DIN EN ISO 10993-10-2014 Biological evaluation of medical devices - Part 10 Tests for irritation and skin sensitization (ISO 10993-10 2010) German version EN ISO 10993-10 2013《医用设备.pdf

1、October 2014Translation by DIN-Sprachendienst.English price group 27No 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).ICS

2、 11.100.20!%;“2249427www.din.deDDIN EN ISO 10993-10Biological evaluation of medical devices Part 10: Tests for irritation and skin sensitization (ISO 10993-10:2010);English version EN ISO 10993-10:2013,English translation of DIN EN ISO 10993-10:2014-10Biologische Beurteilung von Medizinprodukten Tei

3、l 10: Prfungen auf Irritation und Hautsensibilisierung (ISO 10993-10:2010);Englische Fassung EN ISO 10993-10:2013,Englische bersetzung von DIN EN ISO 10993-10:2014-10valuation biologique des dispositifs mdicaux Partie 10: Essais dirritation et de sensibilisation cutane (ISO 10993-10:2010);Version an

4、glaise EN ISO 10993-10:2013,Traduction anglaise de DIN EN ISO 10993-10:2014-10SupersedesDIN EN ISO 10993-10:2010-12www.beuth.deIn case of doubt, the German-language original shall be considered authoritative.Document comprises 77 pages10.14 DIN EN ISO 10993-10:2014-102 A comma is used as the decimal

5、 marker. National foreword The text of ISO 10993-10:2010 has been prepared by Technical Committee ISO/TC 194 “Biological evaluation of medical devices” and has been taken over as EN ISO 10993-10:2013 by Technical Committee CEN/TC 206 “Biological evaluation of medical devices” (Secretariat: NEN, Neth

6、erlands). The responsible German body involved in its preparation was the DIN-Normenausschuss Feinmechanik und Optik (DIN Standards Committee Optics and Precision Mechanics), Working Committee NA 027-02-12 AA Biologische Beurteilung von Medizinprodukten. DIN EN ISO 10993 consists of the following pa

7、rts, 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 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity Part 4: Selection of tests for interactions with blood P

8、art 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 and quantification of potential degradation products Part 10: Tests for irritation and skin sensitization Part 11: Tests for s

9、ystemic toxicity Part 12: Sample preparation and reference 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 degrad

10、ation products from metals and alloys Part 16: Toxicokinetic study design for degradation products and leachables Part 17: Establishment of allowable limits for leachable substances Part 18: Chemical characterization of materials ISO/TS 10993 consists of the following parts, under the general title

11、Biological evaluation of medical devices: Part 19: Physico-chemical, morphological and topographical characterization of materials Part 20: Principles and methods for immunotoxicology testing of medical devices DIN EN ISO 10993-10:2014-10 3 Note This European Standard had to be revised as a result o

12、f an objection by the European Commission to Annexes ZA and ZB concerning the relationship between this European Standard and the essential requirements of EU Directives 93/42/EEC on medical devices and 90/385/EEC on active implantable medical devices. Since the amendments are only relevant for Anne

13、xes ZA and ZB, DIN decided not to publish a draft standard. The DIN Standards corresponding to the International Standards referred to in Clause 2 of this standard are as follows: ISO 10993-1 DIN EN ISO 10993-1 ISO 10993-2 DIN EN ISO 10993-2 ISO 10993-9 DIN EN ISO 10993-9 ISO 10993-12 DIN EN ISO 109

14、93-12 ISO 10993-13 DIN EN ISO 10993-13 ISO 10993-14 DIN EN ISO 10993-14 ISO 10993-15 DIN EN ISO 10993-15 ISO 10993-18 DIN EN ISO 10993-18 ISO 14155-1 DIN EN ISO 14155-1 ISO 14155-2 DIN EN ISO 14155-2 Amendments This standard differs from DIN EN ISO 10993-10:2010-12 as follows: a) Annexes ZA and ZB h

