1、ANSI/AAMI/ISO 10993-5: 2009/(R)2014 Biological evaluation of medical devices Part 5: Tests for in vitro cytotoxicityAmerican 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 rec
2、ommended 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 p
3、atient 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 restrict
4、ive 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 tha
5、t can 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, instructio
6、ns for 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 uniformi
7、ty in 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 th
8、e criteria 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
9、 used 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
10、 practice 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 pe
11、rsonnel 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 whethe
12、r an 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 aut
13、horities). 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 representati
14、ves, 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,
15、 however, 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 pe
16、riodic 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
17、 of 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 obs
18、erved 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
19、 “unsafe“. 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 spe
20、cific 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
21、 in 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
22、Vice 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 exhaust
23、ion 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
24、 been developed and communicated in accordance with this procedure and which is not published, by appropriate notice, as an official interpretation in the AAMI News. American National Standard ANSI/AAMI/ISO 10993-5:2009/(R)2014 (Revision of ANSI/AAMI/ISO 10993-5:1999) Biological evaluation of medica
25、l devices Part 5: Tests for in vitro cytotoxicity Approved 18 June 2009 by Association for the Advancement of Medical Instrumentation Approved 23 June 2009 and reaffirmed 6 February 2014 by American National Standards Institute, Inc. Abstract: AAMI/AAMI/ISO 10993-5 describes test methods to assess t
26、he in vitro cytotoxicity of devices. These methods specify the incubation of cultured cells either directly or through diffusion with extracts of the device, and/or in contact with a device. These methods are designed to determine the biological response of mammalian cells in vitro using appropriate
27、 biological parameters. Keywords: biological evaluation, medical devices, cytotoxicity AAMI Standard This Association for the Advancement of Medical Instrumentation (AAMI) standard implies a consensus of those substantially concerned with its scope and provisions. The existence of an AAMI standard d
28、oes 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 standards are subject to periodic review, and users are cautioned to obtain the latest e
29、ditions. 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 5 years from the date of publication. Interested parties may obtain current information on all AAMI standards
30、 by calling or writing AAMI, or by visiting the AAMI website at www.aami.org. All AAMI standards, recommended practices, technical information reports, and other types of technical documents developed by AAMI are voluntary, and their application is solely within the discretion and professional judgm
31、ent 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 by Association for the Advancement of Medica
32、l Instrumentation 1110 N. Glebe Road, Suite 220 Arlington, VA 22201-4795 www.aami.org 2009 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 publication may be reproduced or di
33、stributed in any form, including an electronic retrieval system, without the prior written permission of AAMI. All requests pertaining to this document 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 of this document (whether in
34、ternally 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 or any part of this docume
