EN ISO 10993-15-2009 en Biological evaluation of medical devices - Part 15 Identification and quantification of degradation products from metals and alloys《医疗设备的生物评估 第15部分 金属与合金降解产.pdf

1、BS EN ISO10993-15:2009ICS 11.100.20NO COPYING WITHOUT BSI PERMISSION EXCEPT AS PERMITTED BY COPYRIGHT LAWBRITISH STANDARDBiological evaluationof medical devicesPart 15: Identification andquantification of degradationproducts from metals and alloys (ISO10993-15:2000)This British Standard was publishe

2、d under the authority of the Standards Policy and Strategy Com-mittee on 31 July 2009. BSI 2009ISBN 978 0 580 68107 3Amendments/corrigenda issued since publicationDate CommentsBS EN ISO 10993-15:2009National forewordThis British Standard is the UK implementation of EN ISO 10993-15:2009. It is identi

3、cal to ISO 10993-15:2000. It supersedes BS EN ISO 10993-15:2001 which is withdrawn.The UK participation in its preparation was entrusted to Technical Committee CH/194, Biological evaluation of medical devices.A list of organizations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 sec

4、retary.This publication 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.EUROPEAN STANDARDNORME EUROPENNEEUROPISCHE NORMEN ISO 10993-15June 2009IC

5、S 11.100.20 Supersedes EN ISO 10993-15:2000 English VersionBiological evaluation of medical devices - Part 15: Identificationand quantification of degradation products from metals andalloys (ISO 10993-15:2000)valuation biologique des dispositifs mdicaux - Partie 15:Identification et quantification d

6、es produits de dgradationissus des mtaux et alliages (ISO 10993-15:2000)Biologische Beurteilung von Medizinprodukten - Teil 15:Qualitativer und quantitativer Nachweis vonAbbauprodukten aus Metallen und Legierungen (ISO10993-15:2000)This European Standard was approved by CEN on 23 May 2009.CEN member

7、s are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this EuropeanStandard the status of a national standard without any alteration. Up-to-date lists and bibliographical references concerning such nationalstandards may be obtained on application t

8、o 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 translationunder the responsibility of a CEN member into its own language and notified to the CEN Management Centre has the sam

9、e status as theofficial 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, Portugal,Roman

10、ia, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom.EUROPEAN COMMITTEE FOR STANDARDIZATIONCOMIT EUROPEN DE NORMALISATIONEUROPISCHES KOMITEE FR NORMUNGManagement Centre: Avenue Marnix 17, B-1000 Brussels 2009 CEN All rights of exploitation in any form and by any means reservedworldw

11、ide for CEN national Members.Ref. No. EN ISO 10993-15:2009: EBS EN ISO 10993-15:2009EN ISO 10993-15:2009 (E) 3 Foreword The text of ISO 10993-15:2000 has been prepared by Technical Committee ISO/TC 194 “Biological evaluation of medical devices” of the International Organization for Standardization (

12、ISO) and has been taken over as EN ISO 10993-15:2009 by 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 endorse

13、ment, at the latest by December 2009, and conflicting national standards shall be withdrawn at the latest by 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 identify

14、ing any or all such patent rights. This document supersedes EN ISO 10993-15:2000. 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 Directive 93/42/EEC on Medical Devices. For rel

15、ationship with the EU Directive, see informative Annex ZA, which is an integral part 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, Cyprus,

16、 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 and the United Kingdom. Endorsement notice The text of ISO 10993

17、-15:2000 has been approved by CEN as a EN ISO 10993-15:2009 without any modification. BS EN ISO 10993-15:2009EN ISO 10993-15:2009 (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 Standar

18、d 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 93/42/EEC on medical devices. Once this standard is cited in the Official Journal of the Europe

19、an 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 ZA confers, within the limits of the scope of this standard, a presumption of conformity with the corresponding Essential Requ

