Abstract
The risk management system, firstly developed in industrial and transport sectors, has been recently applied also in the healthcare to ameliorate patient safety. Among available methods of risk analysis, the Failure Mode and Effects Analysis-FMEA highlights possible errors before adverse events occur and defines the actions to perform to prevent consequences. This qualitative approach can be implemented by the Failure Modes, Effects and Criticality Analysis-FMECA that quantifies errors. Recently, the FMEA/FMECA has been indicated as an option to adopt to analyze potential risks throughout the entire lifecycle of drugs, also including the class of Advanced Therapy Medicinal Products, such as cell-based medicines. Autologous Chondrocyte Implantation is a widely diffused cell-based treatment that can be used to regenerate articular cartilage. Chondrocytes for Autologous Implantation are classified as Advanced Therapy Medicinal Products (Regulation (EC) No 1394/2007), to be manufactured according to Good Manufacturing Practice. Aim of this study is to apply a FMEA/FMECA analysis on the process of ex vivo Good Manufacturing Practice chondrocyte production in a Facility located in a Public Hospital for Autologous Implantation applications. The analysis evidentiated 26 possible criticalities within the whole process (mostly human errors due to manual activity or inadequate personnel training), leading to different consequences for patients, the most dangerous of which were identified as the possibility of contamination by transmissible pathologies etiological agents, non autologous implantation and microbiological contamination. The improvement actions, implemented within 1 year of production and monitoring, allowed to decrease at least the most critical risks. Even if further evaluations and an increased number of patients are needed in order to confirm our results and reduce method’s subjectivity, this approach revealed to be a useful tool to identify and monitor potential issues during chondrocyte manual ex-vivo manufacturing in the Facility.
Keywords: Advanced therapy medicinal products, autologous chondrocyte implantation, FMEA, FMECA, good manufacturing practice, risk management.
Graphical Abstract
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