BS-ISO-17593-2007.pdf
BRITISH STANDARD BS ISO 17593:2007 Clinical laboratory testing and in vitro medical devices Requirements for in vitro monitoring systems for self-testing of oral anticoagulant therapy ICS 11.100.10 ? Licensed Copy: London South Bank University, London South Bank University, Wed May 16 03:42:30 GMT+00:00 2007, Uncontrolled Copy, (c) BSI BS ISO 17593:2007 This British Standard was published under the authority of the Standards Policy and Strategy Committee on 31 May 2007 © BSI 2007 ISBN 978 0 580 50737 3 National foreword This British Standard was published by BSI. It is the UK implementation of ISO 17593:2007. 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. Users are responsible for its correct application. Compliance with a British Standard cannot confer immunity from legal obligations. Amendments issued since publication Amd. No. DateComments Licensed Copy: London South Bank University, London South Bank University, Wed May 16 03:42:30 GMT+00:00 2007, Uncontrolled Copy, (c) BSI Reference number ISO 17593:2007(E) INTERNATIONAL STANDARD ISO 17593 First edition 2007-04-15 Clinical laboratory testing and in vitro medical devices Requirements for in vitro monitoring systems for self-testing of oral anticoagulant therapy Laboratoires d'analyses de biologie médicale et dispositifs médicaux de diagnostic in vitro Exigences relatives aux systèmes d'autosurveillance des traitements par anti-coagulant oraux BS ISO 17593:2007 Licensed Copy: London South Bank University, London South Bank University, Wed May 16 03:42:30 GMT+00:00 2007, Uncontrolled Copy, (c) BSI ii Licensed Copy: London South Bank University, London South Bank University, Wed May 16 03:42:30 GMT+00:00 2007, Uncontrolled Copy, (c) BSI iii Contents Page Foreword. v Introduction. vi 1 Scope . 1 2 Normative references. 1 3 Terms and definitions. 2 4 Design and development . 8 4.1 General requirements. 8 4.2 Measuring interval 8 4.3 Safety . 8 4.4 Risk management. 8 4.4.1 Acceptability of risks 8 4.4.2 Risk assessment. 8 4.5 Ergonomic and human factor aspects . 9 4.6 Quality assurance and risk controls. 9 4.6.1 General. 9 4.6.2 Measurement verification 10 4.6.3 Control of system performance 10 4.6.4 Verification of self-testing performance. 10 4.6.5 Evaluation of user compliance in following the manufacturers and the physicians instructions . 10 4.7 Metrological traceability. 10 5 Information supplied by the manufacturer 11 5.1 General requirements. 11 5.2 Labels for the oral-anticoagulation monitoring instrument. 11 5.3 Instructions for use of the oral-anticoagulation monitoring system 12 5.4 Labels for the reagents and control material. 13 5.5 Instructions for use for reagents and control material. 13 6 Safety and reliability testing 14 6.1 General requirements. 14 6.1.1 Protocol . 14 6.1.2 Instruments and reagents 15 6.1.3 Acceptance criteria. 15 6.2 Protection against electric shock . 15 6.3 Protection against mechanical hazards. 15 6.4 Electromagnetic compatibility. 15 6.5 Resistance to heat 15 6.6 Resistance to moisture and liquids 15 6.7 Protection against liberated gases, explosion and implosion. 15 6.8 Instrument components. 15 6.9 Performance test. 15 6.10 Mechanical resistance to shock, vibration and impact 16 6.10.1 Vibration test protocol 16 6.10.2 Drop test protocol. 16 6.11 Temperature exposure limits. 16 6.11.1 High-temperature test protocol. 16 6.11.2 Low-temperature test protocol 17 6.12 Humidity-exposure test protocol 17 6.13 Reagent storage and use testing 17 BS ISO 17593:2007 Licensed Copy: London South Bank University, London South Bank University, Wed May 16 03:42:30 GMT+00:00 2007, Uncontrolled Copy, (c) BSI iv 7 Training and education programs.17 7.1 Training of healthcare providers.17 7.2 Education of patients and other users .18 8 System performance verification 19 8.1 General.19 8.2 Contributors to measurement uncertainty.19 8.3 System performance verification study19 8.4 Verification of measurement precision.20 8.4.1 General.20 8.4.2 Verification of measurement repeatability .20 8.4.3 Verification of intermediate measurement precision21 8.4.4 Data analysis .22 8.5 Verification of system accuracy24 8.5.1 General requirements.24 8.5.2 Study population.24 8.5.3 Samples25 8.5.4 Instruments and reagents25 8.5.5 Manufacturers selected measurement procedure26 8.5.6 Study design26 8.5.7 Procedure.27 8.5.8 Data analysis .28 8.6 Minimum acceptable system accuracy.31 8.6.1 System accuracy requirement.31 8.6.2 System accuracy assessment.31 8.6.3 Data presentation32 9 User performance evaluation.32 9.1 General.32 9.2 Study sites.32 9.3 Subjects .33 9.4 Instruments and materials .33 9.5 Evaluation of user proficiency.33 9.6 Acceptance criteria and data assessment .34 9.7 Evaluation of instructions for use.34 Annex