Different Approaches to Laboratory Instrument...
Transcript of Different Approaches to Laboratory Instrument...
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Different Approaches to Laboratory Instrument
Validation
April 2012Brendan Somerville
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Content
Pharmaceutical Compliance DriversQualification RequirementsQualification Life CycleGAP AnalysisAgilent ACE
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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....
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Qualification Requirements
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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…
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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
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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)
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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……..
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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> ?
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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”
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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.
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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.......”
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USP, AIQ and GAMP
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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?
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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
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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
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Approaches to Qualification
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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>).
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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
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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.....
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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……
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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
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Agilent EQP for LC-MSLC-MS QQQ (Triple Quadrupole) Qualification Plan
Tests Specific For - Instrument
Masses for Scan Verification
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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
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Questions ?