To describe the equipment qualification approach for medical device manufacturing

1. QUALIFICATION AND
VALIDATION
Nahri Musyrif S.Farm., Apt.
Quality Sr. Engineer
of Alcon – A Novartis Company

2. Reference
• ISPE Vol. 5, Commissioning and Qualification for New
and Renovated Facility.
• ISPE GAMP 5, A Risk-Based Approach to Compliant GxP
Computerized System.
• EU Guidelines for GMP for Medical Product for Human
and Veterinary Use – Annex 15 Qualification and
Validation

3. Definition,
• Qualification, Action of proving and documenting that equipment or
ancillary systems are properly installed, work correctly, and actually lead
to the expected results. Qualification is part of validation, but the
individual qualification steps alone do not constitute process validation.
• Validation, A documented program that provides a high degree of
assurance that a specific process, method, or system will consistently
produce a result meeting pre-determined acceptance criteria.
• Commissioning, the process of assuring that all systems and
components of a building or industrial plant are designed, installed,
tested, operated, and maintained according to the operational
requirements.
• Calibration, The demonstration that a particular instrument or device
produces results within specified limits by comparison with those
produced by a reference or traceable standard over an appropriate
range of measurements.

4. • Computer System, A group of hardware components and associated
software, designed and assembled to perform a specific function or
group of functions.
• Computerized System, A process or operation integrated with a
computer system.
Definition (continue),

5. Mix and Match?
Commissioning
Building
Utility
System
Qualification
Utility
Equipment/System
Instrumentation
Validation
Manufacturing
Process
Cleaning Process
Analytical Process
Aseptic Process
Computerized
System
Calibration
Instrument
Measured Device

6. Equipment – Computer System
Integrated Control System
e.g. PLC, Single Board Computer,
PC, which control a single system or
piece of equipment
Stand-alone System
e.g. Distributed Control System (DCS), Building
Management System (BMS), System Control and Data
Acquisition (SCADA), which link or control multiple
system and equipment

7. Equipment – Computer System
Integrated Control System
e.g. PLC, Single Board Computer,
PC, which control a single system or
piece of equipment
Stand-alone System
e.g. Distributed Control System (DCS), Building
Management System (BMS), System Control and Data
Acquisition (SCADA), which link or control multiple
system and equipment
Typically qualified with “Qualification”
approach
Typically qualified with “Validation”
approach

8. Equipment – Computer System

9. Software Category - GAMP 5 approach
Software
1. Infrastructure
Software
Layered software
Software used to manage
operating environment
3. Non-Configured
Software
Run-time parameters may
be entered and stored
Software cannot be configured
to suit business process
4. Configured
Software
Software that can be configured
by user to meet the specific needs
of business process
Software code is not
altered
5. Customized
Software
Software custom designed
and coded to suit the
business process
You can refer to ISPE GAMP 5, Appendix D5 [page 209 – 212] for the testing
applied to different categories of systems

10. Commissioning & Qualification

11. Commissioning & Qualification

12. System Impact Assessment (SIA) for System Classification
• The purpose of SIA is to focusing the qualification activity to the
system/equipment that impacted to product quality.
• Not all the system/equipment on Site needs to be qualified.

13. System Impact Assessment (SIA)

14. Component Impact Assessment (CIA)
Critical component is part of QA change control.
Installation and operation of the critical component should be verified in System
Qualification.
Critical Component also subjected to preventive maintenance and calibration
activity.

15. System Classification to Qualification Activity

16. Direct Impact System to Qualification Activity
Customized System

17. Direct Impact System to Qualification Activity
Off the Shelf (OTS) System
Equipment
Qualification
(EQ)

18. Indirect Impact System to Qualification Activity

19. Indirect Impact System to Qualification Activity

20. Refer to EU Guidelines Vol.4 Annex.15 – Qualification and Validation
1.4 The key elements of the site qualification and validation program should be
clearly defined and documented in a validation master plan (VMP) or equivalent
document
Validation Master Plan is a high level document which establishes the qualification
and validation policy to satisfy the regulatory authorities. The outline should, not
limited to:
1. Qualification and Validation Strategy
2. Organization structure, role, and responsibility for qualification and validation
activity
3. Summary of facility, equipment, system, and process on Site including the validity
status
4. Change control and deviation management during qualification and validation
activity
VMP should be review periodically, to ensure all qualification and validation activity
during a certain periods is included.
Validation Master Plan

