different approaches to laboratory instrument...

Different Approaches to Laboratory Instrument

Validation

April 2012Brendan Somerville

[email protected]

mailto:[email protected]

Content

Pharmaceutical Compliance DriversQualification RequirementsQualification Life CycleGAP AnalysisAgilent ACE

Compliance Drivers – Pharmaceutical Industry

Regulations are dominated by: 1. Where Manufacturing Occurs2. Where The Compounds are Sold3. What your Quality System Includes

National GxP Regulations for 1. and 2. Apply. 3. Should Satisfy 1. and 2.

How You PerformAnalysis

Pharmacopoeias

Over 42 (Not Harmonised – General Chapters / Monographs) !

USPEPJP

ICH (International Conference on Harmonisation)

Also, CP, IP and WHO – Independent(others may be important - for specific customers !)

For Analytical Instrument QualificationIn Laboratories:

1. USP <1058> - only pharmacopeia guidance

2. Many Sources of “Opinion”3. 2 Sources (& FDA*) Dominate:

USP General Chapter <1058> and GAMP* FDA Warning Letters

What You Do RegulationsRelationship....

Qualification Requirements

PQDQ OQIQ

Does itMeet your USER

REQUIREMENTS

DesignQualification

InstallationQualification

Has it been INSTALLED CORRECTLY

OperationalQualification

PerformanceQualification

Does it WORK as YOU

EXPECTED

Will it CONTINUE to

work CORRECTLY

But, no “Set Rules”, People Don’t Agree on:• WHAT - Some of The Stages Contain• HOW - Often an OQ should be Done• WHO - Performs Some of The Stages (OQ / PQ)• WHAT - Needs to be done during the Life Cycle

4Q Stages…

Instrument Life Cycle

DQ Use

Maintenance

Breakdown

Major Upgrade /Change Use....

Repair

Re-Qualification(Justification)

Re-Qualification(Justification)

OQ

IQ

MoveRe-Location

Different IndustriesUse Different Terms:• Calibration• Qualification• Verification• Validation .. etc

Scientific DataIntegrity(common)

BM BMMaintain Documentation

of Suitability For Intended Use Throughout The Instrument Life Cycle

Co Policy

Confusing Terms……

CommonTerm Where the Term is Used

Reference /Comments

GAMP

USP <1058>

Calibration

Qualification

Validation

Verification

• Internationally Developed GUIDANCE (ISPE) Good Automated Manufacturing Process

Chapter on Analytical Instrument Qualification(AIQ) in USP.

pH MeterKF HPLC

Analytical Instruments

Manufacturing ProcessesSoftwareAnalytical Methods

“Umbrella term that encompasses all types ofapproaches to assuring systems are fit for usequalification, commissioning…… or other”

Adopted by SomeCompanies ?

ISO Definition…..GAMPISO / GAMPFDA – CFR……

USP <1058>

USPFDA

GAMPFDA, Quality Policy

ASTM E2500GAMP

……….…………………Measurement Tool(Such as Temperature Probe)

Analytical Instrument Qualification

Analytical Method Validation

System Suitability Test

QualityControl

Check Samples

Laboratory Compliance- These are not Isolated Stages…..- All are NEEDED to Prove Data VALIDITY

Components of Data Quality USP <1058>

Instrument Working Correctly

Suitable Method

METHODPerformance on the Day

Quality Control System

Analytical Results Control Strategy……..

Components of Data Quality/ Integrity

Definitions• Roles:

• User• QA• Supplier

• Responsibilities• DQ / IQ / OQ / PQ

Flexibility• What is done in OQ / PQ

Risk Management• A / B / C Categorisation

Areas of <1058>

Simplificationof the Process:

What is included in USP <1058> ?

Category A – Lowest Risk

• Specification: Manufacturer• Conformance verified and documented by

observation of operation

“ Group A includes standard equipment with no measurement capability or usual requirement for calibration, where the manufacturer's specification of basic functionality is accepted as user requirements”

Category B – Medium Risk (e.g. Balance)

“Group B includes standard equipment and instruments providing measured values as well as equipment controlling physical

parameters (such as temperature, pressure, or flow) that need calibration, where the user requirements are typically the same as the manufacturer's specification of functionality and operational limits”

Many Category B instruments MUST conform to other regulations:• <21> Thermometers• <31> Volumetric apparatus• <41> Weights and balances ..... Etc.

Category C – Complex Systems - High Risk“Group C includes instruments and computerized analytical systems, where user requirements for functionality, operational, and performance limits are specific for the analytical application”

• Full qualification process required for complex instruments and computerised systems

• Specific function and performance tests

“complicated undertaking and may require assistance of specialists”

DataIntegrity(common)

“In the context of Qualification,

The Set Points Used and Limits Need to be Justified.......”

USP, AIQ and GAMP

GAMP and USP <1058>

CommonGoals Good Issues

• Too Complex ?

• Software Focus

• Verify Vs Qualify

• Category 2 (gone)

• Over Simplified ?

• What AboutSoftware

• What AboutGroup C ……

• DQ “Ownership”

For You?

