Basic Principles of GMP
3. Validation
(and Qualification)
1
Validation, Qualification
Two phylosophies:
• Validation, qualification (and
calibration) are different, although
interrelated activities (e.g. EU GMP)
• Qualification and also calibration
belong to validation activities (e.g.
WHO GMP)
2
Terms
Qualification or validation?
• A system/equipment must be qualified to
operate in a validated process
• Qualify a system and/or equipment
• Validate a process
• Qualification versus validation, e.g. you
qualify the autoclave, while you validate
the whole sterilization process
• (and calibrate a measuring instrument!)
3
Validation
Introduction
Three basic principles of Quality
Assurance:
•
Quality, safety, efficacy
•
Cannot inspect quality into a product
•
Processes must be under control (for this,
they should be validated, whether they can
be under control!
4
Validation
Objectives
• To review the definition and types
of validation
• To understand the requirements for
documentation and key stages in
the process of validation
• To consider models for process
validation
5
Validation
Definition
Validation is the documented act of
proving that any procedure, process,
equipment, material, activity or
system actually leads to the expected
result
6
Validation
Qualification and validation
work require:
• Collaboration of experts
• Budget
• Meticulous and careful
A Validation
Master Plan
helps the
manufacturer
and
inspectorate
planning
7
Validation
Essential Part of GMP
•
•
•
•
•
Predetermined protocols
Written reports
Processes and procedures
Periodic revalidation
Specific attention:
– processing process validation
– testing
analytical method validation
– cleaning
cleaning validation
8
Validation
Types of Manufacturing Process Validation
• Experimental approach
– Prospective validation
– Concurrent validation
• Analysis of historical data
– Retrospective validation
• Revalidation
– Periodic revalidation
– Revalidation after change
9
Prospective validation
• Before starting a new manufacturing
process (or after its significant
change), or revalidation:
• Manufacturing 3 batches only for
validation purposes, all data
documented. Reason: to see that the
process is under control
• As a rule, these batches are not
marketed later, except special
decision to do that
10
Concurrent validation
• In case of rarely produced medicines
(e.g. 2 batches per year: no reason to
produce 3 „validation” batches)
• Concurrent validation: during the
manufacture of „normal” batches to be
marketed
• Strict documentation!
11
Retrospective validation
• This validation means the assessment
of data generated during previous
batch manufacturing
• Only for established technologies, the
GMP is strictly applied, defects are
rare
• Assessment of data of 10-30 batches,
including defective ones (their data
are very valuable to see how the
process can run out of control!)
12
Qualification
Types (Stages) of Qualification
•
•
•
•
Design qualification
(DQ)
Installation qualification
(IQ)
Operational qualification (OQ)
Performance qualification (PQ)
13
Design qualification DQ
• E.g. of a manufacturing equipment
• Before purchasing!
• Collection of data about the similar
equipments available on the market,
assessing our needs, resources to buy
and to operate, space and
maintenance they would need, etc.
• Making the decision
14
Installation Qualification IQ
• E.g. of a manufacturing equipment
• After purchasing (or critical repair)
• Put it on its intended place, connect
with other equipments, electric power,
material flow devices
• Collect its documents incl. Operation
Manual, etc.
