Laboratory Instrument Qualification Demonstrate Suitability for use Jerry Lanese The Lanese Group, Inc. © 2015 The Lanese Group, Inc. 1 IVT Laboratory Compliance Week
Laboratory InstrumentQualification
Demonstrate Suitability for use
Jerry Lanese
The Lanese Group, Inc.
© 2015 The Lanese Group, Inc.1
IVTLaboratory Compliance Week
Why are you here?
© 2015 The Lanese Group, Inc.2
Outline
Requirement for instrument qualification
The industry solution
Maintaining qualification
Interactive exercise
© 2015 The Lanese Group, Inc.3
It is the goal of every analyst and every quality control laboratory to report data
that accurately reflect the measured parameters of the material under test.
© 2015 The Lanese Group, Inc.4
It is:
–Good business
–Good science
© 2015 The Lanese Group, Inc.5
That we provide assurance that each instrument performs as intended with appropriate uncertainty.
It is:
Also required by the regulations.
© 2015 The Lanese Group, Inc.6
Where?
© 2015 The Lanese Group, Inc.7
Where?
Automatic, mechanical, or electronic equipment or other types of equipment, including computers, or related systems that will perform a function satisfactorily, may be used in the manufacture, processing, packing, and holding of a drug product. If such equipment is so used, it shall be routinely calibrated, inspected, or checked according to a written program designed to assure proper performance. Written records of those calibration checks and inspections shall be maintained.
© 2015 The Lanese Group, Inc.8
21CFR211.68
EU
It is a GMP requirement that manufacturers control the critical aspects of their particular operations through qualification and validation over the life cycle of the product and process.
© 2015 The Lanese Group, Inc.9
Annex 15
Each laboratory should implement procedures that provide the highest level of assurance of the quality of
the data reported.
© 2015 The Lanese Group, Inc.10
Components of Data Quality
© 2015 The Lanese Group, Inc.11
Analytical Instrument Qualification
Analytical Method Validation
SystemSuitability Tests
QualityControl
Check Samples
USP <1058>
Components of Analytical Instrument Qualification
Design QualificationInstallation Qualification
Operational QualificationPerformance Qualification
4 Qs
© 2015 The Lanese Group, Inc.12
Define your terms
The boundaries of qualifications activities are fuzzy.
© 2015 The Lanese Group, Inc.13
IQ
PQ
OQDQ
Define your terms
Components of Instrument Qualification
Design QualificationInstallation Qualification
Operational QualificationPerformance Qualification
Instrument Lifecycle
15
ICH Q10 Pharmaceutical Quality System
Pharmaceutical
Development
Technology
Transfer
Commercial
Manufacturing
Product
Discontinuance
GMPInvestigational
Products
Management Responsibilities
Knowledge Management
Quality Risk Management
Process Performance and Product Quality Monitoring System
Corrective Action/Preventive Action (CAPA) System
Change Management System
Management Review
PQS
Elements
Enablers
ICH Q10 – 4 June 2008© 2015 The Lanese Group, Inc.
Components of Instrument Qualification
User RequirementsDesign Qualification
Installation QualificationOperational Qualification
Performance Qualification
© 2015 The Lanese Group, Inc.
16
Development Technology
Transfer
Commercial
Testing
Instrument
Discontinuance
Instrument Lifecycle
Stage 1
Process Design
Stage 2
Process
Qualification
Stage 3
Continued Process
Verification
Measuring Process Lifecycle
© 2015 The Lanese Group, Inc.17
Identify and document intended use
Laboratory Instrument and Equipment Lifecycle
Intended use includes:
What material will be tested?
What other analytes will be present?
What stage of the product lifecycle.
© 2015 The Lanese Group, Inc.18
19
ICH Q10 Pharmaceutical Quality System
Pharmaceutical
Development
Technology
Transfer
Commercial
Manufacturing
Product
Discontinuance
GMPInvestigational
Products
Management Responsibilities
Knowledge Management
Quality Risk Management
Process Performance and Product Quality Monitoring System
Corrective Action/Preventive Action (CAPA) System
Change Management System
Management Review
PQS
Elements
Enablers
ICH Q10 – 4 June 2008© 2015 The Lanese Group, Inc.
