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1、BRITISH STANDARD BS EN ISO 10993-15:2001 Biological evaluation of medical devices Part 15: Identification and quantification of degradation products from metals and alloys ICS 11.040.01; 11.100 NO COPYING WITHOUT BSI PERMISSION EXCEPT AS PERMITTED BY COPYRIGHT LAW Licensed Copy: sheffieldun sheffiel
2、dun, na, Fri Nov 17 09:51:48 GMT+00:00 2006, Uncontrolled Copy, (c) BSI BS EN ISO 10993-15:2001 This British Standard, having been prepared under the direction of the Health and Environment Sector Committee, was published under the authority of the Standards Committee and comes into effect on 15 Jul
3、y 2001 BSI 07-2001 ISBN 0 580 37875 6 National foreword This British Standard reproduces verbatim ISO 10993-15:2000 and implements it as the UK national standard. The UK participation in its preparation was entrusted to Technical Committee CH/26, Biological testing of medical and dental materials an
4、d devices, which has the responsibility to: A list of organizations represented on this committee can be obtained on request to its secretary. Cross-references The British Standards which implement international publications referred to in this document may be found in the BSI Standards Catalogue un
5、der the section entitled “International Standards Correspondence Index”, or by using the “Find” facility of the BSI Standards Electronic Catalogue. A British Standard does not purport to include all the necessary provisions of a contract. Users of British Standards are responsible for their correct
6、application. Compliance with a British Standard does not of itself confer immunity from legal obligations. aid enquirers to understand the text; present to the responsible international/European committee any enquiries on the interpretation, or proposals for change, and keep the UK interests informe
7、d; monitor related international and European developments and promulgate them in the UK. Summary of pages This document comprises a front cover, an inside front cover, the EN ISO title page, the EN ISO Foreword page, the ISO title page, pages ii to vi, pages 1 to 12, the Annex ZA and a back cover.
8、The BSI copyright date displayed in this document indicates when the document was last issued. Amendments issued since publication Amd. No. DateComments Licensed Copy: sheffieldun sheffieldun, na, Fri Nov 17 09:51:48 GMT+00:00 2006, Uncontrolled Copy, (c) BSI EUROPEAN STANDARD NORME EUROPENNE EUROPI
9、SCHE NORM EN ISO 10993-15 December 2000 ICS 01.010.00 English version Biological evaluation of medical devices - Part 15: Identification and quantification of degradation products from metals and alloys (ISO 10993-15:2000) Evaluation biologique des dispositifs mdicaux - Partie 15: Identification et
10、quantification des produits de dgradation issus des mtaux et alliages (ISO 10993-15:2000) Biologische Beurteilung von Medizinprodukten - Teil 5: Qualitativer und quantitativer Nachweis von Abbauprodukten aus Metallen und Legierungen (ISO 10993-15:2000) This European Standard was approved by CEN on 1
11、 December 2000. 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 standards may
12、be obtained on application to the 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 Managem
13、ent Centre has the same status as the official versions. CEN members are the national standards bodies of Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Italy, Luxembourg, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and United Kingdom. EU
14、ROPEAN COMMITTEE FOR STANDARDIZATION COMIT EUROPEN DE NORMALISATION EUROPISCHES KOMITEE FR NORMUNG Management Centre: rue de Stassart, 36 B-1050 Brussels 2000 CENAll rights of exploitation in any form and by any means reserved worldwide for CEN national Members. Ref. No. EN ISO 10993-15:2000 E Licen
15、sed Copy: sheffieldun sheffieldun, na, Fri Nov 17 09:51:48 GMT+00:00 2006, Uncontrolled Copy, (c) BSI gaPe 2 I NESO 01-399152:000 Foreword The text of the International Standard ISO 10993-15:2000 has been prepared by Technical Committee ISO/TC 194 “Biological evaluation of medical devices“ in collab
16、oration with Technical Committee CEN/TC 206 “Biocompatibility of medical and dental materials and 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
17、 June 2001, and conflicting national standards shall be withdrawn at the latest by June 2001. This European Standard 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(s). According to