35、nt, complete the reprint request form at www.aami.org or 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 1-57020-355-5Contents Page Glossary of equivalent standards . iv Committee represen
36、tation vi Background of AAMI adoption of ISO 10993-5:2009 vii Foreword. viii Introduction x 1 Scope 1 2 Normative references . 1 3 Terms and definitions. 1 4 Sample and control preparation 2 4.1 General. 2 4.2 Preparation of liquid extracts of material. 3 4.3 Preparation of material for direct-conta
37、ct tests. 4 4.4 Preparation of controls. 5 5 Cell lines 5 6 Culture medium. 6 7 Preparation of cell stock culture . 6 8 Test procedures 6 8.1 Number of replicates 6 8.2 Test on extracts. 6 8.3 Test by direct contact. 7 8.4 Test by indirect contact 8 8.5 Determination of cytotoxicity 9 9 Test report
38、. 11 10 Assessment of results 11 Annex A (informative) Neutral red uptake (NRU) cytotoxicity test 13 Annex B (informative) Colony formation cytotoxicity test. 21 Annex C (informative) MTT cytotoxicity test 26 Annex D (informative) XTT cytotoxicity test . 32 Bibliography . 37 iv 2009 Association for
39、the Advancement of Medical Instrumentation ANSI/AAMI/SO 10993-5:2009 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
40、table below gives the corresponding 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
41、 not be considered exhaustive. International designation U.S. designation Equivalency IEC 60601-1:2005 ANSI/AAMI ES60601-1:2005 Major technical variations IEC 60601-1-2:2007 ANSI/AAMI/IEC 60601-1-2:2007 Identical IEC 60601-2-2:2009 ANSI/AAMI/IEC 60601-2-2:2009 Identical IEC 60601-2-4:2002 ANSI/AAMI
42、DF80:2003 Major technical variations IEC 60601-2-19:2009 ANSI/AAMI/IEC 60601-2-19:2009 Identical IEC 60601-2-20:2009 ANSI/AAMI/IEC 60601-2-20:2009 Identical IEC 60601-2-21:2009 ANSI/AAMI/IEC 60601-2-21:2009 Identical IEC 60601-2-24:1998 ANSI/AAMI ID26:2004 Major technical variations IEC 60601-2-47:2
43、001 ANSI/AAMI EC38:2007 Major technical variations IEC 60601-2-50:2009 ANSI/AAMI/IEC 60601-2-50:2009 Identical IEC 80601-2-58:2008 ANSI/AAMI/IEC 80601-2-58:2008 Identical IEC/TR 60878:2009 ANSI/AAMI/IEC TIR60878:2003 Identical IEC/TR 62296:2009 ANSI/AAMI/IEC TIR62296:2009 Identical IEC 62304:2006 AN
44、SI/AAMI/IEC 62304:2006 Identical IEC/TR 62348:2006ANSI/AAMI/IEC TIR62348:2006 Identical ISO 5840:2005 ANSI/AAMI/ISO 5840:2005 Identical ISO 7198:1998 ANSI/AAMI/ISO 7198:1998/2001/(R)2004 Identical ISO 7199:2009 ANSI/AAMI/ISO 7199:2009 Identical ISO 8637:2004 ANSI/AAMI RD16:2007 Major technical varia
45、tions ISO 8638:2004 ANSI/AAMI RD17:2007 Major technical variations ISO 10993-1:2003 ANSI/AAMI/ISO 10993-1:2003 Identical 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/(R)200
46、9 and Amendment 1:2006/(R)2009 Identical ISO 10993-5:2009 ANSI/AAMI/ISO 10993-5:2009 Identical ISO 10993-6:2007 ANSI/AAMI/ISO 10993-6:2007 Identical ISO 10993-7:2008 ANSI/AAMI/ISO 10993-7:2008 Identical ISO 10993-9:1999 ANSI/AAMI/ISO 10993-9:1999/(R)2005 Identical ISO 10993-10:2002 and Amendment 1:2
47、006 ANSI/AAMI BE78:2002/(R)2008 ANSI/AAMI BE78:2002/A1:2006/(R)2008 Minor technical variations Identical ISO 10993-11:2006 ANSI/AAMI/ISO 10993-11:2006 Identical ISO 10993-12:2007 ANSI/AAMI/ISO 10993-12:2007 Identical ISO 10993-13:1998 ANSI/AAMI/ISO 10993-13:1999/(R)2004 Identical ISO 10993-14:2001 A
48、NSI/AAMI/ISO 10993-14:2001/(R)2006 Identical ISO 10993-15:2000 ANSI/AAMI/ISO 10993-15:2000/(R)2006 Identical ISO 10993-16:1997 ANSI/AAMI/ISO 10993-16:1997/(R)2009 Identical ISO 10993-17:2002 ANSI/AAMI/ISO 10993-17:2002/(R)2008 Identical ISO 10993-18:2005 ANSI/AAMI BE83:2006 Major technical variation
49、s ISO/TS 10993-19:2006 ANSI/AAMI/ISO TIR10993-19:2006 Identical ISO/TS 10993-20:2006 ANSI/AAMI/ISO TIR10993-20:2006 Identical ISO 11135-1:2007 ANSI/AAMI/ISO 11135-1:2007 Identical 2009 Association for the Advancement of Medical Instrumentation ANSI/AAMI/SO 10993-5:2009 v International designation U.S. designation Equivalency ISO/TS 11135-2:2008 ANSI/AAMI/ISO TIR11135-2:2008 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
