质量管理前沿领域 － TQMS 简介

1. 质量管理前沿领域 －TQMS简介 全面质量管理系统 Total Quality Management

2. Total Quality Management System (TQMS)AstraZeneca Solid Dosage Facility, Plankstadt, Germany Ali Afnan AstraZeneca Pharmaceuticals Engineering Group Alderley House, Alderley Park Macclesfield, UK ali.afnan@astrazeneca.com

3. Implementation of the TQM Strategy In-Process Control & Monitoring • Key Process Operations • Identification / specification of all incoming raw materials in the dispensaries (& the warehouse) • Fluid Bed Drier end point control • Continuous in-line monitoring of blending & end point control • In-line monitoring of Tablet Quality parameters against registered specifications • 21CFR11 compliant data management system • Real-time continuous quality assurance • The platform for parametric release

4. TQMS Benefits- I • Enhanced product quality assurance • Significant manufacturing cost reduction • Reduction of product inventory • The elimination of end-of-line off-line testing • providing opportunity for a new way of working • significant increase in supply chain velocity • Reduces business risk • Increases competitive advantage • Allows “remote” regulatory inspection

5. TQMS- Dispensaries • Systems approach • NIR Analyser • Brimrose AOTF Multiplexed Analyser • Diffuse reflectance measurement (1100-2300 nm) • CIP and WIP probes • Performs the analyses at every dispensing operation • Allows control of recipe management • Release of incoming materials by the plant • Utilising • Bespoke 21CFR11 compliant software • Local panel PC’s • Barcode readers

6. TQMS- Dispensary Operation • Operator scans material barcode (Article No. & Batch No.) • Analyser enabled for operation • Operator prompted through dispensing process • Trigger actuated by operator • Spectra collected with probe in-situ • I.D. reported & confirmed • Qualitative/ qualitative results reported & stored

7. TQMS- FBD • Probe permanently installed FBD • CIP and WIP probe designed to minimise fouling • Operator scans product barcode (Article No. & Batch No.) • Analyser enabled for operation • Predicted moisture values sent to FBD Control System for drying end point.

8. The Blending Process • Process of changing the constituent matrices • Mixing (re-distribution) of particles of differing: • physical characteristics / chemical properties • Process of attrition & agglomeration • A complex process • Currently under scientific scrutiny • Driving a “holistic” re-assessment of blend process understanding and means of monitoring.

9. TQMS- The Blending Process Objectives are: • To monitor the “whole” powder mix in the blending vessel • Non-invasively & non-intrusively • To determine completion of the blending process • During every blending operation • To deliver consistent quality • Applicable to a range of blender types

10. TQMS NIR Blend Monitoring System • IBC with Sapphire window • Brimrose AOTF NIR “Free-Space” Analyser • Portable • Sample (Beam) size: 9 mm x 5 mm • Diffuse reflectance (1100-2300 nm) • Battery & mains operation • CIP and WIP analyser • All solid state hardware • Provides process reproducibility • 21CFR11 compliant package

11. Analyser Interface Eliminates the need for optical coupling

12. Blending System in Position

13. Blending & Monitoring at 10 rpm

14. TQMS Blender Operation • Real-time blend monitoring for “end-point” control &/or other parameters (active or excipient) • Stop signal transmitted to blender control unit on reaching ”end point” • On returning the analyser to Docking Station, data is down-loaded to data storage system • Batteries get recharged • Analyser is in stand-by until next batch

15. TQMS- Operator Interface I

16. TQMS- Operator Interface II

17. TQMS- Operator Interface VII

18. TQMS- Operator Interface IIX

19. TQMS Tablet Analyser • Unique, novel, purpose-built Brimrose AOTF analyser • Transmission (800-1300 nm) and, • Diffuse reflectance (1100-2300 nm) • Non-destructive, real-time tablets analysis of tablets ex press prior to check weighing system • IP65 instrument • CIP and WIP analyser • Vibration resistant • Up to 30 tablets per minute, different tablet size and shapes

20. Analyser in-situ

21. Tablet Analyser- Off-line

22. TQMS Tablet Analyses • For monitoring: • Moisture • I.D. of active (& excipient) • Concentration of active (& excipient) • Dissolution • Disintegration • Hardness • Density

23. TQM System • Manufacturing Operations responsible for Quality Assurance • Quality Control @ time of manufacture • Compliance @ point of use • @ every manufacturing process • Statistical process control • @ Lower cost than existing practices • Extensive testing & Analyses per manufacturing process

24. The NIR Team Mr Robert Chisholm, Tech. Dev. Section Manager, PEG Mr Simon Blackett, Tech. Dev. Section, PEG Mr Ray Bolton, Tech. Dev. Section, PEG Dr Johann Mueller- Plant Manager, PTF, PlankstadtDr Hubert Gotta- QA Manager, PlankstadtDr Christina Gerhaeusser- QA, Plankstadt Dr Thorsten Herkert- QA, Plankstadt Mr Peter Marshall- Process Engineer, Tech. Dev. Section, PEG Mr Peter Jewitt- PTF Project Manager, PEG Mr Daniel Frick, Development IS, Molndal Mr Bengt Boissier, Development IS, Molndal Acknowledgements