Supplementary Training Modules on
Good Manufacturing Practice
Validation
WHO Technical Report Series,
No. 937, 2006. Annex 4.
Validation
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August 2006
Validation
Part 1. General overview on qualification and validation
Part 2. Qualification of HVAC and water systems
Part 3. Cleaning validation
Part 4. Analytical method validation
Part 5. Computerized system validation
Part 6. Qualification of systems and equipment
Part 7. Non sterile product process validation
Validation
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Supplementary Training Modules on
Good Manufacturing Practice
Computerized systems validation
Part 5
WHO Technical Report Series,
No. 937, 2006. Annex 4. Appendix 5
Validation
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August 2006
Validation
Objectives
To discuss validation of computerized systems including:
System specifications
Functional specifications
Security
Back-ups
Validation:
Hardware
Software
Validation
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August 2006
Validation
General
Validated - level appropriate
or their use and application.
Production and quality control.
Computer systems used in planning, specification,
programming, testing, commissioning, document operation,
monitoring and modifying.
Validation: Evidence and confidence
intended use, accuracy, consistency and reliability.
1.1 1.3
Validation
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Validation
General (2)
Both the system specifications and functional
specifications should be validated.
Periodic (or continuous) evaluation should be performed
after the initial validation.
1.4 1.5
Validation
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Validation
Written procedures for:
performance monitoring, change control, programme and
data security, calibration and maintenance, personnel
training, emergency recovery and periodic re-evaluation
During validation, consider:
networks
manual back-ups
input/output checks
process documentation, monitoring
alarms, and
shutdown recovery
1.6 1.7
Validation
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Validation
System specification (Control document)
In place, stating:
objectives of a proposed computer system
the data to be entered and stored
the flow of data
how it interacts with other systems and procedures
the information to be produced
the limits of any variable
the operating programme and test programme
(Examples of each document produced by the programme
should be included)
Validation
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2.1
Validation
System specification (Control document) (2)
System elements that need to be considered in computer
validation include:
hardware (equipment)
software (procedures)
people (users)
2.2
Validation
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Validation
Functional specification (Performance specification)
Provide instructions for:
testing, operating, and maintaining the system
names of the person(s) (development and operation)
When using computer systems, consideration:
location
power supply
(Fluctuations in the electrical supply can influence computer
systems and power supply failure can result in loss of
memory).
temperature
3.1 3.2
magnetic disturbances
Validation
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Validation
Functional specification (Performance specification) (2)
GMP requirements for computer systems:
Verification and revalidation
After a suitable period of running a new system
Independently reviewed and compared with the system
specification and functional specification
Change control
Alterations made in accordance with a defined procedure
Provision for checking, approving and implementing the
change
Checks
Data checked periodically
Confirm accurate and reliable transfer
3.2 3.3
Validation
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Validation
Security
Production as well as in quality control
Data entered or amended - authorized persons
Security systems to prevent unauthorized entry or manipulation
of data
SOPs for entering data, changing or amending incorrect entries
and creating back-ups
Security procedures in writing
Validation
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4.1 4.3
Validation
(continued)
Traceability is of particular importance
Audit trail:
identify the persons who made entries
identify the persons who made changes
identify the persons who released material
identify the persons who performed other critical steps in
production or control
4.4
Validation
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Validation
(continued)
Entry of critical data by an authorized person
Independent verification and release for use by a second
authorized person
e.g. for entry of a master processing formula.
