EN ISO 10993-9-2009 en Biological evaluation of medical devices - Part 9 Framework for identification and quantification of potential degradation products《医疗器械的生物学评定 第9部分 潜在降解产物的识别.pdf

1、BS EN ISO 10993-9: December 2009ICS 11.100.20NO COPYING WITHOUT BSI PERMISSION EXCEPT AS PERMITTED BY COPYRIGHT LAWBRITISH STANDARDBiological evaluation of medical devicesPart 9: Framework for identification and quantification of potential degradation products (ISO 10993-9:2009)Incorporating corrige

2、ndum July 2010This British Standard was published under the authority of the Standards Policy and Strategy Committee on 30 June 2010 BSI 2010ISBN 978 0 580 72079 6Amendments/corrigenda issued since publicationDate CommentsBS EN ISO 10993-9:December 2009National forewordThis British Standard is the U

3、K implementation of EN ISO 10993-9:December 2009. It supersedes BS EN ISO 10993-9:May 2009 which is withdrawn.NOTE CEN issued two standards with the identifier EN ISO 10993-9 in 2009. The first, published in May 2009 was a revision of EN ISO 10993-9:2003 and reflected the changes to the EU Medical D

4、evices Directive. The second, published in December 2009 was the European implementation of the full revision of ISO 10993-9:2003 and superseded the May 2009 publication, which has been withdrawn. BSI has included the month of the CEN publication in the identifier to distinguish between the two edit

5、ions. 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 publication does not purport to include all the necessary provisi

6、ons of a contract. Users are responsible for its correct application.Compliance with a British Standard cannot confer immunity from legal obligations.31 July 2010 Correction to include the CEN month of publication in the identifierEUROPEAN STANDARD NORME EUROPENNE EUROPISCHE NORM EN ISO 10993-9 Dece

7、mber 2009 ICS 11.100.20 Supersedes EN ISO 10993-9:2009English Version Biological evaluation of medical devices - Part 9: Framework for identification and quantification of potential degradation products (ISO 10993-9:2009) valuation biologique des dispositifs mdicaux - Partie 9: Cadre pour lidentific

8、ation et la quantification des produits potentiels de dgradation (ISO 10993-9:2009) Biologische Beurteilung von Medizinprodukten - Teil 9: Rahmen zur Identifizierung und Quantifizierung von mglichen Abbauprodukten (ISO 10993-9:2009) This European Standard was approved by CEN on 18 November 2009. CEN

9、 members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this European Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references concerning such national standards may be obtained on appl

10、ication to the CEN Management Centre or to any CEN member. This European Standard exists in three official versions (English, French, German). A version 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

11、has the same status as the official versions. CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland,

12、Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom. EUROPEAN COMMITTEE FOR STANDARDIZATION COMIT EUROPEN DE NORMALISATION EUROPISCHES KOMITEE FR NORMUNG Management Centre: Avenue Marnix 17, B-1000 Brussels 2009 CEN All rights of exploitation in any form and by any m

13、eans reserved worldwide for CEN national Members. Ref. No. EN ISO 10993-9:2009: EEN ISO 10993-9:2009 (E) 3 Foreword This document (EN ISO 10993-9:2009) has been prepared by Technical Committee ISO/TC 194 “Biological evaluation of medical devices“ in collaboration with Technical Committee CEN/TC 206

14、“Biological evaluation of medical devices” the secretariat of which is 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 June 2010, and conflicting national standards shall be withdrawn

15、 at the latest by June 2010. Attention is drawn to the possibility 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 10993-9:2009. This docume

16、nt has been prepared under a mandate given to CEN by the European Commission and the European Free Trade Association, and supports essential requirements of EU Directives. For relationship with EU Directives, see informative Annex ZA and ZB, which are integral parts of this document. According to th

17、e CEN/CENELEC Internal Regulations, the national standards organizations 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, Lithuan

18、ia, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and the United Kingdom. Endorsement notice The text of ISO 10993-9:2009 has been approved by CEN as a EN ISO 10993-9:2009 without any modification. BS EN ISO 10993-9:December 20094 A

19、nnex ZA (informative) Relationship between 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

20、 conforming to Essential Requirements of the New Approach Directive 93/42/EEC on Medical devices. Once this European Standard is cited in the Official Journal of the European Union under that Directive and has been implemented as a national standard in at least one Member State, compliance with the

21、clauses of this European Standard given in Table ZA.1 confers, within the limits of the scope of this European Standard, a presumption of conformity with the corresponding Essential Requirements of that Directive and associated EFTA regulations. Table ZA.1 Correspondence between this European Standa

22、rd and Directive 93/42/EEC on Medical devices Clause(s)/subclause(s) of this European Standard Essential Requirements (ERs) of Directive 93/42/EEC on Medical devices Qualifying remarks/Notes 4, 5, Annex A Annex I: 7.1, 7.2, 7.5 These relevant Essential Requirements are only partly addressed in this

23、European Standard NOTE Presumption of conformity depends on also complying with all relevant clauses/subclauses of ISO 10993-1. WARNING Other requirements and other EU Directives may be applicable to the product(s) falling within the scope of this standard. BS EN ISO 10993-9:December 2009EN ISO 1099

24、3-9:2009 (E) EN ISO 10993-9:2009 (E) 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 a

