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

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1、BSI Standards Publication PD CEN/TS 16835-1:2015 Molecular in vitro diagnostic examinations Specifications for pre-examination processes for venous whole blood Part 1: Isolated cellular RNAPD CEN/TS 16835-1:2015 PUBLISHED DOCUMENT National foreword This Published Document is the UK implementation of

2、 CEN/TS 16835-1:2015. 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 to include all the necessary provisions of a contract.

3、 Users are responsible for its correct application. The British Standards Institution 2015. Published by BSI Standards Limited 2015 ISBN 978 0 580 85028 8 ICS 11.100.10 Compliance with a British Standard cannot confer immunity from legal obligations. This Published Document was published under the a

4、uthority of the Standards Policy and Strategy Committee on 31 July 2015. Amendments issued since publication Date 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 diagn

5、ostic examinations - Specifications 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-v

6、itro-diagnostische Verfahren - 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

7、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 avail

8、able 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,

9、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, Sw

10、itzerland, 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 2015 CEN All rights of exploitation in any form and by any means reserved worldwide for CEN nati

11、onal Members. Ref. No. CEN/TS 16835-1:2015 EPD CEN/TS 16835-1:2015 CEN/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

12、7 5.1.1 Information about 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 bl

13、ood collection facility 8 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 prean

14、alytical workflow steps on 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 profile

15、s 12 A.2.1 Unstable blood 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 16835-1:2015 CEN/TS 16835-1:2015 (E) 3 Foreword This document (CEN/TS 16835-1:

16、2015) has been prepared by 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 respons

17、ible 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, Fi

18、nland, 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. PD CEN/TS 16835-1:2015 CEN/TS

19、16835-1:2015 (E) 4 Introduction 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

20、can change drastically during 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 d

21、uring the pre-examination process. 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 f

22、or venous whole blood cellular RNA analysis in what is referred to as the preanalytical phase. PD CEN/TS 16835-1:2015 CEN/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 analysi

23、s during the preanalytical phase 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, lab

24、oratory customers, in vitro diagnostics 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 t

25、o secure good quality blood samples 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 nee

26、d to be taken for collecting, 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 No

27、rmative 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 amendment

28、s) 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 15

29、189:2012 and the following apply. 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

30、RNA cellular RNA RNA molecules 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 16835-1:2015 CEN/TS 16835-1:2015 (E) 6 3.5 blood cell

31、ular RNA profile stabilizers compounds, 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 exa

32、mination request, preparation 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.

33、15, modified An additional term 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

34、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 is used here without the original notes. 3.8 RNA ribonucleic acid polymer of ribonucleotides occurring in a double-stranded or s

35、ingle-stranded form SOURCE: EN 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 fo

36、r a specified period of time SOURCE 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

37、 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 com

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

39、. gene induction, gene down regulation, 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 workfl

40、ow. Before or during the design 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

41、not used in accordance with the 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

42、whole blood collection manual 5.1.1 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

43、 type, diet, gender, age); c) the 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 col

44、lection tube by the laboratory 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

45、 not containing any blood cellular 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 w

46、hole blood collection from the 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 routin

47、e procedure (EN ISO 15189:2012, 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

48、 followed. A PD CEN/TS 16835-1:2015 CEN/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

49、 no known specific effect of venous 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 ar