1、BS EN ISO 10993-4:2009ICS 11.100.20NO COPYING WITHOUT BSI PERMISSION EXCEPT AS PERMITTED BY COPYRIGHT LAWBRITISH STANDARDBiological evaluation of medical devicesPart 4: Selection of tests for interactions with bloodNational forewordThis British Standard is the UK implementation of EN ISO 10993-4:200
2、9. It is identical to ISO 10993-4:2002, incorporating amendment 1:2006. It supersedes BS EN ISO 10993-4:2002 which is withdrawn.The start and finish of text introduced or altered by amendment is in-dicated in the text by tags. Tags indicating changes to ISO text carry the number of the ISO amendment
3、. For example, text altered by ISO amendment 1 is indicated by !“.The UK participation in its preparation was entrusted to Technical Committee CH/194, Biological evaluation of medical devices.A list of organizations represented on this committee can be obtained on request to its secretary.This publi
4、cation 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.BS EN ISO 10993-4:2009This British Standard was published under the authority of the Stand
5、ards Policy and Strategy Committee on 28 February 2010 BSI 2010Amendments/corrigenda issued since publicationDate Comments ISBN 978 0 580 65664 4EUROPEAN STANDARDNORME EUROPENNEEUROPISCHE NORMEN ISO 10993-4May 2009ICS 11.100.20 Supersedes EN ISO 10993-4:2002 English VersionBiological evaluation of m
6、edical devices - Part 4: Selection oftests for interactions with blood (ISO 10993-4:2002, includingAmd 1:2006)valuation biologique des dispositifs mdicaux - Partie 4:Choix des essais pour les interactions avec le sang (ISO10993-4:2002, Amd 1:2006 inclus)Biologische Beurteilung von Medizinprodukten -
7、 Teil 4:Auswahl von Prfungen zur Wechselwirkung mit Blut (ISO10993-4:2002, einschlielich nderung 1:2006)This European Standard was approved by CEN on 28 April 2009.CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this EuropeanStandar
8、d the status of a national standard without any alteration. Up-to-date lists and bibliographical references concerning such nationalstandards 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, Ge
9、rman). A version in any other language made by translationunder the responsibility of a CEN member into its own language and notified to the CEN Management Centre has the same status as theofficial versions.CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Cyprus, Czech Re
10、public, Denmark, 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 STANDARDIZATIONCOMIT EUROPEN DE N
11、ORMALISATIONEUROPISCHES KOMITEE FR NORMUNGManagement Centre: Avenue Marnix 17, B-1000 Brussels 2009 CEN All rights of exploitation in any form and by any means reservedworldwide for CEN national Members.Ref. No. EN ISO 10993-4:2009: EForeword The text of ISO 10993-4:2002, including Amd 1:2006 has be
12、en prepared by Technical Committee ISO/TC 194 “Biological evaluation of medical devices” of the International Organization for Standardization (ISO) and has been taken over as EN ISO 10993-4:2009 by Technical Committee CEN/TC 206 “Biological evaluation of medical devices” the secretariat of which is
13、 held by NEN. This European Standard shall be given the status of a national standard, either by publication of an identical text or by endorsement, at the latest by November 2009, and conflicting national standards shall be withdrawn at the latest by March 2010. Attention is drawn to the possibilit
14、y that some of the elements of this document may be the subject of patent rights. CEN and/or CENELEC shall not be held responsible for identifying any or all such patent rights. This document supersedes EN ISO 10993-4:2002. This document has been prepared under a mandate given to CEN by the European
15、 Commission and the European Free Trade Association, and supports essential requirements of EC Directive. For relationship with EC Directive, see informative Annex ZA, which is an integral part of this document. According to the CEN/CENELEC Internal Regulations, the national standards organizations
16、of the following countries are bound 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, Sl
17、ovakia, Slovenia, Spain, Sweden, Switzerland and the United Kingdom. Endorsement notice The text of ISO 10993-4:2002, including Amd 1:2006 has been approved by CEN as a EN ISO 10993-4:2009 without any modification. BS EN ISO 10993-4:2009EN ISO 10993-4:2009 (E)ii Annex ZA (informative) Relationship b
18、etween this European Standard and the Essential Requirements of EU Directive 93/42/EEC on Medical Devices This European Standard has been prepared under a mandate given to CEN by the European Commission and the European Free Trade Association to provide a means of conforming to Essential Requirement
19、s of the New Approach Directive 93/42/EEC on medical devices. Once this standard is cited in the Official Journal of the European Communities under that Directive and has been implemented as a national standard in at least one Member State, compliance with the clauses of this standard given in table