18、 the CEN/CENELEC Internal Regulations, the national standards organizations of the following countries are bound to implement this European Standard: Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Italy, Luxembourg, Netherlands, Norway, Portugal, Spain
19、, Sweden, Switzerland and the United Kingdom. Endorsement notice The text of the International Standard ISO 10993-15:2000 was approved by CEN as a European Standard without any modification. NOTE: Normative references to International Standards are listed in annex ZA (normative). EN ISO 1099315:2000
20、 Licensed Copy: sheffieldun sheffieldun, na, Fri Nov 17 09:51:48 GMT+00:00 2006, Uncontrolled Copy, (c) BSI Reference number ISO 10993-15:2000(E) ISO 2000 INTERNATIONAL STANDARD ISO 10993-15 First edition 2000-12-01 Corrected and reprinted 2001-04-01 Biological evaluation of medical devices Part 15:
21、 Identification and quantification of degradation products from metals and alloys valuation biologique des dispositifs mdicaux Partie 15: Identification et quantification des produits de dgradation issus des mtaux et alliages EN ISO 1099315:2000 Licensed Copy: sheffieldun sheffieldun, na, Fri Nov 17
22、 09:51:48 GMT+00:00 2006, Uncontrolled Copy, (c) BSI ISO -3990151:(0002E) ii EN ISO 1099315:2000 Licensed Copy: sheffieldun sheffieldun, na, Fri Nov 17 09:51:48 GMT+00:00 2006, Uncontrolled Copy, (c) BSI ISO 1-399051:(0002E) iii ContentsPage Foreword.iv Introductionvi 1Scope 1 2Normative references1
23、 3Terms and definitions .2 4Degradation test methods 2 4.1General2 4.2Prerequisites3 5Reagent and sample preparation.3 5.1Sample documentation .3 5.2Test solution (electrolyte).3 5.3Preparation of test samples3 6Electrochemical tests4 6.1Apparatus.4 6.2Sample preparation .4 6.3Test conditions 5 6.4P
24、otentiodynamic measurements .5 6.5Potentiostatic measurements.5 7Immersion test .5 7.1Apparatus.5 7.2Sample preparation .7 7.3Immersion test procedure.7 8Analysis8 9Test report8 Annex A (informative) Schematic diagram of the electrochemical measuring circuit.9 Annex B (informative) Schematic drawing
25、 of an electrolytic cell 10 Annex C (informative) Examples of alternative electrolytes for the electrochemical tests.11 Bibliography12 EN ISO 1099315:2000 Licensed Copy: sheffieldun sheffieldun, na, Fri Nov 17 09:51:48 GMT+00:00 2006, Uncontrolled Copy, (c) BSI ISO -3990151:(0002E) iv Foreword ISO (
26、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 interested in a subject for which a technical commi
27、ttee 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 Electrotechnical Commission (IEC) on all matters of electrotec
28、hnical standardization. International Standards are drafted in accordance with the rules given in 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 approv
29、al by at least 75 % of the member bodies casting a vote. Attention is drawn to the possibility that some of the elements of this part of ISO 10993 may be the subject of patent rights. ISO shall not be held responsible for identifying any or all such patent rights. International Standard ISO 10993-15
30、 was prepared by Technical Committee ISO/TC 194, Biological evaluation of medical devices. ISO 10993 consists of the following parts, under the general title Biological evaluation of medical devices: ?Part 1: Evaluation and testing ?Part 2: Animal welfare requirements ?Part 3: Tests for genotoxicity
31、, 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 8: Selection and qualification of reference materials
32、 for biological tests ?Part 9: Framework for identification and quantification of potential degradation products ?Part 10: Tests for irritation and delayed-type hypersensitiviy ?Part 11: Tests for systemic toxicity ?Part 12: Sample preparation and reference materials ?Part 13: Identification and qua
33、ntification 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 alloys ?Part 16: Toxicokinetic study design for degradation product
34、s and leachables EN ISO 1099315:2000 Licensed Copy: sheffieldun sheffieldun, na, Fri Nov 17 09:51:48 GMT+00:00 2006, Uncontrolled Copy, (c) BSI ISO 1-399051:(0002E) v ?Part 17: Establishment of allowable limits for leachable substances using health-based risk assessment ?Part 18: Chemical characteri
35、zation of materials Future parts will deal with other relevant aspects of biological testing. Annexes A, B and C of this part of ISO 10993 are for information only. EN ISO 1099315:2000 Licensed Copy: sheffieldun sheffieldun, na, Fri Nov 17 09:51:48 GMT+00:00 2006, Uncontrolled Copy, (c) BSI ISO -399
