1、BS EN ISO10993-6:2009ICS 11.100.20NO COPYING WITHOUT BSI PERMISSION EXCEPT AS PERMITTED BY COPYRIGHT LAWBRITISH STANDARDBiological evaluationof medical devicesPart 6: Tests for local effects afterimplantation (ISO 10993-6:2007)Copyright European Committee for Standardization Provided by IHS under li
2、cense with CENNot for ResaleNo reproduction or networking permitted without license from IHS-,-,-This British Standardwas published under theauthority of the StandardsPolicy and StrategyCommittee on 30 June2009. BSI 2009ISBN 978 0 580 65662 0Amendments/corrigenda issued since publicationDate Comment
3、sBS EN ISO 10993-6:2009National forewordThis British Standard is the UK implementation of EN ISO10993-6:2009. It is identical to ISO 10993-6:2007. It supersedes BS ENISO 10993-6:2007 which is withdrawn.The UK participation in its preparation was entrusted to TechnicalCommittee CH/194, Biological eva
4、luation of medical devices.A list of organizations represented on this committee can be obtained onrequest to its secretary.This publication does not purport to include all the necessary provisionsof a contract. Users are responsible for its correct application.Compliance with a British Standard can
5、not confer immunityfrom legal obligations.Copyright European Committee for Standardization Provided by IHS under license with CENNot for ResaleNo reproduction or networking permitted without license from IHS-,-,-EUROPEAN STANDARDNORME EUROPENNEEUROPISCHE NORMEN ISO 10993-6May 2009ICS 11.100.20 Super
6、sedes EN ISO 10993-6:2007 English VersionBiological evaluation of medical devices - Part 6: Tests for localeffects after implantation (ISO 10993-6:2007)valuation biologique des dispositifs mdicaux - Partie 6:Essais concernant les effets locaux aprs implantation(ISO 10993-6:2007)Biologische Beurteilu
7、ng von Medizinprodukten - Teil 6:Prfungen auf lokale Effekte nach Implantationen (ISO10993-6:2007)This European Standard was approved by CEN on 28 April 2009.CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this EuropeanStandard the
8、status of a national standard without any alteration. Up-to-date lists and bibliographical references concerning such nationalstandards 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).
9、 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 same status as theofficial versions.CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Cyprus, Czech Republic
10、, 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 United Kingdom.EUROPEAN COMMITTEE FOR STANDARDIZATIONCOMIT EUROPEN DE NORMALI
11、SATIONEUROPISCHES KOMITEE FR NORMUNGManagement Centre: Avenue Marnix 17, B-1000 Brussels 2009 CEN All rights of exploitation in any form and by any means reservedworldwide for CEN national Members.Ref. No. EN ISO 10993-6:2009: ECopyright European Committee for Standardization Provided by IHS under l
12、icense with CENNot for ResaleNo reproduction or networking permitted without license from IHS-,-,-BS EN ISO 10993-6:2009EN ISO 10993-6:2009 (E) 3 Foreword The text of ISO 10993-6:2007 has been prepared by Technical Committee ISO/TC 194 “Biological evaluation of medical devices” of the International
13、Organization for Standardization (ISO) and has been taken over as EN ISO 10993-6:2009 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 o
14、f an identical text or by endorsement, at the latest by November 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
15、 be held responsible for identifying any or all such patent rights. This document supersedes EN ISO 10993-6:2007. 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 Directives 93/4
16、2/EEC on Medical Devices and 90/385/EEC on Active Implantable Medical Devices. For relationship with EU Directives, see informative Annex ZA and ZB, which is an integral part of this document. According to the CEN/CENELEC Internal Regulations, the national standards organizations of the following co
17、untries are bound to implement this European Standard: Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, S
18、pain, Sweden, Switzerland and the United Kingdom. Endorsement notice The text of ISO 10993-6:2007 has been approved by CEN as a EN ISO 10993-6:2009 without any modification. Copyright European Committee for Standardization Provided by IHS under license with CENNot for ResaleNo reproduction or networ
19、king permitted without license from IHS-,-,-BS EN ISO 10993-6:2009EN ISO 10993-6:2009 (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 Standard has been prepared under a mandate given to
20、 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 European Communities under that Directive and has
21、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 Requirements of that Directive and associated EF
22、TA 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 degradable and/or resorbable; non-solid, such as porous materials,
23、 liquids, pastes and particulates. The test specimen is implanted into a site and animal species appropriate for the evaluation of the biological safety of the material. These implantation tests are not intended to evaluate or determine the performance of the test specimen in terms of mechanical or
24、functional loading. This part of ISO 10993 may also be applied to medical devices that are intended to be used topically in clinical indications where the surface or lining may have been breached, in order to evaluate local tissue responses. The local effects are evaluated by a comparison of the tis
25、sue response caused by a test specimen to that caused by control materials used in medical devices of which the clinical acceptability and biocompatibility characteristics have been established. The objective of the test methods is to characterize the history and evolution of the tissue response aft
26、er implantation of a medical device/biomaterial including final integration or resorption/degradation of the material. In particular for degradable/resorbable materials the degradation characteristics of the material and the resulting tissue response should be determined. This part of ISO 10993 does
27、 not deal with systemic toxicity, carcinogenicity, teratogenicity or mutagenicity. However, the long-term implantation studies intended for evaluation of local biological effects may provide insight into some of these properties. Systemic toxicity studies conducted by implantation may satisfy the re
28、quirements of 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. For undated references, the latest edition of the referenced document (including any amendment
