Osteochondral lesions represent one of the most complex challenges in orthopedics and traumatology, as they simultaneously involve the articular cartilage and the subchondral bone, that are two tissues with very different biological and mechanical characteristics. Current treatment options range from conservative approaches to regenerative or replacement surgical interventions and show significant limitations in terms of long-term effectiveness and restoration of joint functionality. In this context, the use of multilayer biomimetic scaffolds has emerged as one of the most promising solutions thanks to their ability to reproduce the complex architecture of the osteochondral unit and to support differentiated processes of chondrogenesis and osteogenesis. The objective of this thesis was the drafting of a complete technical file for an implantable osteochondral scaffold in compliance with the requirements of Regulation (EU) 2017/745. The activity was carried out by integrating the scientific analysis of the main scaffold manufacturing techniques with the structuring of the regulatory pathway, which included risk management, the definition of design specifications and the planning of verification, validation and clinical evaluation activities. The methodology adopted consisted of several phases: first, a critical review of the scientific literature was performed on the main techniques for fabricating porous and stratified scaffolds, assessing their potential and limitations in the osteochondral field. Then, the drafting of the key sections of the technical file was carried out through the study and application of relevant technical standards and the requirements of the MDR Regulation, supported by additional bibliographic research to identify experimental and clinical data where necessary. Particular attention was dedicated to the integration of harmonized technical standards, the application of validation methodologies for critical processes (cleaning, sterilization, packaging, transport and UDI printing) and the preparation of a clinical evaluation plan based on scientific evidence and post-market follow-up. The work led to the development of a technical file structured in its fundamental sections: analysis of general safety performance requirements, risk management plan and report, declaration of conformity, design documents, labelling and traceability, as well as planning of verification, validation and clinical evaluation activities. The result is a coherent and comprehensive document compliant with current regulatory requirements that demonstrates the complete traceability of the design and development phases of the device, from the definition of initial specifications to the transfer to production, with a systematic approach that combines regulatory rigor and technological innovation. In conclusion, this thesis highlights how the integration of scientific and regulatory aspects is essential for the development and future commercialization of new osteochondral devices, serving as a concrete example of knowledge transfer between academic research, clinical practice and industrial applications.
Le lesioni osteocondrali rappresentano una delle sfide più complesse in ortopedia e traumatologia, in quanto coinvolgono contemporaneamente la cartilagine articolare e l’osso subcondrale, due tessuti con caratteristiche biologiche e meccaniche profondamente diverse. I trattamenti oggi disponibili, che spaziano da approcci conservativi a interventi chirurgici rigenerativi o sostitutivi, mostrano importanti limitazioni in termini di efficacia a lungo termine e di ripristino della funzionalità articolare. In questo contesto, l’impiego di scaffold biomimetici multilayer si è affermato come una delle soluzioni più promettenti, grazie alla capacità di riprodurre la complessa architettura dell’unità osteocondrale e di supportare processi differenziati di condrogenesi e osteogenesi. Il presente lavoro di tesi ha avuto come obiettivo la redazione di un fascicolo tecnico completo relativo a uno scaffold osteocondrale destinato all’impianto, conforme ai requisiti del Regolamento (UE) 2017/745. L’attività è stata condotta integrando l’analisi scientifica delle principali tecniche di produzione di scaffold e la strutturazione del percorso regolatorio, comprendente la gestione dei rischi, la definizione delle specifiche di progettazione e la pianificazione delle attività di verifica, validazione e valutazione clinica. Il metodo seguito ha previsto più fasi; in primo luogo, è stata effettuata una revisione critica della letteratura scientifica sulle principali tecniche di fabbricazione di scaffold porosi e stratificati, valutandone potenzialità e limiti nell’ambito osteocondrale. Successivamente, la redazione delle sezioni cardine del fascicolo tecnico è stata effettuata attraverso lo studio e l’applicazione di norme tecniche di riferimento e dei requisiti del