AstraZeneca NIR FDA Sunum

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

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 : 

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 : 

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 : 

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 : 

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 : 

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 : 

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 : 

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 : 

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 : 

Analyser Interface Eliminates the need for optical coupling

Blending System in Position : 

Blending System in Position

Blending & Monitoring at 10 rpm : 

Blending & Monitoring at 10 rpm

TQMS Blender Operation : 

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 I

TQMS- Operator Interface II : 

TQMS- Operator Interface II

TQMS- Operator Interface VII : 

TQMS- Operator Interface VII

TQMS- Operator Interface IIX : 

TQMS- Operator Interface IIX

TQMS Tablet Analyser : 

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 : 

Analyser in-situ

Tablet Analyser- Off-line : 

Tablet Analyser- Off-line

TQMS Tablet Analyses : 

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

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 TQM System

Acknowledgements : 

Acknowledgements