# Presentation: 586863

## 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**

## 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

## 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

## 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

## 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

## 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.

## 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.

## 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

## 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

## Analyser Interface

- Eliminates the need for optical coupling

## Blending System in Position

## Blending & Monitoring at 10 rpm

## 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

## TQMS- Operator Interface I

## TQMS- Operator Interface II

## TQMS- Operator Interface VII

## TQMS- Operator Interface IIX

## 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

## Analyser in-situ

## Tablet Analyser- Off-line

## TQMS Tablet Analyses

- For monitoring:
- Moisture
- I.D. of active (& excipient)
- Concentration of active (& excipient)
- Dissolution
- Disintegration
- Hardness
- Density

## 

@ every manufacturing process

- 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*

## Acknowledgements