You are on page 1of 88

IVT

Laboratory Compliance Week

Laboratory Instrument
Qualification

Demonstrate Suitability for use


Jerry Lanese
The Lanese Group, Inc.

1
2015 The Lanese Group, Inc.
Why are you here?

2
2015 The Lanese Group, Inc.
Outline
Requirement for instrument qualification
The industry solution
Maintaining qualification
Interactive exercise

3
2015 The Lanese Group, Inc.
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.

4
2015 The Lanese Group, Inc.
It is:
Good business
Good science

That we provide assurance that


each instrument performs as
intended with appropriate
uncertainty.

5
2015 The Lanese Group, Inc.
It is:

Also required by the regulations.

6
2015 The Lanese Group, Inc.
Where?

7
2015 The Lanese Group, Inc.
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.
21CFR211.68
8
2015 The Lanese Group, Inc.
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.

Annex 15

9
2015 The Lanese Group, Inc.
Each laboratory should implement
procedures that provide the highest
level of assurance of the quality of
the data reported.

10
2015 The Lanese Group, Inc.
Components of Data Quality

Quality
Control
Check Samples
System
Suitability Tests

Analytical Method Validation

Analytical Instrument Qualification

USP <1058>
11
2015 The Lanese Group, Inc.
Components of Analytical Instrument Qualification

4 Qs

Design Qualification
Installation Qualification
Operational Qualification
Performance Qualification

Define your terms


12
2015 The Lanese Group, Inc.
The boundaries of qualifications activities are
fuzzy.

DQ IQ
OQ

PQ

Define your terms


13
2015 The Lanese Group, Inc.
Components of Instrument Qualification
Design Qualification
Installation Qualification
Operational Qualification
Performance Qualification
Instrument Lifecycle
ICH Q10 Pharmaceutical Quality System
Pharmaceutical Technology Commercial Product
Development Transfer Manufacturing Discontinuance

Investigational GMP
Products

Management Responsibilities

Process Performance and Product Quality Monitoring System


PQS Corrective Action/Preventive Action (CAPA) System
Change Management System
Elements
Management Review

Knowledge Management
Enablers
Quality Risk Management
2015 The Lanese Group, Inc. 15 ICH Q10 4 June 2008
Components of Instrument Qualification
User Requirements
Design Qualification
Installation Qualification
Operational Qualification
Performance Qualification

Instrument Lifecycle
Development Technology Commercial Instrument
Transfer Testing Discontinuance

Measuring Process Lifecycle

Stage 2 Stage 3
Stage 1 Process Continued Process
Process Design Qualification Verification
16

2015 The Lanese Group, Inc.


Laboratory Instrument and Equipment Lifecycle

Identify and document


intended use

17
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.

18
2015 The Lanese Group, Inc.
ICH Q10 Pharmaceutical Quality System
Pharmaceutical Technology Commercial Product
Development Transfer Manufacturing Discontinuance

Investigational GMP
Products

Management Responsibilities

Process Performance and Product Quality Monitoring System


PQS Corrective Action/Preventive Action (CAPA) System
Change Management System
Elements
Management Review

Knowledge Management
Enablers
Quality Risk Management
2015 The Lanese Group, Inc. 19 ICH Q10 4 June 2008
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

20
2015 The Lanese Group, Inc.
Laboratory Instrument and Equipment Lifecycle

Identify intended use DQ


Qualify vendor
Review Instrument capabilities

Specifications

Receive instrument
Install IQ OQ PQ

Decommission Use

21
2015 The Lanese Group, Inc.
The 4Q Model

DQ IQ OQ PQ

Continued
use
Routine,
Change
periodic
Control
check

Move
Instrument
and original
application
Change
Intended
use

22
2015 The Lanese Group, Inc.
What should be included in the qualification?

