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Presentation Materials of GPFI Seminar Session 6 - 23022017
Presentation Materials of GPFI Seminar Session 6 - 23022017
Presentation Materials of GPFI Seminar Session 6 - 23022017
1
Todays Presenters
Table of Contents
Session 1. Introduction & GMP Guide Part I (Chapter 1 & 2)
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Before starting the presentation
Chapter 2 on Personnel;
The revised GMP Guide entered into force on 1st January 2017.
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Before starting the presentation
Annex 15
Qualification and
validation
What does it look like?
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Before starting the presentation
Principle
General O V E R V I EW
1. Organizing & Planning for Qualification & Validation
2. Documentation, including VMP
3. Qualification Stages for Equipment, Facilities & Systems
- User requirements specification (URS)
- Design qualification (DQ)
- Factory acceptance testing (FAT) /Site acceptance testing (SAT)
- Installation qualification (IQ)
- Operational qualification (OQ)
- Performance qualification (PQ)
4. Re-qualification
5. Process Validation*
- General
- Concurrent validation
- Traditional process validation
- Continuous process verification
- Hybrid approach
- Ongoing Process Verification during Lifecycle
6. Verification of Transportation
7. Validation of Packaging
8. Qualification of Utilities
9. Validation of Test Methods
10. Cleaning Validation *
11. Change Control
12. Glossary
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Before starting the presentation
Bracketing approach
Glossary Change Control
Cleaning Validation
Definitions of terms relating Cleaning verification
to qualification and validation
Concurrent Validation
which are not given in other
sections of the current PIC/S Continuous process verification*
Guide. Control Strategy*
Critical process parameter (CPP)*
Critical quality attribute (CQA)*
Design qualification (DQ)
Design Space*
Installation Qualification (IQ)
Knowledge management*
Lifecycle
Operational Qualification (OQ)
Performance Qualification (PQ)
Process Validation (PV)
Product realization*
Prospective Validation
Quality by design (QbD)
Quality risk management*
Simulated agents
State of control
Traditional approach
User requirements Specification (URS)
Worst Case
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Todays Topics
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1. Principle and General
Principle
This Annex describes the principles of qualification and
validation which are applicable to medicinal products
and API.
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1. Principle and General
What is Critical Aspects?
Functions and/or features of a manufacturing system that
control manufacturing processes
Equipment
Development
Conventional
Technology transfer GMP
Development of API
Commercial production
Development of prescription
Clinical trial medicine
production Procurement control Terminate
Scale up of a raw material
Equipment
Development of an analytical Management of equipment
Storage of
method and facilities
document and
Manufacture management
record
Quality control
Storage of
Quality Assurance
sample
Batch release
Continual
Delivery management
evaluation of the
product value
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1. Principle and General
General
A quality risk management (QRM) approach should be
applied throughout the lifecycle of a medicinal product.
Lifecycle:
All phases in the life of a product, equipment or facility from initial
development or use through to discontinuation of use.
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1. Principle and General
Equipment
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1. Principle and General
For example Engineering flow with QRM approach
Risk Review
UR URS *Monitoring
*Self Inspection
PUR
*Product Quality PUR
*CQA *CPP,GMP *Product Quality
VMP DQ IQ,OQ Commercial
*CQA *CPP,GMP
PQ/PPQ Production
GUR
*Product Capacity
Etc. Critical Aspects
*Facility/System
Specification Risk Control
*Decreasing Risk
*Risk Acceptance
Conceptual Design GUR (Fish Bone, FMEA etc.)
Equipment
*Product Capacity
Etc. Basic Construction
Risk Assessment Detail Maintenance
*Specify Risk Design Design Commissioning Program
*Risk Analysis
(SIA)
*Risk Assess.
Design Concept
Design data etc. Tractability Matrix
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1. Principle and General
For example Engineering flow with QRM approach
Risk Review
UR URS Qualification *Monitoring
*Self Inspection
PUR
*Product Quality PUR
*CQA *CPP,GMP *Product Quality
VMP DQ IQ,OQ Commercial
*CQA *CPP,GMP
PQ/PPQ Production
GUR
*Product Capacity
Etc. Critical Aspects
*Facility/System
Specification Risk Control
*Decreasing Risk
*Risk Acceptance
Conceptual Design GUR (Fish Bone, FMEA etc.)
Equipment
*Product Capacity
Etc. Basic Construction
Risk Assessment Detail Maintenance
*Specify Risk Design Design Commissioning Program
*Risk Analysis
(SIA)
*Risk Assess.
Commissioning
Design Concept
Design data etc. Tractability Matrix
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Todays Topics
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2. Organizing, Planning and Documentation
Action Plan
Research
Master
Change Control
Formula
Validation
Continuous
Improvement
Equipment
Check Do
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2. Organizing, Planning and Documentation
Personnel
Qualification and validation activities should only be
performed by trained personnel who follow approved
procedures.