29、s) applies. ISO 10993-1:2003, Biological evaluation of medical devices Part 1: Evaluation and testing within a risk management system ISO 10993-2, Biological evaluation of medical devices Part 2: Animal welfare requirements ISO 10993-11, Biological evaluation of medical devices Part 11: Tests for sy
30、stemic toxicity Copyright European Committee for Standardization Provided by IHS under license with CENNot for ResaleNo reproduction or networking permitted without license from IHS-,-,-BS EN ISO 10993-6:2009ISO 10993-6:2007(E) 2 ISO 2007 All rights reservedISO 10993-12, Biological evaluation of med
31、ical devices Part 12: Sample preparation and reference materials ISO 10993-16, Biological evaluation of medical devices Part 16: Toxicokinetic study design for degradation products and leachables 3 Terms and definitions For the purposes of this document, the terms and definitions given in ISO 10993-
32、1, ISO 10993-2, ISO 10993-12, ISO 10993-16 and the following apply. 3.1 degradation decomposition of a material ISO 10993-9:1999, definition 3.1 3.2 degradation product product of a material which is generated by the chemical breakdown or decomposition of the material ISO 10993-16:1997, definition 3
33、.1 3.3 biomaterial material intended to interface with biological systems to evaluate, treat, augment or replace any tissue, organ or function of the body Taken from European Society Biomaterials Conference II 4 Common provisions for implantation test methods 4.1 General It is important that the stu
34、dy be planned in sufficient detail such that all relevant information can be extracted from the use of each animal and each study (see ISO 10993-2, ISO 10993-11 and ISO 10993-16). All animal studies shall be performed in a facility approved by a nationally recognised organization and in accordance w
35、ith all appropriate regulations dealing with laboratory animal welfare. These studies shall be performed under good laboratory practices or other recognized quality assurance systems, and comply with the requirements of ISO 10993-2. The provisions of this clause shall apply to the test methods descr
36、ibed in Annexes B, C and D. 4.2 Preparation of specimens for implantation Test sample and reference or control material preparation shall be in compliance with ISO 10993-12. The implant size and shape shall be documented and justified. Test specimens for various implant sites are described in Annexe
37、s B, C and D. Physical characteristics (such as form, density, hardness, surface) can influence the character of the tissue response to the test material and shall be recorded and taken into account when the response is characterized. Each implant shall be manufactured, processed, cleaned of contami
38、nants and sterilized by the method intended for the final product and this shall be confirmed in the study documentation. After final preparation and sterilization, the implant specimens shall be handled aseptically and in such a way as to ensure that they are not damaged or contaminated in any way
39、prior to or during implantation. Copyright European Committee for Standardization Provided by IHS under license with CENNot for ResaleNo reproduction or networking permitted without license from IHS-,-,-BS EN ISO 10993-6:2009ISO 10993-6:2007(E) ISO 2007 All rights reserved 3For materials used as sca
40、ffolds for tissue-engineered medical products, it may be appropriate not to use the final preparation pre-populated with cells, as the immune reaction of the animal to the cellular components of such products and the reaction of the cells to the animal, may interfere with the resulting local tissue
41、response. For composite materials (e.g. bone cements, dental materials), the components may be mixed before use and allowed to set before implantation. However, materials that are designed for use in devices with in situ polymerization shall be introduced in a manner such that in situ polymerization
42、 occurs. For certain types of study other procedures may be used. The procedure used shall be documented and justified. Non-solid materials (including powders) may be contained in open-ended cylindrical tubes for the purpose of testing for local effects after implantation (see ISO 10993-12 for the s
43、election of materials for tubes). Prepare the test material according to the manufacturers instructions and insert the material into the tube until level with the end, taking care not to contaminate the outer surface of the tube with the test material; if contamination occurs the sample shall not be
44、 implanted. Avoid entrapment of air in the tube and ensure that the end surfaces of the inserted material in the tube and the tube ends are smooth. NOTE 1 Polyethylene (PE), polypropylene (PP) or polytetrafluoroethylene (PTFE) tubes are commonly used for this purpose. PE tubes may be deformed by aut
45、oclaving. PTFE tubes are difficult to section in the microtome, and substitution by PE or PP tubes of the same dimensions may be preferable when the tubes are to remain in the tissue blocks during sectioning. Evaluation shall be undertaken by comparing to the tissue reaction to that of a similar spe
46、cimen/material of which the clinical acceptability and biocompatibility characteristics have been established. NOTE 2 For further guidance, see ISO 10993-12. The physical characteristics such as shape, and especially the surface condition of the control(s), shall be as similar to that of the implant
47、 test specimens as is practically possible, with any deviations being explained and justified. When the test material is contained in a tube, the control shall be of the same material as the tube and have the same diameter as the outer diameter of the tube. The choice of the control rod or tube shal
48、l be documented and justified. 5 Test methods, general aspects 5.1 Tissue and implantation site The test sample shall be implanted into the tissues most relevant to the intended clinical use of the material. The justification for the choice of sample numbers, tissue and implantation sites shall be d
49、ocumented. Test methods for various implantation sites are given in Annexes B, C and D. If other implantation sites are chosen, the general scientific principles behind the test methods described in Annexes B, C and D shall still be adhered to and the justification provided. NOTE 1 For special dental usage test, see ISO 7405. For degradable/resorbable materials, the implantat
