1、ANSI/AAMI/ISO 10993-11: 2006/(R)2014Biological evaluation of medical devices Part 11:Tests for systemic toxicityAmerican National StandardObjectives and uses of AAMI standards and recommended practices It is most important that the objectives and potential uses of an AAMI product standard or recomme
2、nded practice are clearly understood. The objectives of AAMIs technical development program derive from AAMIs overall mission: the advancement of medical instrumentation. Essential to such advancement are (1) a continued increase in the safe and effective application of current technologies to patie
3、nt care, and (2) the encouragement of new technologies. It is AAMIs view that standards and recommended practices can contribute significantly to the advancement of medical instrumentation, provided that they are drafted with attention to these objectives and provided that arbitrary and restrictive
4、uses are avoided. A voluntary standard for a medical device recommends to the manufacturer the information that should be provided with or on the product, basic safety and performance criteria that should be considered in qualifying the device for clinical use, and the measurement techniques that ca
5、n be used to determine whether the device conforms with the safety and performance criteria and/or to compare the performance characteristics of different products. Some standards emphasize the information that should be provided with the device, including performance characteristics, instructions f
6、or use, warnings and precautions, and other data considered important in ensuring the safe and effective use of the device in the clinical environment. Recommending the disclosure of performance characteristics often necessitates the development of specialized test methods to facilitate uniformity i
7、n reporting; reaching consensus on these tests can represent a considerable part of committee work. When a drafting committee determines that clinical concerns warrant the establishment of minimum safety and performance criteria, referee tests must be provided and the reasons for establishing the cr
8、iteria must be documented in the rationale. A recommended practice provides guidelines for the use, care, and/or processing of a medical device or system. A recommended practice does not address device performance per se, but rather procedures and practices that will help ensure that a device is use
9、d safely and effectively and that its performance will be maintained. Although a device standard is primarily directed to the manufacturer, it may also be of value to the potential purchaser or user of the device as a frame of reference for device evaluation. Similarly, even though a recommended pra
10、ctice is usually oriented towards healthcare professionals, it may be useful to the manufacturer in better understanding the environment in which a medical device will be used. Also, some recommended practices, while not addressing device performance criteria, provide guidelines to industrial person
11、nel on such subjects as sterilization processing, methods of collecting data to establish safety and efficacy, human engineering, and other processing or evaluation techniques; such guidelines may be useful to health care professionals in understanding industrial practices. In determining whether an
12、 AAMI standard or recommended practice is relevant to the specific needs of a potential user of the document, several important concepts must be recognized: All AAMI standards and recommended practices are voluntary (unless, of course, they are adopted by government regulatory or procurement authori
13、ties). The application of a standard or recommended practice is solely within the discretion and professional judgment of the user of the document. Each AAMI standard or recommended practice reflects the collective expertise of a committee of health care professionals and industrial representatives,
14、 whose work has been reviewed nationally (and sometimes internationally). As such, the consensus recommendations embodied in a standard or recommended practice are intended to respond to clinical needs and, ultimately, to help ensure patient safety. A standard or recommended practice is limited, how
15、ever, in the sense that it responds generally to perceived risks and conditions that may not always be relevant to specific situations. A standard or recommended practice is an important reference in responsible decision-making, but it should never replace responsible decision-making. Despite period
16、ic review and revision (at least once every five years), a standard or recommended practice is necessarily a static document applied to a dynamic technology. Therefore, a standards user must carefully review the reasons why the document was initially developed and the specific rationale for each of
17、its provisions. This review will reveal whether the document remains relevant to the specific needs of the user. Particular care should be taken in applying a product standard to existing devices and equipment, and in applying a recommended practice to current procedures and practices. While observe
18、d or potential risks with existing equipment typically form the basis for the safety and performance criteria defined in a standard, professional judgment must be used in applying these criteria to existing equipment. No single source of information will serve to identify a particular product as “un