Intended use

Risk analysis

IQ OQ PQ

23
2015 The Lanese Group, Inc.
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.
21CFR211.160(a)
24
2015 The Lanese Group, Inc.
ICH Q10 Pharmaceutical Quality System
Pharmaceutical Technology Commercial Product
Development Transfer Manufacturing Discontinuance

Investigational GMP
Products

Management Responsibilities

Process Performance and Product Quality Monitoring System


PQS Corrective Action/Preventive Action (CAPA) System
Change Management System
Elements
Management Review

Knowledge Management
Enablers
Quality Risk Management
2015 The Lanese Group, Inc. 25 ICH Q10 4 June 2008
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.
26
2015 The Lanese Group, Inc.
Validation Master Plan
Qualification of Laboratory
Instruments and Equipment

Determining Receiving new Preparing


intended use laboratory Installation
instruments Qualification
Protocols
Operational Operational
Qualification Qualification Handling Quality Review of
of Balances of HPLCs Deviations to Validation Protocols
Validation and Reports
Trending of Protocols
Performance Archival of
Qualification Qualification
Data Reports 27
2015 The Lanese Group, Inc.
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
28
2015 The Lanese Group, Inc.
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.

USP <1058>

29
2015 The Lanese Group, Inc.
DQ should include:
Record all observations. Use templates where possible

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
30
2015 The Lanese Group, Inc.
Design Qualification
Performed 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.
31
2015 The Lanese Group, Inc.
Design Qualification

VMP may include template for any or all of


the information that should be collected.

32
2015 The Lanese Group, Inc.
Understand and document the
intended use of the instrument.

Type of test
Location
Monitored process
Specifications
Technical competence of users

33
2015 The Lanese Group, Inc.
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.

USP <1058>

34
2015 The Lanese Group, Inc.
IQ should include:
Record all observations. Use templates where possible.

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.
35
2015 The Lanese Group, Inc.
IQ should include:
Record all observations. Use templates where possible

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.
36
2015 The Lanese Group, Inc.
IQ should include:
Record all observations. Use templates where possible

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.
37
2015 The Lanese Group, Inc.
IQ should include:
Record all observations. Use templates where possible

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.

38
2015 The Lanese Group, Inc.
Will IQ be repeated?

DQ IQ OQ PQ

Continued
use
Routine,
Change
periodic
Control
check

Move
Instrument
and original
application
Change
Intended
use

39
2015 The Lanese Group, Inc.
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.

USP <1058>

40
2015 The Lanese Group, Inc.
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?

41
2015 The Lanese Group, Inc.
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 users environment.

USP <1058>

42
2015 The Lanese Group, Inc.
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.

43
2015 The Lanese Group, Inc.
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.

44
2015 The Lanese Group, Inc.
Any vendor protocol or test should
have appropriate internal technical
review and quality approval.

45
2015 The Lanese Group, Inc.
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.

46
2015 The Lanese Group, Inc.
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.

47
2015 The Lanese Group, Inc.
Operational Qualification

Should be repeated routinely


according to a program.

48
2015 The Lanese Group, Inc.
The 4Q Model

DQ IQ OQ PQ

Continued
use
Routine,
Change
periodic
Control
check

Move
Instrument
and original
application
Change
Intended
use

49
2015 The Lanese Group, Inc.
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.

USP <1058>

50
2015 The Lanese Group, Inc.
Continued Process Verification
is a part of
Performance Qualification
Quality
Control
Check Samples

System
Suitability Tests

Analytical Method Validation

Analytical Instrument Qualification

51
2015 The Lanese Group, Inc.
Consistent

Trend
System capability
Statistical evaluation
52
2015 The Lanese Group, Inc.
ICH Q10 Pharmaceutical Quality System
Pharmaceutical Technology Commercial Product
Development Transfer Manufacturing Discontinuance

Investigational GMP
Products

Management Responsibilities

Process Performance and Product Quality Monitoring System


PQS Corrective Action/Preventive Action (CAPA) System
Change Management System
Elements
Management Review

Knowledge Management
Enablers
Quality Risk Management
2015 The Lanese Group, Inc. 53 ICH Q10 4 June 2008
Performance Qualification

Conditions should replicate routine testing


process.

