CEN/TS 16800:2015
(Main)Guideline for the validation of physico-chemical analytical methods
Guideline for the validation of physico-chemical analytical methods
This Technical Specification describes an approach for the validation of physico-chemical analytical methods for environmental matrices.
The guidance in this document addresses two different validation approaches, in increasing order of complexity. These are:
a) method development and validation at the level of single laboratories (intra-laboratory validation);
b) method validation at the level of several laboratories (between-laboratory or inter-laboratory validation), with a focus on methods that are sufficiently mature and robust to be applied not only by a few expert laboratories but by laboratories operating at the routine level.
The concept of these two approaches is strictly hierarchical, i.e. a method shall fulfil all criteria of the first level before it can enter the validation protocol of the second level.
This Technical Specification is applicable to the validation of a broad range of quantitative physico-chemical analytical methods for the analysis of water (including surface water, groundwater, waste water, and sediment). Analytical methods for other environmental matrices, like soil, sludge, waste, and biota can be validated in the same way. It is intended either for analytical methods aiming at substances that have recently become of interest or for test methods applying recently developed technologies.
The minimal requirements that are indispensable for the characterization of the fitness for purpose of an analytical method are: selectivity, precision, bias and measurement uncertainty. The aim of validation is to prove that these requirements are met.
Anleitung zur Validierung physikalisch-chemischer Analysenverfahren
Diese Technische Spezifikation beschreibt einen Ansatz für die Validierung von physikalisch-chemischen Analysenverfahren für Umweltmatrices.
Die Anleitung im vorliegenden Dokument behandelt zwei verschiedene Validierungsansätze mit zunehmender Komplexität. Diese sind:
a) Verfahrensentwicklung und -validierung auf Ebene eines einzelnen Labors (laborinterne Validierung);
b) Verfahrensvalidierung auf Ebene mehrerer Labore (laborübergreifende Validierung) mit Konzen-tration auf Verfahren, die hinreichend ausgereift und robust sind, damit sie nicht nur von einigen Experten¬laboren sondern auch von auf Routineniveau arbeitenden Laboren angewendet werden können.
Das Konzept dieser beiden Ansätze ist strikt hierarchisch, d. h. ein Verfahren muss alle Kriterien der ersten Ebene erfüllen, bevor es in das Validierungsprotokoll der zweiten Ebene aufgenommen wird.
Diese Technische Spezifikation gilt für die Validierung einer Vielfalt von quantitativen physikalisch-chemischen Untersuchungsverfahren für die Analyse von Wasser (einschließlich Oberflächenwasser, Grundwasser, Abwasser und Sediment). Untersuchungsverfahren für andere Umweltprobenmatrices, wie Boden, Schlamm, Abfall und Biota, können in gleicher Weise validiert werden. Sie ist entweder für Untersuchungsverfahren vorgesehen, die auf neue interessierende Stoffe ausgerichtet sind, oder für Untersuchungsverfahren, die neuentwickelte Technologien anwenden.
Die für die Charakterisierung der Gebrauchstauglichkeit eines Analysenverfahrens unabdingbaren Mindest¬anforderungen sind Selektivität, Präzision, systematische Abweichung (Bias) und Messunsicherheit. Das Ziel der Validierung besteht im Nachweis der Einhaltung dieser Anforderungen.
Lignes directrices pour la validation des méthodes d'analyse physico-chimiques
La présente Spécification technique décrit une approche de validation des méthodes d'analyse physico-chimiques destinées aux matrices issues de l'environnement.
Les préconisations du présent document abordent deux approches de validation différentes, par ordre croissant de complexité. Ces approches sont les suivantes :
a) mise au point et validation des méthodes à l'échelle de laboratoires individuels (validation intralaboratoire) ;
b) validation des méthodes à l'échelle de plusieurs laboratoires (validation interlaboratoires), avec ciblage des méthodes suffisamment abouties et robustes pour être appliquées non seulement par quelques laboratoires experts, mais aussi par des laboratoires d'analyses de routine.
Le concept de ces deux approches est strictement hiérarchisé, c'est-à-dire qu'une méthode doit remplir tous les critères du premier niveau avant de pouvoir accéder au protocole de validation de second niveau.
La présente Spécification technique est applicable à la validation d'une large gamme de méthodes d'analyse physico-chimiques quantitatives destinées à l'analyse des eaux (y compris des eaux de surface, des eaux souterraines, des eaux usées et des sédiments). Les méthodes d’analyse destinées à d'autres matrices environnementales, telles que le sol, les boues, les déchets et le biote, peuvent être validées de la même manière. La présente Spécification technique s'adresse soit à des méthodes d’analyse visant des substances qui suscitent un nouvel intérêt, soit à des méthodes d'essai qui appliquent des technologies récemment mises au point.
