1、BSI Standards PublicationWB11885_BSI_StandardCovs_2013_AW.indd 1 15/05/2013 15:06Molecular in vitro diagnostic examinations Specifications for pre-examination processes for snap frozen tissuePart 3: Isolated DNAPD CEN/TS 168263:2018National forewordThis Published Document is the UK implementation of
2、 CEN/TS 168263:2018.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. Use
3、rs are responsible for its correct application. The British Standards Institution 2018 Published by BSI Standards Limited 2018ISBN 978 0 580 51738 9ICS 11.100.10Compliance with a British Standard cannot confer immunity from legal obligations.This Published Document was published under the authority
4、of the Standards Policy and Strategy Committee on 31 July 2018.Amendments/corrigenda issued since publicationDate Text affectedPUBLISHED DOCUMENTPD CEN/TS 168263:2018TECHNICAL SPECIFICATIONSPCIFICATION TECHNIQUETECHNISCHE SPEZIFIKATIONCEN/TS 16826-3July 2018ICS 11.100.10EUROPEAN COMMITTEE FOR STANDA
5、RDIZATIONCOMIT EUROPEN DE NORMALISATIONEUROPISCHES KOMITEE FR NORMUNGCEN-CENELEC Management Centre: Avenue Marnix 17, B-1000 Brussels 2018 CEN Ref. No. CEN/TS 168263:2018: EAll rights of exploitation in any form and by any means reserved worldwide for CEN national MembersMolecular in vitro diagnosti
6、c examinations Specifications for preexamination processes for snap frozen tissue Part 3: Isolated DNATests de diagnostic molculaire in vitro - Spcifications relatives aux processus pranalytiques pour les tissus conglation rapide Partie 3: ADN isolMolekularanalytische invitrodiagnostische Verfahren
7、- Spezifikationen fr pranalytische Prozesse fr schockgefrorene Gewebeproben Teil 3: Isolierte DNAThis Technical Specification (CEN/TS) was approved by CEN on 16 April 2018 for provisional application.The period of validity of this CEN/TS is limited initially to three years. After two years the membe
8、rs 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 level i
9、n 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, Croatia, Cyprus
10、, 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, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and Unit
11、ed Kingdom.English VersionCEN/TS 16826-3:2018 (E)European foreword iiiIntroduction iv1 Scope . 52 Normative references 53 Terms and definitions . 54 General considerations 85 Outside the laboratory . 95.1 Specimen collection 95.1.1 General 95.1.2 Information about the specimen donor/patient 95.1.3 I
12、nformation about the specimen . 95.1.4 Specimen processing .105.2 Fresh tissue transport requirements 105.2.1 General. 105.2.2 Preparations for the transport 105.2.3 During transport .116 Inside the laboratory 116.1 Information about the reception of the specimen .116.2 Evaluation of the pathology o
13、f the specimen and selection of the sample(s) .116.3 Freezing of the specimen or sample(s) . 126.4 Storage requirements . 146.5 DNA isolation . 146.5.1 General. 146.5.2 Using commercial kits 156.5.3 Using the laboratorys own protocols .156.6 Quantity and quality assessment of isolated DNA 156.7 Stor
14、age of isolated DNA 16Bibliography .17iiContents PagePD CEN/TS 168263:2018CEN/TS 16826-3:2018 (E)European forewordThis document (CEN/TS 16826-3:2018) 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
15、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.CEN/TS 16826 consists of the following parts: Molecular in vitro diagnostic examinations Specifications for pre-examinati
16、on processes for snap frozen tissue Part 1: Isolated RNA ; Molecular in vitro diagnostic examinations Specifications for pre-examination processes for snap frozen tissue Part 2: Isolated proteins ; Molecular in vitro diagnostic examinations Specifications for pre-examination processes for snap froze
17、n tissue Part 3: Isolated DNA .According to the CEN/CENELEC Internal Regulations, the national standards organisations of the following countries are bound to announce this Technical Specification: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Former Yugosla
18、v Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the United Kingdom.iiiPD CEN/TS 168263:2018CEN/TS 16826-3:2018
19、(E)IntroductionMolecular in vitro diagnostics, including molecular pathology, has enabled a significant progress in medicine. Further progress is expected with new technologies analysing nucleic acids, proteins, and metabolites in human tissues and body fluids. However, integrity of these molecules
