BS PD CEN TS 16945-2016 Molecular in vitro diagnostic examinations Specifications for pre-examination processes for metabolomics in urine venous blood serum and plasma《分子体.pdf

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1、PD CEN/TS 16945:2016 Molecular in vitro diagnostic examinations Specifications for pre-examination processes for metabolomics in urine, venous blood serum and plasma BSI Standards Publication WB11885_BSI_StandardCovs_2013_AW.indd 1 15/05/2013 15:06PD CEN/TS 16945:2016 PUBLISHED DOCUMENT National for

2、eword This Published Document is the UK implementation of CEN/TS 16945:2016. The UK participation in its preparation was entrusted to Technical Committee CH/212, IVDs. A list of organizations represented on this committee can be obtained on request to its secretary. This publication does not purport

3、 to include all the necessary provisions of a contract. Users are responsible for its correct application. The British Standards Institution 2016. Published by BSI Standards Limited 2016 ISBN 978 0 580 93674 6 ICS 11.100.10 Compliance with a British Standard cannot confer immunity from legal obligat

4、ions. This Published Document was published under the authority of the Standards Policy and Strategy Committee on 31 May 2016. Amendments issued since publication Date Text affectedPD CEN/TS 16945:2016TECHNICAL SPECIFICATION SPCIFICATION TECHNIQUE TECHNISCHE SPEZIFIKATION CEN/TS 16945 May 2016 ICS 1

5、1.100.10 English Version Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for metabolomics in urine, venous blood serum and plasma Tests de diagnostic molculaire in vitro - Spcifications relatives aux processus pranalytiques pour lanalyse du mtabolome dans lu

6、rine et le sang veineux (srum et plasma) Molekularanalytische in-vitro-diagnostische Verfahren - Spezifikationen fr pranalytische Prozesse fr Metabolomuntersuchungen in Urin, venses Blutserum und -plasma This Technical Specification (CEN/TS) was approved by CEN on 22 March 2016 for provisional appli

7、cation. 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 existe

8、nce 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

9、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, Netherlan

10、ds, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey 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 2016 CEN All rights

11、of exploitation in any form and by any means reserved worldwide for CEN national Members. Ref. No. CEN/TS 16945:2016 EPD CEN/TS 16945:2016 CEN/TS 16945:2016 (E) 2 Contents Page European foreword . 3 Introduction 4 1 Scope 5 2 Normative references 5 3 Terms and definitions . 5 4 General Consideration

12、s. 7 5 Urine 8 5.1 Outside the laboratory 8 5.1.1 Urine collection manual 8 5.1.2 Transport requirements. 9 5.2 Inside the laboratory . 9 5.2.1 Specimen reception 9 5.2.2 Storage requirements 9 5.2.3 Urine sample processing . 10 5.2.4 Long-term storage requirements for urine samples . 10 5.2.5 Urine

13、 thawing 10 6 Blood . 10 6.1 Outside the laboratory . 10 6.1.1 Primary blood collection manual . 10 6.1.2 Transport of pre-processed specimens to laboratory 12 6.2 Inside the laboratory 12 6.2.1 Specimen reception . 12 6.2.2 Sample processing . 12 6.2.3 Transport of processed samples to a laboratory

14、 for metabolomics analysis or transport to a biobank . 12 6.2.4 Long-term storage requirements . 13 6.2.5 Serum and plasma thawing and use 13 Annex A (informative) Long-term stability of urine and serum 1 H NMR metabolic profiles 14 A.1 General . 14 A.2 Urine 1 H NMR measurement result 14 A.3 Serum

15、1 H NMR measurement result . 16 A.4 NMR methods for urine and serum . 16 Bibliography . 18 PD CEN/TS 16945:2016 CEN/TS 16945:2016 (E) 3 European foreword This document (CEN/TS 16945:2016) has been prepared by Technical Committee CEN/TC 140 “In vitro diagnostic and medical devices”, the secretariat o

16、f 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 shall not be held responsible for identifying any or all such patent rights. According to the CEN-CENELEC Internal Regulations, the national standards org

17、anizations 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, Luxem

18、bourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the United Kingdom. PD CEN/TS 16945:2016 CEN/TS 16945:2016 (E) 4 Introduction Molecular in vitro diagnostics has enabled a significant progress in medicine. Further progress is ex

