Guidelines for Validation & Qualification, including Change Control, for

Hospital Transfusion Laboratories

British Committee for Standards in Haematology
Address for correspondence:
BCSH Secretary
British Society for Haematology
100 White Lion Street
London
N1 9PF
e-mail bcsh@b-s-h.org.uk
Writing group:
S. Allard1, G Burgess2, B. Cuthbertson3, C Elliott 4, R Haggas5, J Jones6, B
Robertson7, D Sadani 8 K Smith2

Disclaimer
While the advice and information in these guidelines is believed to be true and
accurate at the time of going to press, neither the authors, the British Society for
Haematology nor the publishers accept any legal responsibility for the content
of these guidelines.

Date for guideline review

July 2014

Barts and the London NHS Trust & NHSBT

NHSBT Cambridge,
3
SNBTS Edinburgh
4
James Cook University Hospital, Middlesborough
5
Blood Transfusion Dept, Leeds General Infirmary
6
WBS Cardiff
7
Guys & St. Thomas Hospital NHS Trust
8
Leeds Blood Centre
2

Contents
Introduction

Page 3

Section 1

Glossary

Page 3

Section 2

Acronyms & Abbreviations

Page 7

Section 3

Overview

Page 7

Validation flowchart

Page 8

Key Recommendations

Page 10

Section 4

Purpose and scope

Page 10

Section 5.

Validation policy

Page 10

Section 6.

Validation Master Plan

Page 11

Section 7.

Change Control

Page 12

Change control flowchart

Page 14

Section 8.

Quality Risk Assessment

Page 15

Section 9.

User Requirement Specification

Page 17

Section 10. Functional Design Specification

Page 17

Section 11. Validation Process

Page 18

Section 12. Implementation

Page 21

Section 13.

Page 23

List of appendices

Section 14. Acknowledgements and declarations

of interest
Section 15. References

Page 23
Page 24

Introduction
This is a general guideline aimed at providing laboratories a practical framework
required for the introduction or use of any new or change/relocation of
established critical process, equipment, facilities or systems in the transfusion
laboratory. The following areas are covered in detail:
Change Control - a formal system for managing change
Validation - documented evidence that the process meets predetermined
specifications
Qualification - refers to equipment, facilities and systems
This guideline replaces Recommendations for evaluation, validation and
implementation of new techniques for blood grouping, antibody screening and
cross-matching1 and is based on the European Union (EU) Directives2 as
implemented in the UK through the Blood Safety and Quality Regulations SI
2005:50, as amended. 3,
Validation is a requirement of the Blood Safety and Quality Regulations SI
50/2005 (as amended). This guideline should be read in conjunction with:

EU Directives 2002/98/EC, 2004/33/EC, 2005/62/EC

2005/61/EC
EudraLex - Volume 4, Good manufacturing practice (GMP)
Guidelines, including Annex 15 and 20
International Society for Blood Transfusion (ISBT) Guidelines for
validation of automated systems in Blood Establishments Vox
Sanguinis ISBT Science Series (2010) 98 (Suppl. 1): 119
Good Automated Manufacturing Process (GAMP)- Guide for
Validation of Automated Systems)5
Pharmaceutical Inspection Co-operation Scheme PIC/S. GMP Guide
for Blood Establishments 20076
European Commission Working Party on Control of Medicines and
Inspections Final Version of Annex 15 to the EU Guide to Good
Manufacturing Practice 20017

As there are many terms and abbreviations/acronyms used in this guideline

which the reader may be unfamiliar with we have included the glossary and
abbreviations and acronyms used within the document at the beginning of the
guideline to aid the reader. Also included in the main body of text are
references to example documents which can be found on separately on the
BCSH website

1. Glossary
Acceptance Criteria
The criteria a software product must meet to successfully complete a test phase
or to achieve delivery requirements.