36、0151:(0002E) vi Introduction One of the potential health hazards resulting from medical devices may be due to the interactions of their electrochemically-induced degradation products with the biological system. Therefore, the evaluation of potential degradation products from metallic materials by me
37、thods suitable for testing the electrochemical behavior of these materials is a necessary step in the biological performance testing of materials. The body environment typically contains cations of sodium, potassium, calcium and magnesium and anions of chloride, bicarbonate, phosphate and organic ac
38、ids generally in concentrations between 2?103mol and 150?103mol. A range of organic molecules such as proteins, enzymes and lipoproteins is also present, but their concentrations may vary to a great extent. Earlier studies assumed that organic molecules did not exert a significant influence on the d
39、egradation of metallic implants, but newer investigations indicate that implant protein interactions should be taken into account. Depending on a particular product or application, altering the pH of the testing environment may also need to be considered. In such biological environments, metallic ma
40、terials may undergo a certain degradation and the different degradation products may interact with the biological system in different ways. Therefore, the identification and quantification of these degradation products is an important step in evaluating the biological performance of medical devices.
41、 EN ISO 1099315:2000 Licensed Copy: sheffieldun sheffieldun, na, Fri Nov 17 09:51:48 GMT+00:00 2006, Uncontrolled Copy, (c) BSI INTENRATIONAL TSANDADRISO -3990115:(0002E) 1 Biological evaluation of medical devices Part 15: Identification and quantification of degradation products from metals and all
42、oys 1Scope This part of ISO 10993 provides guidance on general requirements for the design of tests for identifying and quantifying degradation products from finished metallic medical devices or corresponding material samples finished as ready for clinical use. It is applicable only to those degrada
43、tion products generated by chemical alteration of the finished metallic device in an in vitro accelerated degradation test. Because of the accelerated nature of these tests, the test results may not reflect the implant or material behavior in the body. The described chemical methodologies are a mean
44、s to generate degradation products for further assessments. This part of ISO 10993 is not applicable to degradation products induced by applied mechanical stress. NOTEMechanically induced degradation, such as wear, may be covered in the appropriate product-specific standard. Where product-group stan
45、dards provide applicable product-specific methodologies for the identification and quantification of degradation products, those standards should be considered. Because of the wide range of metallic materials used in medical devices, no specific analytical techniques are identified for quantifying t
46、he degradation products. The identification of trace elements (1011?) and a sensitivity and accuracy to detect a change of 1 mV over a potential range between?2 V. 6.1.4Current-measuring instrument capable of measuring a current to?1% of the absolute value over a current range between 109A and 101A.
47、 6.1.5Working electrode (test sample). 6.1.6Counter-electrode(s) such as platinum (grid, plate, or wire) or vitreous carbon with an area at least 10 times that of the working electrode. 6.1.7Reference electrode. 6.1.8pH-meter with a sensitivity of?0,1. A schematic diagram of the electrochemical meas
48、urement circuit which may be used as a system with variable potential is given in annex A. A schematic drawing of an electrolytic cell is given in annex B. 6.2Sample preparation Mount the test sample in a watertight electrode holder so that only the test surface is in contact with the electrolyte. T
49、ake care to avoid the creation of conditions where crevice corrosion can occur due the formation of a crevice between the mounting and the sample. Before testing, clean the specimen ultrasonically for 10 min to 15 min in ethanol, carefully rinse with water of grade 2 in accordance with ISO 3696 and immediately transfer into the test cell. EN ISO 1099315:2000 Licensed Copy: sheffieldun sheffieldun, na, Fri Nov 17 09:51:48 GMT+00:00 2006, Uncontrolled Copy, (c) BSI ISO 1-399051:(0002E) 5 6.3Test conditions Fill the test cell with the test solution (ele