A (normative) Additional requirements for electromagnetic compatibility35 Annex B (informative) Traceability chain examples37 Annex C (informative) Sample size calculation to estimate bias (42 in the Bibliography) 40 Annex D (informative) Example of an uncertainty calculation for a prothrombin INR determination using an oral anticoagulation monitoring system.41 Annex E (informative) Elements of quality assurance of oral-anticoagulation monitoring systems 45 Annex F (informative) Application of performance criteria to published evaluations of oral- anticoagulation monitoring systems 46 Bibliography .51 BS ISO 17593:2007 Licensed Copy: London South Bank University, London South Bank University, Wed May 16 03:42:30 GMT+00:00 2007, Uncontrolled Copy, (c) BSI v Foreword ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies (ISO member bodies). The work of preparing International Standards is normally carried out through ISO technical committees. Each member body interested in a subject for which a technical committee has been established has the right to be represented on that committee. International organizations, governmental and non-governmental, in liaison with ISO, also take part in the work. ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization. International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2. The main task of technical committees is to prepare International Standards. Draft International Standards adopted by the technical committees are circulated to the member bodies for voting. Publication as an International Standard requires approval by at least 75 % of the member bodies casting a vote. Attention is drawn to the possibility that some of the elements of this document may be the subject of patent rights. ISO shall not be held responsible for identifying any or all such patent rights. ISO 17593 was prepared by Technical Committee ISO/TC 212, Clinical laboratory testing and in vitro diagnostic test systems. BS ISO 17593:2007 Licensed Copy: London South Bank University, London South Bank University, Wed May 16 03:42:30 GMT+00:00 2007, Uncontrolled Copy, (c) BSI vi Introduction Oral-anticoagulation monitoring systems are in vitro diagnostic medical devices that measure prothrombin time in fresh, unmodified human blood samples. Prothrombin time is an indicator of the ability of blood to clot. In vitro diagnostic medical devices for self-testing of oral-anticoagulation therapy are used predominantly by individuals who have heart valve replacements, or who are suffering from atrial fibrillation or deep vein thrombosis. Patients must maintain the level of anticoagulant in the blood high enough to reduce thrombin formation, yet low enough to avoid excessive bleeding. An oral-anticoagulation monitoring system allows the user to monitor anticoagulation therapy and take action to control the level of anticoagulant present in the blood. This International Standard applies to oral-anticoagulation monitoring systems to be used by lay persons. The primary objectives are to establish requirements for oral-anticoagulation monitoring systems that will enable lay users to achieve acceptable performance, and to specify procedures for manufacturers and other interested parties to demonstrate conformance of such systems to this standard. Performance criteria for oral-anticoagulation monitoring systems were established, based on the state-of-the- art, which has been shown to offer significant benefit to patients 68, 69. The criteria are given in terms of “system accuracy”, because metrological terms commonly used in International Standards (e.g., trueness and measurement uncertainty) would not be familiar to lay users. System accuracy, which is affected by systematic bias and random effects (and is inversely related to measurement uncertainty), describes the degree to which the individual results produced by an oral-anticoagulation monitoring system agree with correct INR values when the system is used as intended by lay persons. In setting the performance criteria, it is assumed that users will be properly selected and will receive the necessary training, that the device will be properly maintained, and that operating and control procedures will be followed in accordance with the manufacturers instructions for use. It is also assumed that manufacturers will anticipate and mitigate the effects of reasonably foreseeable misuse, including reasonably foreseeable deviations from recommended maintenance, operating and control procedures by the intended users. Requirements that are unique to self-testing with oral-anticoagulation monitoring systems, including specific content of information supplied by the manufacturer, are addressed in this International Standard. General requirements that apply to