[Application of the failure mode and effects analysis (FMEA) to the pharmaceutical process of Casgevy®, an ex vivo gene therapy medicinal product for beta-thalassemia].

INTRODUCTION: Exagamglogene autotemcel (Casgevy®) is an ex vivo gene therapy medicinal product (GTMP), derived from the patient's blood stem cells, intended for the treatment of beta-thalassemia. The complexity of this advanced therapy medicinal product (ATMP) required a specific pharmaceutical process at the university hospital of Lyon. This study aims to analyze potential failure modes throughout the Casgevy® process in order to prioritize interventions that need to be implemented.

METHODS AND MATERIALS: The failure modes and effects analysis (FMEA) method, was conducted as a prospective risk-management approach. The process was mapped to identify potential failure modes and to assess them using three criteria: frequency, likelihood of detection, and severity. The resulting criticality indices (CIs) allowed us to identify the most critical failure modes and to adapt corrective and preventive actions.

RESULTS: The FMEA led to the identification of 74 failure modes across 11 key process steps. Twenty failure modes were considered as "to treat as a priority". The most critical steps were therapy access and product reconstitution. The working team proposed three types of actions to optimize the pharmaceutical circuit: organizational and collaborative measures, training programs, and, finally, material and logistical enhancements.

DISCUSSION AND CONCLUSION: This study presents an original FMECA applied to a process designed ex nihilo. While the method has its limitations, particularly concerning the inherent subjectivity of the ratings, a retrospective analysis, conducted after testing the process under real conditions, will be crucial to refine corrective actions.