1、August 2009DEUTSCHE NORM English price group 13No part of this standard 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 11.100.20!$XM“1539842ww
2、w.din.deDDIN EN ISO 10993-18Biological evaluation of medical devices Part 18: Chemical characterization of materials (ISO 10993-18:2005)English version of DIN EN ISO 10993-18:2009-08Biologische Beurteilung von Medizinprodukten Teil 18: Chemische Charakterisierung von Werkstoffen (ISO 10993-18:2005)E
3、nglische Fassung DIN EN ISO 10993-18:2009-08SupersedesDIN EN ISO 10993-18:2005-10See start of validitywww.beuth.deDocument comprises 27 pagesDIN EN ISO 10993-18:2009-08 2 Start of validity This standard takes effect on 1 August 2009. DIN EN ISO 10993-18:2005-10 may be used in parallel until 21 March
4、 2010. 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
5、in its preparation was the Normenausschuss Feinmechanik und Optik (Optics and Precision Mechanics Standards Committee), Technical Committee NA 027-02-12 AA Biologische Beurteilung von Medizinprodukten. This standard contains specifications meeting the essential requirements set out in EU Directive 9
6、3/42/EEC on medical devices. ISO 10993 consists of the following parts, 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 reproductiv
7、e 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 9: Framework for identification and quantification of potential degradation products Part 1
8、0: Tests for irritation and skin sensitization Part 11: Tests for systemic 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
9、 from ceramics Part 15: Identification and quantification of degradation 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 DIN
10、 EN ISO 10993-18:2009-08 3 Part 19: Physico-chemical, morphological and topographical characterization of materials Technical Specification Part 20: Principles and methods for immunotoxicology testing of medical devices Technical Specification The DIN Standards corresponding to the International Sta
11、ndard referred to in clause 2 of this document are as follows: ISO 10993-1 DIN EN ISO 10993-1 ISO 10993-17 DIN EN ISO 10993-17 ISO 14971 DIN EN ISO 14971 Amendments This standard differs from DIN EN ISO 10993-18:2005-10 as follows: a) Annexes ZA and ZB (informative) concerning the relationship betwe
12、en this European Standard and the essential requirements of EU Directive 93/42/EEC on medical devices have been updated on the basis of EU Directive 2007/47/EC of the European Parliament and of the Council of 5 September 2007 amending Council Directives 90/385/EEC on the approximation of the laws of
13、 the Member States relating to active implantable medical devices and 93/42/EEC on medical devices and EU Directive 98/8/EC on the placing on the market of biocidal products. Previous editions DIN EN ISO 10993-18: 2005-10 National Annex NA (informative) Bibliography DIN EN ISO 10993-1, Biological ev
14、aluation of medical devices Part 1: Evaluation and testing DIN EN ISO 10993-17, Biological evaluation of medical devices Part 17: Establishment of allowable limits for leachable substances DIN EN ISO 14971, Medical devices Application of risk management to medical devices DIN EN ISO 10993-18:2009-08
15、 4 This page is intentionally blank EUROPEAN STANDARD NORME EUROPENNE EUROPISCHE NORM EN ISO 10993-18 April 2009 ICS 11.100.20 Supersedes EN ISO 10993-18:2005 English Version Biological evaluation of medical devices - Part 18: Chemical characterization of materials (ISO 10993-18:2005) valuation biol
16、ogique des dispositifs mdicaux - Partie 18: Caractrisation chimique des matriaux (ISO 10993-18:2005) Biologische Beurteilung von Medizinprodukten - Teil 18: Chemische Charakterisierung von Werkstoffen (ISO 10993-18:2005) This European Standard was approved by CEN on 12 April 2009. CEN members are bo
17、und 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 be obtained on application to the
18、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 translation under the responsibility of a CEN member into its own language and notified to the CEN Management Centre has the same st
19、atus as the official 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, Romani
20、a, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom. EUROPEAN COMMITTEE FOR STANDARDIZATION COMIT EUROPEN DE NORMALISATION EUROPISCHES KOMITEE FR NORMUNG Management Centre: Avenue Marnix 17, B-1000 Brussels 2009 CEN All rights of exploitation in any form and by any means reserved wo
21、rldwide for CEN national Members. Ref. No. EN ISO 10993-18:2009: EContents 2 EN ISO 10993-18:2009 (E) DIN EN ISO 10993-18:2009-08 Page Foreword .3 Introduction.4 1 Scope5 2 Normative references5 3 Terms and definitions .6 4 Symbols and abbreviated terms 7 5 General principles .7 6 Characterization p
22、rocedure8 6.1 General .8 6.2 Step 1 Qualitative information.9 6.3 Step 2 Material equivalence.9 6.4 Step 3 Quantitative information 9 6.5 Step 4 Quantitative risk assessment 9 6.6 Step 5 Estimated clinical exposure to chemicals present .10 7 Chemical characterization parameters and methods10 7.1 Gen
23、eral .10 7.2 Polymers 11 7.3 Metals and alloys.12 7.4 Ceramics 12 7.5 Natural macromolecules.13 8 Reporting of data obtained.14 Annex A (normative) Flowchart summarizing the stepwise generation of chemical characterization data for use in toxicological risk assessment.15 Annex B (informative) Inform
24、ation sources for chemical characterization17 Annex C (informative) Principles for judging toxicological equivalency20 Bibliography21 Annex ZA (informative) Relationship between this European Standard and the Essential Requirements of EU Directive 93/42/EEC on Medical Devices.22 Annex ZB (informativ
25、e) Relationship between this European Standard and the Essential Requirements of EU Directive 90/385/EEC on Active Implantable Medical Devices23 3 DIN EN ISO 10993-18:2009-08 EN ISO 10993-18:2009 (E) Foreword The text of ISO 10993-18:2005 has been prepared by Technical Committee ISO/TC 194 “Biologic
26、al evaluation of medical devices” of the International Organization for Standardization (ISO) and has been taken over as EN ISO 10993-18:2009 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 th
27、e status of a national standard, either by publication of an identical text or by endorsement, at the latest by October 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
