Valid laboratory results are essential for diagnosis, surveillance and trade.

Such results are

achieved by the use of good management practices, valid test and calibration methods, proper
techniques, quality control and quality assurance, all working together within a quality management
system. Laboratory quality management includes technical, managerial and operational elements of
testing and the interpretation of test results. A quality management system enables the laboratory
to demonstrate both competency and an ability to generate consistent technically valid results that
meet the needs of its customers. The need for mutual recognition of test results for international
trade and the acceptance of international standards such as ISO/IEC 1 17025:2005 General
Requirements for the Competence of Testing and Calibration Laboratories (ISO/IEC, 2005) requires
good laboratory quality management systems. This chapter is not intended to reiterate the
requirements of ISO/IEC 17025, nor has it been endorsed by accreditation bodies. Rather, it
outlines the important issues and considerations a laboratory should address in the design and
maintenance of its quality management system, whether or not it has been formally accredited.
Chapter 1.1.1 Management of Veterinary Laboratories gives an introduction to the components of
governance and management of veterinary laboratories that are necessary for the effective delivery
of diagnostic services, and highlights the critical elements that should be established as minimum
requirements.

To ensure that the quality management system is appropriate and effective, the design must be carefully thought
out and, where accreditation is sought, must address all criteria of the appropriate quality standard. The major
categories of consideration and the key issues and activities within each of these categories are outlined in the
following eight sections of this chapter.

Many factors affect the necessary elements and requirements of a quality management system. These factors
include:

i) The type of testing done, e.g. research versus diagnostic work;

ii) The purpose and requirements of the test results, e.g. for import or export, quarantine;
iii) The impact of a questionable or erroneous result, e.g. foot and mouth disease (FMD) in an FMD-free
country;
iv) The tolerance level of risk and liability, e.g. vaccination vs culling or slaughter;
v) Customer needs (e.g. sensitivity and specificity of the test method, cost, turnaround time, strain or genotype
characterisation), e.g. for surveillance, or declaration of freedom after outbreak;
vi) The role of the laboratory in legal work or in regulatory programmes, e.g. for disease eradication and
declaration of disease freedom to the OIE;

1 ISO/IEC: International Organization for Standardization/International Electrochemical Commission.

vii) The role of the laboratory in assisting with, confirming, or overseeing the work of other laboratories (e.g. as a
reference laboratory);
viii) The business goals of the laboratory, including the need for any third party recognition or accreditation.

The laboratory should choose reputable and accepted standards and guides to assist in designing the quality
management system. For laboratories seeking accreditation of testing, and for all OIE Reference Laboratories,
the use of ISO/IEC 17025 (ISO/IEC, 2005) or equivalent will be essential. This standard includes managerial and
technical requirements and laboratories that are compliant are regarded as competent. Further information on
standards may be obtained from the national standards body of each country, from the International Laboratory
Accreditation Cooperation (ILAC)2, and from accreditation bodies, e.g. the National Association of Testing
Authorities (NATA), Australia, the United Kingdom Accreditation Service (UKAS), the American Association for
Laboratory Accreditation (A2LA), etc. Technical and international organisations such as AOAC International (The
Scientific Association Dedicated to Analytical Excellence; formerly the Association of Official Analytical Chemists)
and the International Organization for Standardization (ISO) publish useful references, guides, application
documents and standards that supplement the general requirements of ISO/IEC 17025. Other relevant
documents may include guides and application documents providing interpretative criteria and recommendations
for the application of ISO/IEC 17025 in the field of veterinary testing for both applicant and accredited facilities,
e.g. http://www.nata.com.au/nata/phocadownload/publications/Accreditation_criteria/ISO-IEC-
17025/VET/Veterinary-Testing-ISO-IEC-17025-Application-Document.pdf

The ISO International Standard 9001 (ISO, 2015), is a certification standard for quality management systems and
while it may be a useful supplement to a quality system, its requirements do not necessarily ensure or imply
technical competence (in the areas listed in Section 3 Accreditation). ISO 9001 is assessed by a certification body
that is accredited to undertake such assessments by the national accreditation body. When a laboratory meets
the requirements of ISO 9001, the term registration or certification is used to indicate conformity, not
accreditation.

