CEN TS 16945-2016 Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for metabolomics in urine venous blood serum and plasma《分子体外诊断检查-尿 静脉血清和.pdf

1、PD CEN/TS 16945:2016Molecular in vitro diagnosticexaminations Specificationsfor pre-examination processesfor metabolomics in urine,venous blood serum andplasmaBSI Standards PublicationWB11885_BSI_StandardCovs_2013_AW.indd 1 15/05/2013 15:06PD CEN/TS 16945:2016 PUBLISHED DOCUMENTNational forewordThis

2、 Published Document is the UK implementation of CEN/TS16945:2016.The UK participation in its preparation was entrusted to TechnicalCommittee CH/212, IVDs.A list of organizations represented on this committee can beobtained on request to its secretary.This publication does not purport to include all

3、the necessaryprovisions of a contract. Users are responsible for its correctapplication. The British Standards Institution 2016. Published by BSI StandardsLimited 2016ISBN 978 0 580 93674 6ICS 11.100.10Compliance with a British Standard cannot confer immunity fromlegal obligations.This Published Doc

4、ument was published under the authority of theStandards Policy and Strategy Committee on 31 May 2016.Amendments issued since publicationDate Text affectedPD CEN/TS 16945:2016TECHNICAL SPECIFICATION SPCIFICATION TECHNIQUE TECHNISCHE SPEZIFIKATION CEN/TS 16945 May 2016 ICS 11.100.10 English Version Mo

5、lecular 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 lurine et le sang veineux (sr

6、um 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 application. The period of valid

7、ity 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 s

8、ame 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 membe

9、rs 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, Portuga

10、l, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey andUnited 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 of exploitation in any form

11、and by any means reserved worldwide for CEN national Members. Ref. No. CEN/TS 16945:2016 EPD CEN/TS 16945:2016CEN/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 Considerations. 7 5 Urine 8 5.1 Outside th

12、e 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 thawing 10 6 Blood . 10 6.1

13、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 for metabolomics analysis or

14、 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 1H NMR metabolic profiles 14 A.1 General . 14 A.2 Urine 1H NMR measurement result 14 A.3 Serum 1H NMR measurement result . 16

15、A.4 NMR methods for urine and serum . 16 Bibliography . 18 PD CEN/TS 16945:2016CEN/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 of which is held by DIN. Attention

16、 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 organizations of the following count

17、ries 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

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

19、ng 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 outcome from diagnostics or research

20、 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 to metabolomics analysis is needed.

21、 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. Metabolomics, the global profiling

22、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, which can be semiquantitative or q

23、uantitative, 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 chemically different, and include

24、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. However, new high-throughput techno

25、logies 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 standardized. Equally well establis

26、hed 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 chemical reactions (e.g. oxidation, 4, 5

27、). 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 16945:2016CEN/TS 16945:2016 (E) 5 1 Scope This Technical Specification covers the preanalytical phase

28、 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 of laboratories, in vitro diagnost

29、ics 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 from metabolic profiling analysis. 2 N

30、ormative 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 referenced document (including any amendmen

31、ts) 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 terms and definitions given in EN ISO 1

32、5189:2012 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 isolation is not necessarily required.

33、 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 fluid) 3.3 fasting abstinence from

34、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 16945:2016CEN/TS 16945:2016 (E) 6 3.5 metabolic profiling use of analytical platforms to simultaneously measure the ensemble of metabolites

35、 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 metabolome complete set of metabolites

36、 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 conditions 3.9 MS-based metabolomics us

37、e 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 SOURCE: ISO/TS 80004-6:2013, 4.26 3.11 NM

38、R-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 16945:2016CEN/TS 16945:2016 (E) 7 3.13 pre-examination processes preanalytical phase preanalytic

39、al 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 analytical laboratory, aliquotting, retri

40、eval, 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 additional term was added and more details w

41、ere 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 and definition are used here without

42、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, to maintain a stated property value

43、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 avoidance of cross contaminations) see

44、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 analytical performance, the entire workflow c

45、omprising 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 metabolome, the specimen collection should be

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

47、ection 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 additions or modifications to the spec

48、imen; 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 collection manual 5.1.1.1 Information on the

49、 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, 5.4.4. 5.1.1.2 Selection and labelling