1、September 2007DEUTSCHE NORM English price group 10No part of this standard may be reproduced without prior permission ofDIN Deutsches Institut fr Normung e. V., Berlin. Beuth Verlag GmbH, 10772 Berlin, Germany,has the exclusive right of sale for German Standards (DIN-Normen).ICS 11.100.10!$I=F“13826
2、35www.din.deDDIN EN ISO 20776-2Clinical laboratory testing and in vitro diagnostic test systems Susceptibility testing of infectious agents and evaluation ofperformance of antimicrobial susceptibility test devices Part 2: Evaluation of performance of antimicrobial susceptibility testdevices (ISO 207
3、76-2:2007)English version of DIN EN ISO 20776-2:2007-09Labormedizinische Untersuchungen und In-vitro-Diagnostika-Systeme Empfindlichkeitsprfung von Infektionserregern und Evaluation von Gerten zurantimikrobiellen Empfindlichkeitsprfung Teil 2: Evaluation der Leistung einer Vorrichtung zur antimikrob
4、iellenEmpfindlichkeitsprfung (ISO 20776-2:2007)Englische Fassung DIN EN ISO 20776-2:2007-09www.beuth.deDocument comprises 13 pages 11.07DIN EN ISO 20776-2:2007-09 2 National foreword This standard has been prepared by Technical Committee CEN/TC 140 “In vitro diagnostic medical devices” (Secretariat:
5、 DIN, Germany) in collaboration with Technical Committee ISO/TC 212 “Clinical laboratory testing and in vitro diagnostic test systems”. The responsible German body involved in its preparation was the Normenausschuss Medizin (Medical Standards Committee), Technical Committee NA 063-05-10 AA Chemother
6、apeutische Untersuchungs-methoden. EUROPEAN STANDARD NORME EUROPENNE EUROPISCHE NORM EN ISO 20776-2 July 2007 ICS 11.100.20 English Version Clinical laboratory testing and in vitro diagnostic test systems - Susceptibility testing of infectious agents and evaluation of performance of antimicrobial su
7、sceptibility test devices - Part 2: Evaluation of performance of antimicrobial susceptibility test devices (ISO 20776-2:2007) Systmes dessais en laboratoire et de diagnostic in vitro - Sensibilit in vitro des agents infectieux et valuation des performances des dispositifs pour antibiogrammes - Parti
8、e 2: valuation des performances des dispositifs pour antibiogrammes (ISO 20776-2:2007) Labormedizinische Untersuchungen und In-vitro-Diagnostika-Systeme - Empfindlichkeitsprfung von Infektionserregern und Evalution von Gerten zur antimikrobiellen Empfindlichkeitsprfung - Teil 2: Evalution der Leistu
9、ng einer Vorrichtung zur antimikrobiellen Empfindlichkeitsprfung (ISO 20776-2:2007) This European Standard was approved by CEN on 24 June 2007. CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this European Standard the status of a n
10、ational standard without any alteration. Up-to-date lists and bibliographical references concerning such national standards may be obtained on application to the CEN Management Centre or to any CEN member. This European Standard exists in three official versions (English, French, German). A version
11、in any other language made by translation under the responsibility of a CEN member into its own language and notified to the CEN Management Centre has the same status as the official versions. CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmar
12、k, Estonia, Finland, France,Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom. EUROPEAN COMMITTEE FOR STANDARDIZATION COMIT EUROPEN DE NORMALISATIO
13、N EUROPISCHES KOMITEE FR NORMUNG Management Centre: rue de Stassart, 36 B-1050 Brussels 2007 CEN All rights of exploitation in any form and by any means reserved worldwide for CEN national Members. Ref. No. EN ISO 20776-2:2007: EForeword This document (EN ISO 20776-2:2007) has been prepared by Techn
14、ical Committee CEN/TC 140 “In vitro diagnostic medical devices”, the secretariat of which is held by DIN, in collaboration with Technical Committee ISO/TC 212 “Clinical laboratory testing and in vitro diagnostic test systems”. This European Standard shall be given the status of a national standard,
15、either by publication of an identical text or by endorsement, at the latest by January 2008, and conflicting national standards shall be withdrawn at the latest by January 2008. According to the CEN/CENELEC Internal Regulations, the national standards organizations of the following countries are bou
16、nd to implement this European Standard: Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, S
17、witzerland and United Kingdom. 2 EN ISO 20776-2:2007 (E) 1 Scope This part of ISO 20776 establishes acceptable performance criteria for antimicrobial susceptibility test (AST) devices that are used to determine minimum inhibitory concentrations (MIC) and/or interpretive category determinations of su
18、sceptible, intermediate and resistant (SIR) strains of bacteria to antimicrobial agents in medical laboratories. This part of ISO 20776 specifies requirements for AST devices (including diffusion test systems) and procedures for assessing performance of such devices. It defines how a performance eva