20、irements 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-clause(s) of this EN Essential Requirements (ERs) of Directive 93/42/EEC Qualifying remarks/Notes 4, 5, 6, 7, 8, 9 Annex I: 7.1,

21、 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 10993-15:2009ISO 10993-15:2000(E) ISO 2000 All rights reserved iiiContents PageForeword.ivIntroductionvi1 Scope 12 Normative references 13 Terms and d

22、efinitions .24 Degradation test methods 24.1 General24.2 Prerequisites 35 Reagent and sample preparation.35.1 Sample documentation .35.2 Test solution (electrolyte) .35.3 Preparation of test samples36 Electrochemical tests46.1 Apparatus .46.2 Sample preparation .46.3 Test conditions 56.4 Potentiodyn

23、amic measurements .56.5 Potentiostatic measurements.57 Immersion test .57.1 Apparatus .57.2 Sample preparation .77.3 Immersion test procedure.78 Analysis 89 Test report 8Annex A (informative) Schematic diagram of the electrochemical measuring circuit.9Annex B (informative) Schematic drawing of an el

24、ectrolytic cell 10Annex C (informative) Examples of alternative electrolytes for the electrochemical tests.11Bibliography12BS EN ISO 10993-15:2009ISO 10993-15:2000(E)iv ISO 2000 All rights reservedForewordISO (the International Organization for Standardization) is a worldwide federation of national

25、standards bodies (ISOmember bodies). The work of preparing International Standards is normally carried out through ISO technicalcommittees. Each member body interested in a subject for which a technical committee has been established hasthe right to be represented on that committee. International or

26、ganizations, governmental and non-governmental, inliaison with ISO, also take part in the work. ISO collaborates closely with the International ElectrotechnicalCommission (IEC) on all matters of electrotechnical standardization.International Standards are drafted in accordance with the rules given i

27、n the ISO/IEC Directives, Part 3.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.Attention is drawn to the possibility that

28、 some of the elements of this part of ISO 10993 may be the subject ofpatent rights. ISO shall not be held responsible for identifying any or all such patent rights.International Standard ISO 10993-15 was prepared by Technical Committee ISO/TC 194, Biological evaluation ofmedical devices.ISO 10993 co

29、nsists of the following parts, under the general title Biological evaluation of medical devices:Gbe Part 1: Evaluation and testingGbe Part 2: Animal welfare requirementsGbe Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicityGbe Part 4: Selection of tests for interactions with b

30、loodGbe Part 5: Tests for in vitro cytotoxicityGbe Part 6: Tests for local effects after implantationGbe Part 7: Ethylene oxide sterilization residualsGbe Part 8: Selection and qualification of reference materials for biological testsGbe Part 9: Framework for identification and quantification of pot

31、ential degradation productsGbe Part 10: Tests for irritation and delayed-type hypersensitiviyGbe Part 11: Tests for systemic toxicityGbe Part 12: Sample preparation and reference materialsGbe Part 13: Identification and quantification of degradation products from polymeric medical devicesGbe Part 14

32、: Identification and quantification of degradation products from ceramicsGbe Part 15: Identification and quantification of degradation products from metals and alloysGbe Part 16: Toxicokinetic study design for degradation products and leachablesBS EN ISO 10993-15:2009ISO 10993-15:2000(E) ISO 2000 Al

33、l rights reserved vGbe Part 17: Establishment of allowable limits for leachable substances using health-based risk assessmentGbe Part 18: Chemical characterization of materialsFuture parts will deal with other relevant aspects of biological testing.Annexes A, B and C of this part of ISO 10993 are fo

34、r information only.BS EN ISO 10993-15:2009ISO 10993-15:2000(E)vi ISO 2000 All rights reservedIntroductionOne of the potential health hazards resulting from medical devices may be due to the interactions of theirelectrochemically-induced degradation products with the biological system. Therefore, the

35、 evaluation of potentialdegradation products from metallic materials by methods suitable for testing the electrochemical behavior of thesematerials is a necessary step in the biological performance testing of materials.The body environment typically contains cations of sodium, potassium, calcium and

