Supplementary Training Modules on

Good Manufacturing Practice

Validation

WHO Technical Report Series,

No. 937, 2006. Annex 4.

Validation | Slide 1 of 31 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 | Slide 2 of 31 August 2006

 Supplementary Training Modules on
Good Manufacturing Practice

Computerized systems validation

Part 5

WHO Technical Report Series,

No. 937, 2006. Annex 4. Appendix 5

Validation | Slide 3 of 31 August 2006

 Validation
Objectives

To discuss validation of computerized systems including:

 System specifications
 Functional specifications
 Security
 Back-ups
 Validation:
– Hardware
– Software

Validation | Slide 4 of 31 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 | Slide 5 of 31 August 2006

 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 | Slide 6 of 31 August 2006

 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 | Slide 7 of 31 August 2006

 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) 2.1

Validation | Slide 8 of 31 August 2006

 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 | Slide 9 of 31 August 2006

 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 | Slide 10 of 31 August 2006
 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 | Slide 11 of 31 August 2006

 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

4.1 – 4.3

Validation | Slide 12 of 31 August 2006

 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 | Slide 13 of 31 August 2006

 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 | Slide 14 of 31 August 2006

 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 | Slide 15 of 31 August 2006

 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 | Slide 16 of 31 August 2006

 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 | Slide 17 of 31 August 2006

 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 | Slide 18 of 31 August 2006

 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 | Slide 19 of 31 August 2006

 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 | Slide 20 of 31 August 2006

 Validation
Summary: Validation requirements for Hardware (See table 1 in notes)

Input Output
devices devices

Peripheral Hardware types Signal converter

devices

Central
Distribution Processing
system Unit

Validation | Slide 21 of 31 August 2006

 Validation
Summary: Validation requirements for Hardware (See Table 1 in notes)
:Location
,environment
distances

Key aspects Signal

Maintenance To consider conversion

Command I/O operation

overrides

Validation | Slide 22 of 31 August 2006

 Validation
Summary: Validation requirements for Hardware (See Table 1 in notes)

Revalidation Function

Consistency
and Validation Limits
documentation

Reproducibility Worst case

Validation | Slide 23 of 31 August 2006

 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 | Slide 24 of 31 August 2006

 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 7.2.3 – 7.2.4

Validation | Slide 25 of 31 August 2006

 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 | Slide 26 of 31 August 2006

 Validation
Summary: Validation requirements for Software (See Table 1 in notes)

Application Machine
language language

Level

High level Assembly

language language

Validation | Slide 27 of 31 August 2006

 Validation
Summary: Validation requirements for Software (See Table 1 in notes)

Programme Language
overrides

,Edits Software ,Name

input identification function
manipulation

Fixed and ,Input

Variable output
Set points

Validation | Slide 28 of 31 August 2006

 Validation
Summary: Validation requirements for Software (See Table 1 in notes)

Key aspects

Software Software
development security

Validation | Slide 29 of 31 August 2006

 Validation
Summary: Validation requirements for Software (See Table 1 in notes)

Function
Documentation

Validation
Worst case

Revalidation

Repeats

Validation | Slide 30 of 31 August 2006

 Validation

 Group session

Validation | Slide 31 of 31 August 2006