Accreditation
Procedure by which an authoritative body e.g. Clinical Pathology Accreditation
(CPA) UK gives formal recognition that an organisation e.g. hospital transfusion
laboratory or blood establishment is competent to carry out specific tasks
against defined standards.
Blood component
Therapeutic component of blood prepared at blood establishment includes red
cells, white cells, fresh frozen plasma, cryoprecipitate and platelets
Blood Establishment
Any organisation that is involved in collection and testing of blood or blood
components and their processing, storage and distribution e.g. National Blood
Service Centres. Blood Establishments must be authorised by the Competent
Authority.
Blood product
Therapeutic product derived from human blood or plasma e.g. Anti-D, Intra
Venous Immunoglobulin (IVIg), albumin, plasma derived factor concentrates
Calibration
Demonstration that a particular measuring device produces results within
specified limits by comparison with those produced by a reference standard
device over an appropriate range of measurements. This process results in
corrections that may be applied to optimise accuracy.
Certificates of calibration
Document signed by qualified authorities that testify that a systems
qualification, calibration, validation or revalidation has been performed
appropriately and that the results are acceptable.
Change Control
A formal system of reviewing and documenting proposed or actual change that
might affect the validated status of a system, equipment or process followed by
action to ensure ongoing validated state.
Competent Authority
The designated Competent Authority for the Blood and Safety Quality
Regulations 2005 is the Medicines and Healthcare Products Regulatory Agency
(MHRA) acting on behalf of the Secretary of State.

Design qualification (DQ)

The documented verification that the proposed design of the equipment and
system is suitable for the intended purpose
Design specification for hardware:
Description of the architecture and configuration of the hardware. It includes
controllers, PCs, instrumentation and interfaces

Design specification for software

Description of logical and physical structures of the program, the standards to
be used for file naming, label allocation and module naming. It defines how the
software implements the requirements based on the functional specification.
Good Laboratory Practice (GLP)
This embodies a set of principles that provides a framework within which
laboratory activities are planned, performed, monitored, recorded, reported and
archived. GLP helps assure regulatory authorities that the data submitted are a
true reflection of a laboratorys activities and forms a reliable basis for making
risk/safety assessments.
Good Manufacturing Practice (GMP)
Good Manufacturing Practice is that part of Quality Assurance which ensures
that Products and/or services are consistently produced and controlled to the
quality standards appropriate to their intended use and as required by the
relevant Regulations.
Process Validation
The documented evidence that the process, operated within established
parameters, can perform effectively and reproducibly to produce a
product/result meeting its predetermined specifications and quality attributes.
Qualification
Action of proving any equipment works correctly and leads to the expected
results. There are 3 phases of qualification listed below.
Installation Qualification (IQ)
The documented verification that the equipment and system as installed or
modified, comply with the approved design and the manufacturers
recommendations.
Operational Qualification (OQ)
The documented verification that the equipment and system, as installed or
modified, perform as intended throughout the anticipated operating ranges.
Performance Qualification (PQ)
The documented verification that the equipment and system, as connected
together, can perform effectively and reproducibly, based on the approved
process method and product specification.
Quality
Consistent and reliable performance of services or products conforming with
specified standards.
Quality control
Quality Control is that part of Good Manufacturing Practice which is concerned
with sampling, specifications and testing, and with the organisation,
documentation and release procedures which ensure that the necessary and

relevant tests are actually carried out and that materials are not released for
use until their quality has been judged to be satisfactory.
Quality assurance
Quality Assurance is a wide-ranging concept, which covers all matters, which
individually or collectively influence the quality of a product. It is the sum total of
the organised arrangements made with the objective of ensuring that
products/services are of the quality required for their intended use. Quality
Assurance therefore incorporates Good Manufacturing Practice.
Quality Management System
A quality management system provides the integration of organisational
structure and all procedures, processes and resources needed to fulfil a quality
policy.
Quality Manager
The quality manager is the individual who ensures that the quality management
system functions correctly.
Quality Manual
A quality manual describes the quality management system and includes the
quality policy and arrangements for its implementation.
Quality Risk Assessment
A systematic process for the assessment, control, communication and review of
risks to the quality of the drug (medicinal) product across the product lifecycle.
Standard Operating Procedure (SOP)
Written and approved description of essential steps, their sequence,
responsibilities and precautionary measures necessary to assure that
operations can be accomplished routinely and in a standardised manner.
User Requirements Specification (URS)
Provides a clear and precise definition of what the user wants the system to do.
It defines the functions to be carried out, the data on which the system will
operate and the operating environment. The URS defines also any nonfunctional requirements, constraints such as time and costs and what
deliverables are to be supplied. The emphasis should be on the required
functions and not the method of implementing those functions.
Validation
The documented evidence that the process, equipment, facilities or systems,
operating within established parameters, can perform effectively and
reproducibly giving results meeting predetermined specifications.
Validation Master Plan
Describes the areas of activities within which validation is to take place and
provides an overview of the status of planning. It lists the areas, systems and
projects being managed, defines the status of validation for each and gives a
broad indication of when validation is to be completed. It is a general plan and

