1、 Collection of SANS standards in electronic format (PDF) 1. Copyright This standard is available to staff members of companies that have subscribed to the complete collection of SANS standards in accordance with a formal copyright agreement. This document may reside on a CENTRAL FILE SERVER or INTRA
2、NET SYSTEM only. Unless specific permission has been granted, this document MAY NOT be sent or given to staff members from other companies or organizations. Doing so would constitute a VIOLATION of SABS copyright rules. 2. Indemnity The South African Bureau of Standards accepts no liability for any
3、damage whatsoever than may result from the use of this material or the information contain therein, irrespective of the cause and quantum thereof. ICS 11.100 ISBN 0-626-15242-9 SANS 10993-4:2004 Edition 1 ISO 10993-4:2002 Edition 2 SOUTH AFRICAN NATIONAL STANDARD Biological evaluation of medical dev
4、ices Part 4: Selection of tests for interactions with blood This national standard is the identical implementation of ISO 10993-4:2002 and is adopted with the permission of the International Organization for Standardization Published by Standards South Africa 1 dr lategan road groenkloof ! private b
5、ag x191 pretoria 0001 tel: 012 428 7911 fax: 012 344 1568 international code + 27 12 www.stansa.co.za Standards South Africa 2004 SANS 10993-4:2004 Edition 1 ISO 10993-4:2002 Edition 2 Table of changes Change No. Date Scope Abstract Describes a classification of medical and dental devices that are i
6、ntended for use in contact with blood, the rationale for structured selection of tests according to specific categories and the principles and scientific basis of these tests. Detailed requirements for testing cannot be specified because of limitations in the knowledge and precision of tests for int
7、eractions of devices with blood. Keywords bioassay, biological analysis and testing, blood, dental equipment, implants (surgical), medical equipment, specifications, surgical equipment, testing. Foreword This South African standard was approved by National Committee StanSA SC 5140.37E, Medical devic
8、es Healthcare devices and materials for use in clinics and hospitals, in accordance with procedures of Standards South Africa, in compliance with annex 3 of the WTO/TBT agreement. Reference numberISO 10993-4:2002(E)ISO 2002INTERNATIONAL STANDARD ISO10993-4Second edition2002-10-15Biological evaluatio
9、n of medical devices Part 4: Selection of tests for interactions with blood valuation biologique des dispositifs mdicaux Partie 4: Choix des essais concernant les interactions avec le sang ISO 10993-4:2002(E) PDF disclaimer This PDF file may contain embedded typefaces. In accordance with Adobes lice
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12、en taken to ensure that the file is suitable for use by ISO member bodies. In the unlikely event that a problem relating to it is found, please inform the Central Secretariat at the address given below. ISO 2002 All rights reserved. Unless otherwise specified, no part of this publication may be repr
13、oduced or utilized in any form or by any means, electronic or mechanical, including photocopying and microfilm, without permission in writing from either ISO at the address below or ISOs member body in the country of the requester. ISO copyright office Case postale 56 CH-1211 Geneva 20 Tel. + 41 22
14、749 01 11 Fax + 41 22 749 09 47 E-mail copyrightiso.ch Web www.iso.ch Printed in Switzerland ii ISO 2002 All rights reservedISO 10993-4:2002(E) ISO 2002 All rights reserved iiiContents Page Foreword iv Introduction vi 1 Scope 1 2 Normative references 1 3 Terms and definitions. 1 4 Abbreviated terms.
