EN 18000-1:2026

SLOVENSKI STANDARD
oSIST prEN 18000-1:2023
01-december-2023
Diagnostične analize zdravja živali - Nadzor diagnostičnih reagentov in vitro - 1.
del: Vloga za začetno kontrolo in kontrolo od serije do serije
Animal health diagnostic analyses - Control of in vitro diagnostic reagents - Part 1:
Application file for the initial and the batch-to-batch control
Tiergesundheitsdiagnostische Analysen - Kontrolle von in-vitro-diagnostischen
Reagenzien - Teil 1: Antragsunterlagen für die Erstkontrolle und die Kontrolle von
Charge zu Charge
Analyses de diagnostic en santé animale - Contrôle des réactifs de diagnostic in vitro -
Partie 1 : Dossier de présentation pour le contrôle initial et le contrôle lot à lot
Ta slovenski standard je istoveten z: prEN 18000-1
ICS:
11.100.10 Diagnostični preskusni In vitro diagnostic test
sistemi in vitro systems
11.220 Veterinarstvo Veterinary medicine
oSIST prEN 18000-1:2023 en,fr,de
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

oSIST prEN 18000-1:2023
oSIST prEN 18000-1:2023
DRAFT
EUROPEAN STANDARD
prEN 18000-1
NORME EUROPÉENNE
EUROPÄISCHE NORM
September 2023
ICS
English Version
Animal health diagnostic analyses - Control of in vitro
diagnostic reagents - Part 1: Application file for the initial
and the batch-to-batch control
Analyses de diagnostic en santé animale - Contrôle des Tiergesundheitsdiagnostische Analysen - Kontrolle von
réactifs de diagnostic in vitro - Partie 1 : Dossier de in-vitro-diagnostischen Reagenzien - Teil 1:
présentation pour le contrôle initial et le contrôle lot à Antragsunterlagen für die Erstkontrolle und die
lot Kontrolle von Charge zu Charge
This draft European Standard is submitted to CEN members for enquiry. It has been drawn up by the Technical Committee
CEN/TC 469.
If this draft becomes a European Standard, CEN members are bound to comply with the CEN/CENELEC Internal Regulations
which stipulate the conditions for giving this European Standard the status of a national standard without any alteration.

This draft European Standard was established by CEN in three official versions (English, French, German). A version in any other
language made by translation under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC
Management Centre has the same status as the official versions.

CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway,
Poland, Portugal, Republic of North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Türkiye and
United Kingdom.
Recipients of this draft are invited to submit, with their comments, notification of any relevant patent rights of which they are
aware and to provide supporting documentation.

Warning : This document is not a European Standard. It is distributed for review and comments. It is subject to change without
notice and shall not be referred to as a European Standard.

EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION

EUROPÄISCHES KOMITEE FÜR NORMUNG

CEN-CENELEC Management Centre: Rue de la Science 23, B-1040 Brussels
© 2023 CEN All rights of exploitation in any form and by any means reserved Ref. No. prEN 18000-1:2023 E
worldwide for CEN national Members.

oSIST prEN 18000-1:2023
prEN 18000-1:2023 (E)
Contents Page
European foreword . 3
Introduction . 4
1 Scope . 5
2 Normative references . 5
3 Terms and definitions . 5
4 General control steps and prerequisites . 15
5 Content of the file for the initial control . 15
5.1 General. 15
5.2 Administrative information . 16
5.2.1 General. 16
5.2.2 Presentation . 16
5.3 Technical file of the reagent . 17
5.3.1 Manufacture . 17
5.3.2 Assessment file . 18
5.4 References . 21
6 Content of the file for batch-to-batch control . 21
6.1 Written batch control request. 21
6.2 Results of the applicant’s internal quality control . 21
7 Conformity certificates . 22
8 Modifications of a reagent . 22
8.1 CO and end-user information . 22
8.2 Management of major and minor modifications by the control organization . 22
Annex A (informative) Description form and label of a reference material . 23
Annex B (informative) File to be compiled by the applicant for assessment validation of a
reagent by a control organization. 25
Annex C (normative) Declaration of interest . 28
Annex D (normative) Reagent or batch conformity certificate (issued by the control
organization) . 29
Annex E (informative) Notification of reagent modification . 30
Bibliography . 31