Intended use includes:
What material will be tested? What other analytes will be present? What stage of the product lifecycle. What stage of the production process? What attribute will be determined? What are the attribute specifications? What laboratory will be performing the test? What analysts will be performing the test?
– Education– Training– Experience
© 2015 The Lanese Group, Inc.20
© 2015 The Lanese Group, Inc.21
Identify intended use DQQualify vendor
Review Instrument capabilities
Specifications
Receive instrumentInstall IQ PQ
Laboratory Instrument and Equipment Lifecycle
Decommission
OQ
Use
© 2015 The Lanese Group, Inc.22
IQ OQ PQ
Continued use
Routine, periodic
check
Change Control
Move Instrument and original application
Change Intended
use
DQ
The 4Q Model
What should be included in the qualification?
© 2015 The Lanese Group, Inc.23
Intended use
Risk analysis
IQ OQ PQ
Change Control
The establishment of any specifications, standards, sampling, test procedures, or other laboratory control mechanisms required by this subpart, including any change in such specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms, shall be drafted by the appropriate organizational unit and reviewed and approved by the quality control unit.
© 2015 The Lanese Group, Inc.24
21CFR211.160(a)
25
ICH Q10 Pharmaceutical Quality System
Pharmaceutical
Development
Technology
Transfer
Commercial
Manufacturing
Product
Discontinuance
GMPInvestigational
Products
Management Responsibilities
Knowledge Management
Quality Risk Management
Process Performance and Product Quality Monitoring System
Corrective Action/Preventive Action (CAPA) System
Change Management System
Management Review
PQS
Elements
Enablers
ICH Q10 – 4 June 2008© 2015 The Lanese Group, Inc.
Master Plan
The organization should have a Master Plan for all validation activities. (VMP)
Site or laboratory
Includes instrument/equipment qualifications.
Provides general guidance on each step of the validation and qualification process.
Supported by specific activity SOPs
May include IQ, OQ and OQ templates.
© 2015 The Lanese Group, Inc.26
© 2015 The Lanese Group, Inc.27
Validation Master Plan
Determining intended use
Receiving new laboratory
instruments
Preparing Installation
Qualification Protocols
Archival of Qualification
Reports
Operational Qualification of Balances
Operational Qualification
of HPLCs
Handling Deviations to
Validation Protocols
Quality Review of Validation Protocols
and ReportsTrending of
Performance Qualification
Data
Qualification of Laboratory Instruments and Equipment
Items that might be included in instrument/equipment qualification master plan
Scope of the plan (total site, laboratory)
Responsibilities
Reference to related plans and procedures
Equipment that is to be qualified
Overview to the approach to qualification
Requirement and guidance for risk assessment
The steps of instrument/equipment qualification
Evaluation (qualification) of vendors
Change control
Decommissioning of instruments
Templates
© 2015 The Lanese Group, Inc.28
Design Qualification
DQ
The documented collection of activities that define the functional and operational specifications of the instrument and criteria for the selection of the vendors, based on the intended purpose of the instrument.
© 2015 The Lanese Group, Inc.29
USP <1058>
DQ should include:
Design and produce instrument that meets defined requirements.
Determine intended use.
Identify vendors who operate under a robust quality system and produces an instrument that meets intended use
Select vendor
Qualify vendor
Order
© 2015 The Lanese Group, Inc.30
Record all observations. Use templates where possible
Design QualificationPerformed by
Developer (instrument manufacturer)Robust design
Based on functional requirements
Product specifications
Discussions
User (Organization installing the unit)Understand the test process and why it was selected.
Define intended use of instrument/equipment.
Determine functional requirements and specifications.
Select and evaluate vendor.© 2015 The Lanese Group, Inc.
31
Design Qualification
VMP may include template for any or all of the information that should be collected.
© 2015 The Lanese Group, Inc.32
Understand and document the intended use of the instrument.
• Type of test
• Location
• Monitored process
• Specifications
• Technical competence of users
© 2015 The Lanese Group, Inc.33
Installation Qualification
IQ
The documented collection of activities necessary to establish that an instrument is delivered as designed and specified, and is properly installed in the selected environment, and that this environment is suitable for the instrument.
© 2015 The Lanese Group, Inc.34
USP <1058>
IQ should include:
Assure that the laboratory utilities and facility meet vendor requirements.