21. Validation Plan
Question:
Why we need to prepare Validation Plan if the qualification and validation strategy
was determined in Validation Master Plan?
For the large and/or complex project, separate validation plan may required to
enhance clarity for the strategy and project time line.
Validation plan may also required to the project that have a more than 1 equipment
or integrated system to be qualified or sequence the qualification and validation

22. Risk Assessment in Qualification and Validation
Why and where the Risk Assessment are placed in Qualification?

23. Risk Assessment in Qualification and Validation
GMP Requirement
Quality Risk Assessment Approach
is applied
EU GMP Guideline Vol.4
Annex 15
FDA ICH Q9 Quality
Management System
Process (FMEA)
Safety (HAZOP)

24. DQ is :
“The documented verification that the proposed design of the facilities, systems and
equipment is suitable for the intended purpose.”
Purpose of Design Qualification
To ensure the compliance of the facility/system/equipment design with GMP
Requirement, demonstrated and documented.
How to perform Design Qualification?
Requirement (EU Guideline Annex 15) :
“The requirements of the user requirements specification should be verified during
the design qualification.”
Design Qualification (DQ)

25. IQ is :
“The documented verification that the facilities, systems and equipment, as installed or
modified, comply with the approved design and the manufacturer's
recommendations.”
What items to be verified in IQ?
Not limited to:
Installation Qualification (IQ)
“Installed”
Installation
Requirement
Space Layout Drawing
Environment
Requirement
Critical
Components
Drawing
P&ID (as-built)
E&ID (as-built)
Material List
Certificate of
Calibration
Required Utilities
Control System
Installation
Hardware
Software

26. OQ is :
“The documented verification that the facilities, systems and equipment, as installed or
modified, perform as intended throughout the anticipated operating ranges.”
What the items to be verified?
Not limited to:
Installation Qualification (IQ)
“Operated”
Procedure
Sequence
Operation
Control Function
Security
System Access
Audit Trail
HMI Configuration
Back-up and
RestoreInput Output
Check (I/O)
Interlock and
Alarm
Power Loss and
Recovery
Operating Range
Critical Component
Set Point
Recipe Result Verification

27. PQ is :
“The documented verification that systems and equipment can perform effectively and
reproducibly based on the approved process method and product specification.”
What items to be verified?
It’s depend on the product specification.
The product means the product from the process/method of the system/equipment, and
it should be verifiable (can be measured). It’s not the manufacturer product.
How we link of URS and PQ?
The product specification should be described in the URS.
Performance Qualification (PQ)
System / Equipment
• Qualified IQ and OQ
Process Method
• Normal Operating
Condition
• In Operating Range
• Worst Case Batch Size
(rational)
Product Specification
• Sampling Plan (rational)

28. Gauge Repeatability and Reproducibility (R&R)
Gauge R&R is a statistical tools to investigates:
• Repeatability: How much variability in the measurement system is caused by the
measurement device.
• Reproducibility: How much variability in the measurement system is caused by
differences between operators.
Gauge R&R in scheme:
Gauge R&R is a study to identify the variable in the measurement system.
Gauge R&R cannot be considered as Performance Qualification.
Gauge R&R
Measurement
Device
Qualified
Calibrated
Method / Process
Validated
Operator

29. Qualification Review and Requalification
Qualification state of utilities, system, equipment, and the process should be maintained
through out the operation lifecycle, include for any change of the system.
Qualification State
Re-test
Specific system is required to be
tested in periodic of time
related to performance
Example: Autoclave
Sterilization, Cleanroom
performance
Review
For the system that have
routine monitoring activity
e.g. environment monitoring
review, calibration, routine
verification.
Review result can lead the
further action on re-test or
re-qualification
Re-qualification
Any changes on requirement, design, critical
component, utilities supplied that potentially
impact to system performance