• Its formal „release”: it is ready for
working with
15
Operational Qualification OP
• E.g. of a manufacturing equipment
• „Model manufacturing” experiments
with model materials, similar to those
to be used in the real manufacture
• E.g. qualifying an autoclave we use
culture-media
• Permit the acceptable fluctuations of
parameters, even set the „worst
conditions”
16
„Worst conditions”
• say, an equipment must be operated
within the limits of
– temperature: 20 and 35 oC
– pressure: 0.9 and 1.2 atm
• The worst cases, when it operates at
–
–
–
–
20 oC and 0.9 atm
35 oC and 1.2 atm
20 oC 0.9 and 1.2 atm
35 oC and 0.9 atm
17
Performance Qualification PQ
• Similar to the Operational
Qualification, but the real manufacture
is running
• Permit accepted fluctuations up to
their limits (incl. worse conditions, if
occur)
18
Qualification
19
Validation
Priorities for Process Validation
Type of process
• New
• Existing
Sterile products
 Non-sterile
Requirement
• Every new process before approval for
routine
• All processes affecting the sterility, and
manufacturing environment including
sterilization stage
• Low dose tablets and capsules: mixing and
granulation, content uniformity (possible
other parameters)
• Other tablets and capsules: uniformity of
mass(possible other parameters)
20
Validation
Types of Documentation
•
•
•
•
Validation Master Plan (VMP)
Validation protocols (VP)
Validation reports
(VR)
Standard Operating Procedures
(SOPs)
21
Validation
The Validation Master Plan could consist
of:
–
–
–
–
–
–
–
–
–
–
–
Approval page and table of contents
Introduction and objectives
Facility and process description
Personnel, planning and scheduling
Responsibilities of committee members
Process control aspects
Equipment, apparatus, processes and systems to be validated
Acceptance criteria
Documentation e.g.validation protocols and reports
SOPs
Training requirements
22
Validation
Protocol
– Objectives of the validation and
qualification study
– Site of the study
– Responsible personnel
– Description of the equipment
– SOPs
– Standards
– Criteria for the relevant products
and processes
23
Validation
Report
– Title
– Objective of the study
– Refer to the protocol
– Details of material
– Equipment
– Programmes and cycles use
– Details of procedure and test
methods
24
Let us spend some time on
the Validation Master Plan
now
25
Validation
The Validation Master
Plan
(VMP)
•
Philosophy
•
Content
•
Strategy
26
Validation
Validation Master Plan
•
•
•
•
Recommendation only
Cover manufacturer’s validation policy and
needs
Provides information on validation
organization
It should describe:
 by whom?
– why?
 how?
– what?
–
where?
 when?
27
Validation
Validation Master Plan
•
Prospective validation
•
Concurrent validation
•
Retrospective validation
•
Revalidation
•
Change control
28
Validation
The VMP
•
Identifies validation items (products,
processes, systems)
•
Defines nature and extent of testing
expected
•
Outlines test procedures and protocols
•
Summary document
•
Management agreement
29
Validation
The VMP helps:
•
Management
•
Validation team members
•
Project leaders
•
GMP inspectors
30
Validation
Validation Activities in VMP
•
Every validation activity included
•
Revalidation
•
Validation of new process cycles
•
Large validation projects have separate
VMPs
•
Include reasonable unexpected events
31
Validation
The VMP:
•
Enables overview of entire validation
project
•
Lists items to be validated with the
planning schedule as its heart
•
Is like a map
32
Validation
The “Introduction” to the VMP
•
•
•
•
•
Validation policy
Project scope
Location and timing (including priorities)
Validation procedures
Standards
33
Validation
VMP should state who is responsible for:
•
Preparing the VMP
•
The protocols and SOPs
•
Validation work
•
Report and document preparation and control
•
•
Approval/authorisation of validation protocols and
reports in all stages of validation process
Tracking system
•
Training needs in support of validation
34
Validation
VMP should contain:
• Cross references to documents
• Specific process considerations
• Specific characteristics briefly outlined
• Validation list (What to validate)
– premises, systems and equipment
– processes
– products
35
Validation
VMP should contain, 2:
• Descriptions of
– plant (where to validate)
– processes
– products
• Personnel attributes
– expertise and training
• Key acceptance criteria
36
Validation
VMP should contain, 3:
• Format for protocols and other
documentation
• List of relevant SOPs (How)
• Planning and scheduling (When)
• Location (Where)
• Estimate of staffing requirements (Who)
• A time plan of the project (When)
• Annexes
37
Validation
VMP should contain change control
• Policy and procedure
• Risk assessment
• Authorization
• Failure to properly document changes to the
system means invalidation of the process
38
Validation
Changes that require revalidation
•
•
•
•
•
•
•
Software changes; Controllers
Site changes; Operational changes
Change of source of material
Change in the process
Significant equipment change
Production area changes
Support system changes
39
Validation
In summary, a VMP should contain at
least:
•
•
•
•
•
•
•
Validation policy
Organizational structure
Summary of facilities, systems, equipment,
processes to be validated
Documentation format for protocols and
reports
Planning and scheduling
Change control
Training requirements
40
Finishing Validation Master
Plan, something about the
Validation Protocol and
Report
41
Validation
WHO Model for
Validation Protocol and Report, 1
• Part 1 – Purpose and prerequisites