Les exigences minimales indispensables à la caractérisation de l'aptitude à l'emploi d'une méthode d'analyse sont la sélectivité, la fidélité, le biais et l'incertitude de mesure. La validation a pour objectif de prouver que ces exigences sont satisfaites.
Smernica za validacijo fizikalno-kemijskih analiznih metod
V tej tehnični specifikaciji je opisan pristop za validacijo fizikalno-kemijskih analiznih metod za okoljske vodne matrice.
Navodila v tem dokumentu naslavljajo dva različna pristopa k validaciji, pri čemer stopnja zapletenosti narašča. Ta pristopa sta:
a) razvijanje in validacija metode na ravni posameznih laboratorijev (validacija znotraj laboratorija);
b) validacija metode na ravni več laboratorijev (validacija med laboratoriji ali medlaboratorijska validacija) s poudarkom na metodah, ki so dovolj zrele in robustne, da jih lahko uporabljajo tudi laboratoriji, ki delujejo na rutinski ravni, in ne le nekaj specializiranih laboratorijev.
Koncept teh dveh pristopov je strogo hierarhičen, tj. metoda mora izpolniti vse kriterije na prvi ravni, preden lahko vstopi v protokol validacije na drugi ravni.
Ta tehnična specifikacija velja za validacijo široke palete kvantitavnih fizikalno-kemijskih preskusnih metod za analizo vode (vključno s površinsko vodo, podtalnico, odpadnimi vodami in usedlinami). Preskusne metode za druge okoljske matrice, na primer zemljino, blato, odpad in žive organizme, je mogoče validirati na enak način. Namenjen je za preskusne metode za snovi, ki so nedavno postale zanimive, ali za preskusne metode, pri katerih se uporabljajo nedavno razvite tehnologije.
Minimalne zahteve, ki so nujne za karakterizacijo primernosti za namen analitične metode, so: selektivnost, natančnost, pristranskost, negotovost merjenja. Cilj validacije je potrditev izpolnitve teh zahtev.
General Information
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Standards Content (Sample)
SLOVENSKI STANDARD
01-februar-2016
Smernica za validacijo fizikalno-kemijskih analiznih metod
Guideline for the validation of physico-chemical analytical methods
Anleitung zur Validierung physikalisch-chemischer Analysenverfahren
Lignes directrices pour la validation des méthodes d'analyse physico-chimiques
Ta slovenski standard je istoveten z: CEN/TS 16800:2015
ICS:
13.060.50 3UHLVNDYDYRGHQDNHPLþQH Examination of water for
VQRYL chemical substances
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
CEN/TS 16800
TECHNICAL SPECIFICATION
SPÉCIFICATION TECHNIQUE
December 2015
TECHNISCHE SPEZIFIKATION
ICS 13.060.50
English Version
Guideline for the validation of physico-chemical analytical
methods
Lignes directrices pour la validation des méthodes Anleitung zur Validierung physikalisch-chemischer
d'analyse physico-chimiques Analysenverfahren
This Technical Specification (CEN/TS) was approved by CEN on 14 March 2015 for provisional application.
The period of validity of this CEN/TS is limited initially to three years. After two years the members of CEN will be requested to
submit their comments, particularly on the question whether the CEN/TS can be converted into a European Standard.
CEN members are required to announce the existence of this CEN/TS in the same way as for an EN and to make the CEN/TS
available promptly at national level in an appropriate form. It is permissible to keep conflicting national standards in force (in
parallel to the CEN/TS) until the final decision about the possible conversion of the CEN/TS into an EN is reached.
CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and
United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
CEN-CENELEC Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2015 CEN All rights of exploitation in any form and by any means reserved Ref. No. CEN/TS 16800:2015 E
worldwide for CEN national Members.