19、safe“. A voluntary standard can be used as one resource, but the ultimate decision as to product safety and efficacy must take into account the specifics of its utilization and, of course, cost-benefit considerations. Similarly, a recommended practice should be analyzed in the context of the specifi
20、c needs and resources of the individual institution or firm. Again, the rationale accompanying each AAMI standard and recommended practice is an excellent guide to the reasoning and data underlying its provision. In summary, a standard or recommended practice is truly useful only when it is used in
21、conjunction with other sources of information and policy guidance and in the context of professional experience and judgment. INTERPRETATIONS OF AAMI STANDARDS AND RECOMMENDED PRACTICES Requests for interpretations of AAMI standards and recommended practices must be made in writing, to the AAMI Vice
22、 President, Standards Policy and Programs. An official interpretation must be approved by letter ballot of the originating committee and subsequently reviewed and approved by the AAMI Standards Board. The interpretation will become official and representation of the Association only upon exhaustion
23、of any appeals and upon publication of notice of interpretation in the “Standards Monitor“ section of the AAMI News. The Association for the Advancement of Medical Instrumentation disclaims responsibility for any characterization or explanation of a standard or recommended practice which has not bee
24、n developed and communicated in accordance with this procedure and which is not published, by appropriate notice, as an official interpretation in the AAMI News. AAMI/ American National Standard ANSI/AAMI/ISO 10993-11:2006/(R)2014(Revision of ANSI/AAMI 10993-11:1993) Biological evaluation of medical
25、 devicesPart 11: Tests for systemic toxicity Developed by Association for the Advancement of Medical Instrumentation Approved 19 October 2006 and Reaffirmed 24 September 2014 by American National Standards Institute Inc. Abstract: Specifies requirements and gives guidance on the procedures to be fol
26、lowed in the evaluation of the potential for medical devices and their materials to cause adverse systemic reactions. Keywords: biological evaluation, tests, systemic toxicity AAMI Standard This Association for the Advancement of Medical Instrumentation (AAMI) standard implies a consensus of those s
27、ubstantially concerned with its scope and provisions. The existence of an AAMI standard does not in any respect preclude anyone, whether they have approved the standard or not, from manufacturing, marketing, purchasing, or using products, processes, or procedures not conforming to the standard. AAMI
28、 standards are subject to periodic review, and users are cautioned to obtain the latest editions. CAUTION NOTICE: This AAMI standard may be revised or withdrawn at any time. AAMI procedures require that action be taken to reaffirm, revise, or withdraw this standard no later than five years from the
29、date of publication. Interested parties may obtain current information on all AAMI standards by calling or writing AAMI. All AAMI standards, recommended practices, technical information reports, and other types of technical documents developed by AAMI are voluntary, and their application is solely w
30、ithin the discretion and professional judgment of the user of the document. Occasionally, voluntary technical documents are adopted by government regulatory agencies or procurement authorities, in which case the adopting agency is responsible for enforcement of its rules and regulations. Published b
31、y Association for the Advancement of Medical Instrumentation 1110 N. Glebe Road, Suite 220 Arlington, VA 22201-4795 2006 by the Association for the Advancement of Medical Instrumentation All Rights Reserved This publication is subject to copyright claims of ISO, ANSI, and AAMI. No part of this publi
32、cation may be reproduced or distributed in any form, including an electronic retrieval system, without the prior written permission of AAMI. All requests pertaining to this draft should be submitted to AAMI. It is illegal under federal law (17 U.S.C. 101, et seq.) to make copies of all or any part o
33、f this document (whether internally or externally) without the prior written permission of the Association for the Advancement of Medical Instrumentation. Violators risk legal action, including civil and criminal penalties, and damages of $100,000 per offense. For permission regarding the use of all
34、 or any part of this document, contact AAMI, 1110 N. Glebe Road, Suite 220, Arlington, VA 22201-4795. Phone: (703) 525-4890; Fax: (703) 525-1067. Printed in the United States of America ISBN 1570202761 Contents PageGlossary of equivalent standards . iv Committee representation vi Background of AAMI
35、adoption of ISO 10993-11:2006 vii Foreword viii Introduction x 1 Scope 1 2 Normative references . 1 3 Terms and definitions. 1 4 General considerations 3 4.1 General. 3 4.2 Selection of animal species . 3 4.3 Animal status. 3 4.4 Animal care and husbandry. 3 4.5 Size and number of groups 4 4.6 Route
36、 of exposure. 5 4.7 Sample preparation. 5 4.8 Dosing 5 4.9 Body weight and food/water consumption 6 4.10 Clinical observations 6 4.11 Clinical pathology . 7 4.12 Anatomic pathology 7 4.13 Study designs 8 4.14 Quality of investigation 8 5 Acute systemic toxicity 8 5.1 General. 8 5.2 Study design 8 5.
