1、October 2012 Translation by DIN-Sprachendienst.English price group 15No 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).IC
2、S 11.100.20!$“1919890www.din.deDDIN EN ISO 10993-12Biological evaluation of medical devices Part 12: Sample preparation and reference materials(ISO 10993-12:2012);English version EN ISO 10993-12:2012,English translation of DIN EN ISO 10993-12:2012-10Biologische Beurteilung von Medizinprodukten Teil
3、12: Probenvorbereitung und Referenzmaterialien (ISO 10993-12:2012);Englische Fassung EN ISO 10993-12:2012,Englische bersetzung von DIN EN ISO 10993-12:2012-10valuation biologique des dispositifs mdicaux Partie 12: Prparation des chantillons et matriaux de rfrence (ISO 10993-12:2012);Version anglaise
4、 EN ISO 10993-12:2012,Traduction anglaise de DIN EN ISO 10993-12:2012-10SupersedesDIN EN ISO 10993-12:2009-08www.beuth.deIn case of doubt, the German-language original shall be considered authoritative.Document comprises 30 pages09.12 DIN EN ISO 10993-12:2012-10 2 A comma is used as the decimal mark
5、er. 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 responsible German body involved in
6、its preparation was the Normenausschuss Feinmechanik und Optik (Optics and Precision Mechanics Standards Committee), Working Committee NA 027-02-12 AA Biologische Beurteilung von Medizinprodukten. DIN EN ISO 10993 consists of the following parts, under the general title Biological evaluation of medi
7、cal 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 cytotoxicity Part 6: Tests for l
8、ocal 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 preparation and reference
9、 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 alloys Part 16: Toxicokinet
10、ic study design for degradation products and leachables Part 17: Establishment of allowable limits for leachable substances Part 18: Chemical characterization of materials When applying this standard, the following Technical Specifications should be taken into account: ISO/TS 10993-19, Biological ev
11、aluation of medical devices Part 19: Physico-chemical, morphological and topographical characterization of materials ISO/TS 10993-20, Biological evaluation of medical devices Part 20: Principles and methods for immuno-toxicology testing of medical devices The DIN Standards corresponding to the Inter
12、national Standards referred to in this document are as follows: ISO 10993 (all parts) DIN EN ISO 10993 (all parts) ISO 14971 DIN EN ISO 14971 DIN EN ISO 10993-12:2012-10 3 Amendments This standard differs from DIN EN ISO 10993-12:2009-08 as follows: a) a new Subclause 10.3.12 has been included conta
13、ining a guide for insoluble materials if the standard extraction methods used are inappropriate; b) Annex D (informative) “Exhaustive extraction of polymeric materials for biological evaluation” has been added; Previous editions DIN EN ISO 10993-12: 1996-12, 2005-03, 2008-02, 2009-08 National Annex
14、NA (informative) Bibliography DIN EN ISO 10993 (all parts), Biological evaluation of medical devices DIN EN ISO 14971, Medical devices Application of risk management to medical devices DIN EN ISO 10993-12:2012-10 4 This page is intentionally blank EUROPEAN STANDARD NORME EUROPENNE EUROPISCHE NORM EN
15、 ISO 10993-12 July 2012 ICS 11.100.20 Supersedes EN ISO 10993-12:2009English Version Biological evaluation of medical devices - Part 12: Sample preparation and reference materials (ISO 10993-12:2012) valuation biologique des dispositifs mdicaux - Partie 12: Prparation des chantillons et matriaux de