20、can change during specimen collection, transport, storage, and processing, thus making the outcome from diagnostics or research unreliable or even impossible because the subsequent examination assay will not determine the situation in the patient but an artificial pattern generated during the pre-ex
21、amination process. Therefore, a standardization of the entire process from specimen collection to the DNA examination is needed. Studies have been undertaken to determine the important influencing factors. This document draws upon such work to codify and standardize the steps for frozen tissue with
22、regard to DNA examination in what is referred to as the preexamination phase.DNA integrity in tissues can change during processing and storage. Modifications of the DNA molecules can impact the validity and reliability of the examination test results. Therefore, it is essential to take special measu
23、res to minimize the described DNA changes and modifications for subsequent examination.In this document, the following verbal forms are used: “shall” indicates a requirement; “should” indicates a recommendation; “may” indicates a permission; “can” indicates a possibility or a capability.ivPD CEN/TS
24、168263:2018CEN/TS 16826-3:2018 (E)1 ScopeThis document gives recommendations for the handling, storage, processing and documentation of frozen tissue specimens intended for DNA examination during the preexamination phase before a molecular examination is performed.This document is applicable to mole
25、cular in vitro diagnostic examination including laboratory developed tests performed by medical laboratories and molecular pathology laboratories that evaluate DNA isolated from frozen tissue. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers,
26、biobanks, institutions and commercial organizations performing biomedical research, and regulatory authorities.Tissues that have undergone chemical stabilization pretreatment before freezing are not covered in this document.NOTE International, national or regional regulations or requirements can als
27、o apply to specific topics covered in this document.2 Normative referencesThe following documents are referred to in the text in such a way that some or all of their content constitutes requirements of this document. For dated references, only the edition cited applies. For undated references, the l
28、atest edition of the referenced document (including any amendments) applies.EN ISO 15189:2012, Medical laboratories Requirements for quality and competence (ISO 15189:2012, Corrected version 2014-08-15)EN ISO/IEC 17020:2012, Conformity assessment Requirements for the operation of various types of bo
29、dies performing inspection (ISO/IEC 17020:2012)ISO 15190, Medical laboratories Requirements for safety3 Terms and definitionsFor the purposes of this document, the terms and definitions given in EN ISO 15189 and the following apply.ISO and IEC maintain terminological databases for use in standardiza
30、tion at the following addresses: IEC Electropedia: available at http:/www.electropedia.org/ ISO Online browsing platform: available at http:/www.iso.org/obp3.1aliquotportion of a larger amount of homogenous material, assumed to be taken with negligible sampling errorNote 1 to entry: The term is usua
31、lly applied to fluids. Tissues are heterogeneous and therefore cannot be aliquoted.Note 2 to entry: The definition is derived from the Compendium of Chemical Terminology Gold Book. International Union of Pure and Applied Chemistry. Version 2.3.3., 2014; the PAC, 1990,62,1193 (Nomenclature for sampli
32、ng in analytical chemistry (Recommendations 1990) p. 1206; and the PAC 1990, 62, 2167 (Glossary of atmospheric chemistry terms (Recommendations 1990) p. 2173.3.2ambient temperatureunregulated temperature of the surrounding air5PD CEN/TS 168263:20186 PD CEN/TS 168263:2018CEN/TS 16826-3:2018 (E)3.3ana
33、lytecomponent represented in the name of a measurable quantitySOURCE: EN ISO 17511:2003, 3.2, modified The example was not taken over.3.4analytical test performanceaccuracy, precision, and sensitivity of a test to measure the analyte of interestNote 1 to entry: Other test performance characteristics
34、 such as robustness, repeatability can apply as well.3.5cold ischemiacondition after removal of the tissue from the body until its stabilization or fixation3.6diagnosisidentification of a health or disease state from its signs and/or symptoms, where the diagnostic process can involve examinations an