19、pected by new technologies analysing signatures of nucleic acids, proteins, and metabolites in human tissues and body fluids. However, the profiles of these molecules can change drastically during primary sample collection, transport, storage, and processing thus introducing biases and making the ou

20、tcome from diagnostics or research unreliable or even impossible because the subsequent analytical assay will not determine the situation in the patient but an artificial profile generated during the pre-examination process. Therefore, a standardization of the entire process from sample collection t

21、o metabolomics analysis is needed. Studies have been undertaken to determine the important influencing factors. This Technical Specification draws upon such work to codify and standardize the steps for urine, serum and plasma metabolomics analysis in what is referred to as the preanalytical phase. M

22、etabolomics, the global profiling of metabolites (namely molecules with a molecular weight MW 2 000 Da 3) in biological samples, is the determination of the dynamic multi-parametric metabolic response of living systems to pathophysiological stimuli and/or genetic modification. Metabolomics studies,

23、which can be semiquantitative or quantitative, help in identifying metabolic profiles that are characteristic for given pathological conditions, for disease prognosis, for the evaluation of the individual response to medical intervention and pharmaceutical treatments. Metabolites are physically and

24、chemically different, and include e.g. sugars, acids, bases, and lipids 3. This diversity of metabolites and the dynamic range of their concentration in biological samples complicate the separation and detection methods and make it impossible to identify all the metabolites in a single experiment. H

25、owever, new high-throughput technologies based on NMR (nuclear magnetic resonance) spectroscopy and MS (mass spectrometry) hold great potential due to their ability to look at large parts of the whole metabolome, although with different sensitivity. These two main analytical platforms are now well s

26、tandardized. Equally well established are the statistical approaches needed to extract information from the huge amount of data resulting from metabolomic analysis. The metabolic profiles are very sensitive to preanalytical variations that can result from enzymatic activity in the samples and chemic

27、al reactions (e.g. oxidation, 4, 5). This Technical Specification series provides guidelines arising from systematic studies conducted on the most commonly employed biofluids: urine and blood derivatives, serum and plasma. PD CEN/TS 16945:2016 CEN/TS 16945:2016 (E) 5 1 Scope This Technical Specifica

28、tion covers the preanalytical phase and recommends the handling, documentation and processing of urine, venous blood plasma and serum intended for metabolomics analysis. This Technical Specification is applicable to metabolomics examinations and is of importance to biomedical laboratories, customers

29、 of laboratories, in vitro diagnostics developers and manufacturers, institutions and companies performing biomedical research, biobanks, and regulatory authorities. The adoption of the described procedures for the preanalytical phase make it possible to compare and evaluate the results obtained fro

30、m metabolic profiling analysis. 2 Normative references The following documents, in whole or in part, are normatively referenced in this document and are indispensable for its application. For dated references, only the edition cited applies. For undated references, the latest edition of the referenc

31、ed document (including any amendments) applies. EN ISO 15189:2012, Medical laboratories - Requirements for quality and competence (ISO 15189:2012, Corrected version 2014-08-15) ISO 15190, Medical laboratories Requirements for safety 3 Terms and definitions For the purposes of this document, the term

32、s and definitions given in EN ISO 15189:2012 and the following apply. 3.1 analytical phase processes that start with the isolated analyte and include all kind of parameter testing or chemical manipulation for quantitative or qualitative analysis Note 1 to entry: For metabolomic analysis, analyte iso

33、lation is not necessarily required. 3.2 biofluid biological fluid which can be excreted (such as urine or sweat), secreted (such as breast milk, saliva or bile), obtained with a needle (such as blood or cerebrospinal fluid), or produced as a result of a pathological process (such as blister or cyst

34、fluid) 3.3 fasting abstinence from any solid or liquid food excluding water 3.4 mass spectrometry MS method used to analyse chemical compounds on the basis of their mass to charge ratio PD CEN/TS 16945:2016 CEN/TS 16945:2016 (E) 6 3.5 metabolic profiling use of analytical platforms to simultaneously