With the advent of stronger alliances between medical and veterinary diagnostic testing under initiatives such as
“One Health”, some laboratories may wish to choose other ISO standards such as ISO 15189 (ISO/IEC, 2012),
which include testing of human samples, e.g. for zoonotic diseases.

If the laboratory decides to proceed with formal recognition of its quality management system and testing, then
third party verification of its conformity with the selected standard(s) will be necessary. ILAC has published
specific requirements and guides for laboratories and accreditation bodies. Under the ILAC system, ISO/IEC
17025 is to be used for laboratory accreditation of testing or calibration activities. Definitions regarding laboratory
accreditation may be found in ISO/IEC International Standard 17000: Conformity Assessment – Vocabulary and
Principles (ISO/IEC, 2004a). Accreditation is tied to demonstrated competence, which is significantly more than
having and following documented procedures. Providing a competent and customer-oriented service also means
that the laboratory:

i) Has technically valid and validated test methods, procedures and specifications that are documented in
accordance with the requirements of the applicable standard or guidelines, e.g. Chapter 1.1.6 Principles and
methods of validation of diagnostic assays for infectious diseases and chapters 3.6.1 to 3.6.8
Recommendations for validation of diagnostic tests;
ii) Has appropriately qualified and trained personnel with a depth of technical knowledge commensurate with
appropriate levels of authority;
iii) Has appropriate equipment with planned maintenance or calibration schedules;
iv) Has adequate facilities and environmental control;
v) Has procedures and specifications that ensure accurate and reliable results;
vi) Implements continual improvements in testing and quality management;
vii) Can assess the need for and implement appropriate corrective or preventive actions, e.g. customer
satisfaction;
viii) Accurately assesses and controls uncertainty in testing;

2 ILAC: The ILAC Secretariat, PO Box 7507, Silverwater, NSW 2128, Australia; http://ilac.org/
ix) Demonstrates proficiency in the test methods used (e.g. by participation in proficiency tests on a regular
basis);
x) Has demonstrable competence to generate technically valid results.

To facilitate the acceptance of the laboratory’s test results for trade, the accreditation standard used must be
recognised by the international community and the accreditation body recognised as competent to accredit
laboratories. Programmes for the recognition of accreditation bodies are, in the ILAC scheme, based on the
requirements of ISO/IEC International Standard 17011: General Requirements for Accreditation Bodies
Accrediting Conformity Assessment Bodies (ISO/IEC, 2004b). Information on recognised accreditation bodies
may be obtained from the organisations that recognise them, such as the Asia-Pacific Laboratory Accreditation
Cooperation (APLAC), the Inter-American Accreditation Cooperation (IAAC), and the European Co-operation for
Accreditation (EA).

Accreditation bodies may also be signatory to the ILAC and regional (e.g. APLAC) mutual recognition
arrangements (MRAs). These MRAs are designed to reduce technical barriers to trade and further facilitate the
acceptance of a laboratory’s test results in foreign markets. Further information on the ILAC MRA may be
obtained from the www.ilac.org

The quality management system should cover all areas of activity affecting all testing that is done at the
laboratory. While accredited laboratories are obliged to meet the requirements of the standard as detailed below,
these principles are relevant to all testing laboratories.