Regolamento MDR, con il supporto di ulteriori ricerche bibliografiche utili a identificare dati sperimentali e clinici laddove necessario. Particolare attenzione è stata dedicata all’integrazione delle norme tecniche armonizzate, all’applicazione delle metodologie di validazione dei processi critici (lavaggio, sterilizzazione, confezionamento, trasporto e stampa UDI), e alla predisposizione di un piano di valutazione clinica basato su evidenze scientifiche e follow-up post-market. Il lavoro svolto ha portato alla realizzazione di un fascicolo tecnico strutturato nelle sue parti fondamentali: analisi dei requisiti generali di sicurezza e prestazione, piano e report di gestione dei rischi, dichiarazione di conformità, documenti di progettazione, etichettatura e tracciabilità, nonché pianificazione delle attività di verifica, validazione e valutazione clinica. Il risultato è un documento coerente, organico e conforme alle richieste regolatorie vigenti che dimostra la completa tracciabilità delle fasi di progettazione e sviluppo del dispositivo, dalla definizione delle specifiche iniziali fino al trasferimento in produzione, con un approccio sistematico che coniuga rigore normativo e innovazione tecnologica. In conclusione, la tesi mette in evidenza come l’integrazione tra aspetti scientifici e regolatori sia fondamentale per lo sviluppo e la futura immissione in commercio di nuovi dispositivi osteocondrali, ponendosi come esempio concreto di trasferimento tra ricerca accademica, pratica clinica e applicazioni industriali.
The Process of Preparing the Documentation for an Osteochondral Insert: Technical File Submission in Accordance with Regulation EU 2017/745
ROSSI, CHIARA
2024/2025
Abstract
Osteochondral lesions represent one of the most complex challenges in orthopedics and traumatology, as they simultaneously involve the articular cartilage and the subchondral bone, that are two tissues with very different biological and mechanical characteristics. Current treatment options range from conservative approaches to regenerative or replacement surgical interventions and show significant limitations in terms of long-term effectiveness and restoration of joint functionality. In this context, the use of multilayer biomimetic scaffolds has emerged as one of the most promising solutions thanks to their ability to reproduce the complex architecture of the osteochondral unit and to support differentiated processes of chondrogenesis and osteogenesis. The objective of this thesis was the drafting of a complete technical file for an implantable osteochondral scaffold in compliance with the requirements of Regulation (EU) 2017/745. The activity was carried out by integrating the scientific analysis of the main scaffold manufacturing techniques with the structuring of the regulatory pathway, which included risk management, the definition of design specifications and the planning of verification, validation and clinical evaluation activities. The methodology adopted consisted of several phases: first, a critical review of the scientific literature was performed on the main techniques for fabricating porous and stratified scaffolds, assessing their potential and limitations in the osteochondral field. Then, the drafting of the key sections of the technical file was carried out through the study and application of relevant technical standards and the requirements of the MDR Regulation, supported by additional bibliographic research to identify experimental and clinical data where necessary. Particular attention was dedicated to the integration of harmonized technical standards, the application of validation methodologies for critical processes (cleaning, sterilization, packaging, transport and UDI printing) and the preparation of a clinical evaluation plan based on scientific evidence and post-market follow-up. The work led to the development of a technical file structured in its fundamental sections: analysis of general safety performance requirements, risk management plan and report, declaration of conformity, design documents, labelling and traceability, as well as planning of verification, validation and clinical evaluation activities. The result is a coherent and comprehensive document compliant with current regulatory requirements that demonstrates the complete traceability of the design and development phases of the device, from the definition of initial specifications to the transfer to production, with a systematic approach that combines regulatory rigor and technological innovation. In conclusion, this thesis highlights how the integration of scientific and regulatory aspects is essential for the development and future commercialization of new osteochondral devices, serving as a concrete example of knowledge transfer between academic research, clinical practice and industrial applications.| File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.12075/23375