37、3 Evaluation criteria. 10 5.4 Final report 11 6 Repeated exposure systemic toxicity (subacute, subchronic and chronic systemic toxicity) 12 6.1 General. 12 6.2 Study design 13 6.3 Evaluation criteria. 15 6.4 Final report 16 Annex A (informative) Routes of administration 17 Annex B (informative) Dosa
38、ge volumes 19 Annex C (informative) Common clinical signs and observations 20 Annex D (informative) Suggested haematology, clinical chemistry and urinalysis measurements. 21 Annex E (informative) Suggested organ list for histopathological evaluation . 23 Annex F (informative) Information on material
39、-mediated pyrogens 25 Bibliography . 27 Glossary of equivalent standards International Standards adopted in the United States may include normative references to other International Standards. For each International Standard that has been adopted by AAMI (and ANSI), the table below gives the corresp
40、onding U.S. designation and level of equivalency to the International Standard. NOTE: Documents are sorted by international designation. Other normatively referenced International Standards may be under consideration for U.S. adoption by AAMI; therefore, this list should not be considered exhaustive
41、. International designation U.S. designation Equivalency IEC 60601-1:2005 ANSI/AAMI ES60601-1:2005 Major technical variations IEC 60601-1-2:2001 and Amendment 1:2004 ANSI/AAMI/IEC 60601-1-2:2001 and Amendment 1:2004 Identical IEC 60601-2-2:2006 ANSI/AAMI/IEC 60601-2-2:2006 IdenticalIEC 60601-2-4:200
42、2 ANSI/AAMI DF80:2003 Major technical variations IEC 60601-2-19:1990 and Amendment 1:1996 ANSI/AAMI II36:2004 Major technical variations IEC 60601-2-20:1990 and Amendment 1:1996 ANSI/AAMI II51:2004 Major technical variations IEC 60601-2-21:1994 and Amendment 1:1996 ANSI/AAMI/IEC 60601-2-21 and Amend
43、ment 1:2000 (consolidated texts) Identical IEC 60601-2-24:1998 ANSI/AAMI ID26:2004 Major technical variations IEC 60601-2-50:2001 ANSI/AAMI/IEC 60601-2-50:2006 Identical IEC/TR 60878:2003 ANSI/AAMI/IEC TIR60878:2003 IdenticalIEC/TR 62296:2003 ANSI/AAMI/IEC TIR62296:2003 IdenticalIEC 62304:2006 ANSI/
44、AAMI/IEC 62304:2006 Identical IEC/TR 62348:2006ANSI/AAMI/IEC TIR62348:2006 IdenticalISO 5840:2005 ANSI/AAMI/ISO 5840:2005 Identical ISO 7198:1998 ANSI/AAMI/ISO 7198:1998/2001/(R)2004 Identical ISO 7199:1996 ANSI/AAMI/ISO 7199:1996/(R)2002 IdenticalISO 10993-1:2003 ANSI/AAMI/ISO 10993-1:2003 Identica
45、l ISO 10993-2:2006 ANSI/AAMI/ISO 10993-2:2006 Identical ISO 10993-3:2003 ANSI/AAMI/ISO 10993-3:2003 Identical ISO 10993-4:2002 and Amendment 1:2006 ANSI/AAMI/ISO 10993-4:2002 and Amendment 1:2006 Identical ISO 10993-5:1999 ANSI/AAMI/ISO 10993-5:1999 Identical ISO 10993-6:1994 ANSI/AAMI/ISO 10993-6:1
46、995/(R)2001 Identical ISO 10993-7:1995 ANSI/AAMI/ISO 10993-7:1995/(R)2001 Identical ISO 10993-9:1999 ANSI/AAMI/ISO 10993-9:1999/(R)2005 Identical ISO 10993-10:2002 and Amendment 1:2006 ANSI/AAMI BE78:2002 ANSI/AAMI BE78:2002/A1:2006 Minor technical variations Identical ISO 10993-11:2006 ANSI/AAMI/IS
47、O 10993-11:2006 Identical ISO 10993-12:2002 ANSI/AAMI/ISO 10993-12:2002 Identical ISO 10993-13:1998 ANSI/AAMI/ISO 10993-13:1999/(R)2004 Identical ISO 10993-14:2001 ANSI/AAMI/ISO 10993-14:2001 Identical ISO 10993-15:2000 ANSI/AAMI/ISO 10993-15:2000 Identical ISO 10993-16:1997 ANSI/AAMI/ISO 10993-16:1
48、997/(R)2003 Identical ISO 10993-17:2002 ANSI/AAMI/ISO 10993-17:2002 Identical iv 2006 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO 10993-11:2006 International designation U.S. designation Equivalency ISO 10993-18:2005 ANSI/AAMI BE83:2006 Major technical variations ISO/TS
49、10993-19:2006 ANSI/AAMI/ISO TIR10993-19:2006 Identical ISO/TS 10993-20:2006 ANSI/AAMI/ISO TIR10993-20:2006 Identical ISO 11135:1994 ANSI/AAMI/ISO 11135:1994 Identical ISO 11137-1:2006ANSI/AAMI/ISO 11137-1:2006 Identical ISO 11137-2:2006 (2006-08-01 corrected version)ANSI/AAMI/ISO 11137-2:2006 Identical ISO 11137-3:2006ANSI/AAMI/ISO 11137-3:2006 Identical ISO 11138-1: 2006 ANSI/AAMI/ISO 11138-1:2006 Identical ISO 11138-2: 2006 ANSI/AAMI/ISO 11138-2:2006 Identical ISO 11138-3: 2006 ANSI/AAMI/ISO 11138-3:2006 Identical ISO 11138-4: 2006 ANSI/AAMI/ISO 11138-4:2006 Identical ISO 1