The personnel should report as defined in the
pharmaceutical PQS although this may not necessarily be
to a QM or a QA function. However, there should be
appropriate quality oversight over the whole validation
life cycle.
Minor
Major
Critical
Analysist
A Reviewer
B
Result will be influenced by
analysists experience SMESubject Matter Expert
should be involved
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2. Organizing, Planning and Documentation
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2. Organizing, Planning and Documentation
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2. Organizing, Planning and Documentation
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2. Organizing, Planning and Documentation
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2. Organizing, Planning and Documentation
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Todays Topics
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3. Qualification and Re-qualification
Qualification stages
Qualification activities should consider all stages from
initial development of the user requirements
specification through to the end of use of the equipment,
facility, utility or system.
The main stages and some suggested criteria which
could be included in each stage are indicated below:
Qualification stages
URS User requirements specification
DQ Design qualification
PQ Performance qualification
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3. Qualification and Re-qualification
START
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3. Qualification and Re-qualification
Quality
CQA
PUR CPP Qualification
GMP matter, etc.
Production capacity
Hygiene control
GUR Calibration
Prevention of human error, etc.
Safety
Non- Efficiency Commissioning
GMP Maintenance, etc.
Important !
At URS stage, the PUR, GUR and non-GMP matters can be classified
clearly.
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3. Qualification and Re-qualification
A point of reference throughout the validation life cycle
Protocol
Report OQ
SOP
Draft
Protocol
Report IQ
Supporting
Data Detail Protocol
Design Report DQ
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3. Qualification and Re-qualification
An example of URS
Key word is Development from UR to URS
Equipment: Autoclave
UR URS Impact assessment
1 Supply an object 1.1 Loading area: Sterilization Prep. Room C Environment of handling
for sterilization (Ceiling height FL+3000) area for object of
from Grade C and sterilization
take out under 1.2 Property installation area: AC Machine room F Maintenance
unidirectional flow (Ceiling height FL+4000)
booth installed in
Grade B after 1.3 Cool down area: CD room under clean booth C Environment of handling
(FL+3000) area for object of
completion of
sterilization
sterilization.
Property of 1.4 Maintenance hatch must be installed on the F Maintenance
autoclave must be Grade C side. Provided that all maintenance
installed at Grade must be possible from the side of Grade C.
C.
1.5 Main control panel must be installed on the B Operation
wall of Grade C and Sub panel must be
installed on the wall of Grade B.
1.6 Wall between Grade B/A and Machine room D Maintain environment
AC is installed must be airtight.
A NA (Describe Quality attribute to realize CQA and CPP)
B Control, Monitoring and Operation for Process parameter
C Prevention of contamination by microbes, endotoxin, etc.
For example D Maintain production environment
E Data required by GMP,(Batch records, log book etc.)
F Not influenced to product quality
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3. Qualification and Re-qualification
Protocol
Report OQ
SOP
Draft
Protocol
Report IQ
Supporting
Data Detail Protocol
DQ
Design Report
User Construction company / vendor
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3. Qualification and Re-qualification
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3. Qualification and Re-qualification
Protocol
Report OQ
SOP
Draft
Protocol
Report IQ
Supporting
Data Detail Protocol
DQ
Design Report
User Construction company / vendor
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3. Qualification and Re-qualification
URS DQ FAT/SAT IQ OQ PQ
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3. Qualification and Re-qualification
Protocol
Report OQ
SOP
Draft
Protocol
Report IQ
Supporting
Data Detail Protocol
DQ
Design Report
User Construction company / vendor
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3. Qualification and Re-qualification
URS DQ FAT/SAT IQ OQ PQ
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3. Qualification and Re-qualification
LQA
System System FAT
UR System DR
Aspects Components SAT
GEP
Direct
Impact
ARM System
Critical Critical
GMP PUR DQ IOQ
Aspects Components
(QA)
Lean Qualification
Qualification
comes from excellent
good engineering practice
Commissioning
(GEP)
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3. Qualification and Re-qualification
URS DQ FAT/SAT IQ OQ PQ
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3. Qualification and Re-qualification
Re-qualification
Equipment, facilities, utilities and systems should be
evaluated at an appropriate frequency to confirm that
they remain in a state of control.
Where re-qualification is necessary and performed at a
specific time period, the period should be justified and the
criteria for evaluation defined.
Furthermore, the possibility of small changes over time
should be assessed.
