Hurdles in gene therapy regulatory approval: a retrospective analysis of European Marketing Authorization Applications

Abstract

Gene therapy medicinal products (GTMPs) are innovative and promising treatment strategies. In Europe, the Committee for Advanced Therapies (CAT) is responsible for making marketing authorization recommendations to the Committee of Human Medicinal Products (CHMP). In the current study, we identified major objections, issues, or concerns raised during the Marketing Authorization Application (MAA) process for products resulting from the interaction of both committees between 2008 and 2017. During the first few years following CAT establishment, quality issues were often identified as major deficiencies, whereas issues at the nonclinical level appeared to be less frequent. Clinical efficacy and safety issues appeared to have a major role in unsuccessful MAA outcome for GTMPs. Most deficiencies were addressed through clarification during the MAA review or in postmarketing settings. The MAA procedure for GTMPs is complex and it is anticipated that continuous MAA submissions will further enhance the experience of both regulators and applicants, reducing the attrition rate for approval.