15、 2 5 Types of device in contact with blood (as categorized in ISO 10993-1) . 3 5.1 Non-contact devices . 3 5.2 External communicating devices 3 5.3 Implant devices . 4 6 Characterization of blood interactions . 5 6.1 General requirements . 5 6.2 Categories of tests and blood interactions 8 6.3 Types
16、 of test 11 Annex A (informative) Preclinical evaluation of cardiovascular devices and prostheses 13 Annex B (informative) Laboratory tests Principles, scientific basis and interpretation. 17 Annex C (informative) Evaluation of haemolytic properties of medical devices and their components 23 Bibliog
17、raphy 30 ISO 10993-4:2002(E) iv ISO 2002 All rights reservedForeword 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 commit
18、tees. 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 In
19、ternational 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 3. The main task of technical committees is to prepare International Standards. Draft International
20、 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 part of ISO 10993 ma
21、y be the subject of patent rights. ISO shall not be held responsible for identifying any or all such patent rights. ISO 10993-4 was prepared by Technical Committee ISO/TC 194, Biological evaluation of medical devices. This second edition cancels and replaces the first edition (ISO 10993-4:1992), whi
22、ch has been technically revised. ISO 10993 consists of the following parts, under the general title Biological evaluation of medical devices: Part 1: Evaluation and testing Part 2: Animal welfare requirements Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity Part 4: Selection
23、 of tests for interactions with blood Part 5: Tests for in-vitro cytotoxicity Part 6: Tests for local effects after implantation Part 7: Ethylene oxide sterilization residuals Part 8: Selection and qualification of reference materials for biological tests Part 9: Framework for identification and qua
24、ntification of potential degradation products Part 10: Tests for irritation and sensitization Part 11: Tests for systemic toxicity Part 12: Sample preparation and reference materials Part 13: Identification and quantification of degradation products from polymeric medical devices Part 14: Identifica
25、tion and quantification of degradation products from ceramics Part 15: Identification and quantification of degradation products from metals and alloys ISO 10993-4:2002(E) ISO 2002 All rights reserved v Part 16: Toxicokinetic study design for degradation products and leachables Part 17: Establishmen
26、t of allowable limits for leachable substances Part 18: Chemical characterization of materials Future parts will deal with other relevant aspects of biological testing. Annexes A, B and C of this part of ISO 10993 are for information only. ISO 10993-4:2002(E) vi ISO 2002 All rights reservedIntroduct
27、ion The selection and design of test methods for the interactions of medical devices with blood should take into consideration device design, materials, clinical utility, usage environment and risk benefit. This level of specificity can only be covered in vertical standards. The initial source for d
28、eveloping this part of ISO 10993 was the publication, Guidelines for blood/material interactions, Report of the National Heart, Lung, and Blood Institute 29; chapters 9 and 10. This publication has since been revised 32. INTERNATIONAL STANDARD ISO 10993-4:2002(E) ISO 2002 All rights reserved 1Biolog
29、ical evaluation of medical devices Part 4: Selection of tests for interactions with blood 1 Scope This part of ISO 10993 provides general requirements for evaluating the interactions of medical devices with blood. It describes a) a classification of medical and dental devices that are intended for u
30、se in contact with blood, based on the intended use and duration of contact as defined in ISO 10993-1, b) the fundamental principles governing the evaluation of the interaction of devices with blood, c) the rationale for structured selection of tests according to specific categories, together with t
31、he principles and scientific basis of these tests. Detailed requirements for testing cannot be specified because of limitations in the knowledge and precision of tests for interactions of devices with blood. This part of ISO 10993 describes biological evaluation in general terms and may not necessar
32、ily provide sufficient guidance for test methods for a specific device. 2 Normative references The following normative documents contain provisions which, through reference in this text, constitute provisions of this part of ISO 10993. For dated references, subsequent amendments to, or revisions of,
33、 any of these publications do not apply. However, parties to agreements based on this part of ISO 10993 are encouraged to investigate the possibility of applying the most recent editions of the normative documents indicated below. For undated references, the latest edition of the normative document
