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

1
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_at_astrazeneca.com

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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

3
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

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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 PCs
• 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 operator
• Spectra collected with probe in-situ
• I.D. reported confirmed
• Qualitative/ qualitative results reported
  stored

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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.

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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 agglomeration
• A complex process
• Currently under scientific scrutiny
• Driving 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 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

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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 system
• Batteries get recharged
• Analyser 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 system
• IP65 instrument
• CIP and WIP analyser
• Vibration resistant
• Up 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
• Moisture
• I.D. of active ( excipient)
• Concentration of active ( excipient)
• Dissolution
• Disintegration
• Hardness
• Density

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TQM System

• Manufacturing Operations responsible for Quality
  Assurance

• Quality Control _at_ time of manufacture

• Compliance _at_ point of use

• _at_ every manufacturing process

• Statistical process control

• _at_ Lower cost than existing practices

• Extensive testing Analyses per manufacturing
  process

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Acknowledgements