ATMPs: exceptional manufacturing returns to the patient's bedside
Résumé
Since the publication of the European Regulation (No. 1394/2007) on Advanced Therapy Medicinal Products (ATMPs) in 2007, innovative therapies based on genes, cells, or tissues have reshaped the pharmaceutical landscape. While offering significant opportunities for economic and medical advances, their complex manufacturing raises specific issues on quality and regulatory issues. Detailed guidelines on Good Manufacturing Practices (GMP) specifically tailored to ATMPs have been adopted by the European Commission and have been enforceable since 2017. They address new technological developments, scientific advances, and more suitable production and distribution pathways. To date, 27 ATMPs have obtained a marketing autorisation in Europe, but most are still at the clinical trial stage although they could provide very promising options for addressing unmet medical needs. Making ATMPs accessible to patients remains challenging due to factors such as high cost, the specialized nature of ATMPs manufacturing including stringent safety and efficacy. Moreover, current healthcare infrastructures often require substantial adaptations to accommodate the logistical demands of these treatments.The Hospital Exemption (HE) is a regulatory provision of the European Regulation, that allows the use of certain ATMPs without formal central marketing authorization provided specific criteria are met: a medical prescription for an individual patient, a use within the same Member State, in a hospital setting under the exclusive responsibility of a medical practitioner, a GMP compliant manufacturing. HE implementation and oversight are regulated at the national level by the competent authority of each EU Member State. It provides a practical solution for bypassing the lengthy centralized authorization and facilitating timely access to innovations stemming from academic research and hospital initiatives. In France, a significant regulatory evolution in the field of ATMPs has been recently introduced by the decree on February 16, 2022, pursuant to French Law No. 2021-1017. It establishes a sub-exemption mechanism within the broader HE framework, specifically designed to address the practical challenges of certain ATMPs derived from autologous cells or tissues and involving no substantial manipulation. It authorizes the preparation, distribution, and administration of ATMPs, within the same medical procedure as the procurement of autologous tissues or cells used in their composition, without requiring a specially authorized manufacturing establishment, providing prior validation by the French National Agency for Medicines Safety (ANSM). By formalizing a legal framework for decentralized, bedside production, the decree aligns regulation with the practical realities of personalized medicine, favors more agile healthcare organization and fasters patient access. We aim to present and discuss the first application of this innovative regulatory framework within the MICROPREP III clinical trial (EudraCT No 2023-507683-40). This trial is designed to evaluate in 180 patients the efficacy of intra-articular injections of autologous microfat, optionally combined with autologous platelet-rich plasma (PRP), as an adjunctive therapy for patients with Knee osteoarthritis. The application of the single-step autologous ATMPs exemption needed to implement new measures and agreements between clinicians and manufacturer to ensure compliance to GMP guidelines and ATMPs quality remaining under the responsibility of the authorized establishment despite delocalization.
Domaines
| Origine | Fichiers produits par l'(les) auteur(s) |
|---|---|
| Licence |