all in vitro diagnostic medical devices and are covered by other standards (e.g., IEC 61010, ISO 13485, ISO 14971 and ISO 18113) are incorporated by reference, where appropriate. In addition, national regulations may apply. BS ISO 17593:2007 Licensed Copy: London South Bank University, London South Bank University, Wed May 16 03:42:30 GMT+00:00 2007, Uncontrolled Copy, (c) BSI 1 Clinical laboratory testing and in vitro medical devices Requirements for in vitro monitoring systems for self-testing of oral anticoagulant therapy 1 Scope This International Standard specifies requirements for in vitro measuring systems for self-monitoring of vitamin-K antagonist therapy, including performance, quality assurance and user training and procedures for the verification and validation of performance by the intended users under actual and simulated conditions of use. This International Standard pertains solely to prothrombin time measuring systems used by individuals for monitoring their own vitamin-K antagonist therapy, and which report results as international normalized ratios (INR). This International Standard is applicable to manufacturers of such systems and those other organizations (e.g., regulatory authorities and conformity assessment bodies) having the responsibility for assessing the performance of these systems. This International Standard does not pertain to in vitro measuring systems for coagulation quantities assessing vitamin-K antagonist therapy used by physicians or healthcare providers, provide a comprehensive evaluation of all possible factors that could affect the performance of these systems, or address the medical aspects of oral-anticoagulation therapy. 2 Normative references The following referenced documents are indispensable for the application of this document. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies. ISO 13485, Medical devices Quality management systems Requirements for regulatory purposes ISO 14971, Medical devices Application of risk management to medical devices ISO 15198, Clinical laboratory medicine In vitro diagnostic medical devices Validation of user quality control procedures by the manufacturer ISO 17511, In vitro diagnostic medical devices Measurement of quantities in biological samples Metrological traceability of values assigned to calibrators and control materials BS ISO 17593:2007 Licensed Copy: London South Bank University, London South Bank University, Wed May 16 03:42:30 GMT+00:00 2007, Uncontrolled Copy, (c) BSI 2 ISO 18113-1:1), Clinical laboratory testing and in vitro diagnostic medical systems Information supplied by the manufacturer (labelling) Part 1: Terms, definitions and general requirements ISO 18113-4:1), Clinical laboratory testing and in vitro diagnostic medical systems Information supplied by the manufacturer (labelling) Part 4: In vitro diagnostic reagents for self-testing ISO 18113-5:1), Clinical laboratory testing and in vitro diagnostic medical systems Information supplied by the manufacturer (labelling) Part 5: In vitro diagnostic instruments for self-testing IEC 60068-2-64:1993, Environmental testing Part 2: Test methods Test Fh: Vibration, broad-band random (digital control) and guidance IEC 61010-1:2001, Safety requirements for electrical equipment for measurement, control and laboratory use Part 1: General requirements IEC 61010-2-101:2002, Safety requirements for electrical equipment for measurement, control and laboratory use Part 2-101: Particular requirements for in vitro diagnostic (IVD) medical equipment IEC 61000-4-2, Electromagnetic compatibility (EMC) Part 4-2: Testing and measurement techniques Electrostatic discharge immunity test IEC 61000-4-3, Electromagnetic compatibility (EMC) Part 4-3: Testing and measurement techniques Radiated, radio-frequency, electromagnetic field immunity test IEC 61326, Electrical equipment for measurement, control and laboratory use EMC requirements EN 13532:2002, General requirements for in vitro diagnostic medical devices for self-testing EN 13612, Performance evaluation of in vitro diagnostic medical devices EN 13640, Stability testing of in vitro diagnostic reagents WHO Technical Report Series, No. 889, 1999, Annex 3 Guidelines for thromboplastins and plasma used to control oral-anticoagulant therapy 3 Terms and definitions For the purposes of this document, the terms and definitions in ISO 18113-1 and the following apply. 3.1 accuracy of measurement closeness of agreement between a measurement result and the accepted reference value NOTE 1 The term “measurement accuracy”, when applied to a set of test results, involves a combination of random components and a common systematic error or bias component. (VIM:1993) NOTE 2 For oral-anticoagulation monitoring systems, accuracy is measured by the
