1、ANSI/AAMI/ ISO TIR 15499:2012Technical Information ReportBiological evaluation of medical devicesGuidance on the conduct of biological evaluation within a risk management processAn ANSI Technical Report prepared by AAMI ANSI/AAMI/ISO TIR15499:2012 Biological evaluation of medical devicesGuidance on
2、the conduct of biological evaluation within a risk management process Approved 3 December 2012 by Association for the Advancement of Medical Instrumentation Registered 10 August 2012 by American National Standards Institute, Inc. Abstract: This guidance is applicable to the conduct of biological eva
3、luation of medical devices according to the requirements of ISO 10993-1. It does not add to, or otherwise change, the requirements of ISO 10993-1. This guidance does not include requirements to be used as the basis of regulatory inspection or certification assessment activities. This guidance is app
4、licable to all biological evaluation of all types of medical devices including active, non-active, implantable and non-implantable medical devices. Keywords: biological evaluation, risk management Published by Association for the Advancement of Medical Instrumentation 4301 N. Fairfax Drive, Suite 30
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20、lington, VA 22203-1633. Contents Page Glossary of equivalent standards v Committee representation . viii Background of AAMI adoption of ISO TR 15499:2012 . x FOREWORD . xi INTRODUCTION xii 1 Scope 1 2 Normative references 1 3 Terms and definitions 1 4 Biological evaluation as a risk management pract
21、ice . 2 4.1 General . 2 4.2 The biological evaluation plan 4 5 Guidance on risk management . 6 5.1 Risk assessment . 6 5.2 Risk control . 8 5.3 Evaluation of residual risk acceptability 8 5.4 Post production monitoring . 8 6 Guidance on specific aspects of biological evaluation . 9 6.1 Material char
22、acterization . 9 6.2 Biological evaluation . 10 6.3 Device testing considerations . 10 6.4 Biological safety assessment 11 6.5 General guidance 13 Bibliography 15 2013 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO TIR15499:2012 v Glossary of equivalent standards Internatio
23、nal 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 corresponding U.S. designation and level of equivalency to the International Standard. NOT
24、E: Documents are sorted by international designation. The code in the U.S. column, “(R)20xx” indicates the year the document was officially reaffirmed by AAMI. For example, ANSI/AAMI/ISO 10993-4:2002/(R)2009 indicates that 10993-4, originally approved and published in 2002, was reaffirmed without ch
25、ange in 2009. 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 Equivalency IEC 60601-1:2005 ANSI/AAMI ES60601-1:2005/(R)2012 Major technical
26、variations IEC 60601-1:2005/A1:2012 ANSI/AAMI ES60601-1:2005/A1:2012 A1 identical IEC Technical Corrigendum 1 and 2 ANSI/AAMI ES60601-1:2005/C1:2009/(R)2012 (amdt) C1 identical to Corrigendum 1 biological evaluation is a component of risk management and this Technical Report includes guidance on the
27、 application of ISO 14971 to the conduct of biological evaluation. 2013 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO TIR15499:2012 1 AAMI Technical Information Report ANSI/AAMI/ISO TIR15499:2012Biological evaluation of medical devices Guidance on the conduct of biological
28、 evaluation within a risk management process 1 Scope This Technical Report is applicable to the conduct of biological evaluation of medical devices according to the requirements of ISO 10993-1. It does not add to, or otherwise change, the requirements of ISO 10993-1. This Technical Report does not i
29、nclude requirements to be used as the basis of regulatory inspection or certification assessment activities. This guidance is applicable to all biological evaluation of all types of medical devices including active, non-active, implantable and non-implantable medical devices. 2 Normative references
30、The following documents, in whole or in part, are normatively referenced in this document and are indispensable for its application. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies. ISO 109
31、93-1:2009, Biological evaluation of medical devices Part 1: Evaluation and testing within a risk management process 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 biocompatibility ability of a material to perform
32、 with an appropriate host response in a specific application 3.2 biological risk potential for a substance to cause harm to health by virtue of its toxicity 3.3 biological safety freedom from unacceptable biological risk 2 2013 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO
33、 TIR15499:2012 3.4 risk assessment overall process comprising a risk analysis and a risk evaluation SOURCE: ISO/IEC Guide 51:1999, 3.12 3.5 risk evaluation process of comparing the estimated risk against given risk criteria to determine the acceptability of the risk SOURCE: ISO 14971:2007, 2.21 3.6
