CEN TS 16835-1-2015 Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for venous whole blood - Part 1 Isolated cellular RNA《分子体外诊断检查 静脉全血预审流.pdf

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1、BSI Standards PublicationPD CEN/TS 16835-1:2015Molecular in vitro diagnosticexaminations Specificationsfor pre-examination processesfor venous whole bloodPart 1: Isolated cellular RNAPD CEN/TS 16835-1:2015 PUBLISHED DOCUMENTNational forewordThis Published Document is the UK implementation of CEN/TS1

2、6835-1:2015.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 the necessaryprovisions of a contract. Users are resp

3、onsible for its correctapplication. The British Standards Institution 2015. Published by BSI StandardsLimited 2015ISBN 978 0 580 85028 8ICS 11.100.10Compliance with a British Standard cannot confer immunity fromlegal obligations.This Published Document was published under the authority of theStandar

4、ds Policy and Strategy Committee on 31 July 2015.Amendments issued since publicationDate Text affectedPD CEN/TS 16835-1:2015TECHNICAL SPECIFICATION SPCIFICATION TECHNIQUE TECHNISCHE SPEZIFIKATION CEN/TS 16835-1 July 2015 ICS 11.100.10 English Version Molecular in vitro diagnostic examinations - Spec

5、ifications for pre-examination processes for venous whole blood - Part 1: Isolated cellular RNA Tests de diagnostic molculaire in vitro - Spcifications relatives aux processus pranalytiques pour le sang veineux total - Partie 1 : ARN cellulaire isol Molekularanalytische in-vitro-diagnostische Verfah

6、ren - Spezifikationen fr pranalytische Prozesse fr vense Vollblutproben - Teil 1: Isolierte zellulre RNS This Technical Specification (CEN/TS) was approved by CEN on 30 May 2015 for provisional application. The period of validity of this CEN/TS is limited initially to three years. After two years th

7、e 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

8、 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, Croati

9、a, 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 Uni

10、ted 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. No. CE

11、N/TS 16835-1:2015 EPD CEN/TS 16835-1:2015CEN/TS 16835-1:2015 (E) 2 Contents Page Foreword 3 Introduction .4 1 Scope 5 2 Normative references 5 3 Terms and definitions .5 4 General considerations .6 5 Outside the laboratory 7 5.1 Primary venous whole blood collection manual 7 5.1.1 Information about

12、the primary sample donor .7 5.1.2 Selection of the venous blood collection tube by the laboratory .7 5.1.3 Primary venous whole blood collection from the patient and stabilization procedures .7 5.1.4 Information on the primary blood sample and storage requirements at the blood collection facility 8

13、5.2 Transport requirements 9 6 Inside the laboratory .9 6.1 Sample reception .9 6.2 Storage requirements 9 6.3 Isolation of the cellular RNA 10 6.4 Quality assessment of isolated cellular RNA 11 6.5 Storage of isolated cellular RNA . 11 Annex A (informative) Impact of preanalytical workflow steps on

14、 venous whole blood cellular RNA profiles 12 A.1 General information on operated experiments in Annex A and Annex B. 12 A.2 Influence of blood collection tube type (with or without blood cellular RNA profile stabilizer) on the analysis of specific blood cellular RNA profiles 12 A.2.1 Unstable blood

15、cellular RNA profiles . 12 A.2.2 Stable blood cellular RNA profiles 14 Annex B (informative) Influence of blood storage temperature on blood cellular RNA profiles . 16 Bibliography . 19 PD CEN/TS 16835-1:2015CEN/TS 16835-1:2015 (E) 3 Foreword This document (CEN/TS 16835-1:2015) has been prepared by

16、Technical Committee CEN/TC 140 “In vitro diagnostic medical devices”, 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

17、 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 Repu

18、blic 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. PD CEN/TS 16835-1:2015CEN/TS 16835-1:2015 (E) 4 Introduct

19、ion Molecular in vitro diagnostics has enabled a significant progress in medicine. Further progress is expected by new technologies analyzing signatures of nucleic acids, proteins, and metabolites in human tissues and body fluids. However, the profiles of these molecules can change drastically durin

20、g primary sample collection, transport, storage, and processing thus making the outcome 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 pr

21、ocess. Therefore, a standardization of the entire process from sample collection to RNA 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 venous whole blood cellul

22、ar RNA analysis in what is referred to as the preanalytical phase. PD CEN/TS 16835-1:2015CEN/TS 16835-1:2015 (E) 5 1 Scope This Technical Specification recommends the handling, documentation and processing of venous whole blood specimens intended for cellular RNA analysis during the preanalytical ph

23、ase before a molecular assay is performed. This Technical Specification covers specimens collected by venous whole blood collection tubes. This Technical Specification is applicable to molecular in vitro diagnostic examinations (e.g. in vitro diagnostic laboratories, laboratory customers, in vitro d

24、iagnostics developers and manufacturers, institutions and commercial organizations performing biomedical research, biobanks, and regulatory authorities). Blood cellular RNA profiles can change significantly after collection. Therefore, special measures need to be taken to secure good quality blood s

25、amples for cellular RNA analysis and storage. Different dedicated measures need to be taken for stabilizing blood cell free circulating RNA and RNA in exosomes circulating in blood, which are not described in this Technical Specification. Different dedicated measures need to be taken for collecting,

26、 stabilizing, transporting and storing capillary blood as well as for collecting and storing blood by paper based technologies. These are not described in this Technical Specification. RNA in pathogens present in blood is not covered by this Technical Specification. 2 Normative references The follow

