(CSPOT27) A Comparative Analysis of Imposed Post-Authorization Measures for Advanced Therapy Medicinal Products Approved Between 2009-2013 in Europe and in United States of America

Background: In the contemporary regulatory landscape, regulatory agencies face the challenge of reconciling timely market authorisation for innovative medicines addressing life-threatening conditions and conducting thorough evaluations of their benefits and risks. This challenge is even more pronounced when dealing with advanced therapy medicinal products (ATMPs). Thus, both the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) have established regulatory frameworks for imposing post-authorisation measures to address uncertainties at the time of marketing authorisation, known respectively as Post-Authorisation Measures (PAMs) and Postmarketing Requirements (PMRs).

Objectives: To describe and compare the post-authorisation measures imposed by the EMA and the FDA on ATMP approvals from 2009 to 2023.

Methods: A systematic extraction of all post-authorisation measures from publicly available regulatory documents pertaining to medicinal products classified as ATMPs, approved between 2009 and 2023, in both jurisdictions, was conducted. Descriptive analysis was performed, focusing on post-authorisation measures categories, objectives, study design characteristics, and respective status and registration rates.

Results: A total of 15 ATMPs were approved by both the EMA and the FDA. The EMA imposed 53 PAMs, consisting of 34 Annex II conditions and 19 specific obligations. On the other hand, the FDA imposed 27 PMRs, predominantly required under the FDA Amendments Act authority to assess serious risks, and mainly comprised observational studies. As of December 2023, 15 out of 53 EMA-imposed PAMs were fulfilled, while no FDA PMRs demonstrated a clear fulfilled status. For both regulatory agencies, real-world data (RWD) use was promoted in approximately half of the PAMs imposed (23 by the EMA vs 15 by the FDA). Secondary use of registries data was the most frequent data source, but a considerable number of studies did not disclose enough information regarding the RWD source.

Conclusions: The study highlights disparities between the post-authorisation measures imposed by the EMA and the FDA, both in terms of quantity and nature. The EMA imposed a higher number of PAMs, covering efficacy, safety, and quality aspects; while the FDA required fewer measures, and these were mainly focused on specific safety concerns. The imposition of measures using RWD studies underscores regulators’ growing recognition of RWD for regulatory decision making. However, the information provided seems insufficient for a detailed characterisation of these measures.