《ISO-10993-18-2005.pdf》由会员分享,可在线阅读,更多相关《ISO-10993-18-2005.pdf(24页珍藏版)》请在三一文库上搜索。
1、 Reference number ISO 10993-18:2005(E) ISO 2005 INTERNATIONAL STANDARD ISO 10993-18 First edition 2005-07-01 Biological evaluation of medical devices Part 18: Chemical characterization of materials valuation biologique des dispositifs mdicaux Partie 18: Caractrisation chimique des matriaux ISO 10993
2、-18:2005(E) PDF disclaimer This PDF file may contain embedded typefaces. In accordance with Adobes licensing policy, this file may be printed or viewed but shall not be edited unless the typefaces which are embedded are licensed to and installed on the computer performing the editing. In downloading
3、 this file, parties accept therein the responsibility of not infringing Adobes licensing policy. The ISO Central Secretariat accepts no liability in this area. Adobe is a trademark of Adobe Systems Incorporated. Details of the software products used to create this PDF file can be found in the Genera
4、l Info relative to the file; the PDF-creation parameters were optimized for printing. Every care has been taken to ensure that the file is suitable for use by ISO member bodies. In the unlikely event that a problem relating to it is found, please inform the Central Secretariat at the address given b
5、elow. ISO 2005 All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying and microfilm, without permission in writing from either ISO at the address below or ISOs member bod
6、y in the country of the requester. ISO copyright office Case postale 56 CH-1211 Geneva 20 Tel. + 41 22 749 01 11 Fax + 41 22 749 09 47 E-mail copyrightiso.org Web www.iso.org Published in Switzerland ii ISO 2005 All rights reserved ISO 10993-18:2005(E) ISO 2005 All rights reserved iii Contents Page
7、Foreword iv Introduction. vi 1 Scope . 1 2 Normative references. 1 3 Terms and definitions. 2 4 Symbols and abbreviated terms . 3 5 General principles. 3 6 Characterization procedure. 4 6.1 General. 4 6.2 Step 1 Qualitative information 5 6.3 Step 2 Material equivalence 5 6.4 Step 3 Quantitative info
8、rmation 5 6.5 Step 4 Quantitative risk assessment 5 6.6 Step 5 Estimated clinical exposure to chemicals present. 6 7 Chemical characterization parameters and methods. 6 7.1 General. 6 7.2 Polymers 7 7.3 Metals and alloys 8 7.4 Ceramics 8 7.5 Natural macromolecules 9 8 Reporting of data obtained 10 A
9、nnex A (normative) Flowchart summarizing the stepwise generation of chemical characterization data for use in toxicological risk assessment 11 Annex B (informative) Information sources for chemical characterization . 13 Annex C (informative) Principles for judging toxicological equivalency. 16 Bibli
10、ography. 17 ISO 10993-18:2005(E) iv ISO 2005 All rights reserved Foreword ISO (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 c
11、ommittees. Each member body interested in a subject for which a technical committee 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 t
12、he International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization. International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2. The main task of technical committees is to prepare International Standards. Draft Internat
13、ional Standards adopted by the technical committees are circulated to the member bodies for voting. Publication as an International Standard requires approval by at least 75 % of the member bodies casting a vote. Attention is drawn to the possibility that some of the elements of this document may be
14、 the subject of patent rights. ISO shall not be held responsible for identifying any or all such patent rights. ISO 10993-18 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 evaluat
15、ion of medical devices: Part 1: Evaluation and testing 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 local effects after im
16、plantation Part 7: Ethylene oxide sterilization residuals Part 9: Framework for identification and quantification of potential degradation products Part 10: Tests for irritation and delayed-type hypersensitivity Part 11: Tests for systemic toxicity Part 12: Sample preparation and reference materials
17、 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: Toxicokinetic study d
18、esign for degradation products and leachables Part 17: Establishment of allowable limits for leachable substances ISO 10993-18:2005(E) ISO 2005 All rights reserved v Part 18: Chemical characterization of materials The following parts are under preparation: Part 19: Physico-chemical, mechanical and m
19、orphological characterization Part 20: Principles and methods for immunotoxicology testing of medical devices Future parts will deal with other relevant aspects of biological testing. For the purposes of this part of ISO 10993, the CEN annex regarding fulfilment of European Council Directives has be
20、en removed. ISO 10993-18:2005(E) vi ISO 2005 All rights reserved Introduction ISO 10993-1 provides a framework for a structured 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 th
21、e first consideration should be fitness for purpose. This should have regard to the characteristics and properties of the material, which include chemical, toxicological, physical, electrical, morphological and mechanical properties. This information is necessary prior to any biological evaluation.