35、d tests for classification of an individuals condition into separate and distinct categories or subclasses that allow medical decisions about treatment and prognosis to be made3.7DNAdeoxyribonucleic acidpolymer of deoxyribonucleotides occurring in a double-stranded (dsDNA) or single-stranded (ssDNA)
36、 formSOURCE: EN ISO 22174:2005, 3.1.23.8DNasedeoxyribonucleaseenzyme that catalyzes the degradation of DNA into smaller components3.9examinationanalytical testset of operations having the object of determining the value or characteristics of a propertyNote 1 to entry: Processes that start with the i
37、solated analyte and include all kinds of parameter testing or chemical manipulation for quantitative or qualitative examination.SOURCE: EN ISO 15189:2012, 3.7, modified The term and definition are used here without the original notes.3.10grossinggross examinationinspection of pathology specimens wit
38、h the bare eye to obtain diagnostic information, while being processed for further microscopic examination3.11homogeneousuniform in structure and composition3.12interfering substanceendogenous substance of a specimen/sample or exogenous substance (e.g. stabilization solution) that can alter an exami
39、nation resultCEN/TS 16826-3:2018 (E)3.13pre-examination processpreanalytical phasepreanalytical workflowprocess 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), tran
40、sportation to and within the medical or pathology laboratory, isolation of analytes, and ends when the analytical examination beginsNote 1 to entry: The pre-examination phase includes preparative processes that influence the outcome of the intended examination.SOURCE: EN ISO 15189:2012, 3.15, modifi
41、ed An additional term was added and details were adjusted to the scope of this document.3.14primary samplespecimendiscrete 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 wholeSOURCE: EN ISO 151
42、89:2012, 3.16, modified The term and definition are used here without the original notes.3.15proficiency testevaluation of participant performance against preestablished criteria by means of interlaboratory comparisonsSOURCE: EN ISO/IEC 17043:2010, 3.7, modified The term and definition are used here
43、 without the original notes.3.16room temperaturefor the purposes of this document, temperature in the range of 18 C to 25 CNote 1 to entry: Local or national regulations can have different definitions.3.17sampleone or more parts taken from a primary sampleSOURCE: EN ISO 15189:2012, 3.24, modified Th
44、e example was not taken over.3.18stabilityability of a sample material, when stored under specified conditions, to maintain a stated property value within specified limits for a specified period of timeNote 1 to entry: The analyte for the purpose of this document is DNA.SOURCE: ISO Guide 30:2015, 2.
45、1.15, modified The words “reference material” were replaced by “sample material”.3.19storageprolonged interruption of the preanalytical workflow of a sample or analyte respectively, or of their derivatives e.g., stained sections or tissue blocks, under appropriate conditions in order to preserve the
46、ir propertiesNote 1 to entry: Longterm storage typically occurs in laboratory archives or in biobanks.7PD CEN/TS 168263:2018 performing alternative calculations, comparing a new design specification with a similar proven design specification, undertaking tests and demonstrations, and reviewing docum
47、ents prior to issue.3.22warm ischemiacondition before the tissue is removed from the body, but where it is deprived of its normal blood supply3.23workflowseries of activities necessary to complete a task4 General considerationsFor general statements on medical laboratory quality management systems a
48、nd in particular on specimen collection, reception and handling (including avoidance of cross contaminations) see EN ISO 15189:2012, 4.2, 5.4.4, 5.4.6 or EN ISO/IEC 17020:2012, Clause 8 and 7.2. The requirements on laboratory equipment, reagents, and consumables according to EN ISO 15189:2012, 5.3 s
49、hall be followed; EN ISO 15189:2012, 5.5.1.2 and 5.5.1.3 and EN ISO/IEC 17020:2012, 6.2 can also apply.All steps of a diagnostic workflow can influence the final analytical test result. Thus, the entire workflow including biomolecule stability and sample storage conditions shall be verified and validated. Workflow steps which cannot always be controlled (e.g. warm ischemia) shall be documented. A risk assessment of non-controllable workflow steps including their potential impac