would normally cover all equipment and processes. It should include all
systems for which validation is planned.
Validation Plan
Description of the validation activities, responsibilities and procedures. It
describes specifically how the validation is to be done and details
responsibilities if the Validation Team.
Validation Protocol
Outlines the objectives of validation of a specific equipment or process, testing
protocol including elements such as installation, operational and performance
qualification and documentation.
Validation Report
Presentation of the results of validation activities, interpretation of the results
and the conclusions drawn. If unexpected results are obtained during validation
testing, it defines what changes will need to be made or what workarounds will
be implemented to mitigate risk.
2. Acronyms and Abbreviations
BSQR
CPA
DQ
FDS
GAMP
GMP
GxP
IQ
MHRA

NPSA
OQ
PQ
QA
QC
QMS
RA
SOP
URS
VMP

Blood Safety and Quality Regulations

Clinical Pathology Accreditation (UK) Ltd
Design Qualification
Functional Design Specification
Good Automated Manufacturing Practice
Good Manufacturing Practice
Good Practice
Installation Qualification
Medicines and Healthcare products Regulatory
Agency
National Patient Safety Agency
Operational Qualification
Performance Qualification
Quality Assurance
Quality Control
Quality Management System
Risk Assessment
Standard Operating Procedure
User Requirement Specification
Validation Master Plan

3. Overview
The following flowchart identifies all the stages which should be followed when
validating/qualifying facilities, equipment or process within the laboratory. A
further flowchart showing the steps in change control is included within section
7.

Validation Flowchart

Validation Policy
(Strategic Document)

Validation Master Plan

(Operational Document)

Risk Assessment and

Change Control

Validation Process
Plan
Protocol
Records
Summary report

DQ - design
qualification
IQ - installation
qualification
OQ - operational
qualification
PQ - performance
qualification

Perform
validation of
Processes (e.g.
methods and
reagents)

Perform
qualification of
equipment,
facilities
and systems
Document
via document
control
system

Training to SOPs
Competency assessments

Validation Summary Report

Sign off

Implement

Maintenance of Validated State

3.1 Within the laboratory there should a Validation Policy which is a strategy
document that clearly defines what the validation process is and its purpose
within the laboratory. The policy should make a commitment to maintaining
critical processes and systems in a valid state and should mention applicable
regulations, standards and guidelines that underpin the laboratorys approach to
validation. The validation policy will specify what should be validated and how
validation is executed as defined in the validation master plan. .
3.2 The Validation Master Plan (VMP) details all of the critical processes,
equipment, facilities and systems, when they were last validated and when revalidation is due. The VMP is the operational document which allows the
laboratory to turn the Validation Policy into practice and provides a route map to
how the laboratory ensures critical processes and systems remain valid and fit
for purpose throughout their life-cycle from initial procurement, installation and
routine operation to withdrawal, or replacement. The VMP is a key document
which can be used by laboratories to serve as a tool for ensuring compliance
and may be used by regulatory authorities to check the robustness of the
processes employed in laboratories. The validation policy and VMP may be two
separate documents or integrated as a single document. The VMP should form
part of, or be referenced in, the laboratory quality manual (CPA (UK)
Requirement) 8
3.3 Management of a new (or changed) process, equipment, facilities and
systems should be through Change Control, incorporating a documented
Quality Risk Assessment. Risk assessment is required alongside change
control in order to assess the possible impact of the change so that action can
be taken to reduce or eliminate risk and determine and justify the extent of
validation required.
3.4 Validation Plan. The validation master plan will define the requirement for a
discrete validation plan or in the case of complex systems a series of plans to
validate each component or process. The validation plan will define the need
for a validation protocol(s) describing the scope of the validation and
procedures used.
3.5 A Validation Protocol should be established that specifies how
qualification (Installation, Operational and Performance) of equipment, facilities
and systems or process validation will be conducted. The protocols should be
reviewed and approved both prior to and following execution. The protocol
should specify critical steps and acceptance criteria. The phases of
Validation/Qualification are explained in detail in section 12.2
3.6 Following execution of the protocols a Validation Summary Report should
be prepared detailing the outcome of the validation process. Once all
appropriate training and documentation records are in place the equipment,
facility, system or process can be authorised for use.