15、ave been amended. Previous editions DIN EN ISO 10993-10: 1996-02, 2003-02, 2007-06, 2009-08, 2010-12 DIN EN ISO 10993-10:2014-10 4 National Annex NA (informative) Bibliography DIN EN ISO 10993-1, Biological evaluation of medical devices Part 1: Evaluation and testing within a risk management system

16、DIN EN ISO 10993-2, Biological evaluation of medical devices Part 2: Animal welfare requirements DIN EN ISO 10993-9, Biological evaluation of medical devices Part 9: Framework for identification and quantification of potential degradation products DIN EN ISO 10993-12, Biological evaluation of medica

17、l devices Part 12: Sample preparation and reference materials DIN EN ISO 10993-13, Biological evaluation of medical devices Part 13: Identification and quantification of degradation products from polymeric medical devices DIN EN ISO 10993-14, Biological evaluation of medical devices Part 14: Identif

18、ication and quantification of degradation products from ceramics DIN EN ISO 10993-15, Biological evaluation of medical devices Part 15: Identification and quantification of degradation products from metals and alloys DIN EN ISO 10993-18, Biological evaluation of medical devices Part 18: Chemical cha

19、racterization of materials DIN EN ISO 14155-1, Clinical investigation of medical devices for human subjects Part 1: General require-ments DIN EN ISO 14155-2, Clinical investigation of medical devices for human subjects Part 2: Clinical investi-gation plans EN ISO 10993-10August 2013 ICS 11.100.20 Su

20、persedes EN ISO 10993-10:2010English Version Biological evaluation of medical devices - Part 10: Tests for irritation and skin sensitization (ISO 10993-10:2010) valuation biologique des dispositifs mdicaux - Partie 10:Essais dirritation et de sensibilisation cutane(ISO 10993-10:2010)This European St

21、andard was approved by CEN on 9 July 2013. 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 s

22、uch national standards may be obtained on application to the CEN-CENELEC 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 o

23、wn 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 Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Former Yugoslav Republic of Macedonia, France, Germany,

24、 Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey andUnited Kingdom. CEN-CENELEC Management Centre: Avenue Marnix 17, B-1000 Brussels 2013 CEN All rights of exploitat

25、ion in any form and by any means reserved worldwide for CEN national Members. Ref. No. EN ISO 10993-10:2013: EEUROPEAN COMMITTEE FOR STANDARDIZATIONCOMIT EUROPEN DE NORMALISATIONEUROPISCHES KOMITEE FR NORMUNGEUROPEAN STANDARDNORME EUROPENNEEUROPISCHE NORMBiologische Beurteilung von Medizinprodukten

26、- Teil 10:Prfungen auf Irritation und Hautsensibilisierung(ISO 10993-10:2010)2DIN EN ISO 10993-10:2014-10 EN ISO 10993-10:2013 (E) Contents Page Foreword . 3 Introduction . 4 1 Scope . 5 2 Normative references. 5 3 Terms and definitions 6 4 General principles Step-wise approach 8 5 Pretest considera

27、tions 8 5.1 General 8 5.2 Types of material 9 5.3 Information on chemical composition . 9 6 Irritation tests . 10 6.1 In vitro irritation tests 10 6.2 In vivo irritation tests Factors to be considered in design and selection of in vivo tests . 10 6.3 Animal irritation test 11 6.4 Animal intracutaneo

28、us (intradermal) reactivity test . 15 6.5 Human skin irritation test 18 7 Skin sensitization tests . 19 7.1 Choice of test methods 19 7.2 Murine Local Lymph Node Assay (LLNA) 19 7.3 Guinea pig assays for the detection of skin sensitization . 22 7.4 Important factors affecting the outcome of the test

29、 . 23 7.5 Guinea pig maximization test (GPMT) 24 7.6 Closed-patch test (Buehler test) . 27 8 Key factors in interpretation of test results 30 Annex A (normative) Preparation of materials for irritation/sensitization testing 31 Annex B (normative) Special irritation tests . 33 Annex C (normative) Hum

30、an skin irritation test . 48 Annex D (informative) In vitro tests for skin irritation 52 Annex E (informative) Method for the preparation of extracts from polymeric test materials 58 Annex F (informative) Background information . 61 Annex ZA (informative) Relationship between this European Standard