19、luation of an AST device is to be conducted. This part of ISO 20776 has been developed to guide manufacturers in the conduct of performance evaluation studies. 2 Normative references The following referenced documents are indispensable for the application of this document. For dated references, only
20、 the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies. ISO 20776-1, Clinical laboratory testing and in vitro diagnostic test systems Susceptibility testing of infectious agents and evaluation of performance of antimicrobi
21、al susceptibility test devices Part 1: Reference method for testing the in vitro activity of antimicrobial agents against rapidly growing aerobic bacteria involved in infectious diseases 3 Terms and definitions For the purposes of this document, the following terms and definitions apply. 3.1 Agreeme
22、nt of test results 3.1.1 category agreement CA agreement of SIR results between a breakpoint test or an MIC test and the reference method (ISO 20776-1) Another representation of the concept: CA100NN3 EN ISO 20776-2:2007 (E) where NCAis the number of bacterial isolates with the same SIR category as t
23、he reference method category result; N is the total number of bacterial isolates tested NOTE The overall CA is expressed as a percentage. 3.1.2 essential agreement EA MIC result obtained with the AST device that is within plus or minus one doubling dilution step from the MIC value established with t
24、he reference method (ISO 20776-1) Another representation of the concept: EA100NNwhere NEAis the number of bacterial isolates with an EA; N is the total number of bacterial isolates tested NOTE The overall EA is expressed as a percentage. 3.2 antimicrobial susceptibility test device AST device device
25、 including all specified components used to obtain test results that allow SIR categorization of bacteria with specific antimicrobial agents NOTE Specific components include inoculators, disposables and reagents, media, disks and readers. Non-specific components, such as swabs, pipettes and tubes, a
26、re not part of the device. 3.3 breakpoint BP specific values of parameters, such as MICs, on the basis of which bacteria can be assigned to the clinical categories “susceptible”, “intermediate” and “resistant” NOTE For current interpretive breakpoints, reference can be made to the latest publication
27、s of organizations employing this reference method (e.g. CLSI and EUCAST). 3.3.1 susceptible S bacterial strain inhibited in vitro by a concentration of an antimicrobial agent that is associated with a high likelihood of therapeutic success NOTE 1 Bacterial strains are categorized as susceptible by
28、applying the appropriate breakpoints in a defined phenotypic test system. NOTE 2 This breakpoint can be altered due to changes in circumstances (e.g. changes in commonly used drug dosages, emergence of new resistance mechanisms). 4 EN ISO 20776-2:2007 (E) 3.3.2 intermediate I bacterial strain inhibi
29、ted in vitro by a concentration of an antimicrobial agent that is associated with uncertain therapeutic effect NOTE 1 Bacterial strains are categorized as intermediate by applying the appropriate breakpoints in a defined phenotypic test system. NOTE 2 This class of susceptibility implies that an inf
30、ection due to the isolate can be appropriately treated in body sites where the drugs are physiologically concentrated or when a high dosage of drug can be used. NOTE 3 This class also indicates a “buffer zone”, to prevent small, uncontrolled, technical factors from causing major discrepancies in int
31、erpretations. NOTE 4 These breakpoints can be altered due to changes in circumstances (e.g. changes in commonly used drug dosages, emergence of new resistance mechanisms). 3.3.3 resistant R bacterial strain inhibited in vitro by a concentration of an antimicrobial agent that is associated with a hig
32、h likelihood of therapeutic failure NOTE 1 Bacterial strains are categorized as resistant by applying the appropriate breakpoints in a defined phenotypic test system. NOTE 2 This breakpoint can be altered due to changes in circumstances (e.g. changes in commonly used drug dosages, emergence of new r
33、esistance mechanisms). 3.3.4 non-susceptible NS bacterial strain for which the test result exceeds the susceptible breakpoint and for which there are no established intermediate or resistant breakpoints NOTE This is generally due to lack of strains with resistance to the antimicrobial agent when the
34、 breakpoints are defined. 3.4 breakpoint test BPT test that has the principal objective to provide categorical results (SIR) NOTE This can include limited range dilution tests or diffusion tests. 3.5 coordinator person empowered by the manufacturer or investigator with responsibility for the entire
