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Different Approaches to
Laboratory Instrument
Validation
April 2012
Brendan Somerville
brendan_somerville@agilent.com
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Content
Pharmaceutical Compliance Drivers
Qualification Requirements
Qualification Life Cycle
GAP Analysis
Agilent ACE
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Compliance Drivers Pharmaceutical Industry
Regulations are dominated by:
1. Where Manufacturing Occurs
2. Where The Compounds are Sold
3. What your Quality System Includes
National GxP Regulations for 1. and 2. Apply. 3. Should Satisfy 1. and 2.
How You Perform
Analysis
Pharmacopoeias
Over 42 (Not Harmonised General Chapters / Monographs) !
USP
EP
JP
ICH
(International Conference on Harmonisation)
Also, CP, IP and WHO Independent
(others may be important - for specific customers !)
For Analytical Instrument Qualification
In 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
Regulations
Relationship....
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Qualification
Requirements
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PQ DQ
OQ IQ
Does it
Meet your USER
REQUIREMENTS
Design
Qualification
Installation
Qualification
Has it been
INSTALLED
CORRECTLY
Operational
Qualification
Performance
Qualification
Does it
WORK as YOU
EXPECTED
Will it
CONTINUE to
work
CORRECTLY
But, no Set Rules , People Dont 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
Move
Re-Location
Different Industries
Use Different Terms:
Calibration
Qualification
Verification
Validation .. etc
Scientific Data
Integrity
(common)
BM BM
Maintain Documentation
of Suitability For Intended
Use Throughout The
Instrument Life Cycle
Co Policy
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Confusing Terms
Common
Term
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 Meter
KF
HPLC
Analytical Instruments
Manufacturing Processes
Software
Analytical Methods
Umbrella term that encompasses all types of
approaches to assuring systems are fit for use
qualification, commissioning or other
Adopted by Some
Companies ?
ISO Definition..
GAMP
ISO / GAMP
FDA CFR
USP <1058>
USP
FDA
GAMP
FDA, Quality Policy
ASTM E2500
GAMP
.Measurement Tool
(Such as Temperature Probe)
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Analytical Instrument Qualification
Analytical Method Validation
System Suitability
Test
Quality
Control
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
METHOD
Performance 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>
Simplification
of 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
Data
Integrity
(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>
Common
Goals
Good Issues
Too Complex ?
Software Focus
Verify Vs Qualify
Category 2 (gone)
Over Simplified ?
What About
Software
What About
Group C
DQ Ownership
For
You?
GAMP 5
- 2008
AIQ <1058>
- 2008
ISPE
USP
May
1987
FDA
Process
Validation
Guide
Lines
Simplify Process
Risk by
Categorisation
Roles and
Responsibilities
Maximise use of
Supplier
Documentation
5 pages !
Easy to Follow
A and B Simple
Flexible
Better Than 4
Very
Comprehensive
Great For Custom
Software
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 Pappa
USP Perspective
Cindy Buhse
FDA Perspective
Bob McDowall
EU Perspective
Analytical Instrument Qualification: Towards Globalisation
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Comparison of AAPS 2010 Presentations
Horacio Pappa
USP Perspective
Cindy Buhse
FDA Perspective
Bob McDowall
EU 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 data
integrity:
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 of
the 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.
Operational
Measurement
Wavelength
Flow Rate
Volume
Speed
Rotation
Time
Movement
Temperature
Voltage
Test the equipment what
results does it give for a
reference material ?
Result
Measurement
Accuracy
Samples / Applications
Linearity
Sensitivity
Precision
Carry Over
Geometry
IQ
Temperature, 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 2.0
Released..
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
Efficiency
ACE 2.1
1.77 protocol
1.76 protocol
Coverage
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-MS
LC-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 ?