DIN EN ISO 10993-14-2009 Biological evaluation of medical devices - Part 14 Identification and quantification of degradation products from ceramics (ISO 10993-14 2001) English vers.pdf

1、August 2009DEUTSCHE NORM English price group 12No part of this standard 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).ICS 11.100.20!$XH“1539837ww

2、w.din.deDDIN EN ISO 10993-14Biological evaluation of medical devices Part 14: Identification and quantification of degradation products fromceramics (ISO 10993-14:2001)English version of DIN EN ISO 10993-14:2009-08Biologische Beurteilung von Medizinprodukten Teil 14: Qualitativer und quantitativer N

3、achweis von keramischen Abbauprodukten(ISO 10993-14:2001)Englische Fassung DIN EN ISO 10993-14:2009-08SupersedesDIN EN ISO 10993-14:2002-05See start of validitywww.beuth.deDocument comprises 21 pagesDIN EN ISO 10993-14:2009-08 2 Start of validity This standard takes effect on 1 August 2009. DIN EN I

4、SO 10993-14:2002-05 may be used in parallel until 21 March 2010. 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

5、: NEN, Netherlands). The responsible 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. This standard contains specifications me

6、eting the essential requirements set out in EU Directive 93/42/EEC on medical devices. 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 system Part 2: Animal welfare requirements Part

7、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: Framework for identification a

8、nd 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 medical devices Part 14:

9、 Identification and quantification of degradation products from ceramics Part 15: Identification and quantification of degradation products from metals and alloys Part 16: Toxicokinetic study design for degradation products and leachables Part 17: Establishment of allowable limits for leachable subs

10、tances Part 18: Chemical characterization of materials DIN EN ISO 10993-14:2009-08 3 Part 19: Physico-chemical, morphological and topographical characterization of materials Technical Specification Part 20: Principles and methods for immunotoxicology testing of medical devices Technical Specificatio

11、n 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 ISO 6474 DIN ISO 6474 ISO 6872 DIN EN ISO 6872 ISO 10993-1 DIN EN ISO 10993-1 ISO 10993-9 DIN EN ISO 10993-9 Amendments This standard differs f

12、rom DIN EN ISO 10993-14:2002-05 as follows: a) Annexes ZA (informative) concerning the relationship between this European Standard and the essential requirements of EU Directive 93/42/EEC on medical devices has been updated on the basis of EU Directive 2007/47/EC of the European Parliament and of th

13、e Council of 5 September 2007 amending Council Directives 90/385/EEC on the approximation of the laws of the Member States relating to active implantable medical devices and 93/42/EEC on medical devices and EU Directive 98/8/EC on the placing on the market of biocidal products. Previous editions DIN

14、 EN ISO 10993-14: 2002-05 National Annex NA (informative) Bibliography DIN ISO 3696, Water for analytical laboratory use Specification and test methods DIN ISO 6474, Implants for surgery Ceramic materials based on high purity alumina DIN EN ISO 6872, Dentistry Ceramic materials DIN EN ISO 10993-1, B

15、iological evaluation of medical devices Part 1: Evaluation and testing quantification of potential degradation products DIN EN ISO 10993-9, Biological evaluation of medical devices Part 9: Framework for identification and DIN EN ISO 10993-14:2009-08 4 This page is intentionally blank EUROPEAN STANDA

16、RD NORME EUROPENNE EUROPISCHE NORM EN ISO 10993-14 April 2009 ICS 11.100.20 Supersedes EN ISO 10993-14:2001 English Version Biological evaluation of medical devices - Part 14: Identification and quantification of degradation products from ceramics (ISO 10993-14:2001) valuation biologique des disposi

17、tifs mdicaux - Partie 14: Identification et quantification des produits de dgradation des cramiques (ISO 10993-14:2001) Biologische Beurteilung von Medizinprodukten - Teil 14: Qualitativer und quantitativer Nachweis von keramischen Abbauprodukten (ISO 10993-14:2001) This European Standard was approv

18、ed by CEN on 12 April 2009. 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 such national st

19、andards 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 language and notifie

20、d to the CEN Management Centre 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,

21、 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 2009 CEN All rights of exploit

22、ation in any form and by any means reserved worldwide for CEN national Members. Ref. No. EN ISO 10993-14:2009: EContents2 DIN EN ISO 10993-14:2009-08 EN ISO 10993-14:2009 (E) Page Foreword3 Introduction.4 1 Scope 5 2 Normative references5 3 Terms and definitions .6 4 Test procedures.6 4.1 Principle6

23、 4.2 Testing of dental devices6 4.3 General testing techniques.7 4.4 Extreme solution test 8 4.5 Simulation solution test10 5 Analysis of filtrate13 5.1 General13 5.2 Choice of chemicals or elements to be analysed 13 5.3 Sensitivity of the analysis method.13 6 Test report 13 Bibliography15 Annex ZA

24、(informative) Relationship between this European Standard and the Essential Requirements of EU Directive 93/42/EEC on Medical Devices 16 Annex ZB (informative) Relationship between this European Standard and the Essential Requirements of EU Directive 90/385/EEC on Active Implantable Medical Devices

25、.17 ForewordThe text of ISO 10993-14:2001 has been 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 10993-14:2009 by Technical Committee CEN/TC 206 “Biological evaluatio

26、n 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 October 2009, and conflicting national standards shall be withdrawn at the latest by

27、March 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 10993-14:2001. This document has been prep