If critical, assure that environmental conditions are controlled and recorded.
Assure that all items listed on purchase order have been received.
Determine that there has been no damage to the instrument/equipment during shipment.
© 2015 The Lanese Group, Inc.35
Record all observations. Use templates where possible.
IQ should include:
Verify that the materials and construction are consistent with vendor specifications and user requirements.
Assure that all documents (operating manuals, maintenance and testing procedures, safety procedures, validation certificates) are present and complete.
Install hardware: fittings, tubing for fluid or gas flow, HPLC or GC columns, power cables, date or network cables, other cables.
© 2015 The Lanese Group, Inc.36
Record all observations. Use templates where possible
IQ should include:
Switch instrument and modules on. Ensure that modules power up and software boots up.
Perform any self test routines.
List equipment manuals and pertinent SOPs
Record system and component model numbers and serial numbers.
Record firmware and software revisions.
© 2015 The Lanese Group, Inc.37
Record all observations. Use templates where possible
IQ should include:
Enter instrument model number, serial number and other required instrument data into the instrument asset management database.
Prepare required installation report(s).
Prepare, review and sign IQ documentation.
© 2015 The Lanese Group, Inc.38
Record all observations. Use templates where possible
© 2015 The Lanese Group, Inc.39
IQ OQ PQ
Continued use
Routine, periodic
check
Change Control
Move Instrument and original application
Change Intended
use
DQ
Will IQ be repeated?
Operational Qualification
OQ
The documented collection of activities necessary to demonstrate that an instrument, or equipment, will function according to its operational specifications in the selected environment.
© 2015 The Lanese Group, Inc.40
USP <1058>
Operational Qualification
Typical issues:
What should be tested?
What process should be used for the testing
What are the acceptance criteria?
Who should perform the testing?
© 2015 The Lanese Group, Inc.41
Operational Qualification
USP guidance
Users, or their qualified designees, should perform appropriate tests to verify that the instrument meets manufacturer or user specifications in the user’s environment.
© 2015 The Lanese Group, Inc.42
USP <1058>
Operational Qualification
What should be tested?
Parameters that will demonstrate that the instrument is consistently operating in a state of control in conformance with applicable specifications.
© 2015 The Lanese Group, Inc.43
Operational Qualification
What process should be used for the testing?
All tests should be defined in the protocol.
Vendor protocol and testing may be used.
As much as possible rely on SOPs.
Where internal SOPs do not exist, tests should be described in detail in the protocol.
© 2015 The Lanese Group, Inc.44
Any vendor protocol or test should have appropriate internal technical
review and quality approval.
© 2015 The Lanese Group, Inc.45
Operational Qualification
What are the acceptance criteria?
Acceptance criteria should be based on the intended use of the equipment or instrument. They should be based on good science, risk and process uncertainties.
© 2015 The Lanese Group, Inc.46
Operational Qualification
Who should perform the testing?
Testing may be performed by vendors, contractors or internal resources.
All individuals involved in the qualification process should be qualified with the appropriate education, training and/or experience.
© 2015 The Lanese Group, Inc.47
Operational Qualification
Should be repeated routinely according to a program.
© 2015 The Lanese Group, Inc.48
© 2015 The Lanese Group, Inc.49
IQ OQ PQ
Continued use
Routine, periodic
check
Change Control
Move Instrument and original application
Change Intended
use
DQ
The 4Q Model
Performance Qualification
PQ
The documented collection of activities necessary to demonstrate that an instrument consistently performs according to the specifications defined by the user, and is appropriate for the intended use.
© 2015 The Lanese Group, Inc.50
USP <1058>
Continued Process Verificationis a part of
Performance Qualification
© 2015 The Lanese Group, Inc.51
Analytical Instrument Qualification
Analytical Method Validation
SystemSuitability Tests
QualityControl
Check Samples
© 2015 The Lanese Group, Inc.52
Consistent
TrendSystem capability
Statistical evaluation
53
ICH Q10 Pharmaceutical Quality System
Pharmaceutical
Development
Technology
Transfer
Commercial
Manufacturing
Product
Discontinuance
GMPInvestigational
Products
Management Responsibilities
Knowledge Management
Quality Risk Management
Process Performance and Product Quality Monitoring System
Corrective Action/Preventive Action (CAPA) System
Change Management System
Management Review
PQS
Elements
Enablers
ICH Q10 – 4 June 2008© 2015 The Lanese Group, Inc.
