EN ISO 10993-13-2010 en Biological evaluation of medical devices - Part 13 Identification and quantification of degradation products from polymeric medical devices《医疗装置的生物学评定 第13部分.pdf

1、raising standards worldwideNO COPYING WITHOUT BSI PERMISSION EXCEPT AS PERMITTED BY COPYRIGHT LAWBSI Standards PublicationBS EN ISO 10993-13:2010Biological evaluation ofmedical devicesPart 13: Identification and quantificationof degradation products from polymericmedical devices (ISO 10993-13:2010)B

2、S EN ISO 10993-13:2010 BRITISH STANDARDNational forewordThis British Standard is the UK implementation of EN ISO10993-13:2010. It supersedes BS EN ISO 10993-13:2009 which iswithdrawn.The UK participation in its preparation was entrusted to TechnicalCommittee CH/194, Biological evaluation of medical

3、devices.A list of organizations represented on this committee can beobtained on request to its secretary.This publication does not purport to include all the necessaryprovisions of a contract. Users are responsible for its correctapplication. BSI 2010ISBN 978 0 580 57719 2ICS 11.100.20Compliance wit

4、h a British Standard cannot confer immunity fromlegal obligations.This British Standard was published under the authority of theStandards Policy and Strategy Committee on 31 October 2010.Amendments issued since publicationDate Text affectedEUROPEAN STANDARD NORME EUROPENNE EUROPISCHE NORM EN ISO 109

5、93-13 June 2010 ICS 11.100.20 Supersedes EN ISO 10993-13:2009English Version Biological evaluation of medical devices - Part 13: Identification and quantification of degradation products from polymeric medical devices (ISO 10993-13:2010) valuation biologique des dispositifs mdicaux - Partie 13: Iden

6、tification et quantification de produits de dgradation de dispositifs mdicaux base de polymres (ISO 10993-13:2010) Biologische Beurteilung von Medizinprodukten - Teil 13: Qualitativer und quantitativer Nachweis von Abbauprodukten in Medizinprodukten aus Polymeren (ISO 10993-13:2010) This European St

7、andard was approved by CEN on 5 June 2010. 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 national standard without any alteration. Up-to-date lists and bibliographical references concerning s

8、uch 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 in any other language made by translation under the responsibility of a CEN member into its own langu

9、age 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, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lith

10、uania, Luxembourg, Malta, Netherlands, Norway, Poland, 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 2010

11、CEN All rights of exploitation in any form and by any means reserved worldwide for CEN national Members. Ref. No. EN ISO 10993-13:2010: EBS EN ISO 10993-13:2010EN ISO 10993-13:2010 (E) 3 Foreword This document (EN ISO 10993-13:2010) has been prepared by Technical Committee ISO/TC 194 “Biological eva

12、luation of medical devices“ in collaboration with Technical Committee CEN/TC 206 “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,

13、at the latest by December 2010, and conflicting national standards shall be withdrawn at the latest by December 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

14、 any or all such patent rights. This document supersedes EN ISO 10993-13:2009. This document 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, s

15、ee informative Annex ZA and ZB, which are integral parts of this document. According to the CEN/CENELEC Internal Regulations, the national standards organizations of the following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, De

16、nmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and the United Kingdom. Endorsement notice The text of ISO 10993-13:2010 has been a

17、pproved by CEN as a EN ISO 10993-13:2010 without any modification. BS EN ISO 10993-13:2010EN ISO 10993-13:2010 (E) 4 Annex 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

18、 under a mandate given to CEN by the European Commission and the European Free Trade Association to provide a means of 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 u

19、nder that Directive and has been implemented as a national standard in at least one Member State, compliance with the clauses of this European Standard given in Table ZA.1 confers, within the limits of the scope of this Intenational Standard, a presumption of conformity with the corresponding Essent

20、ial Requirements of that Directive and associated EFTA regulations. Table ZA.1 Correspondence between this European Standard 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 r

21、emarks/notes 4, 5 and 6 7.1 and 7.5 These relevant Essential Requirements are only partly addressed in this standard. General 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 appli

22、cable to the product(s) falling within the scope of this European Standard. BS EN ISO 10993-13:2010EN ISO 10993-13:2010 (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 Europe

23、an 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 Requirements of the New Approach Directive 90/385/EEC on Active Implantable Medical Devices. Once this European Standard is cite

24、d 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 clauses of this European Standard given in Table ZB.1 confers, within the limits of the scope of this European Standard, a presumptio

25、n of conformity with the corresponding Essential Requirements of that Directive and associated 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 Requirem

26、ents (ERs) of Directive 90/385/EEC on Active Implantable Medical Devices Qualifying remarks/notes 4, 5 and 6 9 (first and second indents only) The first and second indents of this relevant Essential Requirement are only partly addressed in this standard. General note: Presumption of conformity depen

