Bob Chisholm

TQMS

STATISTICALLY BASED IN-PROCESS CONTROL WITH REAL TIME QUALITY ASSURANCE

The AstraZeneca Total Quality Management Strategy

R S ChisholmInternational Technology Manager

November 2001Bob.chisholm@astrazeneca.com

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

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

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

Bob Chisholm

ACTIVEDISPENSARY ( 1 )

BLENDEREXCIPIENTDISPENSARY

ACTIVEDISPENSARY ( 2 ) TABLET PRESS 1 TABLET PRESS 2

BRIMSPECT 2

BRIMSPEC

T3

BRIMSPEC

T4

BRIMSPECT

1

OM3.1

OM4.2

FLUID BED DRIER-Control System

BASESTATION

Ethernet

Bed Temperature (4-20 mA)

Bed Fluidised Signal ( digital)

Moisture Content ( 4-20 mA)

NIR Optic Fibre

Ethernet

BlendEnd Point

NIR OpticFibre

NIR OpticFibre

EthernetEthernet

NIR Probe 1.1

For FutureInstallation

NIR Probe 1.2 NIR Probe 1.3 NIR Probe 1.4

NIRSERVER

PTF Ethernet

PACMANServer

Router

Site Ethernet

NIR OpticFibre

WeighManagementSystem

Panel PC 1.3Panel PC 1.1 Panel PC 1.2 Panel PC 1.4 Panel PC 2.1 Panel PC 3.1 Panel PC 4.1

BarcodeReader 1.1

BarcodeReader 1.2

BarcodeReader 1.3

BarcodeReader 1.4

BarcodeReader 2.1

BarcodeReader 3.1

BarcodeReader 4.1

EthernetEthernet

Ethernet

Quality ControlQuality Assurance

TQM System Architecture

Bob Chisholm

A Solid Dosage Facility

FBDrier

Milling

Blender Press

Coater

Sieve

Dispensary

Wet granulation

NIRNIR

NIRNIR

NIRNIR

NIRNIR

Direct Compression

Bob Chisholm

Blend Monitoring Unit

Bob Chisholm

Tablet Analyser – Lab based

Bob Chisholm

In-line TQMS Tablet Analyser