Performed whenever instrument is used.


Frequency dependent on:
Test criticality. RISK
Instrument and system robustness.
Component dependability.
USP <1058>

54
2015 The Lanese Group, Inc.
Components of Instrument Qualification
4 Qs

Design Qualification
Installation Qualification
Operational Qualification
Performance Qualification

The organization should develop a laboratory


equipment and instrument qualification
program that covers the 4Qs.

55
2015 The Lanese Group, Inc.
Complete, in depth qualification of
all laboratory equipment and
instruments requires extensive
resources

Is there an efficient way to


accomplish instrument qualification?

56
2015 The Lanese Group, Inc.
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 57
2015 The Lanese Group, Inc.
The Laboratory Instrument/Equipment World

A B

C
58
2015 The Lanese Group, Inc.
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

59
2015 The Lanese Group, Inc.
Group A

Conformance of equipment with user


requirements may be verified and documented
through visual observation of its operation.

Basic IQ
Limited OQ

60
2015 The Lanese Group, Inc.
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.

61
2015 The Lanese Group, Inc.
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 manufacturers
specification of functionality and operational
limits

62
2015 The Lanese Group, Inc.
Group B
Balances Muffle furnaces
Melting point apparatus Ovens
Refrigerators
Microscopes (light)
Freezers
pH meters
Water baths
Variable pipets Pumps
Refractometers dilutors
Thermometers
Titrators
Viscometers

63
2015 The Lanese Group, Inc.
Group B

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 IQ
Detailed OQ based on site SOPs
Routine PQ based on site SOPs

64
2015 The Lanese Group, Inc.
Group B
Analytical balance

Careful with terminology

65
2015 The Lanese Group, Inc.
Group B
Analytical balance

Careful with terminology

66
2015 The Lanese Group, Inc.
Group B
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.
67
2015 The Lanese Group, Inc.
Group B
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

68
2015 The Lanese Group, Inc.
Group B
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

69
2015 The Lanese Group, Inc.
Group B
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.

70
2015 The Lanese Group, Inc.
Group B
Analytical balance
OQ
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
71
2015 The Lanese Group, Inc.
Group B
Analytical balance
PQ
Perform check weigh procedures
Perform other items listed in USP <1251>, as
appropriate.

72
2015 The Lanese Group, Inc.
Group B
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
73
2015 The Lanese Group, Inc.
Group B
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.

74
2015 The Lanese Group, Inc.
Group B
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.

75
2015 The Lanese Group, Inc.
Group B
Oven, Refrigerator, Freezer
PQ
Monitor controlled parameter.
Trend the parameter.

76
2015 The Lanese Group, Inc.
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).

77
2015 The Lanese Group, Inc.
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
78
2015 The Lanese Group, Inc.
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.

79
2015 The Lanese Group, Inc.
Group C

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.

80
2015 The Lanese Group, Inc.
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

81
2015 The Lanese Group, Inc.
Implementing the concepts
Qualification of laboratory equipment and
instruments is a requirement.

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!
82
2015 The Lanese Group, Inc.
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.
83
2015 The Lanese Group, Inc.
Interactive Exercise

84
2015 The Lanese Group, Inc.
Good Luck!
Questions

85
2015 The Lanese Group, Inc.
For further reference start with:

A Primer:
Analytical Instrument Qualification and System
Verification

By: Ludwig Huber


Agilent Technologies

86
2015 The Lanese Group, Inc.
IVT
Laboratory Compliance Week

Laboratory Instrument
Qualification

Demonstrate Suitability for use


Jerry Lanese
The Lanese Group, Inc.

87
2015 The Lanese Group, Inc.
Contact Information
Jerry Lanese
Ph.D.

The Lanese Group, Inc.


913 915 3276
jerry@lanesegroup.com
www.lanesegroup.com

88
2015 The Lanese Group, Inc.