Laboratories accredited to ISO/IEC 17025 have a specific list of those tests that are accredited, called the
schedule of accreditation or the scope. Veterinary testing facilities include government and private facilities,
veterinary practices, university veterinary schools, and other laboratories for the testing of animals and animal
products for the diagnosis, monitoring and treatment of disease. In principle, if new testing methods are
introduced these must be assessed and accredited before they can be added to the scope, however a flexible
scope can be implemented that assesses the laboratory as competent to add tests to scope, which are then
formally added at the next accreditation visit. The quality management system should ideally cover all areas of
activity affecting all testing that is done at the laboratory. However, it is up to the laboratory to decide which tests
are to be accredited and included in the scope. If an accredited laboratory also offers unaccredited tests, these
must be clearly indicated as such on any reports that claim or make reference to accreditation. Factors that might
affect the laboratory’s choice of tests for scope of accreditation include:

i) The impact of initial accreditation on resources within a given deadline;

ii) A contractual requirement for accredited testing (e.g. for international trade, research projects);
iii) The importance of the test and the impact of an incorrect result;
iv) The cost of maintaining an accredited test;
v) Availability of personnel, facilities and equipment;
vi) Availability of reference standards (e.g. standardised reagents, internal quality control samples, reference
cultures) and proficiency testing schemes;
vii) The quality assurance necessary for materials, reagents and media;
viii) The validation, technical complexity and reliability of the test method;
ix) The potential for subcontracting of accredited tests;

Quality assurance (QA) is the part of quality management focused on providing confidence that quality
requirements will be fulfilled. The requirements may be internal or defined in an accreditation or certification
standard. QA is process orientated and ensures the right things are being done in the right way.

Quality control (QC) is the systematic and planned monitoring of output to ensure the minimum levels of quality
have been met. For a testing laboratory, this is to ensure test processes are working correctly and results are
within the expected parameters and limits. QC is test orientated and ensures the results are as expected.
Proficiency testing (PT), sometimes referred to as external quality assurance or EQA, is the determination of a
laboratory’s performance by testing specimens of undisclosed content. Ideally, PT schemes should be run by an
external independent provider. Participation in proficiency testing enables the laboratory to assess and
demonstrate the reliability of results by comparison with those from other participating laboratories.

All laboratories should, where possible, participate in external proficiency testing schemes appropriate to their
testing. Participation in such schemes is a requirement for accredited laboratories. This provides an independent
assessment of the testing methods used and the level of staff competence. If such schemes are not available,
valid alternatives may be used, such as ring trials organised by reference laboratories, inter-laboratory testing,
use of certified reference materials or internal quality control samples, replicate testing using the same or different
methods, retesting of retained items, and correlation of results for different characteristics of a specimen.

Providers and operators of proficiency testing programmes should be accredited to ISO/IEC 17043 – Conformity
Assessment – General Requirements for Proficiency Testing (ISO/IEC, 2010).

Proficiency testing material from accredited providers has been well characterised and any spare material, once
the proficiency testing has been completed, can be useful to demonstrate staff competence or for test validation.
Information about selection and use of reference samples and panels is available in Chapter 3.6.6 Selection and
use of reference samples and panels.

ISO/IEC 17025 requires the use of appropriate test methods and has requirements for their selection,
development, and validation to show fitness for purpose.

This Terrestrial Manual provides recommendations on the selection of test methods for trade, diagnostic and
surveillance purposes in the chapters on specific diseases. Disease-specific chapters include, or will include in
the near future, a table of the tests available for the disease graded against the test’s fitness for purpose; these
purposes are defined in the OIE Validation Template (chapter 1.1.6), which identifies six main purposes for which
diagnostic tests may be carried out. The table is intended to be a general guide to test application. The fact that a
test is recommended does not necessarily mean that a laboratory is competent to perform it. The laboratory
quality system should incorporate provision of evidence of competency.

In the veterinary profession, other standard methods (published in international, regional, or national standards) or
fully validated methods (having undergone a full collaborative study and that are published or issued by an
authoritative technical body such as the AOAC International) may be preferable to use, but may not be available.
Many veterinary laboratories develop or modify methods, and most laboratories have test systems that use non-
standard methods, or a combination of standard and non-standard methods. In veterinary laboratories, even with
the use of standard methods, some in-house evaluation, optimisation, or validation generally must be done to
ensure valid results.