35、performance evaluation 3.6 Discrepancies 3.6.1 major discrepancy MD test result by the reference method interpreted as S and an AST device result of R Another representation of the concept: MDSREF100NN5 EN ISO 20776-2:2007 (E) where NMDis the number of tests that result in a MD; NSREFis the number o
36、f susceptible bacterial isolates as determined by the reference method (ISO 20776-1) NOTE The overall MD is expressed as a percentage. 3.6.2 minor discrepancy mD test result by the reference method interpreted as R or S and an AST device result of I; or a reference result interpreted as I and an AST
37、 device result of R or S Another representation of the concept: mD100NNwhere NmDis the number of tests that result in a mD; N is the total number of bacterial isolates tested NOTE The overall mD is expressed as a percentage. 3.6.3 very major discrepancy VMD test result by the reference method interp
38、reted as R and an AST device result of S Another representation of the concept: VMDRREF100NNwhere NVMD is the number of tests that result in a VMD; NRREFis the number of resistant bacterial isolates as determined by the reference method (ISO 20776-1) NOTE The overall VMD is expressed as a percentage
39、. 3.7 evaluation plan description of a planned performance evaluation 3.8 evaluation report description of and conclusions from a performance evaluation 6 EN ISO 20776-2:2007 (E) 3.9 Clinical isolates 3.9.1 fresh isolate isolate recovered from a clinical sample within the previous seven days that ha
40、s not been frozen or subcultured more than five times 3.9.2 recent isolate isolate recovered from a clinical sample within the previous twelve months 3.9.3 stock isolate isolate recovered from a clinical sample that has been retained, stored or obtained from a culture collection NOTE Stock isolates
41、are usually included because they have known or rare resistance mechanisms, or are of a genus or species for which the antimicrobial agent is indicated but are not commonly isolated. Such organisms are unlikely to be available in fresh clinical isolates used in the evaluation. 3.10 investigator pers
42、on responsible for the execution of the performance evaluation at a certain location 3.11 minimum inhibitory concentration MIC lowest concentration that, under defined in vitro conditions, prevents visible growth of bacteria within a defined period of time NOTE The MIC is expressed in mg/l. 3.12 MIC
43、 test test that is capable of determining an MIC covering a range of at least five consecutive doubling dilutions, and for which EA can be determined 3.13 on-scale MIC test result result from a MIC test when there is growth in at least one but not all concentrations tested 3.14 reference method refe
44、rence method described in ISO 20776-1 3.15 zone diameter diameter (in mm) of the zone of growth inhibition around a disk containing an antimicrobial agent in an agar diffusion test 4 General requirements for a performance evaluation The manufacturer or investigator takes the responsibility for the i
45、nitiation and the conduct of a performance evaluation according to the evaluation plan. The manufacturer shall define the responsibility and the interrelation of all personnel who manage and conduct a performance evaluation. The manufacturer or investigator shall appoint a coordinator with overall r
46、esponsibility for the performance evaluation and the evaluation report. The coordinator shall assess and document breakpoint criteria used and indicate which performance claims are met. 7 EN ISO 20776-2:2007 (E) 5 Test methods 5.1 Overview An evaluation conducted by a manufacturer shall consist of a
47、ccuracy, reproducibility and quality control testing performed in at least three different laboratories, of which a maximum of one may be the manufacturers laboratory. Testing shall be conducted using both the test device and the reference method. 5.2 Methods 5.2.1 Strain selection An evaluation pro
48、tocol should incorporate at least 300 clinical isolates relevant to an antimicrobial agent. Only one isolate per species per patient shall be included. The collection should include fresh and/or recent isolates from as many genera and species as feasible within the intended use of the device. It sho
49、uld include as many unrelated strains representing different degrees of susceptibility to the antimicrobial agents as possible. If a device is intended for testing a single genus or species, at least 100 clinical isolates should be studied. Stock isolates may be used to supplement the fresh or recent clinical isolates in order to provide resistant strains with different resistance mechanisms. A set of strains shall be defined to assess intra- and inter-laboratory reproducibility of the AST device. The quality control strain collection shall, as a minimum,
