BS PD CEN TS 16800-2015 Guideline for the validation of physico-chemical analytical methods《物理化学分析方法验证指南》.pdf

1、BSI Standards Publication PD CEN/TS 16800:2015 Guideline for the validation of physico-chemical analytical methodsPD CEN/TS 16800:2015 BRITISH STANDARD National foreword This British Standard is the UK implementation of CEN/TS 16800:2015. The UK participation in its preparation was entrusted to Tech

2、nical Committee EH/3/2, Water analysis. A list of organizations represented on this committee can be obtained on request to its secretary. This publication does not purport to include all the necessary provi- sions of a contract. Users are responsible for its correct application. The British Standar

3、ds Institution 2015. Published by BSI Standards Limited 2015 ISBN 978 0 580 87777 3 ICS 13.060.50 Compliance with a British Standard cannot confer immunity from legal obligations. This British Standard was published under the authority of the Standards Policy and Strategy Committee on 31 December 20

4、15. Amendments/corrigenda issued since publication Date Text affectedTECHNICAL SPECIFICATION SPCIFICATION TECHNIQUE TECHNISCHE SPEZIFIKATION CEN/TS 16800 December 2015 ICS 13.060.50 English Version Guideline for the validation of physico-chemical analytical methods Lignes directrices pour la validat

5、ion des mthodes danalyse physico-chimiques Anleitung zur Validierung physikalisch-chemischer 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

6、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

7、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

8、, 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

9、 and United Kingdom. EUROPEAN COMMITTEE FOR STANDARDIZATION COMIT EUROPEN DE NORMALISATION EUROPISCHES KOMITEE FR 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 worldwide for CEN national Members. Ref

10、. No. CEN/TS 16800:2015 EPD CEN/TS 16800:2015 CEN/TS 16800:2015 (E) 2 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

11、 - 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

12、 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 do

13、main 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):

14、 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

15、.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 PD CEN/TS 16800:2015 CEN/TS 16800:2015

16、(E) 3 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

17、 a validation study (V2) 39 Annex F (informative) Robustness testing by systematic variation of influencing factors 44 Bibliography . 46 PD CEN/TS 16800:2015 CEN/TS 16800:2015 (E) 4 European foreword This document (CEN/TS 16800:2015) has been prepared by Technical Committee CEN/TC 230 “Water analysi

18、s”, 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 Reg

19、ulations, 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, Irel

20、and, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the United Kingdom. PD CEN/TS 16800:2015 CEN/TS 16800:2015 (E) 5 Introduction Environmental monitoring of chemical substances is increasingly c

21、arried 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 inte

22、rnational 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 bro

23、ad 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 requi

24、rements 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 st

25、atus 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 mat

26、rix 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 applicabl

27、e from a concentration level of xx g/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

28、 the claimed range. PD CEN/TS 16800:2015 CEN/TS 16800:2015 (E) 6 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

29、 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

30、 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

31、. 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, wa

32、ste, 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 fitne

33、ss 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. 2 Normative references The following documents, in whole or in part, are normatively referenced in this document and are indispensa

34、ble for its application. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies. ISO 78-2, Chemistry Layouts for standards Part 2: Methods of chemical analysis ISO 5725, Chemistry Layouts for stan

35、dards Part 2: Methods of chemical analysis ISO 11352:2012, Water quality Estimation of measurement uncertainty based on validation and quality control data ISO 21748:2010, Guidance for the use of repeatability, reproducibility and trueness estimates in measurement uncertainty estimation ISO/IEC Guid

36、e 99:2007, International vocabulary of metrology Basic and general concepts and associated terms (VIM) 3 Terms and definitions For the purposes of this document, the terms and definitions given in ISO/IEC Guide 99:2007 (VIM) and the following apply. 3.1 accepted reference value value that serves as

37、an agreed-upon reference for comparison, and which is derived as: a) a theoretical or established value, based on scientific principles;PD CEN/TS 16800:2015 CEN/TS 16800:2015 (E) 7 b) an assigned or certified value, based on experimental work of some national or international organization; c) a cons

38、ensus or certified value, based on collaborative experimental work under the auspices of a scientific or engineering group; d) when a), b) and c) are not available, the expectation of the (measurable) quantity, i.e. the mean of a specified population of measurements SOURCE: ISO 3534-2:2006, definiti

39、on 3.2.7 3.2 accuracy closeness of agreement between a test result and the accepted reference value SOURCE: ISO 3534-2:2006, definition 3.3.1 Note 1 to entry: The term accuracy, when applied to a set of test results, involves a combination of random components (usually expressed by a precision measu

40、re) and a common systematic error or bias component (usually expressed by a measure for trueness). Note 2 to entry: The technical term “accuracy“ should not be confused with the term trueness (see definition of “trueness“). 3.3 analyte substance to be analysed (chemical species or physical parameter

41、) Note 1 to entry: The quantity of an analyte is the measurand (3.15). 3.4 bias difference between the expectation of a test result or measurement result and a true value Note 1 to entry: Bias is the total systematic error as contrasted to random error. There may be one or more systematic error comp

42、onents contributing to the bias. A larger systematic difference from the accepted reference value is reflected by a larger bias value. Note 2 to entry: The bias of a measuring instrument is normally estimated by averaging the error of indication over an appropriate number of repeated measurements. T

43、he error of indication is the: “indication of a measuring instrument minus a true value of the corresponding input quantity“. Note 3 to entry: In practice, accepted reference value is substituted for the true value. SOURCE: ISO 3534-2:2006, definition 3.3.2 3.5 blank sample or test scheme without th

44、e analyte known to produce the measured signal Note 1 to entry: Use of various types of blanks enable assessment of which proportion of the measured signal is attributable to the measurand and which proportion to other causes. Various types of blank are available (see definition of reagent blank and

45、 blank sample). PD CEN/TS 16800:2015 CEN/TS 16800:2015 (E) 8 3.6 calibration operation that, under specified conditions, in a first step, establishes a relation between the quantity values with measurement uncertainties provided by measurement standards and corresponding indications with associated

46、measurement uncertainties and, in a second step, uses this information to establish a relation for obtaining a measurement result from an indication Note 1 to entry: A calibration may be expressed by a statement, calibration function, calibration diagram, calibration curve, or calibration table. In

47、some cases, it may consist of an additive or multiplicative correction of the indication with associated measurement uncertainty. Note 2 to entry: Calibration should not be confused with adjustment of a measuring system, often mistakenly called “self-calibration”, nor with verification of calibratio

48、n. SOURCE: ISO/IEC Guide 99:2007, definition 2.39 3.7 certified reference material CRM reference material, accompanied by documentation issued by an authoritative body and providing one or more specified property values with associated uncertainties and traceabilities, using valid procedures SOURCE:

49、 ISO/IEC Guide 99:2007, definition 5.14 3.8 fitness for purpose degree to which data produced by a measurement process enables a user to make technically and administratively correct decisions for a stated purpose 3.9 intermediate precision precision under intermediate precision conditions SOURCE: ISO 3534-2:2006, definition 3.3.15 3.10 intermediate precision conditions conditions where test results or measurement results are obtained with the same method, on identical test/measurement items in the same test or measurement facility, under some dif