Process Analytical Technologies. GE Healthcare Medical Diagnostics (Tidligere Nycomed-Amersham)

Transkript

1 Process Analytical Technologies GE Healthcare Medical Diagnostics (Tidligere Nycomed-Amersham) i Børge Mathisen Manager Process Development, Technology Development/Oslo 16. juni 2010 SF FC /1

2 History of PAT in GEHC MD, M&SC Production of existing suite of products commences. (X-ray, MRI and Ultrasound Contrast Media) FDA PAT Guidance paper The first PAT technology introduced in-line: NIR for the ultrasound product SONAZOID. Helped establish an interest. The first business case for NIR in-line in secondary production approved Implementation was on-going. Then Stopped. Starting up again in parallel with the development of a new product

3 Batch Preparation (X-Ray) Powder transfer to tank containing WFI (Water For Injection) Tanks cleaned with WFI & sanitised with Steam Finished Batch to Filling UF (Ultra Filtration) Rig to remove pyrogens Powder In

4 Process Analytical Technologies Utfordringer for bedriften Kompetanse Regulatorisk Organisasjon Økonomi Teknologi

5 Process Analytical Technologies Kompetanse Krever tilgang på meget god kunnskap om statistikk/modellering/kjemometri Krever tilgang på kunnskap om DoE Krever in-house ingeniør- og forskerkompetanse på høyt nivå Krever kompetanse på å håndtere myndigheter

6 Process Analytical Technologies Regulatorisk Et brudd med det normale for myndigheter og RA Ja takk, begge deler de første årene Komplisert submission-strategi for Real Time Release (RTR) MANGE markeder med ulike RA-mekanismer Vi produserer ikke på ordre, men på forecast - - et problem for logistikk, et problem for QA

7 Process Analytical Technologies Organisasjon Vanskelig å forstå/forklare begrepene for ledelsen Ansvaret for QbD for et nytt produkt er ikke krystallklart FoU/Utvikling/Produksjon? Hvem skal betale for ressurser og investeringer? Kravet til Time-to-market gir liten tid til PAT. Må tenkes nytt. Økende forståelse for QbD for nye og komplekse prosesser i Norge.

8 Process Analytical Technologies Økonomi Vanskelig å argumentere for investeringene Hvordan estimere lønnsomhet i et 10-års perspektiv Høye krav til lønnsomhet i GE kort forventet inntjeningshorisont Investeringslysten i Norge har vært variabel for modne prosesser Vanskelig å løpe etter en etablert prosess med QbD/PAT/DS spesielt i et lavkostland.

9 Process Analytical Technologies Teknologi/Prosess Monitorering av prosesser in-line kan kreve utvikling av avanserte analyse-, prosess- og ITsystemer. De valgte teknologier skal kunne kommunisere med hverandre og med eksisterende IT-systemer helst uten å introdusere redundancy Komplekst kan kreve implementering av mye hardware på én gang Nødvendig med en IT-strategi!

10 The Automated Plant concept PAT Operator input Electronic Batch Record = Process Specification & Process Reporting and Release Bar Code System On Line Systems - PAT - PIMS Middle ware SAP LIMS Lindesnes UV Fo NIR ph RI NIR SF FC /10

11 Business Systems Landscape CMSC - 1 to 3 Years Key Enablers to EBR Core Supply Chain - Enterprise Applications Layer Internal GE Healthcare (INTRANET) Global ERP GEHC BS SAP 4.6c Global LIMS TBD Advanced SC Planning Manugistics DMS (GxP) MEDINA Local Apps Oracle Financials/ HR PCS/PLC/ SCADA/ PAT QC Instruments e.g CDS Bar Coding Applications Middleware (WebMethods) Meta-Data MS Office Windows XP/NT BI - Data Warehouse Business Intelligence Global QMS Trackwise OP Front End/ E-Procurement (GEMS Buy) WEB PORTAL MES (TBD ) eg. PowerSuite Sales & Marketing Management SWB and/or CARS/IS Data Management Standards Consistent & Global SKU s etc Supply Chain Vendor Collaborations External GE (EXTRANET) Supply Chain Customer Collaborations SF FC /12

12 Potential System Architecture Production Thin Client PDA Browser Thick Client Barcode SCADA DCS Citrix Web Server OPC PLC I/O EBR Web Methods Citrix Scan or Refer Ticket Labs CDS Legacy Spreadsheet I/O Ticket Environment WFI Data Acquisition and Analysis Lean - SPC OEE KPI - 6sigma Performance Mgmt Building Rooms ERP HR PM DOC QMS LIMS I/O SAP Oracle Maximo Medina Trackwise Business Applications SQL LIMS Ticket SF FC /13

13 Process Analytical Technologies Eksempel på et variabelrom Process Conc. adjustment Temperature Quantity WFI ph Heat-treatment Temperature Time ph Vial filling/oversealing Temperature in hold tank Hold time Class A environment Dissolution Temperature Time ph Sequence of RM addition Ultra-filtration UF temperature Feed pump pressure Filtrate/retentate pressure Trans-membrane flux Autoclaving Temperature Time RM GE-145 DS Free iodide Endotoxins Water content Exipients Trometamol Sodium calcium edetate Calcium chloride dihydrate Sodium chloride HCl / NaOH Molarity Volume Pack material Materials of construction Dimensions DP Operator Batch record SAP Master recipe Training Equipment Materials of construction Mixing vessel heat transfer Accuracy/Validation status In-line measurement Off-line measurement Release testing Plant Analytical SF FC /14

14 Start Project t PROJEKT Design Space and PAT for NGX kv 3. Kv 4. kv 1. Kv 2. kv 3. kv 4. kv 1. kv 2. kv 3. kv Define project structure Initial Definition & Strategy Phase Q8 Q9 Q10 Q8 Q9 Q10 Studies & Data Gathering. Modelling Re-visit Goals, Strategies & Parameters Define Filing Strategy Options Suggest Filing Strategy for: Decide Filing Strategy for: Release Methods Release Methods Process Parameters Process Parameters PAT Decide RTR Parameters Studies & Data Gathering. Modelling Order In-line NIR/Raman Install & qual. completed Decide Filing Strategy for: RTR Methods Prod. For Clinical Phase 2b & Stab Prod. For Clinical Phase 3& Stab Prod. For Clinical Phase 3& Stab PV batches produced SF FC /15