DIN EN ISO 10993-13-2010 Biological evaluation of medical devices - Part 13 Identification and quantification of degradation products from polymeric medical devices (ISO 10993-13 2.pdf

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1、November 2010 Translation by DIN-Sprachendienst.English price group 13No part of this translation may be reproduced without prior permission ofDIN Deutsches Institut fr Normung e. V., Berlin. Beuth Verlag GmbH, 10772 Berlin, Germany,has the exclusive right of sale for German Standards (DIN-Normen).I

2、CS 11.100.20!$l2$“1731501www.din.deDDIN EN ISO 10993-13Biological evaluation of medical devices Part 13: Identification and quantification of degradation products frompolymeric medical devices (ISO 10993-13:2010)English translation of DIN EN ISO 10993-13:2010-11Biologische Beurteilung von Medizinpro

3、dukten Teil 13: Qualitativer und quantitativer Nachweis von Abbauprodukten in Medizinproduktenaus Polymeren (ISO 10993-13:2010)Englische bersetzung von DIN EN ISO 10993-13:2010-11valuation biologique des dispositifs mdicaux Partie 13: Identification et quantification de produits de dgradation de dis

4、positifsmdicaux base de polymres (ISO 10993-13:2010)Traduction anglaise de DIN EN ISO 10993-13:2010-11SupersedesDIN EN ISO 10993-13:2009-08www.beuth.deIn case of doubt, the German-language original shall be considered authoritative.Document comprises 24 pages11.10 DIN EN ISO 10993-13:2010-11 2 A com

5、ma is used as the decimal marker. National foreword This standard has been prepared by Technical Committee ISO/TC 194 “Biological evaluation of medical devices” in collaboration with Technical Committee CEN/TC 206 “Biological evaluation of medical devices” (Secretariat: NEN, Netherlands). The respon

6、sible German body involved in its preparation was the Normenausschuss Feinmechanik und Optik (Optics and Precision Mechanics Standards Committee), Technical Committee NA 027-02-12 AA Biologische Beurteilung von Medizinprodukten. ISO 10993 consists of the following parts, under the general title Biol

7、ogical evaluation of medical devices: Part 1: Evaluation and testing within a risk management system Part 2: Animal welfare 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 cytotox

8、icity 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 skin sensitization Part 11: Tests for systemic toxicity Part 12: Sample

9、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: Identification and quantification of degradation products from metals and al

10、loys Part 16: Toxicokinetic study design 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 Spec

11、ification Part 20: Principles and methods for immunotoxicology testing of medical devices Technical Specification DIN EN ISO 10993-13:2010-11 3 The DIN Standards corresponding to the International and European Standards referred to in clause 2 of this document are as follows: ISO 3696 DIN ISO 3696 I

12、SO 10993-1 DIN EN ISO 10993-1 ISO 10993-9 DIN EN ISO 10993-9 ISO 10993-12 DIN EN ISO 10993-12 ISO 10993-17 DIN EN ISO 10993-17 ISO 14971 DIN EN ISO 14971 Amendments This standard differs from DIN EN ISO 10993-13:2009-08 as follows: a) tests in a simulated environment have been included in the scope;

13、 b) the standard is only applicable to non-resorbable polymers; c) Table 1 has been changed into a flow chart; d) informative Annex B “Environmental stress cracking (ESC) of polymers” has been included. Previous editions DIN EN ISO 10993-13: 1999-04, 2009-08 National Annex NA (informative) Bibliogra

14、phy DIN ISO 3696, Water for analytical laboratory use Specification and test methods DIN EN ISO 10993-1, Biological evaluation of medical devices Part 1: Evaluation and testing DIN EN ISO 10993-9, Biological evaluation of medical devices Part 9: Framework for identification and quantification of pot

15、ential degradation products DIN EN ISO 10993-12, Biological evaluation of medical devices Part 12: Sample preparation and reference materials DIN EN ISO 10993-17, Biological evaluation of medical devices Part 17: Establishment of allowable limits for leachable substances DIN EN ISO 14971, Medical de

16、vices Application of risk management to medical devices DIN EN ISO 10993-13:2010-11 4 This page is intentionally blank EUROPEAN STANDARD NORME EUROPENNE EUROPISCHE NORM EN ISO 10993-13 June 2010 ICS 11.100.20 Supersedes EN ISO 10993-13:2009English Version Biological evaluation of medical devices - P

17、art 13: Identification and quantification of degradation products from polymeric medical devices (ISO 10993-13:2010) valuation biologique des dispositifs mdicaux - Partie 13: Identification et quantification de produits de dgradation de dispositifs mdicaux base de polymres (ISO 10993-13:2010) Biolog

18、ische Beurteilung von Medizinprodukten - Teil 13: Qualitativer und quantitativer Nachweis von Abbauprodukten in Medizinprodukten aus Polymeren (ISO 10993-13:2010) This European Standard was approved by CEN on 5 June 2010. CEN members are bound to comply with the CEN/CENELEC Internal Regulations whic

19、h 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 application to the CEN Management Centre or to any CEN member. This European St

20、andard 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 has the same status as the official versions. CEN members are the national