oSIST prEN 18000-1:2023
prEN 18000-1:2023 (E)
European foreword
This document (prEN 18000-1:2023) has been prepared by Technical Committee CEN/TC 469 “Animal
health diagnostic analyses”, the secretariat of which is held by AFNOR.
This document is currently submitted to the CEN Enquiry.
oSIST prEN 18000-1:2023
prEN 18000-1:2023 (E)
Introduction
The objective of the EN 18000 series is to facilitate the mutual recognition of the work of the animal health
in vitro diagnostic reagent control organizations at European level (or even more widely) and thus to
eventually allow the use of strategic reagents controlled by a single control organization for a given disease.
The EN 18000 series aims to describe the optimal requirements for in vitro diagnostic reagents in animal
health. It is divided into three parts. The first part concerns the submission of a reagent dossier to a control
organization for control and approval. The second and third parts concern the specific aspects of the control
of an immunological diagnostic reagent and of a polymerase-chain reaction diagnostic reagent for the
detection or quantification of pathogen-specific nucleic acids (PCR), respectively.
Like any standard, it is intended to be voluntary and, if its use is prescribed by a competent authority or any
other animal health stakeholder, it will be up to them to determine for which diseases this standard will be
applied by the control bodies they have designated for this purpose.
oSIST prEN 18000-1:2023
prEN 18000-1:2023 (E)
1 Scope
The level of requirements presented in the EN 18000 series has been established as a priority for infectious
diseases (bacterial, viral, fungal or parasitic) and associated animal species for which harmonization of
practices in this area is necessary, i.e. those for which the national, regional or international regulatory
framework provides for the control of trade in animals and/or animal products and/or the definition of a
health status (absence of infection) of areas, establishments or individuals.
The EN 18000 series is therefore not intended to be applicable to all existing diagnostic reagents, in particular
those for which certain parameters described in this standard cannot be validly evaluated in accordance with
international requirements due, e.g. to the absence of a specific reference method and/or accessible and duly
validated reference materials.
This first part describes the general and specific elements constituting the dossier for the submission of an
animal health in vitro diagnostic reagent, in the above-described framework, to the control and approval by
a control organization. Its purpose is to provide the applicant submitting an animal disease in vitro diagnostic
reagent to control with the general input for the preparation of the control application file. It describes the
optimal administrative and technical information regarding the applicant and the reagent required for the
application file for initial control and for a batch-to-batch control respectively. It specifies, in particular, the
validation parameters of the method using the reagent (objectives, methodology, criteria and results)
according to international standards.
NOTE This document does not cover the step in which the user verifies a reagent (refer to section 3.1 for
definition).
2 Normative references
There are no normative references in this document.
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
NOTE These terms are written in italics throughout the EN 18000 series.
ISO and IEC maintain terminology databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https://www.iso.org/obp/
— IEC Electropedia: available at https://www.electropedia.org/
3.1
analysis method adoption
verification by a laboratory that it can properly perform a method before introducing it by ensuring that it
can achieve the required performance, e.g. in comparison with a second test method
Note 1 to entry: This concept is called “in-house validation” by WOAH.
[SOURCE: EN ISO/IEC 17025:2017]
3.2
analyte
substance to be detected or determined purpose of the analysis method
Note 1 to entry: In this standard, the term analyte may refer to a single analyte or to a given population of analytes
(antibodies, antigens, nucleic acids, live or inactivated organisms, etc.).
oSIST prEN 18000-1:2023
prEN 18000-1:2023 (E)
3.3
analytical sensitivity
measured through the limit of detection (LOD), i.e. the estimated amount of analyte
in a specified matrix that would produce a positive result at least a specified per cent of the time
[SOURCE: WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2022 - Glossary of terms]
3.4
analytical sensitivity
measured through the limit of detection (LOD), i.e. the smallest detectable amount
of analyte that can be measured with a defined certainty (i.e. a signal significantly above a matrix without the
analyte)
[SOURCE: WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2022 - Glossary of terms]
3.5
analytical specificity
degree to which the assay distinguishes between the target analyte and other components in the sample
matrix
Note 1 to entry: The higher the analytical specificity, the lower the level of false positives.
[SOURCE: WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2022 - Glossary of terms]
3.6
applicant
individual or legal entity that submits the dossier of a reagent for initial control or who submits a batch of
reagent for batch-to-batch control
3.7
assay validation
confirmation, through the provision of objective evidence, that the requirements for a specific intended use
or application have been fulfilled
Note 1 to entry: In this standard, for the applicant, this consists in providing assessment results that demonstrate that
the method using the reagent submitted to control is validated according to existing standards, i.e. generic ones (Test