34、risk management systematic application of management policies, procedures and practices to the tasks of analyzing, evaluating, controlling and monitoring risk SOURCE: ISO 14971:2007, 2.22 3.7 toxicological hazard potential for a compound or material to cause an adverse biological reaction, taking in
35、to account the nature of the reaction and the dose required to elicit it 3.8 toxicological risk probability of a specified degree of an adverse reaction occurring in response to a specified level of exposure 3.9 risk analysis systematic use of available information to identify hazards and to estimat
36、e the risk SOURCE: ISO 14971:2007, 2.17, modified 4 Biological evaluation as a risk management practice 4.1 General ISO 10993-1:2009, B.2.2.2 describes a continuous process by which a manufacturer can identify the biological hazards associated with medical devices, estimate and evaluate the risks, c
37、ontrol these risks, and monitor the effectiveness of the control. Appropriate protection of the patient by weighing risks and benefits of medical devices is an essential element of this biological evaluation plan. Benefit to the patient from the use of medical devices entails the acceptance of poten
38、tial risks. These risks will vary depending on the nature and intended use of the specific medical device. The level of risk which is acceptable for a specific device will depend upon the expected benefit provided by its use. Consideration of biological (toxicological) risk is only one aspect of the
39、 risk assessment of a medical device, which should consider all aspects of risk. In some cases it can be specifically necessary to consider the relative benefits of materials of different biological safety profiles in the context of some other characteristic. For example it can be possible that the
40、most biologically safe material available can have 2013 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO TIR15499:2012 3 unacceptable mechanical strength, in which case it would be necessary to consider if an alternate stronger material is of acceptable biological safety. It
41、is fundamental to the conduct of biological evaluation that it be undertaken as part of the overall risk management process required in the design and development of the medical device. Material selection and risk analysis are integral components of the design process for medical devices. The select
42、ion of materials plays a crucial role in evaluating the biological safety and, when approached in a systematic way, allows the collection of relevant data. In line with ISO 9001 and ISO 14971, criteria to define the acceptable biological (toxicological) risk should be established at the start of the
43、 design process. Because starting material, formulation and processing variations could impact final product biocompatibility, these considerations should also be incorporated into the risk assessment. The biological safety evaluation should be designed and performed to demonstrate the achievement o
44、f specified criteria for safety. This evaluation is a component of the risk management plan encompassing identification of all hazards and the estimation of associated risks. Adequate risk assessment requires characterization of toxicological hazards and exposures. A major component in hazard identi
45、fication is material characterization. The following steps can be identified: define and characterize each material, including suitable alternative materials; identify hazards in materials, additives, processing aids, etc.; identify the potential effect of downstream processing (e.g. chemical intera
46、ctions between material components, or final product sterilization) on chemicals present in final product; identify the chemicals that could be released during product use (e.g. intermediate or final degradation products from a degradable implant); estimate exposure (total or clinically available am
47、ounts); review toxicology and other biological safety data (published/available). Information on biological safety to be reviewed can include: toxicology data on relevant component materials/compounds; information on prior use of relevant component materials/compounds; data from biological safety te
48、sts. The risks posed by the identified hazards should then be evaluated. At this stage it should be possible to determine whether there is an undue toxicological risk from the material. If it can be concluded from existing data that risks are acceptable then no additional toxicity testing is needed.
49、 Testing is also unwarranted if risks are found to be unacceptable. When existing data are insufficient, additional information should be obtained. The purpose of testing is to obtain additional data which can assist in reaching a conclusion. A rationale for testing should therefore be based on an analysis of the relevant risks which are indicated from the existing data. The results of any tests should be assessed. Test reports should include descriptive evidence, an assessment of the findings and qualitative assessment of their acceptab