Customers and laboratory staff must have a clear understanding of the performance characteristics of the test,
and customers should be informed if the method is non-standard. Many veterinary testing laboratories will
therefore need to demonstrate competence in the development, adaptation, and validation of test methods.

This Terrestrial Manual provides more detailed and specific guidance on test selection, optimisation,
standardisation, and validation in chapter 1.1.6. Chapter 1.1.6 refers to chapters 3.6.1–3.6.8 Recommendations
for validation of diagnostic tests that deal with the development and optimisation of fundamentally different assays
such as antibody, antigen and nucleic acid detections tests, measurement uncertainty, statistical approaches to
test validation, selection and use of reference samples and panels, validation of diagnostic tests for wildlife and
comparability experiments after changes in a validated test method.

The following are key test method issues for those involved in the quality management of the laboratory.

Valid results begin with the selection of a test method that meets the needs of the laboratory’s
customers in addressing their specific requirements (fitness for purpose). Some issues relate directly to
the laboratory, others to the customer.

i) International acceptance;
ii) Scientific acceptance;
 iii) Appropriate or current technology;
iv) Suitable performance characteristics (e.g. analytical and diagnostic sensitivity and
specificity, repeatability, reproducibility, isolation rate, limits of detection, precision,
trueness, and uncertainty);
v) Suitability of the test in the species and population of interest;
vi) Sample type (e.g. serum, tissue, milk) and its expected quality or state on arrival at the
laboratory;
vii) Test target (e.g. antibody, antigen, live pathogen, nucleic acid sequence);
viii) Test turnaround time;
ix) Resources and time available for development, adaptation, evaluation;
x) Intended use (e.g. export, import, surveillance, screening, diagnostic, confirmatory);
xi) Safety factors;
xii) Customer expectations;
xiii) Throughput of test samples required;
xiv) Cost of test, per sample;
xv) Availability of reference standards, reference materials and proficiency testing schemes.
(See also chapter 3.6.6.)

Once the method has been selected, it must be set up at the laboratory. Additional optimisation is
necessary, whether the method was developed in-house or imported from an outside source.
Optimisation establishes critical specifications and performance standards for the test process as used
in a specific laboratory.

i) Critical specifications for equipment and instruments;

ii) Critical specifications for reagents (e.g. chemicals, biologicals), reference standards,
reference materials, and internal controls;
iii) Robustness – critical control points and acceptable ranges, attributes or behaviour at
critical control points, using statistically acceptable procedures;
iv) Quality control activities necessary to monitor critical control points;
v) The type, number, range, frequency, and arrangement of test run controls;
vi) Criteria for non-subjective acceptance or rejection of a batch of test results;
vii) Criteria for the interpretation and reporting of test results;
viii) A documented test method and reporting procedure for use by laboratory staff;
ix) Evidence of technical competence for those who perform the test processes and interpret
results.

Validation evaluates the test for its fitness for a given use by establishing test performance
characteristics, such as sensitivity, specificity, and isolation rate; and diagnostic parameters such as
positive or negative cut-off, and titre of interest or significance. Validation should be done using an
optimised, documented, and fixed procedure. The extent and depth of the validation process will
depend on logistical and risk factors. It may involve any number of activities and amount of data, with
subsequent data analysis using appropriate statistical methods.

i) Field or epidemiological studies, including disease outbreak investigations;

ii) Development of testing algorithms for specific purposes, e.g. surveillance, outbreak
investigations, etc.;
 iii) Repeat testing to establish the effect of variables such as operator, reagents, equipment;
iv) Comparison with other, preferably standard, methods and with reference standards (if
available);
v) Collaborative studies with other laboratories using the same documented method. Ideally
organised by a reference laboratory and including testing a panel samples of undisclosed
composition or titre with expert evaluation of results and feedback to the participants;
vi) Reproduction of data from an accepted standard method, or from a reputable publication;
vii) Experimental infection or disease outbreak studies;
viii) Analysis of internal quality control data.