validation according to WOAH) and disease-specific ones (according to the state of art, e.g. disease-specific standards,
scientific literature).
Note 2 to entry: The control organization does not strictly speaking validate the reagent itself, but verifies through the
documentation provided and by the implementation of a limited number of appropriate tests, that the elements of the
application file and the submitted batch comply with the requirements.
[SOURCE: WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2018 - Chapter 1.1.6]
oSIST prEN 18000-1:2023
prEN 18000-1:2023 (E)
3.8
batch
production batch
defined amount of material, either starting material, intermediate or finished product which is uniform in its
properties and has been produced in one process or series of processes
Note 1 to entry: FDA (FDA’s Code of Federal Regulations 21 CFR 210.3) definition considers "A certain amount of a
material that is intended to have a uniform character and quality within defined limits and is manufactured according
to a single production order during the same manufacturing cycle". Therefore, to avoid any ambiguity, according to FDA
definition, one process or series of processes should be understood as a single production order during the same
manufacturing cycle.
Note 2 to entry: The circumstances under which the conditions are assumed to be uniform cannot be defined in general
terms; for example, a change of the material or the tool used, or an interruption of the manufacturing process can
produce different conditions.
[SOURCE: EN 13975:2003]
3.9
batch conformity certificate
document issued by the control organization guaranteeing that a specific reagent batch meets the previously
defined requirements, when used according to one or more specified technical protocols
3.10
batch number
a given reagent batch number corresponds to a particular batch number for each of its components
Note 1 to entry: The reagent batch number is inseparable from the version number of the instructions for use, except
otherwise clearly specified on the reagent final package.
3.11
batch-to-batch control
when necessary, applies to a single reagent associated with a defined technical protocol and a single
production batch and consists of a control at the start of the batch by the applicant and the control
organization, prior to distribution to the user, and a control in the course of batch validity, where appropriate,
by the control organization
3.12
certified reference material
reference material accompanied by a certificate, of which one or more values of the specified properties are
certified by a procedure that establishes the accurate production of the unit, which the values of the property
are given and for which each certified value is associated with an uncertainty at a specified level of confidence
[SOURCE: ISO Guide 30:1992, 2.1, modified - ISO 16140-1]
3.13
characterization of a reagent
determination of the characteristics of a reagent, when used according to one or more specified technical
protocols
EXAMPLE Analytical specificity, analytical sensitivity (limit of detection), precision.
oSIST prEN 18000-1:2023
prEN 18000-1:2023 (E)
3.14
coefficient of variation
CV
relative standard deviation
RSD
statistical measure that reports the relative dispersion of a set of data, calculated by the ratio of the standard
deviation of numerical data to their mean, obtained under conditions of repeatability or reproducibility
3.15
component
part of a finished, packaged and labelled diagnostic reagent
EXAMPLE Raw material, substance, piece, part, software, firmware or labelling.
Note 1 to entry: Typical immunological diagnostic kit components include antibody solutions, antigen preparation
(solutions, coated plates), buffer solutions, calibrators, and/or control materials.
[SOURCE: ISO 18113-1]
3.16
control
measurement, examination, testing or gauging of one or more characteristics of a product or service and
comparing them with specific requirements in order to verify their conformity
Note 1 to entry: The term “control” is also commonly used to refer to a control sample as defined below. In this
standard, to avoid confusion, when the term “control” is used, only the definition above applies.
[SOURCE: ISO 3534-2:2006]
3.17
control organization
CO
entity of a recognized scientific and diagnostic expertise for a specified animal disease and for its analysis
methodology, and designated as such by the competent authority
Note 1 to entry: This expertise includes the capability for the characterization and/or the assignment of values to
reference materials.
[SOURCE: WOAH definition of a Reference laboratory modified by adding “designated as such by the
competent authority”]
3.18
control sample
substance, material or article intended by its manufacturer to be used to verify the performance properties
of a diagnostic reagent
EXAMPLES Positive control samples, negative control samples.
[SOURCE: ISO 18113-1]
oSIST prEN 18000-1:2023
prEN 18000-1:2023 (E)
3.19
diagnostic kit
set of components that are packaged together and intended to be used to perform one or more specific in
vitro diagnostic examinations
[SOURCE: ISO 18113-1]
3.20
diagnostic sensitivity
proportion of reference animals known to be infected and producing a positive result upon analysis
Note 1 to entry: The infected reference animals that produce a negative result are considered to be “false negatives”.
[SOURCE: WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2022 - Glossary of terms]
3.21
diagnostic specificity
proportion of reference animals known to be uninfected and producing a negative result upon analysis
Note 1 to entry: The uninfected reference animals that produce a positive result are considered to be “false positives”.
[SOURCE: WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2022 - Glossary of terms]
3.22