Performance Qualification
Conditions should replicate routine testing process.
Performed whenever instrument is used.
Frequency dependent on:
Test criticality.
Instrument and system robustness.
Component dependability.
© 2015 The Lanese Group, Inc.54
USP <1058>
RISK
Components of Instrument Qualification
Design QualificationInstallation Qualification
Operational QualificationPerformance Qualification
4 Qs
© 2015 The Lanese Group, Inc.55
The organization should develop a laboratory equipment and instrument qualification
program that covers the 4Qs.
Complete, in depth qualification of all laboratory equipment and
instruments requires extensive resources
© 2015 The Lanese Group, Inc.56
Is there an efficient way to accomplish instrument qualification?
© 2015 The Lanese Group, Inc.57
Industry recognition of the issue
Formation of an industry committee
Evaluation of the risk associated with equipment and instruments
Identification of risk groups
USP <1058>
Instrument/equipment Groups
© 2015 The Lanese Group, Inc.58
The Laboratory Instrument/Equipment World
A
C
B
Group A
Standard equipment with no measurement capability, or requirement for calibration. The manufacturers specification of the functionality is accepted as user requirement.
Nitrogen evaporators
Magnetic stirrers
Vortex mixers
centrifuges
© 2015 The Lanese Group, Inc.59
Group A
Conformance of equipment with user requirements may be verified and documented through visual observation of its operation.
© 2015 The Lanese Group, Inc.60
Basic IQLimited OQ
Group A
Magnetic stirrer
DQ
Verify that specifications for the identified stirrer demonstrate that it will stir the target liquid at the desired rpms.
IQ
Verify that ordered item and accessories were delivered.
OQ
Verify that the stirrer will stir the target liquid.
© 2015 The Lanese Group, Inc.61
Group B
Standard equipment and instruments that provide measured values. Also, equipment controlling physical parameters that need calibration where the user requirements are typically the same as the manufacturer’s specification of functionality and operational limits
© 2015 The Lanese Group, Inc.62
Group B
Balances
Melting point apparatus
Microscopes (light)
pH meters
Variable pipets
Refractometers
Thermometers
Titrators
Viscometers
© 2015 The Lanese Group, Inc.63
Muffle furnaces
Ovens
Refrigerators
Freezers
Water baths
Pumps
dilutors
Group B
© 2015 The Lanese Group, Inc.64
Conformance of the instrument or equipment to user requirements is determined in accordance with SOPs for the item. It is documented during IQ or OQ.
Basic IQDetailed OQ based on site SOPsRoutine PQ based on site SOPs
Group B
© 2015 The Lanese Group, Inc.65
Analytical balance
Careful with terminology
Group B
© 2015 The Lanese Group, Inc.66
Analytical balance
Careful with terminology
Group B
© 2015 The Lanese Group, Inc.67
Analytical balance
DQ
• Identify vendors that market analytical balances that operate in a range that meets the intended use.
• Identify which models will operate in the desired range.
• Determine if vendor provides desired support.
• Determine if marketed balance performs, in accordance with user requirements and specifications.
Group B
© 2015 The Lanese Group, Inc.68
Analytical balance
IQ
• Verify that the correct item and accessories were delivered without damage.
• Verify that the area environment is consistent with manufacturers or users requirements and USP <1251>.
• HVAC
• Free of vibration
• Free of air currents
• Low humidity
Group B
© 2015 The Lanese Group, Inc.69
Analytical balance
IQ (continued)
• Verify balance is in the appropriate asset control system.
• Verify that appropriate SOPs are in place.
• Operating
• Operational Qualification
• Calibration
• Other, as appropriate
• Performance qualification
• Weight checks
• Other, as appropriate
Group B
© 2015 The Lanese Group, Inc.70
Analytical balance
IQ (Continued)
• Verify that operators have documented and appropriate training.
• Education, training, experience
• Verify that balance is installed correctly.
• Verify that balance will turn on and execute defined start-up routine.
• Verify that appropriate standards and accessories are in place.
