[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.