SOPs for certain systems or processes validated
e.g. action in case of system failure or breakdown
including disaster recovery procedure in the event of a
breakdown
4.5 4.6
Validation
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Validation
Back-ups
Regular back-ups of all files and data
Secure storage (prevent intentional or accidental damage)
Validation
Validation process should include:
Planning
Validation policy
Project plan and SOPs
5.1 6.1
Validation
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Validation
Validation (2)
Define computer-related systems and vendors
Vendor and product evaluated
System designed and constructed
Consider types, testing and quality assurance of the
software
Extent of qualification depends on complexity of the system
6.2
Validation
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Validation
Validation (3)
Qualification includes:
Installation
Evaluation of the system
Performance
Change control, maintenance and calibration, security,
contingency planning, SOPs, training, performance monitoring
and periodic re-evaluation
6.3
Validation
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Validation
Validation of hardware
Appropriate tests and challenges to the hardware
No influence of static, dust, power-feed voltage fluctuations and
electromagnetic interference
Hardware is considered to be equipment
focus on location, maintenance and calibration as part of
the qualification
7.1.1 7.1.2
Validation
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Validation
Validation of hardware (2)
It should prove:
Appropriate capacity
Operational limits
e.g. memory, connector ports, input ports
Performance under worst-case conditions
e.g. long hours, temperature extremes
Reproducibility/consistency
e.g. by performing at least three runs under different
conditions
7.1.3
Validation
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Validation
Validation of hardware (3)
Written qualification protocols; results in qualification reports
kept
Revalidation in case of significant changes
Validation may be performed by the vendor but ultimate
responsibility remains with the company
If records kept by supplier, manufacturer still has to have
sufficient records to allow assessment of the adequacy of the
validation
A mere certification of suitability from the vendor, for example,
will be inadequate
7.1.4 7.1.7
Validation
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Validation
Summary: Validation requirements for Hardware (See table 1 in notes)
Input
devices
Peripheral
devices
Hardware types
Distribution
system
Validation
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Output
devices
August 2006
Signal converter
Central
Processing
Unit
Validation
Summary: Validation requirements for Hardware (See Table 1 in notes)
: Location
, environment
distances
Key aspects
To consider
Maintenance
Command
overrides
Validation
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August 2006
Signal
conversion
I/O operation
Validation
Summary: Validation requirements for Hardware (See Table 1 in notes)
Function
Revalidation
Consistency
and
documentation
Reproducibility
Validation
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Limits
Validation
August 2006
Worst case
Validation
Validation of Software
Software:
is the term used to describe the complete set of programmes
used by a computer, and which should be listed in a menu
Records are considered as software
Focus should be placed on:
accuracy, security, access, retention of records, review,
double checks, documentation and accuracy of
reproduction
7.2.1 7.2.2
Validation
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Validation
Key computer programmes to be identified:
language, name, function (purpose of the programme)
input (determine inputs), output (determine outputs)
fixed set point (process variable that cannot be changed by the
operator), variable set point (entered by the operator)
edits (reject input/output that does not conform to limits and
minimize errors, e.g. four- or five-character number entry), input
manipulation (and equations) and programme overrides (e.g. to
stop a mixer before time)
Identification of authorized personnel
to write, alter or have access to programmes
Validation
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7.2.3 7.2.4
Validation
Validation of Software (2)
Points to be considered may include:
Consistency in performance: Within pre-established limits)
Function: Matching the assigned operational function (e.g.
generate batch documentation, different batches of material
used in a batch listed)
Worst case: Validation under different conditions (e.g.
speed, data volume, frequency)
Repeats: Sufficient number of times (e.g. replicate data
entries)
Documentation: Protocols and reports
Revalidation: In case of significant changes made
7.2.5
Validation
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Validation
Summary: Validation requirements for Software (See Table 1 in notes)
Machine
language
Application
language
Level
High level
language
Validation
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August 2006
Assembly
language
Validation
Summary: Validation requirements for Software (See Table 1 in notes)
Programme
overrides
, Edits
input
manipulation
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,Name
function
Software
identification
Fixed and
Variable
Set points
Validation
Language
August 2006
,Input
output
Validation
Summary: Validation requirements for Software (See Table 1 in notes)
Key aspects
Software
development
Validation
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August 2006
Software
security
Validation
Summary: Validation requirements for Software (See Table 1 in notes)
Function
Documentation
Validation
Worst case
Revalidation
Repeats
Validation
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Validation
Group session
Validation
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August 2006
