo Almeida1,2 · Diana Mandslay1 · Peter G. M. Mol3 · Bruno Sepodes1,2 · Carla Torre1,2 Accepted: 22 July 2025 / Published online: 26 August 2025 © The Author(s) 2025 Abstract Background Advanced therapy medicinal products (ATMPs) often require long-term monitoring to assess both safety and efficacy post-authorisation due to uncertainties identified during the approval process. This study aims to characterise the use of real-world data (RWD) in post-authorisation measures (PAMs) for ATMPs approved in the European Union. Methods A systematic extraction of all PAMs from publicly available European Medicines Agency (EMA) regulatory documents for ATMPs approved between January 2013 and December 2024 was performed, followed by the identification of the presence and sources of RWD. Additional databases including the HMA-EMA Catalogue of RWD studies and sources and ClinicalTrials.gov were consulted. Results Amongst 25 ATMPs approved by the European Commission over the study period, a total of 118 PAMs were identified, of which 49 (41.5%) involved RWD. Most RWD-PAMs were imposed by the EMA (n = 34; 69.4%), secondary data use was the most referenced data use type (n = 28; 57.1%) and registries were the main source of RWD being mentioned (n = 26; 53.1%). Further, 5 (10.2%) included a comparator group and 13 (32.5%) incorporated patient-reported outcomes. Conclusions This study emphasises the instrumental role of RWD in the post-authorisation monitoring of ATMPs in the European Union. PAMs reflect the regulatory flexibility for these products, shifting some efforts to the post-authorisation phase to address benefit–risk gaps. Enhancing the use of RWD in this context could improve evidence generation, minimise uncertainties and support more informed regulatory decisions. 1 Introduction Unlike traditional medicines, advanced therapy medicinal products (ATMPs) are derived from cells and tissues and involve complex manufacturing processes that rely on innovative technologies. Their development is particularly Bruno Sepodes and Carla Torre have contributed equally. * Carla Torre 1 Faculdade de Farmácia, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649‑003 Lisbon, Portugal 2 Laboratory of Systems Integration Pharmacology, Clinical and Regulatory Science, Research Institute for Medicines of the University of Lisbon (iMED.ULisboa), Avenida Professor Gama Pinto, 1649‑003 Lisbon, Portugal 3 Department of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands Key Points Advanced therapy medicinal products (ATMPs) are often approved under considerable uncertainties, with submissions based on limited clinical trial data, therefore requiring post-authorisation evidence to fill benefit–risk data gaps. Real-world data (RWD) plays a crucial role in the postauthorisation monitoring of ATMPs, with regulators imposing RWD-based post-authorisation measures to address long-term efficacy and safety. Despite its potential, RWD face challenges in integration, requiring reliable data sources, better transparency and early stakeholder engagement to enhance its role in decision-making. Vol.:(0123456789) 928 challenging, costly and lengthy, especially when targeting rare diseases or conditions with a high prevalence of unmet medical needs. These challenges span across manufacturing, non-clinical development, clinical trials, marketing authorisation and post-market surveillance [1, 2]. In recognition of the unique characteristics of ATMPs, the European Medicines Agency (EMA) established the Committee for Advanced Therapies (CAT) in 2009 following the implementation of Regulation 1394/2007 [3]. In 2016, the EMA introduced the PRIority MEdicines (PRIME) scheme to accelerate the development of treatments addressing unmet medical needs [4]. Whilst this framework allows for faster patient access with smaller datasets, it also needs more rigorous post-authorisation safety and efficacy monitoring [5]. Although clinical trials correspond to the major body of evidence for marketing authorisation (MA), they are inherently limited in their ability to fully represent realworld patient populations [6, 7]. Strict inclusion criteria and controlled study settings create a gap between trialgenerated data and clinical practice. To bridge this gap, real-world evidence (RWE) generated through real-world data (RWD) serves as a fundamental tool for follow-up assessments post-authorisation [7]. These data could be especially important in the context of ATMPs, as their complexity, their potential to fulfil unmet medical needs, the frequent indication for rare diseases and reliance on small, uncontrolled clinical trials contribute to the challenges of having robust evidence at the time of authorisation [8]. Given these uncertainties, long-term monitoring is crucial to ensure the safety and effectiveness of ATMPs in real-world settings. To address these concerns, the EMA issued the ‘Guideline on Safety and Efficacy Follow-up and Risk Management of Advanced Therapy Medicinal Products’, emphasising the need for continued data collection beyond initial approval [9]. In line with this, the European regulatory framework foresees the implementation of post-authorisation measures (PAMs), for which marketing authorisation holders (MAHs) are required to generate additional evidence after the marketing authorisation to further support and refine benefit–risk assessments over time [10]. Assessing the integration of RWD into PAMs is then crucial, as these data provide valuable insights into longterm efficacy and safety in routine clinical care settings, thus complementing the data obtained from clinical trials [11]. A more up-to-date analysis of RWD use in the post-authorisation setting would be highly relevant in evaluating the effectiveness of efforts by regulatory agencies, MAHs, academia, patient organisations and other stakeholders in leveraging such data for decision-making. D. Almeida et al. Amongst the various types of RWD sources, patient registries have gained increasing relevance. As structured systems for collecting uniform data on patients diagnosed with a particular condition or receiving specific treatments, registries are particularly useful for tracking disease progression, standard-of-care practices, and longterm outcomes [12]. The growing importance of these organised RWD infrastructures is reflected in the EMA’s Patient Registry Initiative, launched in 2015, which underscores the regulatory effort to harness registries as RWD sources for more informed decision-making, including in the post-authorisation setting [13]. Hence, this study aims to analyse the use of RWD in pos (...truncated)