Summary of Key Recommendations

Validation, Qualification and Change Control must be an integral
part of the quality management systems in hospital transfusion
laboratories
Each Hospital Transfusion Laboratory should develop its own
Change Control and Validation Policy
The communication and documentation required for these areas
to be GMP compliant must be written within a formal policy
document reflecting the specific intended use of the process
There should be documentation to record each step of the
validation process which is adequate, legible, complete,
reproducible and traceable.
All processes should be adequately challenged and
demonstrated to be robust under most conditions
All staff working within hospital transfusion laboratories should
have documented training in using these policies and protocols
within their own organisation
It is essential to have processes that ensure the maintenance of
the validated state
4
4.1

PURPOSE AND SCOPE

This document refers to all processes and activities that are
performed by hospital transfusion laboratories. It follows the same
principles of Good Manufacturing Practice (GMP) used for the
manufacture of medicinal products and will assist laboratory managers
to identify key principles and outlines for Validation, Qualification and
Change Control and the documentation required for the hospital
transfusion laboratory with reference to some practical examples.

5.

VALIDATION POLICY

5.1

There must be a written policy that clearly defines what the validation
and qualification process is and its purpose within the laboratory. The
policy should make a commitment to maintaining critical processes,
equipment, facilities and systems in a valid state and should mention
applicable regulations, standards and guidelines that underpin the
laboratorys approach to validation.

5.2

The policy should cover at least the following:

In the transfusion laboratory, validation must comply with the
requirements of Regulation 9 (1) c of the Blood Safety and Quality
Regulations (SI 2005 no. 50) as amended and should also satisfy the
CPA (UK) Medical Laboratory Standards.
An outline of the organisational responsibility for validation.
An outline of the key principles to be applied to the validation
programme, such as the use of risk and criticality* assessment in
planning what should be subject to validation and how it should be
validated.

10

 A commitment to documenting what process, equipment, facilities

and systems are subject to validation and how they will be validated in
the form of a Validation Master Plan supported by written validation
procedures or protocols and validation records.
* criticality determines the critical nature of the process, equipment,
facilities or systems in relation to the safety of the overall transfusion
process
Recommendation:
There should be a Validation Policy, which is an over arching
management document that details the arrangements for
undertaking validation and qualification.

VALIDATION MASTER PLAN

6.1

The Validation Master Plan (VMP) is a quality management system

document. It should be a controlled document, approved by senior
laboratory management and regularly reviewed and, if necessary,
revised in response to organisational and operational changes.

6.2

The VMP should be based on and refer to the Validation Policy (See
section 5). The VMP should clarify:
under what circumstances
who is responsible
how the validation will be performed and documented
how the validated state will be maintained through regular
servicing and calibration and re-qualification.

6.3

A VMP should be produced for each laboratory or network of laboratories

if they are operating under a common quality system and should cover
the processes and systems in use.

6.4

For large projects such as the implementation of a new Laboratory

Information System or relocation of the laboratory to new facilities, it may
be appropriate to have a project-specific VMP. The VMP will inform those
working as part of the project team to ensure that the project delivers
processes and systems that are in a validated state and fit for use. Also,
it may be desirable for reasons of complexity to have separate VMPs
covering different systems such as computer systems and automated
test systems.