• Part 2 – Presentation of the process
• Part 3 – Validation protocol
42
Validation
WHO Model for
Validation Protocol and Report, 2
• Part 4 – Installation qualification
• Part 5 – Qualification protocol/report
• Part 6 – Product characteristics
43
Validation
WHO Model for
Validation Protocol and Report, 3
• Part 7 – Evaluation
• Part 8 – Certification
• Part 9 – Summary
44
Special validation types
Validation of
•cleaning
•manuf. process
•QC related
processes
45
Cleaning validation
46
Cleaning validation
Objectives
To review:
• General requirements
• Validation protocol requirements
• How to check limits
• Analytical requirements
• Sampling methods
47
Cleaning validation
Why cleaning validation is so important (1)
• Pharmaceuticals can be contaminated by
potentially dangerous substances
• Essential to establish adequate cleaning
procedures
48
Cleaning validation
Why cleaning validation is so important
(2)
• “Particular attention should be accorded to
the validation of … cleaning procedures”
(WHO)
• “Cleaning validation should be performed in
order to confirm the effectiveness of a
cleaning procedure” (PIC/S)
• “The data should support a conclusion that
residues have been reduced to an
‘acceptable’ level” (FDA)
49
Cleaning validation
Possible contaminants
•
•
•
•
•
•
Product residues
Cleaning agent residues and breakdown
Airborne matter
Lubricants, ancillary material
Decomposition residues
Bacteria, mould and pyrogens
50
Cleaning validation
Strategy on cleaning validation
• Product contact surfaces
• After product changeover
• Between batches in campaigns
• Bracketing products for cleaning validation
• Periodic re-evaluation and revalidation
51
Cleaning validation
Cleaning validation protocol (1)
Should include :
•
Objective of the validation
•
Responsibility for performing and
approving validation study
•
Description of equipment to be used
52
Cleaning validation
Cleaning validation protocol (2)
Should include:
• Interval between end of production and
cleaning, and commencement of cleaning
procedure
• Cleaning procedures to be used
• Any routine monitoring equipment used
• Number of cleaning cycles performed
consecutively
• Sampling procedures used and rationale
• Sampling locations (clearly defined)
53
Cleaning validation
Record of cleaning validation
Should include :
•
Data on recovery studies
•
Analytical methods including Limit of
Detection and Limit of Quantitation
•
Acceptance criteria and rationale
•
When revalidation will be required
•
Must have management and QA involvement
•
Management commitment and QA
involvement
54
Cleaning validation
Results and reports
• Cleaning record signed by operator,
checked by production and reviewed by
QA
• Final Validation Reports, including
conclusions
55
Cleaning validation
Personnel
• Manual cleaning methods are difficult to
validate
• Cannot validate people; can measure
proficiency
• Must have good training
• Must have effective supervision
56
Cleaning validation
Microbiological aspects
• Include in validation strategy
• Analyse risks of contamination
• Consider equipment storage time
• Equipment should be stored dry
• Sterilization and pyrogen contamination
57
Cleaning validation
How to take samples
• Swab/swatch
• Rinse fluid
• Placebo
• The sample transport and storage conditions
should be defined
58
Cleaning validation
Swab samples
•
•
•
•
•
Direct sampling method
Reproducibility
Extraction efficiency
Document swab locations
Disadvantages
– inability to access some areas
– assumes uniformity of contamination surface
– must extrapolate sample area to whole surface
59
Cleaning validation
Rinse samples
• Indirect method
• Combine with swabs
• Useful for cleaning agent residues
• pH, conductivity
• Insufficient evidence of cleaning
• Sample very large surface areas
60
Cleaning validation
Analytical method (1)
• Validate analytical method
• Must be sensitive assay procedure:
– HPLC, GC, HPTLC
– pH
– conductivity
– UV
– ELISA
61
Cleaning validation
Analytical method (2)
Check:
• Precision, linearity, selectivity
• Limit of Detection (LOD)
• Limit of Quantitation (LOQ)
• Recovery, by spiking
• Consistency of recovery
62
Cleaning validation
Setting limits (1)
• Regulatory authorities do not set limits for
specific products
• Logically based
• Limits must be practical, achievable and
verifiable
• Allergenic and potent substances
• Limit setting approach needed
63
Cleaning validation
Setting limits (2)
• Uniform distribution of contaminants not
guaranteed
• Decomposition products to be checked
• Setting limits; cleaning criteria:
– visually clean
– 10 ppm in another product
– 0.1% of therapeutic dose
64
Cleaning validation
Setting limits: “Visually clean”
• Always first criteria
• Can be very sensitive but needs verification
• Use between same product batches of same
formulation
• Illuminate surface
• Spiking studies
65
Cleaning validation
Setting limits: “10 ppm”
•
•
•
•
Historical
In some poisons regulations
Pharmacopoeias limit test
Assumes residue to be harmful as heavy
metal
• Useful for materials for which no available
toxicological data
• Not for pharmacologically potent material
66
Cleaning validation
Setting limits: not more than 0.1%
• Proportion of MINIMUM daily dose of
current product carried over into
MAXIMUM daily dose of subsequent
product
• Need to identify worst case
67
Cleaning validation
Other issues
• Clean-In-Place (CIP) systems
• Placebo studies
• Detergent residues; composition should be
known
• Scrubbing by hand
68
Cleaning validation
Questions for the GMP Inspector to ask
• How is equipment cleaned?