16、rfrence (ISO 10993-12:2012) Biologische Beurteilung von Medizinprodukten - Teil 12: Probenvorbereitung und Referenzmaterialien This European Standard was approved by CEN on 30 June 2012. CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for givi
17、ng 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-CENELEC Management Centre or to any CEN member. This European Standard exists in three offi
18、cial 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-CENELEC Management Centre has the same status as the official versions. CEN members are the national standards bodies of
19、 Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain,
20、Sweden, Switzerland, Turkey and United Kingdom. Management Centre: Avenue Marnix 17, B-1000 Brussels 2012 CEN All rights of exploitation in any form and by any means reserved worldwide for CEN national Members. Ref. No. EN ISO 10993-12:2012: E(ISO 10993-12:2012) EUROPEAN COMMITTEE FOR STANDARDIZATIO
21、NCOMIT EUROPEN DE NORMALISATIONEUROPISCHES KOMITEE FR NORMUNGContents Page Foreword . 3 Introduction . 4 1 Scope . 5 2 Normative references 5 3 Terms and definitions 5 4 General requirements 7 5 Reference materials (RMs) 8 5.1 General 8 5.2 Certification of RMs for biological safety testing . 8 6 Us
22、e of RMs as experimental controls 8 7 Test sample selection 9 8 Test sample and RM preparation 9 9 Selection of representative portions from a device . 9 10 Preparation of extracts of samples 10 10.1 General 10 10.2 Containers for extraction 10 10.3 Extraction conditions and methods . 10 10.4 Extrac
23、tion conditions for hazard identification and risk estimation in the exaggerated-use condition (points to consider in relation to Annex D) 13 11 Records . 13 Annex A (informative) Experimental controls . 14 Annex B (informative) General principles on, and practices of, test sample preparation and sa
24、mple selection . 16 Annex C (informative) Principles of test sample extraction 18 Annex D (informative) Exhaustive extraction of polymeric materials for biological evaluation . 21 Bibliography 23 Annex ZA . 25 Annex ZB . 26 2DIN EN ISO 10993-12:2012-10EN ISO 10993-12:2012 (E) Foreword This document
25、(EN ISO 10993-12:2012) 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 secretariat of which is held by NEN. This European Standard shall be given the statu
26、s of a national standard, either by publication of an identical text or by endorsement, at the latest by January 2013, and conflicting national standards shall be withdrawn at the latest by January 2013. Attention is drawn to the possibility that some of the elements of this document may be the subj
27、ect 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 10993-12:2009. This document has been prepared under a mandate given to CEN by the European Commission and the European Free Trade Association, and su
28、pports essential requirements of EU Directives. For relationship with EU Directives, see informative Annex ZA and ZB, which are an integral parts of this document. According to the CEN/CENELEC Internal Regulations, the national standards organizations of the following countries are bound to implemen
29、t this European Standard: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Sl