Validation is always a balance between cost, risk, and technical possibilities. There may be cases
where quantities such as accuracy and precision can only be given in a simplified way. Criteria and
procedures for the correlation of test results for diagnosis of disease status or for regulatory action
must be developed. The criteria and procedures developed should account for screening methods,
retesting and confirmatory testing.

Test validation is covered in chapter 1.1.6.

Measurement of Uncertainty (MU) is “a parameter associated with the result of a measurement that
characterises the dispersion of values that could reasonably be attributed to the measure” (Eurachem,
2012). Uncertainty of measurement does not imply doubt about a result but rather increased
confidence in its validity. It is not the equivalent to error, as it may be applied to all test results derived
from a particular procedure.

Laboratories must estimate the MU for each test method resulting in a measurement included in their
scope of accreditation and for any methods used to calibrate equipment (ISO/IEC 17025, 2005).

Tests can be broadly divided into two groups: quantitative (biochemical assays, enzyme-linked
immunosorbent assays [ELISA], titrations, real-time polymerase chain reactions [PCR], pathogen
enumeration, etc.); and qualitative (bacterial culture, parasite identification, virus isolation, endpoint
PCR, immunofluorescence, etc.).

The determination of MU is well established in quantitative measurement sciences (ANSI, 1997). It

may be given as a numeric expression of reliability and is commonly shown as a stated range.
Standard deviation (SD) and confidence interval (CI) are examples of the expression of MU, for
example the optical density result of an ELISA expressed as ± n SD, where n is usually 1, 2 or 3. The
confidence interval (usually 95%) gives an estimated range in which the result is likely to fall, calculated
from a given set of test data.

The application of the principles of MU to qualitative testing is less well defined. The determination and
expression of MU has not been standardised for veterinary (or medical, food, or environmental) testing
laboratories, but sound guidance exists and as accreditation becomes more important, applications are
being developed. The ISO/IEC 17025 standard recognises that some test methods may preclude
metrologically and statistically valid calculation of uncertainty of measurement. In such cases the
laboratory must attempt to identify and estimate all the components of uncertainty based on knowledge
of the performance of the method and making use of previous experience, validation data, internal
control results, etc.

Many technical organisations and accreditation bodies (e.g. AOAC International, ISO, NATA, A2LA,
Standards Council of Canada, UKAS, Eurachem, the Cooperation of International Traceability in
Analytical Chemistry) teach courses or provide guidance on MU for laboratories seeking accreditation.

The ISO/IEC 17025 requirement for “quality control procedures for monitoring the validity of tests”
implies that the laboratory must use quality control procedures that cover all major sources of
uncertainty. There is no requirement to cover each component separately. Laboratories may establish
acceptable specifications, criteria, ranges, etc., at critical control points for each component of the test
process. The laboratory can then implement appropriate quality control measures at these critical
points, or seek to reduce or eliminate the uncertainty effect of each component. Measurement
Uncertainty is covered in chapter 3.6.4.
 i) Sampling;
ii) Contamination;
iii) Sample transport and storage conditions;
iv) Sample processing;
v) Reagent quality, preparation and storage;
vi) Type of reference material;
vii) Volumetric and weight manipulations;
viii) Environmental conditions;
ix) Equipment effects;
x) Analyst or operator bias;
xi) Biological variability;
xii) Unknown or random effects.

Systematic errors or bias determined by validation must be corrected by changes in the method,
adjusted for mathematically, or have the bias noted as part of the report statement.

If an adjustment is made to a test or procedure to reduce uncertainty or correct bias then a new source
of uncertainty is introduced (the uncertainty of the correction). This must be assessed as part of the MU
estimate.