36、 magnesium and anions ofchloride, bicarbonate, phosphate and organic acids generally in concentrations between 2 Gb4 103mol and150 Gb4 103mol. A range of organic molecules such as proteins, enzymes and lipoproteins is also present, but theirconcentrations may vary to a great extent. Earlier studies

37、assumed that organic molecules did not exert asignificant influence on the degradation of metallic implants, but newer investigations indicate that implant protein interactions should be taken into account. Depending on a particular product or application, altering thepH of the testing environment m

38、ay also need to be considered.In such biological environments, metallic materials may undergo a certain degradation and the differentdegradation products may interact with the biological system in different ways. Therefore, the identification andquantification of these degradation products is an imp

39、ortant step in evaluating the biological performance ofmedical devices.BS EN ISO 10993-15:2009INTERNATIONAL STANDARD ISO 10993-15:2000(E) ISO 2000 All rights reserved 1Biological evaluation of medical devices Part 15:Identification and quantification of degradation products frommetals and alloys1 Sc

40、opeThis part of ISO 10993 provides guidance on general requirements for the design of tests for identifying andquantifying degradation products from finished metallic medical devices or corresponding material samples finishedas ready for clinical use. It is applicable only to those degradation produ

41、cts generated by chemical alteration of thefinished metallic device in an in vitro accelerated degradation test. Because of the accelerated nature of thesetests, the test results may not reflect the implant or material behavior in the body. The described chemicalmethodologies are a means to generate

42、 degradation products for further assessments.This part of ISO 10993 is not applicable to degradation products induced by applied mechanical stress.NOTE Mechanically induced degradation, such as wear, may be covered in the appropriate product-specific standard.Where product-group standards provide a

43、pplicable product-specific methodologies for the identification and quantification ofdegradation products, those standards should be considered.Because of the wide range of metallic materials used in medical devices, no specific analytical techniques areidentified for quantifying the degradation pro

44、ducts. The identification of trace elements (1011G57) and a sensitivity and accuracy todetect a change of 1 mV over a potential range between Gb1 2V.6.1.4 Current-measuring instrument capable of measuring a current to Gb1 1% of the absolute value over acurrent range between 109A and 101A.6.1.5 Worki

45、ng electrode (test sample).6.1.6 Counter-electrode(s) such as platinum (grid, plate, or wire) or vitreous carbon with an area at least 10times that of the working electrode.6.1.7 Reference electrode.6.1.8 pH-meter with a sensitivity of Gb1 0,1.A schematic diagram of the electrochemical measurement c

46、ircuit which may be used as a system with variablepotential is given in annex A.A schematic drawing of an electrolytic cell is given in annex B.6.2 Sample preparationMount the test sample in a watertight electrode holder so that only the test surface is in contact with the electrolyte.Take care to a

47、void the creation of conditions where crevice corrosion can occur due the formation of a crevicebetween the mounting and the sample. Before testing, clean the specimen ultrasonically for 10 min to 15 min inethanol, carefully rinse with water of grade 2 in accordance with ISO 3696 and immediately tra

48、nsfer into the testcell.BS EN ISO 10993-15:2009ISO 10993-15:2000(E) ISO 2000 All rights reserved 56.3 Test conditionsFill the test cell with the test solution (electrolyte). If the electrochemical behaviour is temperature-sensitive in therange of 10 Gb0Cto50Gb0C, maintain the electrolyte cell at (37

49、 Gb1 1) C. Reduce the oxygen level in the electrolyte bybubbling oxygen-free nitrogen or argon at a rate of approximately 100 cm3Gd7min1for not less than 30 min prior tothe start of the test. The electrolyte shall be agitated either by the bubbling gas or mechanical means to avoidconcentration gradients. If gas agitation is used, take care not to have any gas bubbles adhering to the active testsurface.Magnetic stirrers often interfere with electrochemical test cells. If they are used, their effect on the test cell shall bedetermined as part of t