28、 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 10993-18:2005. This document has been prepared under a mandate given to CEN by the European Commission and the European Free Trade Association, a
29、nd supports essential requirements of EU Directives 93/42/EEC on Medical Devices and 90/385/EEC on Active Implantable Medical Devices. For relationship with the EU Directives, see informative Annexes ZA and ZB, which is an integral part of this document. According to the CEN/CENELEC Internal Regulat
30、ions, the national standards organizations of the following countries 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, Netherl
31、ands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and the United Kingdom. Endorsement notice The text of ISO 10993-18:2005 has been approved by CEN as a EN ISO 10993-18:2009 without any modification. Introduction ISO 10993-1 provides a framework for a structured
32、 programme of assessment for the evaluation of biological safety. Clause 3 of ISO 10993-1:2003 states that in the selection of materials to be used for device manufacture the first consideration should be fitness for purpose. This should have regard to the characteristics and properties of the mater
33、ial, which include chemical, toxicological, physical, electrical, morphological and mechanical properties. This information is necessary prior to any biological evaluation. Subclause 7.2 of ISO 10993-1:2003 notes that the continuing acceptability of a biological evaluation is an aspect of a quality
34、management system. Also ISO 14971 points out that a toxicological risk analysis should take account of the chemical nature of the materials. The requirements specified in this document are intended to yield the following information, which will be of value in predicting the biological response of th
35、e materials: The chemical composition of the materials used in the manufacturing process including processing additives and residues e.g. trace chemicals, cleaning, disinfection and testing agents, acids and caustic substances. The characterization of materials to be used in the production of medica
36、l devices, as well as in devices in their final form. Identification of the materials of construction of the medical device. The potential of medical device materials to release substances or breakdown products due to the manufacturing process. Changes in the materials of construction, which result
37、from changes in the manufacturing process or insufficient control of the manufacturing process. The compositional characteristics of the materials of manufacture are mainly under the control of the suppliers of these materials. However other characteristics are chiefly influenced by the requirements
38、 to be met by the finished medical device as well as the processes used by the medical device manufacturer. 4 EN ISO 10993-18:2009 (E) DIN EN ISO 10993-18:2009-08 1 Scope This part of ISO 10993 describes a framework for the identification of a material and the identification and quantification of it
39、s chemical constituents. The chemical characterization information generated can be used for a range of important applications, for example: As part of an assessment of the overall biological safety of a medical device (ISO 10993-1 and 14971). Measurement of the level of a leachable substance in a m
40、edical device in order to allow the assessment of compliance with the allowable limit derived for that substance from health based risk assessment (ISO 10993-17). Judging equivalence of a proposed material to a clinically established material. Judging equivalence of a final device to a prototype dev
41、ice to check the relevance of data on the latter to be used to support the assessment of the former. Screening of potential new materials for suitability in a medical device for a proposed clinical application. This part of ISO 10993 does not address the identification or quantification of degradati
42、on products, which is covered in ISO 10993-9, ISO 10993-13, ISO 10993-14 and ISO 10993-15. The ISO 10993 series of standards is applicable when the material or device comes into contact with the body directly or indirectly (see 4.2.1 of ISO 10993-1:2003). This part of ISO 10993 is intended for suppl
43、iers of materials and manufacturers of medical devices, when carrying out a biological safety assessment. 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, th
44、e latest edition of the referenced document (including any amendments) applies. ISO 10993-1:2003, Biological evaluation of medical devices Part 1: Evaluation and testing ISO 10993-17, Biological evaluation of medical devices Part 17: Establishment of allowable limits for leachable substances ISO 149
45、71:2000, Medical devices Application of risk management to medical devices 5 DIN EN ISO 10993-18:2009-08 EN ISO 10993-18:2009 (E) 3 Terms and definitions For the purposes of this document, the terms and definitions given in ISO 10993-1 and the following apply. 3.1 supplier person or company who manu
46、factures and/or supplies the basic starting materials to be used in the manufacture of a medical device 3.2 manufacturer natural or legal person with responsibility for the design, manufacture, packaging and labelling of a device before it is placed on the market under his own name, regardless of wh
47、ether these operations are carried out by that person himself or on his behalf by a third party 3.3 component item which is manufactured from a basic starting material but is not itself a medical device, since it forms only one part of a medical device 3.4 convertor person or company who converts or
48、 fabricates a basic raw material into a semi-finished product (e.g. lengths of rod, tubing or lay-flat film) 3.5 chemical characterization identification of a material and the identification and quantification of the chemicals present in materials or finished medical devices 3.6 exhaustive extractio
49、n extraction until the amount of residues in a subsequent extraction is less than 10 % of that detected in the first extraction NOTE Extraction is a complex process influenced by time, temperature, surface-area-to-volume-ratio, extraction medium and the phase equilibrium of the material. The phase equilibrium of a material controls the relative amounts of amorphous and crystalline phases present. For the amorphous phase, the glass transition temperature, Tg, dictates the polymer chain m