20、 ZA confers, within the limits of the scope of this standard, a presumption of conformity with the corresponding Essential Requirements of that Directive and associated EFTA regulations. Table ZA Correspondence between this European Standard and Directive 93/42/EEC on medical devices Clause(s)/sub-c
21、lause(s) of this EN Essential Requirements (ERs) of Directive 93/42/EEC Qualifying remarks/Notes 6 Annex I: 7.1, 7.2, 7.5 WARNING Other requirements and other EU Directives may be applicable to the product(s) falling within the scope of this standard. BS EN ISO 10993-4:2009EN ISO 10993-4:2009 (E)iii
22、 5 Annex ZB (informative) Relationship between this European Standard and the Essential Requirements of EU Directive 90/385/EEC on Active Implantable Medical Devices This European Standard has been prepared under a mandate given to CEN by the European Commission and the European Free Trade Associati
23、on to provide a means of conforming to Essential Requirements of the New Approach Directive 90/385/EEC on active implantable medical devices. Once this standard is cited in the Official Journal of the European Communities under that Directive and has been implemented as a national standard in at lea
24、st one Member State, compliance with the clauses of this standard given in table ZB confers, within the limits of the scope of this standard, a presumption of conformity with the corresponding Essential Requirements of that Directive and associated EFTA regulations. Table ZB Correspondence between t
25、his European Standard and Directive 90/385/EEC on active implantable medical devices Clause(s)/sub-clause(s) of this EN Essential Requirements (ERs) of Directive 90/385/EEC Qualifying remarks/Notes 6 Annex I : 9 6 I.9 of Annex I of 90/385/EEC 6.1.10 18 of 86/609/EEC A.1 I.9 of Annex I of 90/385/EEC
26、WARNING Other requirements and other EU Directives may be applicable to the product(s) falling within the scope of this standard. BS EN ISO 10993-4:2009EN ISO 10993-4:2009 (E)iv Contents Page Foreword vi Introductionviii 1 Scope 1 2 Normative references 1 3 Terms and definitions. 1 4 Abbreviated ter
27、ms. 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 9 6.3 Ty
28、pes of test 12 Annex A (informative) Preclinical evaluation of cardiovascular devices and prostheses 14 Annex B (informative) Laboratory tests Principles, scientific basis and interpretation. 18 Annex C (informative) Evaluation of haemolytic properties of medical devices and their components 24 Bibl
29、iography 31 BS EN ISO 10993-4:2009EN ISO 10993-4:2009 (E)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 committ
30、ees. 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 Int
31、ernational 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
32、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 may
33、 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), whic
34、h 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
35、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 quan
36、tification 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: Identificat
37、ion and quantification of degradation products from ceramics Part 15: Identification and quantification of degradation products from metals and alloys BS EN ISO 10993-4:2009EN ISO 10993-4:2009 (E)vi Part 16: Toxicokinetic study design for degradation products and leachables Part 17: Establishment of
38、 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. BS EN ISO 10993-4:2009EN ISO 10993-4:2009 (E)vii Introduction Th
39、e 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 develop
40、ing 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. BS EN ISO 10993-4:2009EN ISO 10993-4:2009 (E)viii INTERNATIONAL STANDARDBiological ev
41、aluation 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 use in c
42、ontact 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 the prin
43、ciples and scientific basis of these tests. 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, any of these publications d
44、o 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 referred to applies. Members
45、 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 and definitions For the purp
46、oses of this part of ISO 10993, the terms and definitions given in ISO 10993-1 and the following apply. Detailed requirements for testing cannot be specified because of the limitations in knowledge and precision of tests for interactions of devices with blood. Further, this part of ISO 10993 describ
47、es biological evaluation in general terms and may not necessarily provide sufficient guidance for test methods for a specific device. The selection and design of test methods 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. !“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 the device NOTE Such effects may or may
