1、ANSI/AAMI/ISO 10993-17: 2002/(R)2012Biological evaluation of medical devices Part 17:Methods for the establishment of allowable limits for leachable substancesAmerican National StandardThe Objectives and Uses of AAMI Standards andRecommended PracticesIt is most important that the objectives and pote
2、ntial uses of an AAMIproduct standard or recommended practice are clearly understood.The objectives of AAMIs technical development program derivefrom AAMIs overall mission: the advancement of medicalinstrumentation. Essential to such advancement are (1) a continuedincrease in the safe and effective
3、application of current technologiesto patient care, and (2) the encouragement of new technologies. It isAAMIs view that standards and recommended practices cancontribute significantly to the advancement of medicalinstrumentation, provided that they are drafted with attention to theseobjectives and p
4、rovided that arbitrary and restrictive uses are avoided.A voluntary standard for a medical device recommends to themanufacturer the information that should be provided with or on theproduct, basic safety and performance criteria that should be con-sidered in qualifying the device for clinical use, a
5、nd the measurementtechniques that can be used to determine whether the device conformswith the safety and performance criteria and/or to compare the per-formance characteristics of different products. Some standards em-phasize the information that should be provided with the device,including perform
6、ance characteristics, instructions for use, warningsand precautions, and other data considered important in ensuring thesafe and effective use of the device in the clinical environment.Recommending the disclosure of performance characteristics oftennecessitates the development of specialized test me
7、thods to facilitateuniformity in reporting; reaching consensus on these tests canrepresent a considerable part of committee work. When a draftingcommittee determines that clinical concerns warrant the establishmentof minimum safety and performance criteria, referee tests must beprovided and the reas
8、ons for establishing the criteria must bedocumented in the rationale.A recommended practice provides guidelines for the use, care,and/or processing of a medical device or system. A recommendedpractice does not address device performance per se, but ratherprocedures and practices that will help ensur
9、e that a device is usedsafely and effectively and that its performance will be maintained.Although a device standard is primarily directed to the manufac-turer, it may also be of value to the potential purchaser or user of thedevice as a fume of reference for device evaluation. Similarly, eventhough
10、 a recommended practice is usually oriented towards healthcare professionals, it may be useful to the manufacturer in betterunderstanding the environment in which a medical device will beused. Also, some recommended practices, while not addressing deviceperformance criteria, provide guidelines to in
11、dustrial personnel onsuch subjects as sterilization processing, methods of collecting data toestablish safety and efficacy, human engineering, and otherprocessing or evaluation techniques; such guidelines may be useful tohealth care professionals in understanding industrial practices.In determining
12、whether an AAMI standard or recommendedpractice is relevant to the specific needs of a potential user of thedocument, several important concepts must be recognized:All AAMI standards and recommended practices are voluntary(unless, of course, they are adopted by government regulatory orprocurement au
13、thorities). The application of a standard or recom-mended practice is solely within the discretion and professionaljudgment of the user of the document.Each AAMI standard or recommended practice reflects thecollective expertise of a committee of health care professionals andindustrial representative
14、s, whose work has been reviewed nationally(and sometimes internationally). As such, the consensusrecommendations embodied in a standard or recommended practiceare intended to respond to clinical needs and, ultimately, to helpensure patient safety. A standard or recommended practice is limited,howeve
15、r, in the sense that it responds generally to perceived risks andconditions that may not always be relevant to specific situations. Astandard or recommended practice is an important reference inresponsible decision-making, but it should never replace responsibledecisionmaking.Despite periodic review
16、 and revision (at least once every fiveyears), a standard or recommended practice is necessarily a staticdocument applied to a dynamic technology. Therefore, a standardsuser must carefully review the reasons why the document wasinitially developed and the specific rationale for each of itsprovisions