27、ds 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 European Standard. BS EN ISO 10993-13:2010ISO 10993-13:2010(E) ISO 2010 All rights reserved iiiContents Pa

28、ge Foreword iv Introductionvi 1 Scope1 2 Normative references1 3 Terms and definitions .2 4 Degradation test methods 2 4.1 General procedures.2 4.2 Accelerated degradation test .5 4.3 Real-time degradation test in a simulated environment .6 5 Test procedures.6 5.1 General .6 5.2 Initial material cha

29、racterization6 5.3 Accelerated degradation test .6 5.4 Real-time degradation test in a simulated environment .9 6 Test report10 Annex A (informative) Analytical methods.11 Annex B (informative) Environmental stress cracking (ESC) of polymers.12 Bibliography14 BS EN ISO 10993-13:2010ISO 10993-13:2010

30、(E) iv ISO 2010 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 committees. Each member body in

31、terested 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 Electrotechni

32、cal 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

33、 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.

34、 ISO shall not be held responsible for identifying any or all such patent rights. ISO 10993-13 was prepared by Technical Committee ISO/TC 194, Biological evaluation of medical devices. This second edition cancels and replaces the first edition (ISO 10993-13:1998), which has been technically revised.

35、 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 welfare requirements Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity Part 4: Selectio

36、n 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: Framework for identification and quantification of potential degradation products Part 10: Tests for irritation and

37、 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 medical devices Part 14: Identification and quantification of degradation products from ceramics Part 15: Ide

38、ntification and quantification of degradation products from metals and alloys BS EN ISO 10993-13:2010ISO 10993-13:2010(E) ISO 2010 All rights reserved v Part 16: Toxicokinetic study design for degradation products and leachables Part 17: Establishment of allowable limits for leachable substances Par

39、t 18: Chemical characterization of materials Part 19: Physico-chemical, morphological and topographical characterization of materials Technical specification Part 20: Principles and methods for immunotoxicology testing of medical devices Technical specification BS EN ISO 10993-13:2010ISO 10993-13:20

40、10(E) vi ISO 2010 All rights reservedIntroduction Degradation products covered by this part of ISO 10993 are formed primarily by chemical bond scission due to hydrolytic and/or oxidative processes in an aqueous environment such as the human body. It is recognised that additional biological factors,

41、such as enzymes, other proteins and cellular activity, can alter the rate and nature of degradation. It should be kept in mind that a polymeric device can contain residuals and leachables such as monomers, oligomers, solvents, catalysts, additives, fillers and processing aids. These components which

42、, if present, can interfere with the identification and quantification of the degradation products need to be considered and accounted for. It should be recognised that residual monomers can generate the same degradation products as the polymer itself. If the reader is solely interested in using the

43、 results from a degradation test as input to further biological evaluation tests, the reader might not be interested in distinguishing between a leachable and a degradation product. If this is the case, then the care taken to separate the leachable from the degradation product may not be needed. Bec

44、ause of the generalized nature of this part of ISO 10993, product standards, when available, that address degradation product formation under more relevant conditions of use, may be considered as an alternative. This part of ISO 10993 is suitable for screening new polymeric materials and/or modified

45、 polymeric materials with unknown degradation behaviour in body contact. This part of ISO 10993 does not reproduce degradation in vivo. The user of this part of ISO 10993 can consider running additional degradation tests addressing in vivo degradation issues. Long-term implants might not degrade wit

46、hin the time frame of the tests shown in this part of ISO 10993. The intention of this part of ISO 10993 is to help determine the biological hazards from potential degradation products from polymer components of medical devices. As noted above, those products might come from a variety of degradation

47、 mechanisms. This part of ISO 10993 is not intended to be a complete analysis of the degradation of the medical device and the impact on its performance. The interested user is referred to the relevant product standards. The identified and quantified degradation products form the basis for biologica

48、l evaluation in accordance with ISO 10993-1, for risk assessment in accordance with ISO 10993-17 and, if appropriate, for toxicokinetic studies in accordance with ISO 10993-16. BS EN ISO 10993-13:2010INTERNATIONAL STANDARD ISO 10993-13:2010(E) ISO 2010 All rights reserved 1Biological evaluation of m

49、edical devices Part 13: Identification and quantification of degradation products from polymeric medical devices 1 Scope This part of ISO 10993 provides general requirements for the design of tests in a simulated environment for identifying and quantifying degradation products from finished polymeric medical devices ready for clinical use. This part of ISO 10993 describes two test methods to generate degradation products, an accelerated degradation test as a screening method and a real-time degradation tes