1、 Collection of SANS standards in electronic format (PDF) 1. Copyright This standard is available to staff members of companies that have subscribed to the complete collection of SANS standards in accordance with a formal copyright agreement. This document may reside on a CENTRAL FILE SERVER or INTRA
2、NET SYSTEM only. Unless specific permission has been granted, this document MAY NOT be sent or given to staff members from other companies or organizations. Doing so would constitute a VIOLATION of SABS copyright rules. 2. Indemnity The South African Bureau of Standards accepts no liability for any
3、damage whatsoever than may result from the use of this material or the information contain therein, irrespective of the cause and quantum thereof. ISBN 978-0-626-20099-2 SANS 10993-11:2008 Edition 2 ISO 10993-11:2006 Edition 2 SOUTH AFRICAN NATIONAL STANDARD Biological evaluation of medical devices
4、Part 11: Tests for systemic toxicity This national standard is the identical implementation of ISO 10993-11:2006 and is adopted with the permission of the International Organization for Standardization. Published by Standards South Africa 1 dr lategan road groenkloof private bag x191 pretoria 0001 t
5、el: 012 428 7911 fax: 012 344 1568 international code + 27 12 www.stansa.co.za Standards South Africa This standard may only be used and printed by approved subscription and freemailing clients of the SABS.SANS 10993-11:2008 Edition 2 ISO 10993-11:2006 Edition 2 Table of changes Change No. Date Scop
6、e National foreword This South African standard was approved by National Committee StanSA SC 5140.37E, Medical devices Healthcare devices and materials for use in clinics and hospitals, in accordance with procedures of Standards South Africa, in compliance with annex 3 of the WTO/TBT agreement. This
7、 SANS document was published in April 2008. This SANS document supersedes SANS 10993-11:2003 (edition 1). This standard may only be used and printed by approved subscription and freemailing clients of the SABS. Reference number ISO 10993-11:2006(E) ISO 2006INTERNATIONAL STANDARD ISO 10993-11 Second
8、edition 2006-08-15 Biological evaluation of medical devices Part 11: Tests for systemic toxicity valuation biologique des dispositifs mdicaux Partie 11: Essais de toxicit systmique SANS 10993-11:2008This standard may only be used and printed by approved subscription and freemailing clients of the SA
9、BS.ISO 10993-11:2006(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
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12、ress given below. ISO 2006 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 ISO
13、s member body 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 2006 All rights reservedSANS 10993-11:2008This standard may only be used and prin
14、ted by approved subscription and freemailing clients of the SABS.ISO 10993-11:2006(E) ISO 2006 All rights reserved iii Contents Page Foreword iv Introduction . vi 1 Scope . 1 2 Normative references . 1 3 Terms and definitions. 1 4 General considerations 2 4.1 General. 2 4.2 Selection of animal speci
15、es. 3 4.3 Animal status 3 4.4 Animal care and husbandry. 3 4.5 Size and number of groups . 3 4.6 Route of exposure 4 4.7 Sample preparation 4 4.8 Dosing 5 4.9 Body weight and food/water consumption 6 4.10 Clinical observations 6 4.11 Clinical pathology. 6 4.12 Anatomic pathology . 7 4.13 Study desig
16、ns . 7 4.14 Quality of investigation 7 5 Acute systemic toxicity 7 5.1 General. 7 5.2 Study design . 8 5.3 Evaluation criteria. 9 5.4 Final report 10 6 Repeated exposure systemic toxicity (subacute, subchronic and chronic systemic toxicity) 11 6.1 General. 11 6.2 Study design . 12 6.3 Evaluation cri
17、teria. 14 6.4 Final report 15 Annex A (informative) Routes of administration. 16 Annex B (informative) Dosage volumes. 18 Annex C (informative) Common clinical signs and observations. 19 Annex D (informative) Suggested haematology, clinical chemistry and urinalysis measurements . 20 Annex E (informa
18、tive) Suggested organ list for histopathological evaluation 22 Annex F (informative) Information on material-mediated pyrogens . 24 Bibliography . 26 SANS 10993-11:2008This standard may only be used and printed by approved subscription and freemailing clients of the SABS.ISO 10993-11:2006(E) iv ISO
19、2006 All rights reservedForeword 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 committees. Each member body interested in
20、 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 the International Electrotechnical Commiss
21、ion (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 International Standards adopted by the technical
22、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 the subject of patent rights. ISO shall
23、not be held responsible for identifying any or all such patent rights. ISO 10993-11 was prepared by Technical Committee ISO/TC 194, Biological evaluation of medical devices. This second edition cancels and replaces the first edition (ISO 10993-11:1993) which has been technically revised. ISO 10993 c
24、onsists of the following parts, under the general title Biological evaluation 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
25、: 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 delayed-type hypersensitivity Part 11: Tests
26、 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 from ceramics Part 15: Identification and quantification of
27、degradation products from metals and alloys SANS 10993-11:2008This standard may only be used and printed by approved subscription and freemailing clients of the SABS.ISO 10993-11:2006(E) ISO 2006 All rights reserved v Part 16: Toxicokinetic study design for degradation products and leachables Part 1
28、7: Establishment of allowable limits for leachable substances Part 18: Chemical characterization of materials Part 19: Physico-chemical, morphological and topographical characterization Part 20: Principles and methods for immunotoxicology testing of medical devices SANS 10993-11:2008This standard ma
29、y only be used and printed by approved subscription and freemailing clients of the SABS.ISO 10993-11:2006(E) vi ISO 2006 All rights reservedIntroduction Systemic toxicity is a potential adverse effect of the use of medical devices. Generalized effects, as well as organ and organ system effects can r