17、. This review will reveal whether the document remainsrelevant to the specific needs of the user.Particular care should be taken in applying a product standard toexisting devices and equipment, and in applying a recommendedpractice to current procedures and practices. While observed orpotential risk
18、s with existing equipment typically form the basis for thesafety and performance criteria defined in a standard, professionaljudgment must be used in applying these criteria to existing equip-ment. No single source of information will serve to identify aparticular product as “unsafe“. A voluntary st
19、andard can be used asone resource, but the ultimate decision as to product safety andefficacy must take into account the specifics of its utilization and, ofcourse, cost-benefit considerations. Similarly, a recommendedpractice should be analyzed in the context of the specific needs andresources of t
20、he individual institution or firm. Again, the rationaleaccompanying each AAMI standard and recommended practice is anexcellent guide to the reasoning and data underlying its provision.In summary, a standard or recommended practice is truly usefulonly when it is used in conjunction with other sources
21、 of informationand policy guidance and in the context of professional experience andjudgment.INTERPRETATIONS OF AAMI STANDARDSAND RECOMMENDED PRACTICESRequests for interpretations of AAMI standards and recommendedpractices must be made in writing, to the Manager for TechnicalDevelopment. An official
22、 interpretation must be approved by letterballot of the originating committee and subsequently reviewed andapproved by the AAMI Standards Board. The interpretation willbecome official and representation of the Association only uponexhaustion of any appeals and upon publication of notice of interpre-
23、tation in the “Standards Monitor“ section of the AAMI News. TheAssociation for the Advancement of Medical Instrumentationdisclaims responsibility for any characterization or explanation of astandard or recommended practice which has not been developed andcommunicated in accordance with this procedur
24、e and which is notpublished, by appropriate notice, as an official interpretation in theAAMI News.American National Standard ANSI/AAMI/ISO 10993-17:2002/(R)2012 Biological evaluation of medical devices Part 17: Establishment of allowable limits for leachable substances Approved 15 November 2002 by A
25、ssociation for the Advancement of Medical Instrumentation Approved 17 December 2002 and reaffirmed 30 November 2012 by American National Standards Institute Abstract: Specifies the method to be used to determine allowable limits for leachable substances in medical devices. Keywords: biological evalu
26、ation, medical devices, leachable substances AAMI StandardThis Association for the Advancement of Medical Instrumentation (AAMI) standard implies a consensus of thosesubstantially concerned with its scope and provisions. The existence of an AAMI standard does not in any respectpreclude anyone, wheth
27、er they have approved the standard or not, from manufacturing, marketing, purchasing, orusing products, processes, or procedures not conforming to the standard. AAMI standards are subject to periodicreview, and users are cautioned to obtain the latest editions.CAUTION NOTICE: This AAMI standard may
28、be revised or withdrawn at any time. AAMI procedures require thataction 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 by calling or writing AAMI.All AAMI standards, re
29、commended practices, technical information reports, and other types of technical documentsdeveloped by AAMI are voluntary, and their application is solely within the discretion and professional judgment of theuser of the document. Occasionally, voluntary technical documents are adopted by government
30、 regulatory agenciesor procurement authorities, in which case the adopting agency is responsible for enforcement of its rules andregulations.Published byAssociation for the Advancement of Medical Instrumentation1110 N Glebe Road, Suite 220Arlington, VA 22201-4795 2003 by the Association for the Adva
31、ncement of Medical InstrumentationAll Rights ReservedThis publication is subject to copyright claims of ISO, ANSI, and AAMI. No part of this publication may be reproducedor distributed in any form, including an electronic retrieval system, without the prior written permission of AAMI. Allrequests pe
32、rtaining 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 of this document (whether internally or externally) without the prior writtenpermission of the Association for the Advancement of Medical Instrumentation. Vio
33、lators risk legal action, includingcivil and criminal penalties, and damages of $100,000 per offense. For permission regarding the use of all or any partof 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 U
