Total Quality Management System (TQMS)AstraZeneca Solid Dosage Facility, Plankstadt, Germany

Ali AfnanAstraZenecaPharmaceuticals Engineering GroupAlderley House, Alderley ParkMacclesfield, UKali.afnan@astrazeneca.com

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Implementation of the TQM Strategy

In-Process Control & MonitoringKey Process Operations

Identification / specification of all incoming raw materials in the dispensaries (& the warehouse)Fluid Bed Drier end point controlContinuous in-line monitoring of blending & end point controlIn-line monitoring of Tablet Quality parameters against registered specifications21CFR11 compliant data management system

Real-time continuous quality assuranceThe platform for parametric release

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TQMS Benefits- I

Enhanced product quality assuranceSignificant manufacturing cost reductionReduction of product inventoryThe elimination of end-of-line off-line testing

providing opportunity for a new way of workingsignificant increase in supply chain velocity

Reduces business riskIncreases competitive advantage Allows “remote” regulatory inspection

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TQMS- Dispensaries

Systems approachNIR 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

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TQMS- Dispensary Operation

Operator scans material barcode (Article No. & Batch No.)Analyser enabled for operation

Operator prompted through dispensing process

Trigger actuated by operatorSpectra collected with probe in-situ

I.D. reported & confirmedQualitative/ qualitative results reported & stored

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TQMS- FBD

Probe permanently installed FBDCIP and WIP probe designed to minimise foulingOperator scans product barcode (Article No. & Batch No.)

Analyser enabled for operation

Predicted moisture values sent to FBD Control System for drying end point.

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The Blending Process

Process of changing the constituent matrices Mixing (re-distribution) of particles of differing:

physical characteristics / chemical properties

Process of attrition & agglomerationA complex processCurrently under scientific scrutinyDriving a “holistic” re-assessment of blend process understanding and means of monitoring.

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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

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TQMS NIR Blend Monitoring System

IBC with Sapphire windowBrimrose AOTF NIR “Free-Space” AnalyserPortableSample (Beam) size: 9 mm x 5 mmDiffuse reflectance (1100-2300 nm)Battery & mains operationCIP and WIP analyserAll solid state hardwareProvides process reproducibility21CFR11 compliant package

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Analyser Interface

Eliminates the need for optical coupling

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Blending System in Position

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Blending & Monitoring at 10 rpm

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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 systemBatteries get rechargedAnalyser is in stand-by until next batch

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TQMS- Operator Interface I

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TQMS- Operator Interface II

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TQMS- Operator Interface VII

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TQMS- Operator Interface IIX

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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 systemIP65 instrumentCIP and WIP analyserVibration resistantUp to 30 tablets per minute, different tablet size and shapes

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Analyser in-situ

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Tablet Analyser- Off-line

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TQMS Tablet Analyses

For monitoring:MoistureI.D. of active (& excipient)Concentration of active (& excipient)DissolutionDisintegrationHardnessDensity

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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

TQM System

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Acknowledgements

Dr Johann Mueller- Plant Manager, PTF, Plankstadt Dr Hubert Gotta- QA Manager, Plankstadt Dr 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

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