21、standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland

22、and United Kingdom. EUROPEAN COMMITTEE FOR STANDARDIZATION COMIT EUROPEN DE NORMALISATION EUROPISCHES KOMITEE FR NORMUNG Management Centre: Avenue Marnix 17, B-1000 Brussels 2010 CEN All rights of exploitation in any form and by any means reserved worldwide for CEN national Members. Ref. No. EN ISO

23、10993-13:2010: EContents EN ISO 10993-13:2010 (E) DIN EN ISO 10993-13:2010-11 2 Page Foreword3 Introduction .4 1 Scope 5 2 Normative references 5 3 Terms and definitions .6 4 Degradation test methods 6 4.1 General procedures.6 4.2 Accelerated degradation test .9 4.3 Real-time degradation test in a s

24、imulated environment10 5 Test procedures.10 5.1 General10 5.2 Initial material characterization10 5.3 Accelerated degradation test .10 5.4 Real-time degradation test in a simulated environment13 6 Test report 14 Annex A (informative) Analytical methods .15 Annex B (informative) Environmental stress

25、cracking (ESC) of polymers .16 Bibliography 18 Annex ZA (informative) Relationship between this European Standard and the Essential Requirements of EU Directive 93/42/EEC on Medical Devices .19 Annex ZA (informative) Relationship between this European Standard and the Essential Requirements of EU Di

26、rective 90/385/EEC on Active Implantable Medical Devices 20 Foreword This document (EN ISO 10993-13:2010) has been prepared by Technical Committee ISO/TC 194 Biological evaluation of medical devices” in collaboration with Technical Committee CEN/TC 206 “Biological evaluation of medical devices” the

27、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 December 2010, and conflicting national standards shall be withdrawn at the latest by December 2010. Attention

28、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 10993-13:2009. This document has been prepared under a mandate g

29、iven 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 the CEN/CENELEC Internal Regulations, th

30、e national standards organizations of the following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Nether

31、lands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and the United Kingdom. Endorsement notice The text of ISO 10993-13:2010 has been approved by CEN as a EN ISO 10993-13:2010 without any modification. EN ISO 10993-13:2010 (E) DIN EN ISO 10993-13:2010-11 3 “ Intr

32、oduction 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, such as enzymes, other proteins and cellu

33、lar 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, if present, can interfere with the iden

34、tification 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 results from a degradation test as input

35、 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. Because of the generalized nature of this pa

36、rt 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 polymeric materials with unknown degrada

37、tion 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 within the time frame of the tests shown in

38、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 mechanisms. This part of ISO 10993 is no

39、t 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 biological evaluation in accordance with ISO 10993

40、-1, for risk assessment in accordance with ISO 10993-17 and, if appropriate, for toxicokinetic studies in accordance with ISO 10993-16. EN ISO 10993-13:2010 (E) DIN EN ISO 10993-13:2010-11 4 1 Scope This part of ISO 10993 provides general requirements for the design of tests in a simulated environme

41、nt 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 test in a simu

42、lated environment. For materials that are intended to polymerize in situ, the set or cured polymer is used for testing. The data generated are used in the biological evaluation of the polymer. This part of ISO 10993 considers only non-resorbable polymers. Similar but appropriately modified procedure

43、s may be applicable for resorbable polymers. This part of ISO 10993 considers only those degradation products generated by a chemical alteration of the finished polymeric device. It is not applicable to degradation of the device induced during its intended use by mechanical stress, wear or electroma

44、gnetic radiation or biological factors such as enzymes, other proteins and cellular activity. NOTE An informative text discussing environmental stress cracking (ESC) of polymers is included as a potential aid to the design of degradation studies (see Annex B). The biological activity of the debris a

45、nd soluble degradation products is not addressed in this part of ISO 10993, but should be evaluated according to the principles of ISO 10993-1, ISO 10993-16 and ISO 10993-17. Because of the wide range of polymeric materials used in medical devices, no specific analytical techniques are identified or

46、 given preference. No specific requirements for acceptable levels of degradation products are provided in this part of ISO 10993. 2 Normative references The following referenced documents are indispensable for the application of this document. For dated references, only the edition cited applies. Fo

47、r undated references, the latest edition of the referenced document (including any amendments) applies. ISO 3696, Water for analytical laboratory use Specification and test methods ISO 10993-1, Biological evaluation of medical devices Part 1: Evaluation and testing within a risk management process I

48、SO 10993-9, Biological evaluation of medical devices Part 9: Framework for identification and quantification of potential degradation products EN ISO 10993-13:2010 (E) DIN EN ISO 10993-13:2010-11 5 ISO 10993-12, Biological evaluation of medical devices Part 12: Sample preparation and reference mater

49、ials ISO 10993-17, Biological evaluation of medical devices Part 17: Establishment of allowable limits for leachable substances 3 Terms and definitions For the purposes of this document, the following terms and definitions apply. 3.1 residual monomer unreacted chemical compound(s) used to build the polymeric chains, which is still present in the final polymeric material 3.2 degradation product chemical compound derived from the breakdown of the polymeric material, including any compound produced