Qualification

Existing Paradigm

Science and Risk-Based Approach to The V model with full protocol driven documentation
Qualification of Utilities Comprehensive verification of installation and
operation against detailed specifications
Focus on all aspects not just quality outcome aspects
QA oversight and sign off of all steps
IQ and OQ are part of qualification, not seen as pre-
requisites
SeerPharma Pty Ltd
This training program is copyright to SeerPharma Pty Ltd and may not be modified, reproduced,
Repeat of vendor commissioning work
sold, loaned, hired or traded in any form without the express written permission of SeerPharma.
Regulatory inspection of evidence based on detailed
documentation, includes GEP commissioning
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Traditional / Current
Typical Qualification Documentation V Model Approach to Validation

For each unit of equipment/service typically see:

R
User Requirements Specification Independent Quality Assurance
Oversight & Release
e
Functional Specification g
u
Design Specification Process Cleaning Computer l
FAT and SAT Documents Validation Validation Validation a
t
IQ Protocol, IQ records and IQ Report o
OQ Protocol and
OQ Protocol, OQ Records and OQ Report PQ Protocol and
Report
IQ Protocol and r
Report Report
y
PQ Protocol, PQ Records and PQ Report
Deviation, Failure and Corrective Action Records URS for each Design Build R
Functional Design
Equipment Item Qualification FAT & SAT e
Signature lists etc Specification Specification
v
i
Documentation e
All (at least), edited, drafted, reviewed, approved and triple Documentationas
asEvidence
Evidenceof
ofCompliance
Compliance
w
signed

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Typical Validation Manager

Is validation really value added ?

Expensive and resource hungry

In-efficient.,
work is duplicated
Complex, multi-disciplined

Often ends up on the critical path in a

new project
Driven by regulation and the need for
compliance
Documentation as evidence

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 Compliance Risk Management
Qualification and Validation Principles
Some Industry Trends

It is a requirement of GMP that manufacturers identify

Manufacturers are now expected to know their risks what validation work is needed to prove control of the
and demonstrate how they are being managed. critical aspects of their particular operations.

More formalised risk management programs being

Significant changes to the facilities, the equipment and
put in place.
the processes, which may affect the quality of the
product, should be validated.
Slow shift from compliance focus to ensuring
patient and user safety in GMPs Regulators play
a role here A risk assessment approach should be used to
determine the scope and extent of validation.
PIC/S Code of GMP- Annex 15 Clause 1
Potential for abuse by industry - risk manage and
rationalise away real problems
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Some definitions to keep in mind A New Paradigm in Qualification

(ICH Q9 Guidance - Quality Risk Management)

Itis commonly understood that ASTM E 2500 - Standard for Specification,

risk is defined as the
combination of the probability of
occurrence of harm and the
severity of that harm.
Design & Verification of Pharmaceutical &
Biopharmaceutical Manufacturing Systems
& Equipment

The evaluation of the risk to ISPE White Paper - Risk Based Qualification
quality should ultimately link - March 2005
back to the protection of the
patient;
Note: Severity is sometimes referred to as Consequences

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Commissioning & Qualification

New Paradigm Principles
(C&Q) Principles
The current qualification process(es) add little value 1. Focus effort on what affects product quality
and is not very cost effective. (ISPE) 2. User requirements are based on the needs of the process
- not equipment
Both FDA and Industry have recognised qualification
3. Apply risk assessments to identify critical process
has become expensive, document driven and time
parameters (CPP) - start at process / product level.
consuming
4. Only CPPs will be used as the basis to define formal
For simple standard industry use equipment the qualification
required effort should be far less than for complex or 5. Different equipment = different risks = different effort
custom built equipment. 6. All activities must contribute value - not just regulatory
compliance
C & Q activity should depend on product quality driven 7. Tests should only be carried out once (not by vendors and
outcomes the manufacturer)
8. Use of qualified supplier programs - leverage their work
Use system impact assessments to eliminate or
govern qualification of in-direct or no impact systems.
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 Critical Product Quality Attributes (CQAs) Qualification to Verification
and Critical Process Parameters (CPPs) Approach

Product and Process knowledge reports identify CQAs and CPPs

and these form the basis of the Product and Process URS V Model Qualification consists of a series of IQ, OQ,
and PQ Protocols and reports
The Product and Process URS become the basis for design
Multidisciplinary team develop the URS and QA approves.
V Model Quality Assurance reviews each and every
Use risk assessment of the manufacturing process to identify Protocol / Test and involved in all non-conformances.
CPPs of interest.