GAMP 5- 2008

AIQ <1058>- 2008

ISPE

USP

May1987

FDA Process

Validation GuideLines

• Simplify Process

• Risk by Categorisation

• Roles andResponsibilities

• Maximise use of SupplierDocumentation

• 5 pages !

• Easy to Follow

• A and B Simple

• Flexible

• Better Than 4

• Very Comprehensive

• Great For CustomSoftware

GAMP 4- 2001

• Examine your practices?

•Are you doing enough?

• Is risk analysis a good way to categorize your equipment?

•Can you simplify instrument qualification?

AAPS Round Table Discussion <1058> Nov. 2010

• 2 Hour Round Table Session – Standing Room Only (Paul Smith of Agilent was co-chair)• Three Invited Speakers - 15 Minute Presentation• 75 Minute “Open” Q&A / Discussion Forum

Horacio PappaUSP Perspective

Cindy BuhseFDA Perspective

Bob McDowallEU Perspective

Analytical Instrument Qualification: Towards Globalisation

Comparison of AAPS 2010 PresentationsHoracio PappaUSP Perspective

Cindy BuhseFDA Perspective

Bob McDowallEU Perspective

“Note that the amount of rigor applied to the qualification process will depend on the complexity and intended use of the instrumentation”

• Roles & Responsibilities• V-Model• Definitions

Why AIQ is Important Good

“AIQ is foundation for ensuring reliable and quality data”

• Top 10 Product Recalls• AIQ Warning Letters• WHY AIQ ?

• ISO 17025 – 5.52• 21CFR211 – 22, 160, 194• ICH

• Better than GAMP

• Data Triangle

• 4 Q Model

• Group B - Software

• No EP Equivalent !• <1058> Information

• ? <21>, <41> ..Etc.

• GAMP 5 Alignment ?• No Risk

Assessment !

• DQ – Who ?• Calculations ?• Software ?

USP <1058> Strategy:

Mandatory

Informational – Strong Guidance

Bad

An integral part of scientific dataintegrity:

• Qualify Instrument • Validate Method• Test Samples .....etc

Approaches to Qualification

Scientific Data Integrity ? - Prove the VALIDITY of your data ?

• The Instrument was Qualified…. Etc.

• The Method Limits Was Validated

• The Correct Reference Materials Were Used

• Training Records - The Analyst Was Trained

• System Suitability – The Method Was Working Correctly

These are all components ofthe Data Quality Triangle (USP <1058>).

Different Types of Instrument Evaluation

Suitability of Environment

Turn a dial, push a button. Set a value on the

equipment & measure what it actually does.

OperationalMeasurement

Wavelength

Flow Rate

Volume

SpeedRotation

Time

Movement

Temperature

Voltage

Test the equipment – what results does it give for a

reference material ?

ResultMeasurement

Accuracy

Samples / ApplicationsLinearity

Sensitivity

PrecisionCarry Over

Geometry

IQTemperature, Humidity, Direct Sunlight,Draughts, Support, Vibration

Services, Electrical Supply.. Etc…..

Direct - Metrology

Indirect – System Use

Component / Module

Instrument / System

Agilent Uses A Balanced Approach to

Include All These

Agilent Automated Compliance Engine (ACE)

Ace 2.0Released..

ACE is a well Established OQ Software Platform

• Faster Implementation of Varian Products• Agilent and Other Manufacturers Systems• Full System Validation Life Cycle• Full Laboratory Compliance Platform….......

Agilent Compliance Road Map

Chromatography (HPLC, GC, UPLC, GC-MS, LC-MS, QQQ)

Dissolution

And many more....... UV-VIS NMR

FT-IR AA / ICP

EfficiencyACE 2.1

1.77 protocol

1.76 protocolCoverage

Customers Decide.....

Partner Edition.....

Instrument Qualification

Simple Instruments – Such as USP <1058> Category B – CALIBRATE as your SOP

Complex Instruments – Such as USP <1058> Category C:

Qualification Principles should be universally applied (Harmonised Approach)• Management of Protocol Plans and Reports is Essential• How Failures are Managed – is Critical !

Qualification Detail:Depends on the Technology (e.g. QQQ MS Vs Dissolution Vs HPLC… etc).

Agilent Equipment Qualification Plan Documents

•Downloadable – From the Web•PDF Format•User Configurable……

Electronic Equipment Qualification Plan (EQP)

Streamlined Approval, From Plan to Report

Standard Agilent Recommended Set Points

Variance Agilent Validated Range for Set Points- User Selectable in EQP

Optional User Selectable Additional Tests……. (Extra Costs):

Part of Agilent HPLC EQP

Agilent EQP for LC-MSLC-MS QQQ (Triple Quadrupole) Qualification Plan

Tests Specific For - Instrument

Masses for Scan Verification

Summary

• Qualification Principles – are simple to understand

• Qualification – needs Specialist Capability

• USP <1058> is a key reference document

• USP Qualification needs are Evolving

• Agilent is Involved in this Evolution

• ACE makes it:• Easy to Keep Compliant • Up to date

Questions ?