30、ovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the United Kingdom. Endorsement notice The text of ISO 10993-12:2012 has been approved by CEN as a EN ISO 10993-12:2012 without any modification. ”“3DIN EN ISO 10993-12:2012-10 EN ISO 10993-12:2012 (E) Introduction7KLVSDUWRI,62VSHFLHVPHWKRGVRI
31、VDPSOHSUHSDUDWLRQDQGSURYLGHVUHTXLUHPHQWVDQGJXLGDQFHIRUthe selection of reference materials for the biological evaluation of medical devices.It is important that sample preparation methods be appropriate for both the biological evaluation methods DQGWKHPDWHULDOVEHLQJHYDOXDWHG(DFKELRORJLFDOWHVWPHWKRGU
32、HTXLUHVWKHVHOHFWLRQRIPDWHULDOVHWUDFWLRQsolvents and conditions.7KLVSDUWRI,62LVEDVHGRQHLVWLQJQDWLRQDODQGLQWHUQ DWLRQDOVSHFLFDWLRQVUHJXODWLRQVDQGVWDQGDUGVZKHUHYHUSRVVLEOH,WLVSHULRGLFDOOUHYLHZHGDQGUHYLVHG4DIN EN ISO 10993-12:2012-10EN ISO 10993-12:2012 (E) 1 Scope7KLVSDUWRI,62VSHFLHVUHTXLUHPHQWVDQGJLYH
33、VJXLGDQFHRQWKHSURFHGXUHVWREHIROORZHGLQWKHSUHSDUDWLRQRIVDPSOHVDQGWKHVHOHFWLRQRIUHIHUHQFHPDWHULDOVIRUPHGLFDOGHYLFHWHVWLQJLQELRORJLFDOVVWHPVLQDFFRUGDQFHZLWKRQHRUPRUHSDUWVRI,626SHFLFDOO WKLVSDUWRI,62DGGUHVVHVWKHIROORZLQJ test sample selection; selection of representative portions from a device; test sam
34、ple preparation; experimental controls; VHOHFWLRQRIDQGUHTXLUHPHQWVIRUUHIHUHQFHPDWHULDOV preparation of extracts.7KLVSDUWRI,62LVQRWDSSOLFDEOHWROLYHFHOOVEXWFDQEHUHOHYDQWWRWKHPDWHULDORUGHYLFHFRPSRQHQWVof combination products containing live cells.2 Normative referencesThe following referenced documents
35、 are indispensable for the application of this document. For dated UHIHUHQFHVRQOWKHHGLWLRQFLWHGDSSOLHV)RUXQGDWHGUHIHUHQFHVWKHODWHVWHGLWLRQRIWKHUHIHUHQFHGGRFXPHQW LQFOXGLQJDQDPHQGPHQWV DSSOLHV,62 DOOSDUWV Biological evaluation of medical devices,62Medical devices Application of risk management to med
36、ical devices3 Terms and denitions)RUWKHSXUSRVHVRIWKLVGRFXPHQWWKHIROORZLQJWHUPVDQGGHQLWLRQVDSSO3.1accelerated extractionHWUDFWLRQWKDWSURYLGHVDPHDVXUHRIWKHOHDFKDEOHRUHWUDFWDEOHPDWHULDOVRIWKHGHYLFHRUPDWHULDOXVLQJconditions that shorten the time for leaching of the substances into the extraction vehicle
37、 but do not result in a chemical change of the substances being extracted(;$03/(OHYDWHGWHPSHUDWXUHDJLWDWLRQFKDQJLQJRIWKHHWUDFWLRQYHKLFOH3.2ElanNHWUDFWLRQYHKLFOHQRWFRQWDLQLQJWKHWHVWPDWHULDOZKLFKLVU HWDLQHGLQDYHVVHOLGHQWLFDOWRWKDWKROGLQJWKHWHVWVDPSOHDQGVXEMHFWHGWRFRQGLWLRQVLGHQWLFDOWRWKHRQHVWKHWHVWVDP
38、SOHLVVXEMHFWHGWRGXULQJLWVHWUDFWLRQ127( 7KHSXUSRVHRIWKHEODQNLVWRHYDOXDWHSRVVLEOHFRQIRXQGLQJHIIHFWVGXHWRWKHHWUDFWLRQYHVVHOHWUDFWLRQvehicle and extraction process.5DIN EN ISO 10993-12:2012-10 EN ISO 10993-12:2012 (E) 3.3CRMcertied reference materialUHIHUHQFHPDWHULDODFFRPSDQLHGEDFHUWLFDWHRQHRUPRUHRIZKRV
39、HSURSHUWYDOXHVDUHFHUWLHGEDSURFHGXUHZKLFKHVWDEOLVKHVLWVWUDFHDELOLWWRDQDFFXUDWHUHDOLDWLRQRIWKHXQLWLQZKLFKWKHSURSHUWYDOXHVDUHHSUHVVHGDQGIRUZKLFKHDFKFHUWLHGYDOXHLVDFFRPSDQLHGEDQXQFHUWDLQWDWDVWDWHGOHYHORIFRQGHQFH,62*XLGHGHQLWLRQ3.4exaggerated extractionextraction that is intended to result in a greater a
40、mount of a chemical constituent being released as compared to the amount generated under the simulated conditions of useNOTE It is important to ensure that the exaggerated extraction does not result in a chemical change of the material.3.5exhaustive extractionHWUDFWLRQFRQGXFWHGXQWLOWKHDPRXQWRIHWUDFWDEOHPDWHULDOLQDVXEVHTXHQWHWUDFWLRQLVOHVVWKDQEJUDYLPHWULFDQDOVLVRIWKDWGHWHFWHGLQWKHLQLWLDOHWUDFWLRQ127( $VLWLVQRWSRVVLEOHWRGH