ASTM Model - Subject Matter Experts** confirm that

Mitigation of unacceptable CPP risks: all acceptance criteria have been met and that the
1. Elimination by re-design of the process critical attributes are verified (fit for use). This
2. Elimination by automated control and/ or PAT
confirmation should be documented.
3. Validate out the risk
4. Elimination by procedural controls
** not necessarily a QA representative
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GEP and Commissioning Risk Based Commissioning and

(ASTM E 2500) Principles Qualification (ASTM E 2500) Flow

Product and Process Knowledge

SMEs / Engineers develop a commissioning plan based on Development Knowledge Operational
CQAs and CPPs Design / GMP Reviews Requirements
Vendors involved in commissioning Vendors
If critical elements under commissioning fail:
Refer to the SME for assessment Product User Process User Commissioning
Requirements Requirements SME Plan
QA to review impact on product and process
SME
Publish a commissioning report based on Good Engineering SME/QA
Practices. Use the report as part of the verification plan Process Performance Commission
performance testing (PT) Support SOPs Testing Testing (GEP)

Prepare a final Qualification Report (QR) after PT completion
Process SME Final Package
Validation QA of Reports
Auditable by regulators ?
Risk Assessment
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Risk Based Approach to Qualification Risk-Based Approach (Utilities)

(ASTM E 2500 standard and ICH Q9)
Engineering Change Management Does a Does
Does
QA Change Control measuring Operation /
Current Does
Function /
instrument Installation
Operation Would Are
Function / control or causes
Is it create malfunction materials of
Design involved in
Operation
(electronic) impact
measure contaminati
constructio GMP
Development Equipment Name directly quality on risk of
Product X data which directly on n in direct IMPACT
impact critical product or
Enhanced Process process? are the product contact with
PQ product processing of the
Commissioning basis for quality? product?
Design Review Validation quality?
GMP related
steps / facility
parameters environmen
activities?
? t?
IQ OQ Dust collector YES NO NO NO NO YES NO YES
Oil-free air
YES NO NO YES NO NO YES YES
compressor
Engineering Change Management
purified water
QA Change Control YES NO NO YES YES NO YES YES
New Risk Based Approach system
Air Handing Unit
YES NO NO YES NO YES NO YES
Design (AHU)
Development ozone generator YES NO NO YES NO YES NO YES
Verification Process
Design Review PT boiler NO NO NO NO NO NO NO NO
Testing Validation
diesel oil power
NO NO NO NO NO NO NO NO
generator
Air conditioning unit NO NO NO NO NO NO NO NO
Performance
Testing
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 Example Purified Water System
HVAC Example- Old way
Risk-Based Approach (Utilities)
Commissioning Qualification
System Direct Indirect No Verifica Perform Rationale
Drawings verification Drawings verification Verify items cleaned and
Impact Impact Impact tion ance
Testing Testing Utilities verification Utilities verification sanitised properly
Analog I/O verification Analog I/O verification Staff trained to operate
RO Unit X X X Water Purification
Digital I/O verification Digital I/O verification SOPs (cleaning,
Water X X Supplies softened water to RO unit Critical installed hardware/ Critical installed hardware/ calibration, operation,
Softener GEP Commissioning Procedures components verification components verification maintenance)
Heat X X X Product contact. Temp Control
Software verification Software verification Air velocity Air changes
Exchanger Instrumentation verification Instrumentation verification Air flow pattern
Configuration and settings Configuration and settings Recovery test
Break Tank X X Holding Tank for Softened Water
verifications verifications Particulate monitoring
Store X X X Product contact. HEPA filter Integrity test HEPA filter Integrity test Pressure differential
Tank/distrib Critical variables Check - Critical variables Check - Temperature/humidity
ution loop
operating range (high and operating range (high and Microbial monitoring
UV Lamp X X Controls Bioburden low) low)
PW Pump X X Manages Flow Rate and Supply rate Control functions tests Control functions tests
Services
(PLC Controller, (PLC Controller,
sequences, prints . sequences, prints .
Power X X Alarms and reject devices Alarms and reject devices
Comp. Air X X Non Product contact Power up, power down and Power up, power down and
power failure recovery power failure recovery
Clean Steam X X X Sterilisation -Tank and Pipework
Integration between Integration between
system components system components

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HVAC Example- New way Any Questions ?

Melbourne
Commissioning Performance Testing Level 1 38 - 40 Prospect St
Training
Training
DRAWINGS VERIFICATION Verify items cleaned and Box Hill Vic.
Ph. + 613 98971990 &
& eLearn
eLearn
UTILITIES VERIFICATION sanitised properly
ANALOG I/O VERIFICATION Staff trained to operate
DIGITAL I/O VERIFICATION SOPs (cleaning, calibration, Validation Automated
CRITICAL INSTALLED operation, maintenance) Sydney & CFR 11 QA system
Suite 2 level 3 376 Bay St.
HARDWARE/ COMPONENTS Air velocity Air changes Brighton Le Sands NSW 2216
VERIFICATION Air flow pattern Ph. +613 9567 2444 Integrated
SOFTWARE VERIFICATION Recovery test solutions
INSTRUMENTATION Particulate monitoring Singapore
VERIFICATION Pressure differential 10 Anson Road #27-10/11 Risk
CONFIGURATION AND Temperature/humidity International Plaza Singapore Productivity
Ph. +65 67745800 Management
SETTINGS VERIFICATIONS Microbial monitoring & PAT
HEPA filter Integrity test
Critical variables Check - United Kingdom GxP
operating range (high and low) PO Box 63 York YO61 1WY compliance
Control functions tests (PLC United Kingdom
Ph. + 44 1347 833 101
Controller, sequences, prints .
Alarms and reject devices
Power up, power down and South Korea www.seerpharma.com
power failure recovery #208 Hyosungintelian 1594-1
Kwanyang-dong, Korea
Integration between system Ph. 82 31 381 3490
components
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