31、and the Essential Requirements of EU Directive 93/42/EEC on Medical Devices 65 Annex ZB (informative) Relationship between this European Standard and the Essential Requirements of EU Directive 90/385/EEC on Active Implantable Medical Devices . 66 Bibliography 67 ForewordThe text of ISO 10993-10:2010

32、 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 10993-10:2013 by Technical Committee CEN/TC 206 “Biological evaluation of medical devices” the secretariat of w

33、hich 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 February 2014, and conflicting national standards shall be withdrawn at the latest by February 2014. Attention is drawn to the

34、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 10993-10:2010. This document has been prepared under a mandate given to CEN by t

35、he European Commission and the European Free Trade Association, and supports essential requirements of EU Directives. For relationship with EU Directives, see informative Annex ZA and ZB, which are integral parts of this document. According to the CEN-CENELEC Internal Regulations, the national stand

36、ards organizations of the following countries are bound to implement 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, Lu

37、xembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the United Kingdom. Endorsement notice The text of ISO 10993-10:2010 has been approved by CEN as EN ISO 10993-10:2013 without any modification. “3DIN EN ISO 10993-10:2014-10EN

38、ISO 10993-10:2013 (E)Introduction This part of ISO 10993 assesses possible contact hazards from chemicals released from medical devices, which may produce skin and mucosal irritation, eye irritation or skin sensitization. Some materials that are included in medical devices have been tested, and thei

39、r skin or mucosal irritation or sensitization potential has been documented. Other materials and their chemical components have not been tested and may induce adverse effects when in contact with human tissue. The manufacturer is thus obliged to evaluate each device for potential adverse effects pri

40、or to marketing. Traditionally, small animal tests are performed prior to testing on humans to help predict human response. More recently, in vitro tests as well as human tests have been added as adjuncts or alternatives. Despite progress and considerable effort in this direction, a review of findin

41、gs suggests that currently no satisfactory in vitro test has been devised to eliminate the requirement for in vivo testing. Where appropriate, the preliminary use of in vitro methods is encouraged for screening purposes prior to animal testing. In order to reduce the number of animals used, this par

42、t of ISO 10993 presents a step-wise approach, with review and analysis of test results at each stage. An animal test is usually required prior to human testing. It is intended that these studies be conducted using Good Laboratory Practice and comply with regulations related to animal welfare. Statis

43、tical analysis of data is recommended and should be used whenever appropriate. This part of ISO 10993 is intended for use by professionals, appropriately qualified by training and experience, who are able to interpret its requirements and judge the outcomes of the evaluation for each medical device,

44、 taking into consideration all the factors relevant to the device, its intended use and the current knowledge of the medical device provided by review of the scientific literature and previous clinical experience. The tests included in this part of ISO 10993 are important tools for the development o

45、f safe products, provided that these are executed and interpreted by trained personnel. This part of ISO 10993 is based on numerous standards and guidelines, including OECD Guidelines, U.S. Pharmacopoeia and the European Pharmacopoeia. It is intended to be the basic document for the selection and co

46、nduct of tests enabling evaluation of irritation and dermal sensitization responses relevant to safety of medical materials and devices. 4DIN EN ISO 10993-10:2014-10 EN ISO 10993-10:2013 (E) 1 Scope This part of ISO 10993 describes the procedure for the assessment of medical devices and their consti

47、tuent materials with regard to their potential to produce irritation and skin sensitization. This part of ISO 10993 includes: a) pretest considerations for irritation, including in silico and in vitro methods for dermal exposure; b) details of in vivo (irritation and sensitization) test procedures;

48、c) key factors for the interpretation of the results. Instructions are given in Annex A for the preparation of materials specifically in relation to the above tests. In Annex B several special irritation tests are described for application of medical devices in areas other than skin. 2 Normative ref

49、erences 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 amendments) applies. ISO 10993-1:2009, Biological evaluation of medical devices Part 1: Evaluation and testing within a risk management process ISO 10993-2, Biological evaluat