6.5

As a minimum, a VMP should cover:

The organisational structure and responsibilities for validation
activities
Summary or list of process, equipment, facilities or systems to be
validated and qualified
11

6.6

How validation is planned and scheduled

The formats for validation documentation
The role of validation in change control (See section 7) and
project management.
Links to other relevant Quality System processes (e.g. supplier
control, document control, training, equipment calibration and
maintenance.)

An example of a what should be included in VMP is available in

Appendix 1
An example of a specific VMP is available in Appendix 2

Recommendation:
Each organisation should have a VMP in place as part of its
Quality System
The VMP should outline responsibilities for ensuring all
process, equipment, facilities and systems remain validated

7.

CHANGE CONTROL

7.1

Uncontrolled change carries significant risk of loss of the validated state

for laboratory processes, equipment, facilities or systems. Therefore
Change Control should be initiated by a proposed change that impacts
upon any laboratory process, equipment, facilities or systems. The steps
of change control are shown in Figure 2. Changes may result from:

a planned change in a laboratory process or inputs (e.g.

equipment, materials),
the systematic review of a procedure
audit finding(s)
quality incident(s)
complaint(s)

7.2

Some laboratory changes e.g. using new equipment of the same type, or
relocating the process may not require any alteration to documented
procedures, but these changes should still be subject to change control.

7.3

Minor amendments to written procedures may not need to be subject to

Change Control, but must be managed through the document control
process.

7.4

Each change must be planned and records maintained to confirm the

successful outcome of each stage. When all stages are complete there
must be an independent review and formal approval by a person
designated by the laboratory Responsible Person, for the new or
changed process to go live in the laboratory.

12

7.5

An example of a change request form is available in Appendix 3. . This is

completed for changing of a reagent but the same template could be
used for any change request.

Recommendation:
Change Control must be an integral portion of the transfusion
laboratory quality system
Change Control should be achieved through a formal, documented
system to ensure that compliance and quality standards are
maintained during and following a change.
After completion of each stage of change control a formal release
for the next step should be made as a written authorisation.

13

Change control flowchart

REQUEST FOR
CHANGE

Impact and Risk

Assessment on laboratory
processes/system

YES

Is validation /
qualification required?

NO

Does documentation
need changing?
Yes
Perform
Validation /
qualification

Approve

Documentation

No

No change to
documentation
No additional
training required

Update documentation
via document control
system

Training - task based SOP

Competency assessment

Implement
change

Review, sign off and close

change

14

8.

Quality Risk Assessment

8.1

Quality risk assessment is required alongside change control in order to

assess the possible impact of the change so that action can be taken to
reduce or eliminate risk. This must include all risks to patients,
environment and laboratory systems. The assessment may be used to
determine the extent of validation required. Consideration should be
given to Annex 20 of the EU GMP9.
Further information on Risk Assessment is available in the NPSA
Healthcare Risk Assessment made easy 200710.

8.2

Quality risk assessment consists of the identification of hazards and the

analysis and evaluation of risks associated with exposure to those
hazards (as defined below). Quality risk assessments begin with a welldefined problem description or risk question. When the risk in question is
well defined, the types of information needed to address the risk question
will be more readily identifiable. As an aid to clearly defining the risk(s)
for risk assessment purposes, three fundamental questions are often
helpful:
1. What might go wrong?
2. What is the likelihood (probability) it will go wrong?
3. What are the consequences (severity) of its going wrong?
Risk is the combination of likelihood and consequence of a hazard being
realised.
Risk assessment can be complex and requires input from persons who
both understand risk assessment and the processes and systems being
assessed.

8.3

There are four basic steps in a risk assessment

Step 1 Risk Identification Identify the hazards - (what might go
wrong?)
Step 2 Risk Analysis Evaluate the risks (how bad? how often?) and
decide on the precautions (is there a need for further action?)
Step 3 Record your findings and any proposed risk control or risk
reduction (action to mitigate against the risk).
Step 4 Review assessments and update as necessary.

8.4

Risk identification is a systematic use of information to identify hazards

referring to the risk question or problem description. Information can
include historical data, theoretical analysis, informed opinions, and the
concerns of stakeholders. Risk identification addresses the What might
go wrong? question, including identifying the possible consequences.
This provides the basis for further steps in the quality risk management
process.