28、ared under a mandate given to CEN by the European Commission and the European Free Trade Association, and supports essential requirements of EU Directive 93/42/EEC on Medical Devices. For relationship with the EU Directive, see informative Annex ZA, which is an integral part of this document. Accord

29、ing to the 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

30、, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and the United Kingdom. Endorsement notice The text of ISO 10993-14:2001 has been approved by CEN as a EN ISO 10993-14:2009 without any modification. 3 DIN EN ISO 10993-14:2

31、009-08 EN ISO 10993-14:2009 (E) IntroductionThis part of ISO 10993 consists of two tests for the biological evaluation of medical devices: an extreme solutiontest and a simulation solution test. The extreme solution test is developed as a worst-case environment and thesimulation test is developed as

32、 a very common environment.Degradation products covered by this part of ISO 10993 are formed primarily by dissolution in an aqueousenvironment. It is recognized that additional biological factors such as enzymes and proteins can alter the rate ofdegradation. Degradation by such outside factors is no

33、t addressed in this part of ISO 10993.It should be kept in mind that a ceramic device might have extraneous chemical phases and/or elements inextremely minor amounts. Whilst these components might not be named in the original specification, they can oftenbe suspected by the relationship that the mat

34、erial in question has to other materials and the expected history of thematerials processing.Once identified and quantified, the chemical composition of the degradation products form the basis for riskassessment and, if appropriate, biological safety studies according to the principles of ISO 10993-

35、1.4 DIN EN ISO 10993-14:2009-08 EN ISO 10993-14:2009 (E) 1 ScopeThis part of ISO 10993 specifies two methods of obtaining solutions of degradation products from ceramics(including glasses) for the purposes of quantification. It also gives guidance on the analysis of these solutions inorder to identi

36、fy the degradation products. Because of the generalized nature of this part of ISO 10993, productspecific standards, when available, that address degradation product formation under more relevant conditions ofuse, should be considered first.This part of ISO 10993 considers only those degradation pro

37、ducts generated by a chemical dissociation ofceramics during in vitro testing. No degradation induced by mechanical stress or external energy is covered. It isnoted that while ISO 6872 and ISO 9693 cover chemical degradation tests, they do not address the analysis ofdegradation products.Because of t

38、he range of ceramics used in medical devices and the different requirements for accuracy andprecision of the results, no specific analytical techniques are identified. Further, this part of ISO 10993 provides nospecific requirements for acceptable levels of degradation products.Although these materi

39、als are intended for biomedical applications, the biological activity of these degradationproducts is not addressed in this part of ISO 10993.2 Normative referencesThe following normative documents contain provisions which, through reference in this text, constitute provisions ofthis part of ISO 109

40、93. For dated references, subsequent amendments to, or revisions of, any of these publicationsdo not apply. However, parties to agreements based on this part of ISO 10993 are encouraged to investigate thepossibility of applying the most recent editions of the normative documents indicated below. For

41、 undatedreferences, the latest edition of the normative document referred to applies. Members of ISO and IEC maintainregisters of currently valid International Standards.ISO 3310-1, Test sieves Technical requirements and testing Part 1: Test sieves of metal wire clothISO 3696, Water for analytical l

42、aboratory use Specification and test methodsISO 5017, Dense shaped refractory products Determination of bulk density, apparent porosity and true porosityISO 6474, Implants for surgery Ceramic materials based on high purity aluminaISO 6872:1995, Dental ceramicISO 10993-1, Biological evaluation of med

43、ical devices Part 1: Evaluation and testing5 DIN EN ISO 10993-14:2009-08 EN ISO 10993-14:2009 (E) ISO 10993-9, Biological evaluation of medical devices Part 9: Framework for identification and quantification ofpotential degradation products3 Terms and definitionsFor the purposes of this part of ISO

44、10993, the terms and definitions given in ISO 10993-1 and ISO 10993-9 as wellas the following apply.3.1ceramicstypically crystallized materials that are physically nonmetallic and chemically inorganic3.2blank discnoncoated circular plate made of the substrate material to be used in the finished devi

45、ce3.3retentateundissolved solids remaining in the filter paper after filtration3.4filtratesolution which passes through the filter paper4 Test procedures4.1 PrincipleThis part of ISO 10993 consists of two tests. The first test, an extreme solution test conducted at low pH, serves asa screen for most

46、 ceramics for the observation of possible degradation products. The second test simulates a morefrequently encountered in vivo pH. A flowchart of the decision process for using these test methods is given inFigure 1.The test methods described in this part of ISO 10993 shall be used for ceramics in b

47、ulk and granular form as wellas ceramic coatings.When deviations from the recommended test specimen or solution volumes are used, full justification shall beprovided.4.2 Testing of dental devices4.2.1 GeneralThis part of ISO 10993 is intended to simulate worst-case exposure to tissue environments. F

48、or dental ceramicsexposed to the oral cavity (e.g. ceramic veneering material), a more appropriate test environment is given inISO 6872. However, for dental devices not exposed to the oral cavity, such as dental implant stems, thespecifications given in 4.4 of this part of ISO 10993 shall apply.4.2.

49、2 Test methods for dental devices exposed to the oral cavityFor dental devices exposed to the oral cavity, the method given in 8.4 of ISO 6872:1995 shall be used as theextreme solution test.6 DIN EN ISO 10993-14:2009-08 EN ISO 10993-14:2009 (E) Figure 1 Flowchart of the decision-making process for the extreme solution test and the simulationsolution tests (see text for details)4.2.3 Specimen characterizationThe specimen shall be characterized as described in 4.4.4. If the specimen density is greater th