35、 measure the ensemble of metabolites that are accessible to the employed (or selected) technique EXAMPLE Examples for such techniques are NMR and MS. 3.6 metabolites small molecules ( 2000 Da) that are intermediates and/or products of metabolism Note 1 to entry: For further information see 3. 3.7 me

36、tabolome complete set of metabolites to be found within an organism or a biological sample Note 1 to entry: For further information see 3. 3.8 metabolomics scientific study of the whole metabolome present within a biological sample (e.g., organism, cell, tissue or biofluids) under a given set of con

37、ditions 3.9 MS-based metabolomics use of mass spectrometry to measure metabolites in biological samples 3.10 Nuclear magnetic resonance spectroscopy NMR method where the resonance magnetic properties of atomic nuclei are used to determine physical and chemical properties of atoms and molecules SOURC

38、E: ISO/TS 80004-6:2013, 4.26 3.11 NMR-based metabolomics use of NMR spectroscopy to measure metabolites in biological samples 3.12 plasma liquid part of unclotted blood Note 1 to entry: Plasma samples can contain anti-coagulants. PD CEN/TS 16945:2016 CEN/TS 16945:2016 (E) 7 3.13 pre-examination proc

39、esses preanalytical phase preanalytical workflow processes that start, in chronological order, from the clinicians request and include the examination request, preparation and identification of the patient, collection of the primary sample(s), temporary storage, transportation to and within the anal

40、ytical laboratory, aliquotting, retrieval, isolation of analytes, and end when the analytical examination begins Note 1 to entry: The preanalytical phase can include preparative processes that can influence the outcome of the intended examination. SOURCE: EN ISO 15189:2012, 3.15, modified An additio

41、nal term was added and more details were included. 3.14 primary sample specimen discrete portion of a body fluid, breath, hair or tissue taken for examination, study or analysis of one or more quantities or properties assumed to apply for the whole SOURCE: EN ISO 15189:2012, 3.16, modified The term

42、and definition are used here without the original notes. 3.15 room temperature temperature which is defined as 18 C to 25 C for the purpose of this document 3.16 serum liquid that can be separated from clotted blood 3.17 stability ability of a sample material, when stored under specified conditions,

43、 to maintain a stated property value within specified limits for a specified period of time Note 1 to entry: The analytes for the purpose of this document are metabolites. SOURCE: ISO Guide 30:1992, 2.7 4 General Considerations For general statements on specimen collection and handling (including av

44、oidance of cross contaminations) see EN ISO 15189:2012, 5.2.6, 5.4.4. Consumables including kits shall be verified before use in examination (see EN ISO 15189:2012, 5.3.2.3); EN ISO 15189:2012, 5.5.1.2 and 5.5.1.3 can also apply. As all steps of a diagnostic workflow can influence the final analytic

45、al performance, the entire workflow comprising the preanalytical steps, including information on specimen stability and storage conditions, and analytical steps should be verified and validated (see EN ISO 15189). In the absence of suitable specimen stabilization technologies, regarding the metabolo

46、me, the specimen collection should be carried out in hospital premises or institutions where there are immediate suitable biofluid processing procedures available. PD CEN/TS 16945:2016 CEN/TS 16945:2016 (E) 8 Specifically for specimens intended to be analysed by metabolomics, the following steps sha

47、ll be considered: a) the specimen collection from the patient; b) the selection of collection containers and packages (e.g. cooling box, box for storing and transportation); c) the selection of stabilization procedures (e.g. any compounds added for stabilizing the specimen); d) the recording of any

48、additions or modifications to the specimen; e) the recording of types and quantity and description of specimens. Safety regulations on facilities, transport and handling shall be considered (see EN ISO 15189:2012, 5.2.3 and 5.4.5, and ISO 15190). 5 Urine 5.1 Outside the laboratory 5.1.1 Urine collec

49、tion manual 5.1.1.1 Information on the primary specimen donor The documentation should include, but is not limited to: a) the specimen donor/patient ID, which can be in the form of a code; b) the health status and relevant lifestyle factors of the urine donor (e.g. healthy, disease type, diet, gender, age); c) the information about medical treatment and special treatment prior to urine collection (e.g. anaesthetics, medications); d) the collection time, including information about fasting, previous activities. See also EN ISO 15189:2012, 5.