15

8.5

Risk analysis is the estimation of the risk associated with the identified
hazards. It is the qualitative or quantitative process of linking the
likelihood of occurrence and severity of harms. In some risk
management tools, the ability to detect the harm (detectability) is also a
factor in the estimation of risk.

8.6

Risk Control includes decision making to reduce and/or accept risks.

The purpose of risk control is to reduce the risk to an acceptable level.
The amount of effort used for risk control should be proportional to the
significance of the risk. Decision makers might use different processes,
including benefit-cost analysis, for understanding the optimal level of risk
control.
Risk control might focus on the following questions:
a. is the risk above an acceptable level?
b. what can be done to reduce or eliminate risks?
c. what is the appropriate balance among benefits, risks and
resources?
d. are new risks introduced as a result of the identified risks being
controlled?

8.7

Risk reduction focuses on processes for mitigation or avoidance of

quality risk when it exceeds a specified (acceptable) level. Risk reduction
might include actions taken to mitigate the severity and probability of
harm. Processes that improve the detectability of hazards and quality
risks might also be used as part of a risk control strategy.

8.8

Review: the implementation of risk reduction measures can introduce

new risks into the system or increase the significance of other existing
risks. Hence, it might be appropriate to revisit the risk assessment to
identify and evaluate any possible change in risk after implementing a
risk reduction process.

8.9

An example of a risk assessment is available at

www.transfusionguidelines.org.uk , as part of the change control
documentation. The risk assessment form has been completed to
assess the risks of changing screening panel cells but this form could be
used to assess any risk within the blood transfusion laboratory.
Recommendation:
A quality risk assessment must be performed when any planned
change to laboratory processes/systems is undertaken
Staff who undertake the risk assessment should have been trained
in risk assessment and should have knowledge of the processes
and systems being assessed.

16

9.

User Requirement Specification (URS)

9.1

The User Requirement Specification is an essential document produced

by, or on behalf of your organisation, before the purchase of new or
replacement process, equipment, facilities or systems. The URS should
be written by the end users in conjunction with the quality department.

9.2

The URS:
documents the purposes for which a process, equipment, facilities
or systems is required
describes essential (musts) and desirable (wants) requirements.
defines the functions to be carried out
defines the operating environment within which the system will
operate
defines any non-functional requirements such as time and costs
and what deliverables are to be supplied.

9.3

Functional Requirements: Statements that specify what the

process, equipment, facilities or systems must be able to do.

9.4

Non-Functional Requirements: Covering the way in which the process,

equipment, facilities or systems should behave in respect of the
compliance to external requirements (e.g. legislative requirements) and
elements of good practice (GxP).

9.5

The URS should express requirements and not design solutions

9.6

Each requirement should be testable or verifiable in some way.

9.7

Wherever possible, requirements should be prioritised with essential

requirements and desirable features distinguished.

9.8

The URS should be reviewed and approved then authorised by an

appropriate person within the organisation.

9.9

An example of what should be included in a URS in Appendix 4 and a

specific URS for purchasing a grouping analyser is available in Appendix
5.

Recommendation:
A URS should be written for all new purchases
10.

Function Design Specification (FDS)

10.1

The FDS is a description of the system to be supplied/implemented in

terms of:
a) the functions it will perform and
b) facilities required in order to meet the user requirements as
defined in the URS.

17

10.2

A system acceptance test specification should be produced based on the

FDS, it is often beneficial to produce these documents in parallel.

10.3

The FDS is normally written by the supplier as part of the supplier

response although further revisions may be prepared in conjunction with
the user. The FDS links to operational qualification (OQ), which tests all
the functions specified.