27、ing 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 amendments) applies. EN ISO 15189:2012

28、, 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 15189:2012 and the following ap

29、ply. 3.1 ambient temperature unregulated temperature of the surrounding air 3.2 analytical phase processes that start with the isolated analyte and include all kind of parameter testing or chemical manipulation for quantitative or qualitative analysis 3.3 blood cellular RNA cellular RNA RNA molecule

30、s present in blood cells 3.4 blood cellular RNA profiles amounts of different RNA molecules, that are present in blood cells and that can be measured in the absence of any losses, inhibition and interference PD CEN/TS 16835-1:2015CEN/TS 16835-1:2015 (E) 6 3.5 blood cellular RNA profile stabilizers c

31、ompounds, solutions or mixtures that are designed to minimize changes of the blood cellular RNA profile 3.6 pre-examination processes preanalytical phase preanalytical workflow processes that start, in chronological order, from the clinicians request and include the examination request, preparation

32、and identification of the patient, collection of the primary sample(s), temporary storage, transportation to and within the analytical laboratory, aliquotting, retrieval, isolation of analytes, and end when the analytical examination begins SOURCE: EN ISO 15189:2012, 3.15, modified An additional ter

33、m was added and more details were included. Note 1 to entry: The preanalytical phase may include preparative processes that may influence the outcome of the intended examination. 3.7 primary sample specimen discrete portion of a body fluid, breath, hair or tissue taken for examination, study or anal

34、ysis 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 is used here without the original notes. 3.8 RNA ribonucleic acid polymer of ribonucleotides occurring in a double-stranded or single-stranded form SOURCE: EN

35、 ISO 22174:2005, 3.1.3 3.9 room temperature temperature which is defined as 18 C to 25 C for the purposes of this document 3.10 stability ability of a sample material, when stored under specified conditions, to maintain a stated property value within specified limits for a specified period of time S

36、OURCE ISO Guide 30:1992, 2.7 Note 1 to entry: The measured constituent for the purpose of this document is blood cellular RNA. 4 General considerations For general statements on primary sample collection and handling (including avoidance of cross contaminations), see EN ISO 15189:2012, 5.2.6, 5.4.4.

37、 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 comprising the preanalytical step

38、s, including information on sample stability and storage conditions, and the analytical steps should be verified and validated (see EN ISO 15189). PD CEN/TS 16835-1:2015CEN/TS 16835-1:2015 (E) 7 Blood cellular RNA profiles can change significantly after collection (e.g. gene induction, gene down reg

39、ulation, RNA degradation) 3, 4, 5, 6. These changes can vary individually in different blood donors / patients blood 3, 7, 8, 9, 10. The stability of the specific blood cellular RNA profile of interest should be investigated throughout the complete preanalytical workflow. Before or during the design

40、 of the analytical test system it should be investigated and ensured that the specific blood cellular RNA molecule/s amount/s intended to be analyzed in the analytical test is/are not affected by the envisioned entire preanalytical workflow. If a commercial product is not used in accordance with the

41、 manufacturers instructions, responsibility for its validation, verification, use and performance lies with the user. Safety regulations on transport and handling shall be considered (EN ISO 15189:2012, 5.4.5 and ISO 15190). 5 Outside the laboratory 5.1 Primary venous whole blood collection manual 5

42、.1.1 Information about the primary sample donor The documentation should include, but is not limited to: a) the primary donor / patient ID, which can be in the form of a code; b) the health status and relevant lifestyle factors of the blood donor (e.g. healthy, disease type, diet, gender, age); c) t

43、he information about medical treatment and special treatment prior to blood collection (e.g. anaesthetics, medications, fasting status); d) the type and purpose of the analytical test requested. See also EN ISO 15189:2012, 5.4.4. 5.1.2 Selection of the venous blood collection tube by the laboratory

44、Due to the high instability of blood cellular RNA profiles in individual patients/donors 3, 7, 8, 9, 10, commercially available blood collection tubes containing blood cellular RNA profile stabilizers should be used 7, 8, 10, 11, 12 (Figure A.1). Blood collection tubes not containing any blood cellu

45、lar RNA profile stabilizer should only be used, if the specific blood cellular RNA molecule or the blood cellular RNA profile to be analyzed is stable after blood draw (Figure A.2) or if the requested analytical test allows the use of such tubes. 5.1.3 Primary venous whole blood collection from the

46、patient and stabilization procedures 1. The identity of the person collecting the sample and the time of blood collection according to EN ISO 15189:2012, 5.4.4.3, f) shall be documented. 2. For the labelling (sample identification) of the blood collection tube a routine procedure (EN ISO 15189:2012,

47、 5.4.4.3, e) or a procedure with additional information (e.g. 2D-barcode) shall be used. 3. Standard venepuncture technique can be used. Steps for preventing possible backflow may be required. The manufacturers instructions for using the blood collection tubes shall be followed. A PD CEN/TS 16835-1:

48、2015CEN/TS 16835-1:2015 (E) 8 blood collection set and needle holder can be required when using blood cellular RNA profile stabilizer containing tubes. In this case, the instructions of the collection set and needle holder manufacturer shall be followed. NOTE There is no known specific effect of ven

49、ous whole blood draw procedure on the cellular RNA. Routine procedures can therefore be used. 4. Blood collection tubes shall be filled in accordance to the manufacturers instructions and attention should be drawn to the correct positioning of the collection tube during the blood draw as well as the required volume. 5. Blood collection tube manufacturers instructions, for mixing or inverting the tube immediately after blood collection, shall be followed. NOTE Unless additives are homogenously mixed with the blo