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Todays Topics
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4. Process Validation
Three stages of process validation
Stage 1
Lab Scale Product/process Stage 2
Qualification knowledge Commercial Scale
Qualification
Product distribute
Continuous Traditional
Process Process
Verification Can be introduced at any time Validation
of the lifecycle of the product
Concurrent
Hybrid approach Process
Validation
Stage 3
Continued
Product distribute Verification
Exceptional
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4. Process Validation
Stage 1 Stage 2
Operator
Operator Training
Process
Performance
Qualification
Equipment URS DQ IQ OQ
Verification by
Development of Manufacturing process Actual equipment
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4. Process Validation
Old concept
Qualification Validation Verification
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4. Process Validation
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4. Process Validation
What is Bracketing?
A risk based validation approach such that only batches on the
extremes of certain predetermined and justified design factors
are tested.
The design assumes that validation of any intermediate levels is
represented by validation of the extremes.
Could be applicable if the strengths are identical or very closely
related in composition.
Can be applied to different container sizes or different fills in
the same container closure system.
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4. Process Validation
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4. Process Validation
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4. Process Validation
Five types of activity associated with validation
Stage 1
Lab Scale Product/process Stage 2
Qualification knowledge Commercial Scale
Qualification
Continuous Traditional
Process Process
Verification Can be introduced at any time Validation
of the lifecycle of the product
Concurrent
Hybrid approach Process
Validation
Stage 3
Continued
Product distribute Verification Product distribute
Ongoing Exceptional
Process
Verification
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4. Process Validation
Concurrent validation
In exceptional circumstances, it may be acceptable not to
complete a validation programme before routine
production starts.
The decision to carry out concurrent validation must be
justified, documented in the VMP and approved.
There should be sufficient data to support a conclusion
that any given batch of product is uniform and meets the
defined acceptance criteria.
The results and conclusion should be formally
documented prior to certification of the batch.
Traditional validation
Prospective validation
Continuous verification
Process validation Concurrent validation
Retrospective validation * no longer acceptable
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4. Process Validation
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4. Process Validation
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4. Process Validation
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4. Process Validation
Control strategy: Planned set of controls, derived from current product and
process understanding that ensures process performance and product quality.
Product realization: Achievement of a product with the quality attributes to
meet the needs of patients, health care professionals and regulatory authorities
and internal customer requirements. (ICH Q10)
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4. Process Validation
Hybrid approach
A hybrid of the traditional approach and continuous process
verification could be used where there is a substantial
amount of product and process knowledge and
understanding which has been gained from manufacturing
experience and historical batch data.
This approach may also be used for any validation activities
after changes or during ongoing process verification even
though the product was initially validated using a traditional
approach.
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4. Process Validation
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5. Verification of Transportation
Transportation verification
Finished medicinal products, investigational medicinal
products, bulk product and samples should be transported
from manufacturing sites in accordance with the
conditions defined in the MA.
Verification of transportation may be challenging due to
the variable factors involved however, transportation
routes should be clearly defined.
A risk assessment should be performed to consider the
impact of variables in the transportation process.
Due to the variable conditions, continuous monitoring and
recording of any critical environmental conditions should
be performed, unless otherwise justified.
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Todays Topics
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6. Validation of Packaging
Packaging validation
Variation in equipment processing parameters especially
during primary packaging may have a significant impact
on the integrity and correct functioning of the pack;
therefore primary and secondary packaging equipment for
finished and bulk products should be qualified.
Qualification of the equipment used for primary packing
should be carried out at the minimum and maximum
operating ranges defined for the critical process
parameters.
For example
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Todays Topics
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7. Qualification of Utilities
Qualification of Utilities
The quality of steam, water, air, other gases etc. should be
confirmed following installation using the qualification
steps.
The period and extent of qualification should reflect any
seasonal variations and the intended use of the utility.
A risk assessment should be carried out where there may
be direct contact with the product, e.g. HVAC systems, or
indirect contact such as through heat exchangers.
Boilers
Heating Circulation Airflow
system PumpsChillers pattern
system + pressure
Piping
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Todays Topics
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8. Validation of Test Methods
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9. Cleaning Validation
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9. Cleaning Validation
EMA Guideline on setting health based exposure limits for use in risk
identification in the manufacture of different medicinal products in
shared facilities
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9. Cleaning Validation
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9. Cleaning Validation
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9. Cleaning Validation
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9. Cleaning Validation
2. L1 ADE
ADE = NOAEL Body weight / uncertainty factor
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9. Cleaning Validation
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Todays Topics
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10. Change Control
Knowledge management:
A systematic approach to acquire, analyze, store and disseminate
information.
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10. Change Control
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Before ending the presentation
A bonus hint
Validation
The documented evidence that the
process can perform to produce a
medical product meeting its
predetermined specifications and quality
attributes. now and in future
Verification
Documented evidence that the process remains
in a state of control during commercial
manufacture. past and now
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Thanks
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