• Are different cleaning processes required?
• How many times is a cleaning process repeated
before acceptable results are obtained?
• What is most appropriate solvent or detergent?
• At what point does system become clean?
• What does visually clean mean?
69
Cleaning validation
Conclusion
• The manufacturer needs a cleaning validation
strategy
• Assess each situation on its merits
• Scientific rationale must be developed
– equipment selection
– contamination distribution
– significance of the contaminant
• “Visually clean” may be all that is required
70
Process validation
71
Process validation
Objectives
To review:
• Validation, risk analysis, and critical
steps of processing
• Points to consider in process
validation of:
– solid dose mixing
– tablet compression
– sterilization
• Finalization of validation
72
Process validation
Reliable, repeatable, under control
• At least first 3 consecutive batches repeatable
• Must investigate failures
• The rationale should be documented if
experimental method is changed
– document deviations, decisions and reasoning
• Does not improve processes
• Should not validate bad processes
73
Process validation
DQ, IQ, OQ and PQ
Design user or process requirements
Install installation qualification
Operate operational qualification
Perform performance qualification
and process validation
Review periodically (+ change control)
74
Process validation
Critical factors or parameters
• Need to be determined
• Need to be monitored during
validation
• May affect the quality of the product
75
Process validation
Setting Limits
• Marketing authorization limits
– stability specifications
• Release specification
• Validation limits
Marketing authorisation limits
based on stability specifications
Batch release limits
Validation limits
76
Process validation
Determining critical control point:
example of a tablet granulation process
• Particle size distribution of the active(s)
• Blending time for the powder
• Granulating time and speed,
• Amount of granulating fluid-binder
concentration
• Drying time - final moisture content, granule
particle size distribution
• Granule active content and homogeneity,
blending time of external phase
77
Process validation
Determining critical control points
78
Process validation
•
•
•
•
•
•
Solid dose mixing (1)
Homogeneity in blending – the
key to quality!
Sampling strategy
Sample site, label, container
Storage
Transport
Sample thief
79
Process validation
Solid dose mixing (2)
• In situ analysis
• Methods of analysis
• Statistical analysis
– inter-batch
– intra-batch
– within-sample-site
80
Process validation
•
•
•
•
•
•
Tablet compression
variables
Fill volume
Pre-compression force,
compression
force
Turntable speed
Dwell time
Granule size and feed
Ejection force, lubrication
81
Process validation
Tablet compression
parameters
Tablet coating
variables

Mass

Spray rate

Hardness

Inlet and outlet air temp

Moisture

Coating weight

Friability

Disintegration

Dissolution

Thickness
82
Process validation
Sterilization validation (1)
• Sterility test
• Physical measurements
• Chemical and biological indicators
• Loading patterns
83
Process validation
•
•
•
•
•
•
Sterilization validation (2)
Cooling fluid or gas
Automated process
Leak tests
Control instrumentation
Steam quality
Heat distribution
84
Process validation
Dry heat sterilization
• Parameters
• Air circulation, positive air
pressure, HEPA filter
• Advantages
– microorganisms destroyed
– depyrogenation possible
• Disadvantages
– poor heat transfer
– higher temperatures for long
periods
85
Process validation
Process variation
Controllable causes of variation may
include:
• Temperature, humidity
• Variations in electrical supply
• Vibration
• Environmental contaminants
• Light
• Human factors
• Variability of materials
• Wear and tear of equipment
86
Process validation
Change control
• Must be a review procedure for
validated processes
• From time to time changes may be
necessary
• Documented change control
procedure needed
• “Like for like" changes do not require
re-validation
87
Process validation
Mixing validation liquid and solid dose
change control and scale up
• Mixer type and size
• Batch size
• Pilot study scale up
• Limit on the proportion of the scale up
88
Process validation
Finalization of validation process
• Final report required
• Summarize and reference protocols and
results
• Conclusion required: “Is the process valid”
• Final report should be reviewed and approved
by
– the validation team
– “authorized person”
89
Tablet manufacturing flow chart
90
Quality Control related
validation
91
QC related
validation
Introduction
• Why is analytical monitoring
necessary?
