Year: 2026
Type: article
Abstract: BACKGROUND: During marketing authorisation applications (MAAs), regulators assess extensive data, identifying issues and uncertainties requiring clarification before a medicine reaches the market. Despite structured reviews, quantitative evaluation of regulatory assessment complexity remains limited, constraining systematic insights into challenges of assessments. MATERIALS AND METHODS: Focusing on oncology, this study analysed the regulatory complexity of MAAs submitted to the European Medicines Agency, based mainly on the number of distinct issues raised during initial dossier assessment. Issues were disaggregated into quality, nonclinical, and clinical domains to identify primary drivers of complexity, temporal trends, and product- or pathway-specific differences. As a complementary measure, European public assessment report (EPAR) length was examined as the final public documentation of the assessment outcome. RESULTS: Between 2015 and 2024, the number of issues increased substantially across all domains (+60%), most prominently clinical issues, driven largely by efficacy-related concerns. Advanced therapy medicinal products generated more quality-related issues, reflecting complex manufacturing, whereas tumour-agnostic indications elicited more clinical issues, consistent with paradigm-shifting trial designs. Conditional marketing authorisation, introduced to manage uncertainty, was associated with higher overall issue counts. Trends in EPAR length paralleled those observed for clinical issue counts, indicating that regulatory assessment complexity during initial review is reflected in the final public documentation. CONCLUSIONS: The growing number of distinct issues raised during initial dossier assessment highlights a marked increase in regulatory complexity in oncology MAAs over the past decade. The measures capture both product-specific and systemic procedural influences, providing a quantitative foundation to inform resource allocation, process optimisation, and regulatory strategy.
Source: ESMO Open
Authors: T. Pabsch, F. Pignatti, F. Day, B. Sepodes, H. Enzmann
Language: English
Subfield: Economics and Econometrics
Domain: Social Sciences
Open Access status: gold
Estimated APC paid: $3,910
OpenAlex ID: W7161845565