10.4

A table giving suggested sections and sub-sections that can be included

in the FDS is available in Appendix 6

Recommendation:
A FDS should be written when purchasing large, multi-functional
process, equipment, facilities or systems
11. Validation Process:
Each part of the validation process should be documented. There should
be a written plan for performing each validation to specify who is
responsible for managing and performing the various validation tasks such
as production of validation protocols and approvals of validation
documentation. Validation protocols should be written for each phase of
the validation to include acceptance criteria. The validation plan and the
validation protocols may be combined into a single document. The
outcome of each phase of validation should be recorded and the overall
conclusions, with a scientific assessment of any failures should be
documented in a validation summary report. The validation records and
summary report must be reviewed and approved before putting the
process or system affected into use.
11.1

Validation Plan

11.1.1 The plan should first identify:

What is being validated
where the validation will take place
why the validation is taking place providing reference to any
relevant change control records, risk assessments, URS and
FDS.
the validation stages required
validation time-frames
11.1.2 The plan should also identify the validation team and define
responsibilities for:
overall management of the validation
production of protocols
performing the validation and recording the outcome
reviewing and approving the protocols and validation records
reviewing the validation outcomes and signing off the validation
as acceptable.

18

11.1.3The review, approvals and sign-off should be assigned to a senior

member of staff who is independent of those performing the validation
tasks.
An example of a validation plan is available Appendix 7
11.2 Validation Protocol

11.2.1 A validation protocol is an integral element of the validation plan. The

protocol describes:
the qualification/validation phase (IQ,OQ,PQ or method process
validation)
that tests will be performed
the test procedures
the objectives of the validation in terms of acceptance criteria for
each test
records to be completed.
11.2.2 What needs to be tested, how many tests to do and the acceptance
criteria at each validation phase will be specific to each validation and
must be founded on the scientific and technical basis of the processes
and systems involved. It should be possible to establish the specific
requirements by reference to the relevant risk assessments, URS, FDS,
published standards, regulations & guidelines.
11.2.3 Validation record proformas should be completed as part of the protocol
and approved along with the protocol.
11.2.4 The phases of qualification for process, equipment, facilities or systems
are:
a. Installation Qualification (IQ)
This involves verification of good engineering practice in installation
of equipment, and should consider electrical safety, safety issues,
location siting, maintenance/calibration schedules and should confirm
that the installation has been carried out as specified with the
appropriate supporting documentation. This activity can be delegated
to the supplier, provided that the content of the IQ document is
approved in advance by the laboratory.
b. Operational Qualification (OQ)
This is the verification of process, equipment and facilities over its
operating range and is assessed against the specifications as
defined in the URS. During this stage, a range of tests will be carried
out to demonstrate the integrity and functionality of the system,
including the ability to operate under worst case conditions.
Confirmation that all calibration, operating and cleaning processes
have been defined and tested will be required. Definition of the
required programme of planned preventative maintenance (PPM)
19

should be considered. OQ can be carried out by the supplier and/or

by laboratory, or a combination of both. In any case, this must be
performed using an agreed OQ protocol.
c. Performance Qualification (PQ)
This is performed to demonstrate that the process, equipment or
facility performs as required under routine operational conditions and
as defined in the URS. This is sometimes referred to as Process
Validation and is the stage of the exercise when the equipment or
process is assessed in its practical application, with operational
outputs/product being assessed for acceptability.
11.2.5 Following the qualification of process, equipment and systems full
process or method validation may be desirable, which involves a period
of routine operation
11.2.6 Examples of applications of the IQ, OQ and PQ portion of the testing are
available in Appendix 8 and 9 and these identify the component parts of
the qualification and an example of the validation protocol document.
An example of each phase of the qualification (IQ, OQ and PQ) is
available in Appendix 10

11.3

Validation Records :

11.3.1 The outcome of the various validation tests described in the protocol
must be recorded at the time the tests are performed.
11.3.2 The Validation record pro-formas or test scripts should be used for
recording the outcomes.
11.3.3 When the testing for each validation phase is complete the result must
be reviewed and a summary report produced. The summary report
should confirm that acceptance criteria have been achieved and provide
the overall conclusions.
11.3.4 There should be a scientific assessment of any failures.
11.3.5 At the end of each phase, the validation/qualification records and
summary report must be reviewed by the appointed responsible person
and the decision regarding the acceptability of the validation recorded.
11.3.6 Records should be maintained for minimum of the life of the validated
process/equipment etc.
11.3.7 An example of a validation report is available in Appendix 11.
Recommendation:
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 Each stage of the validation process should be fully

documented, reviewed, authorised and signed off
There should be a formal review of each stage of validation and
documented approval before proceeding to the next stage