Group B
© 2015 The Lanese Group, Inc.71
Analytical balanceOQ
• Verify that balance performs in accordance with USP <1251>
• Mechanical mobility
• Control of stable indication
• Manually triggered or automatic adjustments
• Operation of ancillary equipment
• Tare function
• Calibration
• Sensitivity
• Linearity
• Eccentricity
• Repeatability
• Minimum weight
Group B
© 2015 The Lanese Group, Inc.72
Analytical balancePQ
• Perform check weigh procedures
• Perform other items listed in USP <1251>, as appropriate.
Group B
© 2015 The Lanese Group, Inc.73
Oven, Refrigerator, Freezer
IQ
• Verify that the correct item and accessories were delivered without damage.
• Verify that the area environment is consistent with manufacturers specifications.
• Verify item is in the appropriate asset control system.
• Verify that appropriate SOPs are in place.
• Operating
• Operational Qualification
• Calibration
• Other, as appropriate
• Performance qualification
Group B
© 2015 The Lanese Group, Inc.74
Oven, Refrigerator, Freezer
IQ (Continued)
• Verify that operators have documented and appropriate training.
• Education, training, experience
• Verify that item is installed correctly.
• Verify that item will turn on.
Group B
© 2015 The Lanese Group, Inc.75
Oven, Refrigerator, Freezer
OQ
• Turn on equipment
• Demonstrate that it will come to and hold a defined temperature. (Dependent upon intended use.)
• Where required (dependent upon intended use) map the temperatures throughout the chamber.
Group B
© 2015 The Lanese Group, Inc.76
Oven, Refrigerator, Freezer
PQ
• Monitor controlled parameter.
• Trend the parameter.
Group C
Instruments and computerized analytical systems. User requirements for functionality, operational limits and functional limits are specific to the intended use (the analytical application).
© 2015 The Lanese Group, Inc.77
Group C
Atomic absorption spectrometer Differential scanning calorimeter Thermal gravimetric analyzer Dissolution system Electron microscope HPLC GC Mass spectrometer Microplate reader X-ray fluorescence X-ray diffraction Densitometer Elemental analyzer IR and NIR spectrometer Vis/UV Spectrophotometer
© 2015 The Lanese Group, Inc.78
Group C
Conformance to user requirements is demonstrated by specific function tests and performance tests.
Installation (and qualification) of the instrument is complicated and may require assistance.
A full qualification process is required.
© 2015 The Lanese Group, Inc.79
Group C
© 2015 The Lanese Group, Inc.80
Extensive IQ
Extensive OQ – in part based on site SOPs
Routine or continuing PQ, in part based on specific test system suitability, control sample testing or specific site SOPs.
In order to have an effective instrument qualification program, other Quality System systems must be in place and functional. These include:
– Training
– Documentation (policies and procedures)
– Records
– Maintenance
– Calibration
– Deviation
– Investigation
– CAPA
– Control samples
– Total validation program
© 2015 The Lanese Group, Inc.81
Implementing the concepts
Qualification of laboratory equipment and instruments is a requirement.
© 2015 The Lanese Group, Inc.82
There is no requirement that an organization use the concepts of USP <1058>
If the organization has an adequate, alternate plan –use it.
Design and implement a system for the qualification of laboratory equipment and
instruments!
Implementing AIQ
Validation system
VMP
Instrument qualification SOP
Divide all instruments into the three categories.
Establish general procedures for the qualification of instruments in each category.
Establish procedures for specific instrument calibration, performance testing and related activities.
Create a priority list based on risk.
Qualify each instrument according to a plan.
© 2015 The Lanese Group, Inc.83
Interactive Exercise
© 2015 The Lanese Group, Inc.84
Good Luck!
Questions
© 2015 The Lanese Group, Inc.85
For further reference – start with:
A Primer:
Analytical Instrument Qualification and System Verification
By: Ludwig Huber
Agilent Technologies
© 2015 The Lanese Group, Inc.86
Laboratory InstrumentQualification
Demonstrate Suitability for use
Jerry Lanese
The Lanese Group, Inc.
© 2015 The Lanese Group, Inc.87
IVTLaboratory Compliance Week
Contact Information
Jerry LanesePh.D.
The Lanese Group, Inc.
913 915 3276
www.lanesegroup.com
© 2015 The Lanese Group, Inc.88