Nouvelle approche de validation Novo Nordisk

Transcription

1 44 ème Congrès International SFSTP 6 et 7 juin 2012 LA CONNAISSANCE SCIENTIFIQUE AU SERVICE DE LA QUALITE PRODUIT Apports du «Quality by Design» et retours d expd expériences Nouvelle approche de validation Novo Nordisk

2 Validation and Quality Risk Management

3 Evolution réglementaire Life Cycle Approach to validation and Quality Risk ISPE: GAMP 5 (Automation & Comp. Systems) & Baseline Guide Volumes 5 &12 (C&Q, Verification) Management ICH: Q8/9/10 (Pharma Dev, QRM, Quality Systems) (Novo Nordisk New Validation Concept) ASTM: E2500 (Standard for Specs, Design, & Verif.) FDA: Qual. Systems Approach to Pharma cgmp Regs

4 New Validation Approach

5 FDA Process validation overview Manufacturing Process Validation in NN

6 A Life Cycle Approach. Development Pilot Launch Production Process Qualification Equipment & Facilities (Stage 2.1) Manufacturing Process Design (Stage 1) Process Performance Qualification (Stage 2.2) Continued Process Verification (Stage 3) Control Strategy Quality Risk Management

7 ZANDILE SIGNORIA MZAYIFANI South Africa Zandile has type 2 diabetes Validation and Quality Risk Management New Validation Approach Manufacturing Process Design Stage 1

8 11 June 2012 Purpose of Process design Stage 1 Le but de «process justification» est de démontrer que le procédé de production, fonctionnant dans les plages établies, fournira un produit répondant aux spécifications.

9 Quality in the product life cycle Quality Target Product profile (QTPP) Critical Quality Attributes (CQA) Critical Process Parameters (CPP) Production Equipment (URS & DQ) Control Strategy (CS) Les CQA et leur sévérité sont utilisés pour le QRM Un outil permettant de mettre en évidence les paramètres les plus importants S ils ont un impact signifiant sur la qualité du produit, cela permettra de contrôler ceux ci et de diminuer le risque

10 ZANDILE SIGNORIA MZAYIFANI South Africa Zandile has type 2 diabetes Validation and Quality Risk Management New Validation Approach Manufacturing Process Qualification Equipment & Facilities - Stage 2.1

11 Process qualification Equipment and facility Stage 2.1 Application au projet «FLACONS» site NN Chartres

12 Quality project strategy / Risk management URS risk assessment procurement FAT SAT IQ OQ PQ Redondance des activités Beaucoup de documents générés Analyse de criticité simpliste Planning long Coûts supérieurs CRITICAL STEP URS risk assessment procurement FAT SAT PQ supplier involment teams with experts of all départements Multi compétences inspection follow up during construction IQ OQ Accroitre le management de la qualité en amont des phases projet Mise en place d une équipe et d un planning Qualité très tôt dans le projet

13 Quality project strategy Benefices QUALITY Meilleure compréhension des procédés Meilleure maitrise des risques Esprit Qualité totale Implication de tous les experts (. fournisseur.) HUMAN RESSOURCES Management du risque Esprit d équipe Meilleures connaissances des procédés BUSINESS Pas de redondance des activités Temps de qualification réduit Coûts réduits, maitrisés

14 SPECIFICATIONS PHASE Risk Identification DESIGN AND MANUFACTURE PHASE Risk analysis Risk reduction OPERATION PHASE Risk acceptance safety risk identification ADVICES safety risk analysis (impact) USER GxP risk identification business risk identification GxP risk analysis (impact) business risk analysis (impact) Identification of critical functions and elements per system Action plan for risk reduction Evaluation acceptance of residual risk Risk management/control control system training plans documentation / instructions disaster recovery plan periodical evaluation / validation maintenance calibration plans

15 User/supplier cooperation approach BASIC DESIGN Purchasing package URS + Tech doc + Q strategy Technical and Quality alignment CONTRACT DETAILED DESIGN Quality assessment by Q PM CONSTRUCTION PHASE follow up on shop floor by engineering and technical experts COMMISSIONNIG PHASE QUALIFICATION PHASE Mid project evaluation End project evaluation Quality Status by Q PM

16 SPECIFICATIONS PHASE DESIGN AND MANUFACTURE PHASE OPERATION PHASE BASIC DESIGN DETAILED DESIGN CONSTRUCTION PHASE COMMISSIONNIG PHASE QUALIFICATION PHASE VMP URS FS Inspections follow up be on shop floor DOCUMENTATION (PROCEDURES, INSTRUCTIONS, MAINTENANCE PLAN, CALIBRATION PLAN, VALIDATION PERIODICITY.) IQ Risk assessmentcriticality impact (RAR, RCL/FMEA.) DESIGN REVIEW pre tests pre tests OQ FACTORY FACTORY ACCEPTANCE ACCEPTANCE TESTS TESTS TRAINING PQ TRAINING PPQ HANDOVER User supplier User + supplier

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18 New Validation Approach Process performance qualification - Stage 2.1

19 Number of PPQ batches Process performance qualification Old Term Process Validation (PV) New Term Process Performance Qualification (PPQ) 3 lots: ce n est plus un nombre magique! Cependant, dans la plupart des cas, 3 lots seront exécutés mais avec un rationnel. Un rationnel sera aussi nécessaire pour le nombre de lots choisis Le nombre de lots doit être suffisant pour démontrer la reproductibilité les données de laboratoire et d'études préliminaires ainsi que les données issues des études cliniques peuvent être employées pour le rationnel Le PPQ doit avoir un nombre important de prélèvements et définir quelles données doivent être collectées et évaluées La reproductibilité doit être démontrée : comparaison d un lot à l autre et variation dans un même lot

20 Validation and Quality Risk Management GERALD JOHN GARWOOD South Africa Gerald has type 2 diabetes New Validation Approach Continued Process Verification Stage 3

21 Continued Process Verification L assurance en continu que le processus demeure sous contrôle pendant la fabrication Les données devraient être statistiquement analysées et passées en revue par un personnel qualifié. Des contrôles de tendances réguliers doivent donner l assurance que les attributs de qualité sont sous contrôle

22 Continued Process Verification Review Long term Short term Annual Product Review (APR) Periodic System evaluation (PSE) Environmental monitoring Control Chart Script (CCS) Risk Review

23 Short term review process = Review of trends in control charts On-going data collection and generation of control charts from CQA To be reviewed at least every second week Evaluation meeting Document conclusions Start trend investigation Take improvement action No action needed

24 Examples of Control Charts Scrips Control charts makes it possible to: Overview and understand the process. React timely if a process is out of trend. UCL and LCL = Control chart limits USL and LSL = Specification limits

25 GERALD JOHN GARWOOD South Africa Gerald has type 2 diabetes Validation and Quality Risk Management New Validation Approach Control Strategy

26 Validation and control strategy Context The elements in the Control Strategy Process steps and parameters People Training and right competences Quality Attributes Materials DS, DP, raw materials and components Equipment Facility and equipment operating conditions Measurements In-process controls, finished product specifications and associated methods Environment Room classification and monitoring Control strategy report

27 Validation and control strategy Context Stage 3 Facility FMECA Design URS DQ PQ OQ IQ Test Stage 2.1 PSE CSR review Changes and incidents Stage 1 Stage 2.2 Short term review Process parameters Impact Assessment Process steps Process FMECA Critical PP Non critical PP Control Monitor Process justification Process Performance Qualification (PPQ) Manufacture APR Control strategy defined Control strategy verified Control strategy implemented

28 MERCI!