25、nd the European Free Trade Association to provide a means of conforming to Essential Requirements of the New Approach Directive 90/385/EEC on Active Implantable Medical Devices. Once this European Standard is cited in the Official Journal of the European Union under that Directive and has been imple

26、mented as a national standard in at least one Member State, compliance with the clauses of this European Standard given in Table ZB.1 confers, within the limits of the scope of this European Standard, a presumption of conformity with the corresponding Essential Requirements of that Directive and ass

27、ociated EFTA regulations. Table ZB.1 Correspondence between this European Standard and Directive 90/385/EEC on Active Implantable Medical Devices Clause(s)/subclause(s) of this European Standard Essential Requirements (ERs) of Directive 90/385/EEC on Active Implantable Medical Devices Qualifying rem

28、arks/Notes 4, 5, Annex A Annex I: 9 (First and second indents only) The first and second indents of this relevant Essential Requirement are only partly addressed in this European Standard NOTE Presumption of conformity depends on also complying with all relevant clauses/subclauses of ISO 10993-1. WA

29、RNING Other requirements and other EU Directives may be applicable to the product(s) falling within the scope of this standard. BS EN ISO 10993-9:December 2009 ISO 2009 All rights reserved iiiContents Page Foreword iv Introductionvi 1 Scope1 2 Normative references1 3 Terms and definitions .2 4 Princ

30、iples for design of degradation studies .2 4.1 General .2 4.2 Preliminary considerations 3 4.3 Study design 3 4.4 Characterization of degradation products from medical devices4 5 Study report .4 Annex A (normative) Consideration of the need for degradation studies5 Annex B (informative) Biodegradati

31、on study considerations 7 Bibliography9 BS EN ISO 10993-9:December 2009EN ISO 10993-9:2009 (E) ISO 10993-9:2009(E) iv ISO 2009 All rights reservedForeword ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies (ISO member bodies). The work of

32、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,

33、 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 t

34、ask 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. Attent

35、ion 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 10993-9 was prepared by Technical Committee ISO/TC 194, Biological evaluation of medical devices. This

36、second edition cancels and replaces the first edition (ISO 10993-9:1999), which 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 within a risk management process Part 2: Animal we

37、lfare requirements Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity Part 4: Selection 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 9: Framew

38、ork for identification and quantification of potential degradation products Part 10: Tests for irritation and skin sensitization Part 11: Tests for systemic toxicity Part 12: Sample preparation and reference materials Part 13: Identification and quantification of degradation products from polymeric

39、medical devices Part 14: Identification and quantification of degradation products from ceramics Part 15: Identification and quantification of degradation products from metals and alloys BS EN ISO 10993-9:December 2009ISO 10993-9:2009(E) ISO 2009 All rights reserved v Part 16: Toxicokinetic study de

40、sign for degradation products and leachables Part 17: Establishment of allowable limits for leachable substances Part 18: Chemical characterization of materials Part 19: Physico-chemical, morphological and topographical characterization of materials Technical Specification Part 20: Principles and me

41、thods for immunotoxicology testing of medical devices Technical Specification Future parts will deal with other relevant aspects of biological evaluation. BS EN ISO 10993-9:December 2009ISO 10993-9:2009(E) vi ISO 2009 All rights reservedIntroduction This part of ISO 10993 is intended to present the

42、general principles on which the specific material investigations to identify and quantify degradation products described in ISO 10993-13 (polymers), ISO 10993-14 (ceramics) and ISO 10993-15 (metals and alloys) are based. Information obtained from these studies is intended to be used in the biologica

43、l evaluations described in the remaining parts of ISO 10993. The materials used to construct medical devices can form degradation products when exposed to the biological environment, and in the body these products might behave differently to the bulk material. Mechanical wear causes mostly particula

44、te debris, whereas the release of substances from surfaces due to leaching, chemical breakdown of structures or corrosion can lead to free ions or to different kinds of reaction products in the form of organic or inorganic compounds. The degradation products can be either reactive or stable and with

45、out biochemical reaction with their environment. Accumulations of substantial quantities of stable degradation products can, however, have physical effects on the surrounding tissues. Degradation products might remain at the location of their generation or might be transported within the biological

46、environment by various mechanisms. The level of biological tolerability of degradation products depends on their nature and concentration, and should be primarily assessed through clinical experience and focused studies. For theoretically possible, new and/or unknown degradation products, relevant t

47、esting is necessary. For well-described and clinically accepted degradation products, no further investigation may be necessary. Note that the safety and efficacy of a medical device can be compromised as a result of degradation, and the degradation should be considered in the risk management of the

48、 device. BS EN ISO 10993-9:December 2009INTERNATIONAL STANDARD ISO 10993-9:2009(E) ISO 2009 All rights reserved 1Biological evaluation of medical devices Part 9: Framework for identification and quantification of potential degradation products 1 Scope This part of ISO 10993 provides general principl

49、es for the systematic evaluation of the potential and observed biodegradation of medical devices and for the design and performance of biodegradation studies. Information obtained from these studies can be used in the biological evaluation described in the ISO 10993 series. This part of ISO 10993 considers both non-resorbable and resorbable materials. This part of ISO 10993 is not applicable to: a) evaluation of degradation which occurs by purely mechanical processes; methodolog