34、referred to applies. Members of ISO and IEC maintain registers of currently valid International Standards. ISO 10993-1:1997, Biological evaluation of medical devices Part 1: Evaluation and testing ISO 10993-2:1992, Biological evaluation of medical devices Part 2: Animal welfare requirements 3 Terms
35、and definitions For the purposes of this part of ISO 10993, the terms and definitions given in ISO 10993-1 and the following apply. 3.1 blood/device interaction any interaction between blood or any component of blood and a device resulting in effects on the blood, or on any organ or tissue, or on th
36、e device NOTE Such effects may or may not have clinically significant or undesirable consequences. Annex A contains further information on these interactions. ISO 10993-4:2002(E) 2 ISO 2002 All rights reserved3.2 ex vivo term applied to a test system that shunts blood directly from a human subject o
37、r test animal into a test chamber located outside the body NOTE If using an animal model, the blood may be shunted directly back into the animal (recirculating) or collected into test tubes for evaluation (single pass). 3.3 thrombosis in vivo phenomenon resulting in the partial or complete occlusion
38、 of a vessel or device by a thrombus NOTE 1 Characterization of thrombosis includes ex vivo and in vivo methods, in either animals or the clinical setting. NOTE 2 A thrombus is composed of a mixture of red cells, aggregated platelets, fibrin and other cellular elements. 3.4 coagulation phenomenon th
39、at results from activation of the clotting factor cascade NOTE Factors of the coagulation cascade and fibrinolytic systems can be measured following exposure to devices either in vitro or in vivo. 3.5 platelet anuclear, cellular body that is present in the circulation which adheres to surfaces and a
40、ggregates to form a hemostatic plug to minimize bleeding NOTE Platelet testing includes quantification of platelet numbers as well as analysis of their structure and function. The testing can include analysis of platelet factors, or components on the platelet surface which are released from platelet
41、s or adherent to the device surface. 3.6 haematology study of blood, including quantification of cellular and plasma components of the blood 3.7 complement system part of the innate immune system, consisting of several plasma proteins, including enzymes and cellular receptors NOTE Effector molecules
42、 produced from complement components are involved in inflammation, phagocytosis and cell lysis. 4 Abbreviated terms Bb product of alternative pathway complement activation -TG beta-thromboglobulin C4d product of classical pathway complement activation C3a, C5a (active) complement split products from
43、 C3 and C5 CD62L L-selectin CH-50 50% total haemolytic complement CT computerized tomography D-Dimer specific fibrin degradation products (F XIII cross-linked fibrin) ECMO extracorporeal membrane oxygenator ISO 10993-4:2002(E) ISO 2002 All rights reserved 3ELISA enzyme/linked immunosorbent assay EM
44、electron microscopy FDP fibrin/fibrinogen degradation products FPA fibrinopeptide A F1+2prothrombin activation fragment 1 + 2 iC3b product of central C complement activation IVC inferior vena cava MRI magnetic resonance imaging PAC-1 monoclonal antibody which recognizes the activated form of platele
45、t surface glycoprotein IIb/IIIa PET positron emission tomography PF-4 platelet factor 4 PRP platelet-rich plasma PT prothrombin time PTT partial thromboplastin time P-selectin receptor exposed during either platelet or endothelial cell release reaction RIA radioimmunoassay S-12 monoclonal antibody,
46、which recognizes the alpha-granule membrane component P-selectin exposed during the platelet release reaction SC5b-9 product of terminal pathway complement activation TAT thrombin-antithrombin complex TCC terminal complement complex TT thrombin time VWF von Willebrand factor 5 Types of device in con
47、tact with blood (as categorized in ISO 10993-1) 5.1 Non-contact devices An in vitro diagnostic device is an example of a non-contact device. 5.2 External communicating devices These are devices that contact the circulating blood and serve as a conduit into the vascular system. Examples include but a
48、re not limited to those in ISO 10993-1. a) External communicating devices that serve as an indirect blood path include but are not limited to cannulae, extension sets, blood collection devices, devices for the storage and administration of blood and blood products (e.g. tubing, needles and bags), ce
49、ll savers. ISO 10993-4:2002(E) 4 ISO 2002 All rights reservedb) External communicating devices in contact with circulating blood include but are not limited to atherectomy devices, blood monitors, catheters, guidewires, intravascular endoscopes, intravascular ultrasound, intravascular laser systems, retrograde coronary perfusion catheters, cardiopulmonary bypass circuitry, extracorporeal membrane oxygenators, haemodialysis/haemofiltration equipment, donor and