dose-response relationship
correlation between successive dilutions of an analyte and the corresponding values obtained using a
specified reagent and a technical protocol within the range of concentrations where this linear relationship
exists
3.23
exclusivity
capacity of an assay to detect an analyte or genomic sequence that is unique to a targeted organism, and
excludes all other known organisms that are potentially cross-reactive
[SOURCE: WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2018 - Chapter 1.1.6]
3.24
false negative reaction
negative reactivity in an assay of a test sample obtained from an animal infected with the organism in
question
Note 1 to entry: It may be due to lack of analytical sensitivity, restricted analytical specificity or analyte degradation.
Note 2 to entry: It decreases diagnostic sensitivity.
[SOURCE: WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2022 - Glossary of terms]
oSIST prEN 18000-1:2023
prEN 18000-1:2023 (E)
3.25
false positive reaction
positive reactivity in an assay that is not attributable to exposure to or infection with the organism in
question
Note 1 to entry: It may be due to immunological (or genic) cross-reactivity, cross-contamination of the test sample or
non-specific reactions.
Note 2 to entry: It decreases diagnostic specificity.
[SOURCE: WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2022 - Glossary of terms]
3.26
inclusivity
capability of a test to detect several strains or subtypes of the same species, several species of the same type
or a group of closely related organisms or antibodies
[SOURCE: WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2018 - Chapter 1.1.6]
3.27
initial conformity control
applies to a single reagent associated with a defined technical protocol and includes the characterization and
validation of the reagent by the applicant and the assessment of the application dossier and the initial control
of the reagent by the control organization, prior to distribution to the user
3.28
instructions for use
IFU
information (detailed, action-oriented, step-by-step written and visual instructions) provided by the
manufacturer or supplier to inform the user of the intended purpose of a product about its correct use, as
well as on any precautions to be taken
[SOURCE: FDA Instructions for Use — Patient Labeling for Human Prescription Drug and Biological Products
— Content and Format - Guidance for Industry, July 2022]
3.29
interlaboratory reproducibility
ability of a test method to provide consistent results, as determined by estimates of precision, when applied
to aliquots of the same sample tested by the same method in different laboratories
Note 1 to entry: WOAH then mentions that "to assess the reproducibility of an assay, each of at least three laboratories
should test the same panel of samples (blinded) containing a suggested minimum of 20 samples, with identical aliquots
going to each laboratory”.
[SOURCE: WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2018 - Chapter 1.1.6]
3.30
internal reference material
reference material whose reference value is attributed by the user, in comparison with the certified values
or with the consensus values of the reference materials or by adding a known quantity of the analyte to the
matrix that is free of that analyte
oSIST prEN 18000-1:2023
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3.31
international reference material
reference material by which all other reagents and assays are calibrated and prepared and distributed by an
International Reference Laboratory
Note 1 to entry: This concept is called “international standard reagent” by WOAH.
[SOURCE: WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2022 - Glossary of terms]
3.32
linearity
capability, within a certain range, to produce results proportional to the quantity of analyte to be assayed in
the sample
3.33
manufacturer
company that produces the finished reagent, and then sells it to users (diagnostic laboratories) or to suppliers
Note 1 to entry: This term refers to a single manufacturer, to a group of manufacturers or to a supplier.
3.34
matrix
different biological materials that are used as samples subjected to analysis that may have different chemical
compositions and physical states
EXAMPLES Whole-blood, blood serum, blood plasma, meat juice, milk, skimmed milk, blotting paper, pool of blood
sera, tank milk, ear biopsy, biological tissues.
3.35
minimum level of detection
specified level of dilution of a reference material (RM) containing the analyte, which, for a given reagent, will
produce a positive response with a specified technical protocol, and which is defined by the regulations,
standards or, otherwise, by the control organization
3.36
national reference material
reference material calibrated by comparison with International Standard Reagents and prepared and
distributed by a National Reference Laboratory
Note 1 to entry: This concept is called “national standard reagent” by WOAH.
[SOURCE: WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2022 - Glossary of terms]
3.37
precision
closeness of agreement between independent test results obtained under stipulated conditions
Note 1 to entry: Precision depends only on the distribution of random errors and does not relate to the true value or
the specified value.
Note 2 to entry: The measure of precision is usually expressed in terms of imprecision and computed as a standard
deviation of the test results. Less precision is reflected by a larger standard deviation.
Note 3 to entry: “Independent test results” means results obtained in a manner not influenced by any previous result
on the same or similar test object. Quantitative measures of precision depend critically on the stipulated conditions.
Repeatability and reproducibility conditions are particular sets of extreme conditions.