12. Implementation
12.1 Documentation
All the documentation which is part of the validation process should be
maintained by the document control system and retained for a minimum of
15 years or the life time of the process, equipment, facilities or systems,
whichever is the longest. SOPs should be written and authorised prior to
the equipment/method/system being brought into routine use.
12.2 Training
All staff who may be involved in using the equipment that has been qualified
or the system validated must be trained before using the former. Training
and competency assessments should be completed and the records kept.
12.3 Validation Final Summary Report
A Validation Summary Report that cross-references the qualification and/or
validation protocol should be prepared, summarising the results obtained,
commenting on any deviations observed, and drawing the necessary
conclusions, including recommending changes necessary to correct
deficiencies. Any changes to the plan as defined in the protocol should be
documented with appropriate justification. This report should be cross
referenced to the change control document and the quality risk assessment
matrix.

Retention of all records and documents from the validation/qualification

should be retained and easily available to reconstruct the entire validation
history.
The whole process should be reviewed, each step formally authorised and
signed off before accepting into routine use.

12.4 Maintaining the validated state

It is imperative that the information which has been collected at the PQ
stage of the validation process is used to determine how the maintenance of
the validated state can be attained. The VMP must also be updated to
account for any new process, equipment, facilities or systems. Issues for
consideration should include:

maintenance
cleaning schedules
internal quality controls
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manufacturers instructions
software/hardware upgrades

12.5 Revalidation
Revalidation should be determined and included in the VMP. Revalidation
may occur when no changes, upgrades have occurred and therefore may
not require change control to be undertaken. The timescale for revalidation
should be clearly indicated in the VMP e.g. annual revalidation of transport
boxes

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13. List of Appendices

The appendices to this guideline have been compiled as a separate
document that can also be downloaded from the BCSH website.
1.
2.
3.
4.

Information to be included in the Validation Master Plan (VMP)

Example of a VMP currently in use in an NHS Hospital
Change Control Request Form
Specifications of what could be included in a User Requirement
Specification
5. Example of a User Requirement Specification
6. Specifications for inclusion in FDS
7. Example of a Validation Plan
8. Installation Qualification, Operational Qualification and Process
Qualification
9. Example of Validation Protocol
10. Example of a qualification Proforma
11. Validation sign off report

14. Acknowledgements and declarations of interest

None of the authors have declared a conflict of interest.
The Transfusion Task Force membership at the time of writing this guideline
was:
Derek Norfolk, Andrea Harris, Shubha Allard, Sarah Allford, Hafiz Qureshi,
Joan Jones, Clare Taylor, Jenny White

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15. References
1. Scott et al. 1995 Recommendations for evaluation, validation and
implementation of new techniques for grouping, antibody screening and
crossmatching. Transfusion Medicine 1995; 5, 145-150
2. Directive 2002/98/EC
http://ec.europa.eu/health/ph_threats/human_substance/legal_blood_en.
htm
3. The Blood Safety & Quality Regulations 2005 No. 50 as amended (the
principal Regulations) were signed by authority of the Secretary of State
for Health, as were the amending Regulations (SI 2005/1098, SI
2005/2898, SI 2006/2013 & SI 2007/604).
http://www.opsi.gov.uk/stat.htm
Blackwell Publishing Ltd.

4. ISBT Guidelines for validation and maintaining the validation state of

automated systems in blood banking. Vox Sanguinis (2003) 85 (Suppl.
1), S1S14
5. The Good Automated Manufacturing Practice (GAMP) Guide for
Validation of Automated Systems in Pharmaceutical Manufacture
6. Pharmaceutical Inspection Co-operation Scheme PIC/S. GMP Guide for
Blood Establishments 2007
7. European Commission Working Party on Control of Medicines and
Inspections Final Version of Annex 15 to the EU Guide to Good
Manufacturing Practice 2001
8. CPA 2007. Standards for Medical Laboratories
9. http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/homev4.htm
10. NPSA (March 2007) Healthcare Risk Assessment made easy.
http://www.npsa.nhs.uk/EasySiteWeb/GatewayLink.aspx?alId=5616

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