• What is the purpose of analytical
validation?
92
QC related validation
Objectives
To introduce the concepts of :
• Protocol development
• Instrument qualification
• Analytical procedure
• Extent of validation
• Method transfer
• Chemical and physical, biological, and
microbiological test validation
93
QC related validation
Validation of analytical procedures
requires:
•
Qualified and calibrated instruments
•
Documented methods
•
Reliable reference standards
•
Qualified analysts
•
Sample integrity
94
QC related validation
Validation protocol for analytical method
•
•
•
•
•
Statement of purpose and scope
Responsibilities
Documented test method
List of materials and equipment
Procedure for the experiments for each
parameter
• Statistical analysis
• Acceptance criteria for each performance
parameter
95
QC related validation
Qualification of the instrument
• Make, model and maker’s manual
• Modifications
• Installation and operational qualification
• Calibration programs
• Maintenance schedules
96
QC related validation
Characteristics of analytical
procedures (1)
•
Accuracy
•
Precision
•
Repeatability
•
Reproducibility
97
QC related validation
Relationship between accuracy and
precision
In a c c u ra te &
im p re c is e
In a c c u ra te b u t
p re c is e
A c c u ra te b u t
im p re c is e
Accurate AND Precise
98
QC related validation
Characteristics of analytical
procedures (2)
•
•
•
Ruggedness
Robustness
Variability caused by:
–
–
–
–
–
–
–
Day-to-day variations
Analyst-to-analyst
Laboratory-to-laboratory
Instrument-to-instrument
Chromatographic column-to-column
Reagent kit-to-kit
Instability of analytical reagents
99
QC related validation
Characteristics of analytical procedures
(3)
•
•
•
•
•
Linearity and range
Specificity
Sensitivity
Limit of detection
Limit of quantitation
100
0.040
0.035
0.030
0.025
0.020
0.015
0.010
0.01
Calculated analyte in mg/mL
QC related validation
Table of values (x,y)
Linearity
of an analyte in a material
0.015
Reference material mg/ml
0.02
0.025
0.03
0.035
0.04
x
y
#
Reference
material mg/ml
Calculated
mg/ml
1
0.0100
0.0101
2
0.0150
0.0145
3
0.0200
0.0210
4
0.0250
0.0260
5
0.0300
0.0294
6
0.0400
0.0410
101
QC related validation
Linearity Statistics
•
•
Intercept -0.0002
Limit of Linearity and Range
0.005 – 0.040 mg/mL
•
•
Slope 1.0237
Correlation coefficient
–
–
Pearson
Olkin and Pratt
0.9978
0.9985
• Relative procedure standard
deviation 3.4%
102
QC related validation
LOQ, LOD and SNR
• Limit of Quantitation
• Limit of Detection
• Signal to Noise Ratio
Peak B
LOQ
Peak A
LOD
Baseline
noise
103
QC related validation
Different classes of analytical tests
• Class A: To establish identity
• Class B: To detect and quantitate
impurities
• Class C: To determine quantitatively the
concentration
• Class D: To assess the characteristics
104
QC related validation
Characteristic
A
B
quant.