22、Subclause 7.2 of ISO 10993-1:2003 notes that the continuing acceptability of a biological evaluation is an aspect of a quality 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 th
23、is document are intended to yield the following information, which will be of value in predicting the biological response of the materials: The chemical composition of the materials used in the manufacturing process including processing additives and residues e.g. trace chemicals, cleaning, disinfec
24、tion and testing agents, acids and caustic substances. The characterization of materials to be used in the production of medical 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 rel
25、ease substances or breakdown products due to the manufacturing process. Changes in the materials of construction, which result from changes in the manufacturing process or insufficient control of the manufacturing process. The compositional characteristics of the materials of manufacture are mainly
26、under the control of the suppliers of these materials. However other characteristics are chiefly influenced by the requirements to be met by the finished medical device as well as the processes used by the medical device manufacturer. INTERNATIONAL STANDARD ISO 10993-18:2005(E) ISO 2005 All rights r
27、eserved 1 Biological evaluation of medical devices Part 18: Chemical characterization of materials 1 Scope This part of ISO 10993 describes a framework for the identification of a material and the identification and quantification of its chemical constituents. The chemical characterization informati
28、on 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 medical device in order to allow the assessment of compliance wit
29、h 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 device to check the relevance of data on the latter to be used to s
30、upport 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 degradation products, which is covered in ISO 10993-9, ISO 10993-13, ISO
31、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 suppliers of materials and manufacturers of medical devices, when car
32、rying 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, the latest edition of the referenced document (including any amend
33、ments) 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 14971:2000, Medical devices Application of risk management to medic
34、al devices ISO 10993-18:2005(E) 2 ISO 2005 All rights reserved 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 manufactures and/or supplies the basic starting materials to be used in
35、 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 whether these operations are carried out by that person himself or on
36、 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 fabricates a basic raw material into a semi-finished product (e.g.
37、 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 extraction extraction until the amount of residues in a subsequent extractio
38、n 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
39、 and crystalline phases present. For the amorphous phase, the glass transition temperature, Tg, dictates the polymer chain mobility and the diffusion rate in the phase. Usually the diffusion rate is considerably higher above the Tg compared with that below. The diffusion rate is lowest in the crysta
40、lline phase. The extraction conditions should not alter the phase equilibrium of the material. Phase alteration may affect the amount and type of extractables. The effects of higher temperatures or other conditions on extraction kinetics and the identity of the extractant(s) should be considered car
41、efully if exhaustive extraction is used. For example, there are a few concerns in using elevated temperatures: a) the energy of the increased temperature may cause increased cross-linking of a polymer and therefore decrease the amount of free monomer that is available to migrate from the polymer; b)
42、 the increased temperature could cause degradant materials to form that are not typically found in the finished device under use conditions; c) the increased temperature could cause the disappearance of a leachable material typically found in the finished device. 3.7 simulated extraction extraction
43、for evaluating potential risk to the patient or user during routine use of a device, using an extraction method with an appropriate medium that simulates product use NOTE See NOTE to 3.6. ISO 10993-18:2005(E) ISO 2005 All rights reserved 3 4 Symbols and abbreviated terms The following abbreviated te
44、rms are used in Clause 7. Table 1 Methodology abbreviations Abbreviated term Analytical method DMTA Dynamic mechanical thermal analysis DSC Differential scanning calorimetry EDX-SEM Electron dispersal X-ray analysis scanning electron microscopy FTIR Fourier transform infra red (spectroscopy) GC Gas
45、chromatography MS Mass spectroscopy a GPC Gel permeation chromatography HPLC High performance liquid chromatography ICP Inductively coupled plasma IR Infrared (spectroscopy) NMR Nuclear magnetic resonance (spectroscopy) UV Ultraviolet (spectroscopy) XPS X-ray photoelectron spectroscopy XRF X-ray flu
46、orescence 2D PAGE Two-dimensional polyacrylamide gel electrophoresis a Mass spectroscopy is frequently combined with chromatographic techniques such as GC-MS, LC-MS and MS-MS. 5 General principles Consideration of the chemical characterization of the materials from which a medical device is made is
47、a necessary first step in assessing the biological safety of the device. It is also important in judging equivalence of a) a proposed material to a clinically established material, and b) a prototype device to a final device. An overview of the chemical characterization procedure outlined in this do
48、cument and its relationship to risk assessment is given in Annex A. Qualitative data shall be obtained to describe the chemical composition of a material. When relevant to biological safety, quantitative data shall also be obtained. For some materials compositional information may be readily availab
49、le as part of the material specification. Materials such as polymers may possess more complex formulations and compositional details should be obtained from the supplier of the material. In the absence of such details appropriate analytical techniques should be applied to a material to yield compositional data. Identification of the constituents of a material intended for use in the manufacture of a medical device enables the intrinsic toxicity of each constituen
链接地址:https://www.31doc.com/p-3775563.html