1. Bob Chisholm TQMS STATISTICALLY BASED IN-PROCESS CONTROL WITH REAL TIME QUALITY ASSURANCE The AstraZeneca Total Quality Management Strategy R S Chisholm International Technology Manager November 2001 Bob.chisholm@astrazeneca.com

2. Bob Chisholm TQMS Traditional QA  Validated Processes managed by standard operation procedures  End of Batch off-line QA Testing on a small random sample TQMS  Real Time In Process Monitoring and Control  Real Time Quality Assurance statistically based throughout Batch Manufacture – Increased testing providing the Platform for parametric release

3. Bob Chisholm TQMS – THE IMPLEMENTATION OF THE STRATEGY Sponsorship by the Senior Executive Team of AZ – THE PARADIGM SHIFT Creation of a Process Analytical Centre of Excellence Integration of TQMS into design of potent product solid dosage facility sanctioned early 1999 in Plankstadt (Germany)  THE PTF PROJECT

4. Bob Chisholm IMPLEMENTATION OF THE TQM STRATEGY Statistically Based 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

5. Bob Chisholm Quality Control Quality Assurance TQM System Architecture

6. Bob Chisholm A Solid Dosage Facility FB Drier Milling Blender Press Coater Sieve Dispensary Wet granulationNIRNIR NIR NIR Direct Compression

7. Bob Chisholm Blend Monitoring Unit

8. Bob Chisholm Tablet Analyser – Lab based

9. Bob Chisholm In-line TQMS Tablet Analyser