30、esult from absorption, distribution and metabolism of leachates from the device or its materials to parts of the body with which they are not in direct contact. This part of ISO 10993 addresses the evaluation of generalized systemic toxicity, not specific target organ or organ system toxicity, even
31、though these effects may result from the systemic absorption and distribution of toxicants. Because of the broad range of medical devices, and their materials and intended uses, this part of ISO 10993 is not overly prescriptive. Whilst it addresses specific methodological aspects to be considered in
32、 the design of systemic toxicity tests, proper study design must be uniquely tailored to the nature of the devices materials and its intended clinical application. Other elements of this part of ISO 10993 are prescriptive in nature, including those aspects that address compliance with good laborator
33、y practices and elements for inclusion in reporting. While some systemic toxicity tests (e.g. long term implantation or dermal toxicity studies) can be designed to study systemic effects as well as local, carcinogenic or reproductive effects, this document focuses only on those aspects of such studi
34、es, which are intended to address systemic effects. Studies which are intended to address other toxicological endpoints are addressed in ISO 10993-3, ISO 10993-6, ISO 10993-10 and ISO/TS 10993-20. Pyrogenicity (see Annex F) represents an additional systemic effect which has historically been include
35、d in this part of ISO 10993. However, efforts are being taken to address pyrogenicity in a dedicated, stand-alone standard. Finally, toxicology is an imperfect science. The outcome of any single test should not be the sole basis for making a determination of whether a device is safe for its intended
36、 use. SANS 10993-11:2008This standard may only be used and printed by approved subscription and freemailing clients of the SABS.INTERNATIONAL STANDARD ISO 10993-11:2006(E) ISO 2006 All rights reserved 1 Biological evaluation of medical devices Part 11: Tests for systemic toxicity 1 Scope This part o
37、f ISO 10993 specifies requirements and gives guidance on procedures to be followed in the evaluation of the potential for medical device materials to cause adverse systemic reactions. 2 Normative references The following referenced documents are indispensable for the application of this document. Fo
38、r undated references, the latest edition of the referenced document (including any amendments) applies. ISO 10993-1, Biological evaluation of medical devices Part 1: Evaluation and testing ISO 10993-2, Biological evaluation of medical devices Part 2: Animal welfare requirements ISO 10993-12, Biologi
39、cal evaluation of medical devices Part 12: Sample preparation and reference materials 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 dose dosage amount of test sample administered (e.g. mass, volume) expressed pe
40、r unit of body weight or surface area 3.2 dose-effect relationship between the dosage and the magnitude of a defined biological effect either in an individual or in a population sample 3.3 dose-response relationship of dosage to the spectrum of effects related to the exposure NOTE There are two type
41、s of dose-response relationships. The first type is the response of an individual to a range of doses. The second type is the distribution of responses of a population of individuals to a range of doses. 3.4 leachable substance chemical removed from a device or material by the action of water or oth
42、er liquids related to the use of the device NOTE Examples of leachable substances are additives, sterilant residues, process residues, degradation products, solvents, plasticizers, lubricants, catalysts, stabilizers, anti-oxidants, colouring agents, fillers and monomers. SANS 10993-11:2008This stand
43、ard may only be used and printed by approved subscription and freemailing clients of the SABS.ISO 10993-11:2006(E) 2 ISO 2006 All rights reserved3.5 limit test use of a single group treated at a suitable dosage of test sample in order to delineate the presence or absence of a toxic hazard 3.6 system
44、ic toxicity toxicity that is not limited to adverse effects at the site of contact between the body and the device NOTE Systemic toxicity requires absorption and distribution of a toxicant from its entry point to a distant site at which deleterious effects are produced. 3.7 acute systemic toxicity a
45、dverse effects occurring at any time after single, multiple or continuous exposures of a test sample within 24 h 3.8 subacute systemic toxicity adverse effects occurring after multiple or continuous exposure between 24 h and 28 d NOTE Since this term is semantically incorrect, the adverse effects oc
46、curring within the specified time period may also be described as a short-term repeated exposure systemic toxicity study. The selection of time intervals between 14 d and 28 d is consistent with most international regulatory guidelines and considered a reasonable approach. Subacute intravenous studi
47、es are generally defined as treatment durations of 24 h but 14 d. 3.9 subchronic systemic toxicity adverse effects occurring after the repeated or continuous administration of a test sample for a part of the lifespan NOTE Subchronic toxicity studies are usually 90 d in rodents but not exceeding 10 %
48、 of the lifespan of other species. Subchronic intravenous studies are generally defined as treatment durations of 14 d to 28 d. 3.10 chronic systemic toxicity adverse effects occurring after the repeated or continuous administration of a test sample for a major part of the life span NOTE Chronic tox
49、icity studies usually have a duration of 6 months to 12 months. 3.11 test sample material, device, device portion, component, extract or portion thereof that is subjected to biological or chemical testing or evaluation 4 General considerations 4.1 General Selection of the appropriate test(s) for a device shall be in accordance with ISO 10993-1, giving due consideration to mode and duration of contact. Testing shall be performed on the final product and/or representative component samples of the f