B
Limit
test
C
D
Accuracy
X
X
X*
Precision
X
X
X
X
X
X
X
X
X
Robustness
X
Linearity and range
Specificity
X
X
X
X
Limit of detection
Limit of quantitation
X
X
X
X
* A degree of bias may be allowed
105
QC related validation
Extent of validation
•
•
•
New methods require complete
validation
Pharmacopoeial methods require
partial validation (or verification)
Significant changes mean partial
revalidation
– equipment changes
– formula changed
– changed suppliers of critical reagents
106
QC related validation
Analytical method transfer
• Method transfer protocol and procedure
– precision
– accuracy
– ruggedness
• Written and approved specific test method
• Proficiency check
• Formal acceptance by new laboratory
107
QC related validation
Chemical laboratory validation
requirements (1)
•
•
Balances
Chromatography
–
•
•
•
•
HPLC, HPTLC, GC, TLC
Dissolution or disintegration apparatus
Karl Fischer moisture determination
Melting, softening or freezing point apparatus
Ovens, refrigerators, incubators
108
QC related validation
Chemical laboratory validation
requirements (2)
• pH meter
• Polarimeter - optical rotation
• Refractometer
• Spectrophotometer UV/Vis, IR, FTIR, Raman,
AA
• Timers
• Viscometer
• Volumetric equipment
109
QC related validation
Typical validation of HPCL assay (1)
• System suitability (performance check)
–
–
–
–
system precision
column efficiency
symmetry factor
capacity factor
110
QC related validation
Typical validation of HPLC assay (2)
•
Method validation
–
–
–
–
–
specificity
accuracy
precision
linearity
robustness
111
QC related validation
Biological assays
• Can be difficult to "validate"
• "Validity" on a case by case basis
• Strictly adhere to the Biological Testing
monographs in pharmacopoeias
112
QC related validation
Microbiological testing requiring validation
• Microbial limit testing
• Microbial count
• Sterility testing
• Preservative effectiveness testing
• Environmental monitoring program
• Biological testing
113
QC related validation
Validation of microbial test procedures
(1)
• Virtually impossible to completely validate
test procedures for every microorganism
• Neutralize /inactivate inhibitory
substances, or dilute
• Periodic media challenge
• Media QC
• Reliable methods
114
QC related validation
Validation of microbial test procedures
(2)
• Incubation temperature and time
• Media may not grow all microorganisms
• Variations in media may affect recovery
• Inhibitory disinfectants or preservatives
• Sample
– procedures
– handling, storage, transport
115
QC related validation
Microbiological viable count method
validation (1)
•
Methods
– pour plate / spread plate
– membrane filtration
– Most Probable Number
•
•
•
Sample size
Test dilution
Inoculation size
116
QC related validation
Microbiological viable count method
validation (2)
•
Membrane filtration conditions
•
Incubation conditions
•
Acceptance criteria
117
QC related validation
Sterility testing validation requirements
•
Media growth promotion, sterility, pH
•
Product validation
•
Stasis testing
•
Environmental monitoring
•
Negative controls
•
Challenge organisms
118
Validation
Personnel - Validation team members
•
•
•
•
Quality Assurance
Engineering
Manufacturing
Other disciplines may be involved
depending on the product and process:
–
–
–
–
–
laboratory, technical services
research and development, regulatory affairs
clinical
chemical engineering
purchasing/planning
119
Validation
Protocol development (1)
• Identification of process
• Objective and measurable criteria
• Length and duration of the validation
• Shifts, equipment
• Identification and quality of utilities
• Identification of operators and operator
training and qualification
120
Validation
Protocol development (2)
• Complete description of the process
• Relevant specifications and tests
• Samples and sampling methods
• Special controls or conditions
• Process parameters to be monitored
• Methods for controlling and monitoring
121
Validation
Protocol development (3)
• Objective and subjective criteria used to
evaluate the product
• Definition of non-conformance
• Statistical methods
• Maintenance and repairs
• Criteria for revalidation
• Criteria for change control
122
Validation
GMP Inspector’s check list for validation
(1)
Check that the manufacturer has:
• A VMP and multi-functional team for
validation
• Planned approach, defined requirements
• Identified and described processes
• Analyse the amount of validation work to
perform
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Validation
GMP Inspector’s check list for
validation (2)
Check that the manufacturer has:
• Selected methods and tools for validation
• Created protocols
• Performed DQ, IQ, OQ, PQ and
documented results
• Exerted change control, set revalidation
time
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Validation: summary
Validation
• A quality tool that makes sense
• A prevention-based activity
• Expensive
• In danger of becoming
overwhelming
• Risk-based assessment of what
needs to be validated or verified
• The process must be under control
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We are now validated!
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Exam topics
127
Validation and Qualification in
GMP
•
•
•
•
•
Definitions. What is their difference?
Their importance
Describe the 3 process validation types
Describe the 4 qualification types
Validation documentation (special
emphasis to VMP)
• What is change control, why to do it?
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Validation of clening processes
and analytical procedures in
GMP
• Cleaning validation
– Its 2 targets
– How to perform it (examples)
• Analytical method validation
– List the main method characteristics
– Classes of testing for validation
– Analytical instrument validation (examples)
– Microbiology
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