Contents Page
European foreword . 4
Introduction . 5
1 Scope . 6
2 Normative references . 6
3 Terms and definitions . 6
4 Concept . 13
4.1 The concept of two validation levels . 13
4.2 First level - Validation 1 (V1) . 13
4.3 Second level - Validation 2 (V2) . 13
4.4 Method validation using a modular approach . 13
4.4.1 Validation modules . 13
4.4.2 Module A: Test method definition, documentation and general requirements . 13
4.4.3 Module B: Applicability domain and pre-validation . 14
4.4.4 Module C: Intra-laboratory performance . 14
4.4.5 Module D: Inter-laboratory performance . 14
4.5 Method classification . 15
5 Documentation of the validation process . 16
6 Validation 1 (V1): Intra-Laboratory Validation . 17
6.1 General . 17
6.2 Module A: Test method definition, documentation and general requirements . 17
6.3 Module B: Applicability domain and pre-validation . 18
6.4 Module C: Intra-laboratory performance . 18
6.4.1 General . 18
6.4.2 Bias . 18
6.4.3 Precision . 19
6.4.4 Calibration data and function . 20
6.4.5 Limits and application range . 21
6.4.6 Selectivity . 22
6.4.7 Robustness. 23
6.4.8 Measurement uncertainty . 23
7 Validation 2 (V2): Inter-Laboratory Validation . 23
7.1 General . 23
7.2 Method definition and description . 24
7.3 Module C: Intra-laboratory performance . 24
7.4 Module D: Inter-laboratory performance . 24
7.4.1 General . 24
7.4.2 General set-up of the inter-laboratory study . 25
7.4.3 The inter-laboratory study . 26
7.4.4 Statistical analysis and calculation of the results . 27
7.4.5 Evaluation of the fitness for purpose . 28
7.5 Documentation, publication and standardization . 31
Annex A (normative) Module A: Test method definition, documentation and general
requirements . 32
Annex B (normative) Module B: Applicability domain and pre-validation . 34
Annex C (normative) Module C: Intra-laboratory performance . 35
Annex D (normative) Module D: Requirements for an inter-laboratory validation study . 37
Annex E (informative) Structure and content of the documentation for a validation study
(V2) . 39
Annex F (informative) Robustness testing by systematic variation of influencing factors . 44
Bibliography . 46
European foreword
This document (CEN/TS 16800:2015) has been prepared by Technical Committee CEN/TC 230 “Water
analysis”, the secretariat of which is held by DIN.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN [and/or CENELEC] shall not be held responsible for identifying any or all such patent
rights.
According to the CEN-CENELEC Internal Regulations, the national standards organizations of the
following countries are bound to announce this Technical Specification: Austria, Belgium, Bulgaria,
Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Former Yugoslav Republic of Macedonia,
France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta,
Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland,
Turkey and the United Kingdom.
Introduction
Environmental monitoring of chemical substances is increasingly carried out within a European
framework, and there is concern about the comparability of data at the European level. In particular
methods used for the monitoring of substances with recent interest have often not been properly
validated either in-house (i.e. within a single laboratory) or at the international level.
These issues may be addressed by adopting a harmonized approach towards method development and
validation. The main objective of this document is to provide a common European approach to the
validation of chemical methods for the respective monitoring of chemical substances in a broad range of
matrices. Although the development of this approach was triggered by the needs for monitoring of
emerging pollutants, it is of general nature and can be applied to the measurement of a wide range of
substances in a variety of matrices.
This guidance takes into account the different requirements for the level of method maturity and
validation at different stages of the investigation or regulation of chemical substances.
In the case of a specific monitoring task, this protocol will guide the user through the following steps:
— classification of existing methods with respect to their status of validation, and the selection of the
appropriate validation approach;
— development of a method so as to extend its application; for example, if a method for determining a
required target compound in a particular matrix is available, but is not suitable for the same
compound in a different matrix of interest;
— the validation procedures to be carried out in order to effectively demonstrate the validation status
of a selected method according to the two approaches adopted.
Many (national and international) standards currently contain in their scope a statement like “this
method is applicable from a concentration level of xx µg/l or yy mg/kg dry matter”, without any
statement how this concentration level was established. When the limit of quantification (LOQ) is
evaluated using the procedure of this Technical Specification, there is a possibility that it does not meet
the lower limit of the claimed range.
1 Scope
This Technical Specification describes an approach for the validation of physico-chemical analytical
methods for environmental matrices.
The guidance in this document addresses two different validation approaches, in increasing order of
complexity. These are:
a) method development and validation at the level of single laboratories (intra-laboratory validation);
b) method validation at the level of several laboratories (between-laboratory or inter-laboratory
validation), with a focus on methods that are sufficiently mature and robust to be applied not only
by a few expert laboratories but by laboratories operating at the routine level.
The concept of these two approaches is strictly hierarchical, i.e. a method shall fulfil all criteria of the
first level before it can enter the validation protocol of the second level.
This Technical Specification is applicable to the validation of a broad range of quantitative physico-
chemical analytical methods for the analysis of water (including surface water, groundwater, waste
water, and sediment). Analytical methods for other environmental matrices, like soil, sludge, waste, and
biota can be validated in the same way. It is intended either for analytical methods aiming at substances
that ha
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