Additional information on the analysis of uncertainty may be found in the Eurachem Guides to
Quantifying Uncertainty in Measurement (Eurachem, 2012) and Use of uncertainty information in
compliance assessment (Eurachem, 2007).

Training should be a planned and structured activity with steps to ensure adequate supervision is
maintained while analysts are being trained. Analysts should be able to demonstrate proficiency in
using the test method prior to producing reported results, and on an ongoing basis.

The laboratory must be able to demonstrate traceability for all accredited tests and the principle should
apply to all tests whether accredited or not. This covers all activities relating to test selection,
development, optimisation, standardisation, validation, implementation, reporting, personnel, quality
control and quality assurance. Traceability is achieved by using appropriate documented project
management, record keeping, data management and archiving systems.

Laboratories should have evidence of continual improvement, which is an obligatory requirement for accredited
laboratories. The laboratory must be knowledgeable of and stay current with the quality and technical
management standards and with methods used to demonstrate laboratory competence and establish and
maintain technical validity. Evidence of this may be provided by:
i) Attendance at conferences, organisation of in-house or external meetings on diagnostics and quality
management;
ii) Participation in local and international organisations;
iii) Participation in writing national and international standards (e.g. on ILAC and ISO committees);
iv) Current awareness of publications, writing and reviewing publications about diagnostic methods;
v) Training programmes, including visits to other laboratories;
vi) Conducting research;
vii) Participation in cooperative programmes (e.g. Inter-American Institute for Cooperation in Agriculture);
viii) Exchange of procedures, methods, reagents, samples, personnel, and ideas;
ix) Planned, continual professional development and technical training;
x) Management reviews;
xi) Analysis of customer feedback;
xii) Root cause analysis of anomalies and implementation of corrective, preventive and improvement actions.

ANSI (AMERICAN NATIONAL STANDARDS INSTITUTE) (1997). ANSI/NCSL3 Z540-2-1997 (R2012), US Guide to the
Expression of Uncertainty in Measurement, First Edition. American National Standards Institute, www.ansi.org.

EURACHEM (2007). Eurachem/CITAC Guide: Use of Uncertainty Information in Compliance Assessment, First
Edition. Eurachem Secretariat. www.eurachem.org.

EURACHEM (2012). Eurachem/CITAC4 Guide (CG4): Quantifying Uncertainty in Analytical Measurement, Third
Edition. Eurachem Secretariat. www.eurachem.org.

ISO (2015). ISO 9001:2015. Quality Management Systems – Requirements. International Organization for
Standardization (ISO), www.iso.org.

ISO/IEC (2004a). ISO/IEC 17000:2004. Conformity Assessment – Vocabulary and General Principles.
International Organization for Standardization (ISO), www.iso.org.

ISO/IEC (2004b). ISO/IEC 17011:2004. Conformity Assessment – General Requirements for accreditation Bodies
Accrediting Conformity Assessment Bodies. International Organization for Standardization (ISO), www.iso.org.

ISO/IEC (2005). ISO/IEC 17025:2005. General Requirements for the Competence of Testing and Calibration
Laboratories. International Organization for Standardization (ISO), www.iso.org.

ISO/IEC (2010). ISO/IEC 17043:2010. Conformity Assessment – General Requirements for Proficiency Testing.
International Organization for Standardization (ISO), www.iso.org

ISO/IEC (2012). ISO/IEC 15189:2012. Medical laboratories – Requirements for Quality and Competence.
International Organization for Standardization (ISO), www.iso.org

*
* *

NB: FIRST ADOPTED IN 1996 AS GOOD LABORATORY PRACTICE, QUALITY CONTROL AND QUALITY ASSURANCE.
MOST RECENT UPDATES ADOPTED IN 2017

3 NCSL: The National Conference of Standards Laboratories.

4 CITAC: The Cooperation of International Traceability in Analytical Chemistry.