34、nited States of AmericaISBN 1570201781ContentsPageGlossary of equivalent standards.vCommittee representation viiBackground of ANSI/AAMI adoption of ISO 10993-17:2002. viiiForeword.ixIntroduction x1 Scope12 Normative reference .13 Terms and definitions14 General principles for establishing allowable
35、limits.35 Establishment of tolerable intake (TI) for specific leachable substances 55.1 General 55.2 Exposure considerations for TI calculation.55.2.1 Data used 55.2.2 Exposure duration considerations55.2.3 Considerations of route of exposure 65.3 Collection and evaluation of data .65.4 Set TI for n
36、oncancer endpoints 75.4.1 General75.4.2 Determination of uncertainty factors 75.4.3 Determination of the modifying factor 85.5 Set TI for cancer endpoints85.5.1 Procedure for carcinogenic leachable substances.85.5.2 Options for substances that pass the weight-of-evidence test.95.5.3 Procedure when w
37、eight-of-evidence test fails or is equivocal95.6 Establishment of tolerable contact levels (TCLs) .95.6.1 General95.6.2 Exposure consideration for TCL calculation.95.6.3 Set TCL for irritation endpoint95.7 Risk assessment of mixtures .106 Calculation of tolerable exposure (TE)116.1 General 116.2 Exp
38、osure population 116.2.1 Body mass.116.2.2 Devices specifically intended for use in neonates and children .116.3 Calculation of utilization factor from intended use pattern116.3.1 General116.3.2 Concomitant exposure factor (CEF) 126.3.3 Proportional exposure factor (PEF) .126.4 Tolerable exposure 13
39、7 Feasibility evaluation.138 Benefit evaluation .139 Allowable limits .1310 Reporting requirements 14AnnexesA Some typical assumptions for biological parameters 15B Risk assessment for mixtures of leachable substances17C Conversion of allowable limits for systemic exposure and for body surface conta
40、ctto maximum dose to patient from a medical device 18D Risk analysis report.20Bibliography .21Figure1 Establishment of allowable limits for leachable substances4 2003 Association for the Advancement of Medical Instrumentation ! ANSI/AAMI/ISO 10993-17:2002 vGlossary of equivalent standardsInternation
41、al standards adopted in the United States may include normative references to other internationalstandards. For each international standard that has been adopted by AAMI (and ANSI), the table below gives thecorresponding U.S. designation and level of equivalency to the international standard. (Note:
42、 Documents are sortedby 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.International designation U.S. designation EquivalencyIEC 60601-1-2:2001 ANSI/AAMI/IEC
43、 60601-1-2:2001 IdenticalIEC 60601-2-21:1994 andAmendment 1:1996ANSI/AAMI/IEC 60601-2-21 b) determining the tolerable exposure (TE) of the patient to the leachable substance (see clause 6) by determining appropriate patient body mass (mB), and modifying the product of tolerable intake and body mass
44、based upon a device utilization factor (UTF);c) determining feasibility and applying benefit when appropriate. If the feasibility evaluation determines that theTE is both technically and economically feasible, the TE becomes the allowable limit. In the event that theTE is not technically or economic
45、ally feasible (see clause 7), further modification of the TE based uponbenefit evaluation shall be performed on a case-by-case basis to establish the allowable limit (see clause 8).4 2003 Association for the Advancement of Medical Instrumentation ! ANSI/AAMI/ISO 10993-17:2002Figure 1Establishment of
46、 allowable limits for leachable substances 2003 Association for the Advancement of Medical Instrumentation ! ANSI/AAMI/ISO 10993-17:2002 54.2 Knowledgeable and experienced individuals, capable of making informed decisions based on the scientificdata available, shall implement the requirements of thi
47、s part of ISO 10993 through the application of professionaljudgement. This requires experience in the interpretation of toxicological data and toxicological risk assessment ofmedical devices, together with knowledge of the use and benefit of medical devices and the feasibility of achievingallowable
48、limits determined.4.3 The safety of medical devices requires an absence of unacceptable health risk. An analysis of the health risksposed by specific leachable substances allows exposure limits to be established that permit an appropriate degree ofprotection from harm to health in the event that the
49、 hazardous leachable substance would be released into the bodyduring the clinical use of the device. The degree of protection deemed appropriate in any situation is dependent upona number of factors, such as the nature of the hazard identified, the practicality of risk reduction and the magnitude ofthe benefit derived from the use of the medical device. Assessment of the acceptability of a health risk thus requiresseveral complex factors to be investigated and balanced. Confidence in the risk assessment is a function of thequality and quantity of data evaluated.4.4 In the br
