Projet ARMED Assessment and Risk Management of MEdical Devices in plasticized polyvinylchloride

Transcription

1 Projet ARMED Assessment and Risk Management of MEdical Devices in plasticized polyvinylchloride Evaluation et Gestion des risques liés aux Dispositifs Médicaux en polychlorure de vinyle Plastifié V. Sautou, Réunion EA 4676 C-Biosenss, 23 Octobre 2012

2 Contexte AAP ANSM (ex-afssaps): Soumission Mars 2012 Loi 30/12/2011 relative au renforcement de la sécurité sanitaire du médicament et des produits de santé Objectif: solliciter la recherche académique à but non lucratif sur des questions de sécurité, de qualité et de rapport Bénéfice / Risque des produits de santé 5 axes orientés + 1 axe libre (116 projets) Pas de recherche biomédicale Pas de développement de nouveau produit

3 Projet ARMED Contexte et justification du projet Retrait du DEHP en 2010 Substitution par divers plastifiants: pas d évaluation Objectifs Evaluation et hiérarchisation des risques liés au relargage des plastifiants à partir des DM en PVC Gestion des risques: modèles de migration, limites, modélisation mathématique* Impacts potentiels Optimiser la surveillance de la sécurité des DMS commercialisés et à Faire évoluer l évaluation de ces DMS avant commercialisation afin d anticiper un risque d exposition des patients à des composés toxiques. Financement par l ANSM:

4 Task 0 : Management and steering committee Migration : evaluation and prediction Task 1 Characterization of plasticizers in the MDs Biomonitoring Task 4: Development of analytical methods of plasticizers and their metabolites in biological fluids Task 3: Mathematical modeling Task 2: Migration et transfer analysis Task 5: Patient exposure Toxicity Informations on plasticizers/mds Quantities in MDs Migration ability Exposure doses Task 6: Cytotoxicity tests Task 7: Analysis of bibliographic data on toxicity Concentrations of plasticizers and metabolites in humans Data on plasticizers and their metabolites toxicity Task 0: Management and steering committee Plasticizers risk priorization Proposal of tolerable migration limits Proposal of acceptable quantities of plasticizers in MDs

5 Les partenaires Porteur du projet CHU Clermont-Ferrand Coordinateur scientifique: V. Sautou Services impliqués: Pharmacie, CREPTA, services cliniques (réa), DRCI Partenaires EA GRIOTT, Lille LIOAD UMR 791, Nantes Prestataires UMR 990, UDA EA 4676 C-Biosenss, UDA Casimir INRA Massy

6 C-Biosenss dans le projet Tâche 1: Caractérisation des plastifiants dans les DM Partner 1 Clermont University Hospital (Pharmacy) GC-MS Partner 2 EA GRIIOT Lille HPLC, RMN Consensus Panel Task 1.1 Development and comparaison of methods Comparaison of methods C H O I C E Identification méthods Quantification methods Task 1.2 Validation of selected method Task 1.3 Characterization of plasticizers in marketed MDs Provider 1 EA C-Biosenss Provider 2 CRT Casimir Reference document Review of plasiticizers in MDs IR, ATG GC-FID

7 C-Biosenss dans le projet Tâche 2: Migration et analyse des transferts Partner 1 Clermont University Hospital (Pharmacie) Partner 2 2 EA GRIOTT Lille Provider 2 CRT Casimir Independant experts Consensus Panel Task 2.1 Developement of migration models Migration models Proposed text for a normative basis Partner 1 Clermont University Hospital (Pharmacie) Task 2.2 Migration tests Comparison of plasticizers migration abilities Provider 1 EA C-Biosenss Task 2.3 Transfer analysis Physico-chemical database of plasticizers and plasticized PVC

8 C-Biosenss dans le projet Tâche 3: Modélisation mathématique Provider 1 EA C-Biosenss Partner 1 Clermont University Hospital (Pharmacie) Provider 2 CRT Casimir Task 3.1 Determination of diffusivity and partition parameters Task 3.2 Construction of the predictive model Provider 2 CRT Casimir INRA Database of physico-chemical properties of palsticizers and PVC to increment the model Tache 3.3 Validation of the predictive tool Provider 2 CRT Casimir INRA Predictive tool

9 Les moyens Task Partner Item Type Budget Quantity Unit Total Total per task Task 1 CHU Clermont-Ferrand Extraction method development Operating cost Task 1 CHU Clermont-Ferrand Subcontracting : Synthesis of PVC standard Operating cost Task 1 CHU Clermont-Ferrand Analytical method development Operating cost Task 1 EA GRIIOT Analytical method development Operating cost Task 1 CHU Clermont-Ferrand Method validation Operating cost Task 1 CHU Clermont-Ferrand Analysis of marketed medical device Operating cost Task 2 CHU Clermont-Ferrand Migration tests Operating cost Task 2 CHU Clermont-Ferrand Technician (year) Staff 0, Task 2 CHU Clermont-Ferrand Subcontracting : C-Biosenss (Transfert studies) Operating cost Task 2 CHU Clermont-Ferrand Master 2 (month) Staff Task 2 CHU Clermont-Ferrand Climatic chamber Equipment Task 2 CHU Clermont-Ferrand Enteral nutrition pump Equipment Task 2 CHU Clermont-Ferrand Parenteral nutrition pump Equipment Task 3 CHU Clermont-Ferrand Subcontracting : CASIMIR (Senior engineer) Staff Task 3 CHU Clermont-Ferrand Subcontracting : CASIMIR (Junior engineer) Staff Task 3 CHU Clermont-Ferrand Master 2 (month) Staff Task 3 CHU Clermont-Ferrand Master 2 (month) Staff Task 3 CHU Clermont-Ferrand Subcontracting : CASIMIR Staff Task 3 CHU Clermont-Ferrand Subcontracting : CASIMIR Operating cost Task 3 CHU Clermont-Ferrand Subcontracting : CASIMIR Travel Task 3 CHU Clermont-Ferrand Subcontracting : CASIMIR Equipment Task 4 CHU Clermont-Ferrand CREPTA : Analytical method development Operating cost Task 4 CHU Clermont-Ferrand CREPTA : Technician (year) Staff Task 4 CHU Clermont-Ferrand Subcontracting : INSERM U990 - Metabolite synthesis Operating cost Task 4 CHU Clermont-Ferrand Subcontracting : INSERM U990 - Technician (year) Staff 0, Task 5 CHU Clermont-Ferrand Clinical Research Associate Staff 1, Task 5 CHU Clermont-Ferrand Transport of biological sample Operating cost Task 5 CHU Clermont-Ferrand Insurance Operating cost Task 5 CHU Clermont-Ferrand CREPTA : Monitoring of biological sample Operating cost Task 5 CHU Clermont-Ferrand CREPTA : Technician (year) Staff Task 6 UMR INSERM U791 - LIOAD Technician (year) Staff 0,

10 ARMED/C-Biosenss Impact sécurité des DM Publications Développement de modèles utilisables pour tester autres matériaux (ex: Tubulures coatées) Matériel à disposition: enceinte climatique, pousseseringues, pompes