[SOURCE: ISO 3534-1 & ISO 5725-1]
oSIST prEN 18000-1:2023
prEN 18000-1:2023 (E)
3.38
reagent
diagnostic reagent
product or set of products intended for an analysis according to one or several defined technical protocols,
used exclusively in vitro for screening or diagnostic purposes
Note 1 to entry: When the reagent is made up of a set of components, it may be called a (diagnostic) kit.
Note 2 to entry: Products and reagents for general laboratory use shall not be considered as reagents.
Note 3 to entry: This concept is called “IVD medical device” in ISO 18113-1.
[SOURCE: ISO 18113-1]
3.39
reagent conformity certificate
document issued by the control organization guaranteeing that a reagent meets the previously defined
requirements, when used according to one or more specified technical protocols
3.40
reference animal population
animal population selected for estimating diagnostic sensitivity and diagnostic specificity of an assay
Note 1 to entry: Selection of reference animals requires that important variables in the target population are
represented in animals chosen for being infected or exposed to the target agent, or that have never been infected or
exposed. The variables to be noted include but are not limited to species, age, sex, breed, stage of infection, vaccination
history, and relevant herd disease history.
[SOURCE: WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2018 - Chapter 1.1.6]
3.41
reference laboratory
national (NRL) or international laboratory of recognized scientific and diagnostic expertise for a particular
animal disease or testing methodology, and designated as such by the competent authority
Note 1 to entry: This includes capability for the characterization and the assignment of values to reference reagents and
samples.
[SOURCE: WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2022 - Glossary of terms]
3.42
reference material
RM
material or substance whose property values are sufficiently homogeneous and well established to be used
for the calibration of an apparatus, the assessment of a measurement method, or for assigning values to
materials
Note 1 to entry: The term reference material corresponds to the term "Reference Measurement standard" defined by
WOAH as "measurement standard designated for the calibration of other measurement standards for quantities of a
given kind in a given organization or at a given location". In this document, the term “standard” is used exclusively to
refer to a norm (national, European or international) (See standard definition).
[SOURCE: ISO Guide 30:1992, 2.1, modified - ISO 16140-1]
oSIST prEN 18000-1:2023
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3.43
reference method
internationally recognized and widely accepted method
[SOURCE: ISO 16140-1]
3.44
repeatability
agreement between repeated analyses of the same sample, in the same series of tests, under identical
operating conditions, with the same reagent and according to a defined technical protocol
[SOURCE: ISO 5725-1]
3.45
repeatability conditions
conditions where independent test results are obtained with the same method on identical test items in the
same laboratory by the same operator using the same equipment within short intervals of time
[SOURCE: ISO 3534-1 & ISO 5725-1]
3.46
reproducibility conditions
conditions where test results are obtained with the same method on identical test items in different
laboratories with different operators using different equipment
[SOURCE: ISO 3534-1 & ISO 5725-1]
3.47
robustness
validation of conditions of use
agreement between repeated analyses of the same samples, with the same reagent, in the same laboratory
under the extreme conditions of use specified by the technical protocol
Note 1 to entry: Interlaboratory reproducibility is an additional mean of assessing the robustness.
[SOURCE: WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2018 - Chapter 1.1.6]
3.48
sample
material that is derived from a specimen and used for testing purposes
3.49
selectivity
extent to which the method can accurately quantify the targeted analyte in the presence of e.g. 1) interferents
such as matrix components (e.g. inhibitors of enzymes in the reaction mix), 2) degradants (e.g. toxic factors),
3) nonspecific binding of reactants to a solid phase (e.g. conjugate of an ELISA adsorbed to a well of microtitre
plate), 4) antibodies to vaccination that may be confused with antibodies to active infection
Note 1 to entry: Such interferents may cause falsely reduced or elevated responses in the assay that negatively affect
its analytical specificity.
[SOURCE: WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2018 - Chapter 1.1.6]
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3.50
specimen
biological or laboratory specimen
animal tissue, fluid or other body material used for laboratory analysis
3.51
standard
norm
document designed to be used as a rule, guideline or definition
Note 1 to entry: The term standard is used exclusively to refer to a norm (national, European or international).
3.52
supplier
company or person who aims at marketing the reagent submitted to control
Note 1 to entry: This may be the manufacturer or another entity, e.g. distributor, reseller.
3.53
test result
outcome of an analytical procedure or method
3.54
test result interpretation
interpretation of the test result as positive, negative or other, if applicable, after modification of the raw data
by a specific calculation method
Note 1 to entry: "other" relates to a result which cannot be interpreted as positive or negative (e.g., according to the
test, anticomplementary, unreadable, contamination, inconclusive, intermediate).
3.55
test series validation
validation of a series of tests by verification of criteria predefined by the method, usually expected results for
the control samples
3.56
threshold of positivity (cut-off)
...