BS DD ISO TS 10993-20-2006 Biological evaluation of medical devices - Principles and methods for immunotoxicology testing of medical devices《医疗设备的生物学评定 医疗设备的免疫毒理学试验的原理和方法》.pdf

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1、DRAFT FOR DEVELOPMENTDD ISO/TS 10993-20:2006Biological evaluation of medical devices Part 20: Principles and methods for immunotoxicology testing of medical devicesICS 11.100.20g49g50g3g38g50g51g60g44g49g42g3g58g44g55g43g50g56g55g3g37g54g44g3g51g40g53g48g44g54g54g44g50g49g3g40g59g38g40g51g55g3g36g54

2、g3g51g40g53g48g44g55g55g40g39g3g37g60g3g38g50g51g60g53g44g42g43g55g3g47g36g58DD ISO/TS 10993-20:2006This Draft for Development was published under the authority of the Standards Policy and Strategy Committee on 29 September 2006 BSI 2006ISBN 0 580 49228 1National forewordThis Draft for Development w

3、as published by BSI. It is the UK implementation of ISO/TS 10993-20:2006. This publication is not to be regarded as a British Standard.It is being issued in the Draft for Development series of publications and is of a provisional nature. It should be applied on this provisional basis, so that inform

4、ation and experience of its practical application can be obtained.Comments arising from the use of this Draft for Development are requested so that UK experience can be reported to the international organization responsible for its conversion to an international standard. A review of this publicatio

5、n will be initiated not later than 3 years after its publication by the international organization so that a decision can be taken on its status. Notification of the start of the review period will be made in an announcement in the appropriate issue of Update Standards.According to the replies recei

6、ved by the end of the review period, the responsible BSI Committee will decide whether to support the conversion into an international Standard, to extend the life of the Technical Specification or to withdraw it. Comments should be sent to the Secretary of the responsible BSI Technical Committee at

7、 British Standards House, 389 Chiswick High Road, London W4 4AL.The UK participation in its preparation was entrusted to Technical Committee CH/194, Biological evaluation of medical devices.A list of organizations represented on CH/194 can be obtained on request to its secretary.This publication doe

8、s not purport to include all the necessary provisions of a contract. Users are responsible for its correct application.Amendments issued since publicationAmd. No. Date CommentsReference numberISO/TS 10993-20:2006(E)TECHNICAL SPECIFICATION ISO/TS10993-20First edition2006-08-01Biological evaluation of

9、 medical devices Part 20: Principles and methods for immunotoxicology testing of medical devices valuation biologique des dispositifs mdicaux Partie 20: Principes et mthodes relatifs aux essais dimmunotoxicologie des dispositifs mdicaux DD ISO/TS 10993-20:2006ii iiiContents Page Foreword iv Introduc

10、tion . vi 1 Scope . 1 2 Normative references . 1 3 Terms and definitions. 1 4 Risk assessment and risk management.2 5 Identification of hazards 2 6 Methods of assessment of immunotoxicity. 4 6.1 General. 4 6.2 Inflammation 5 6.3 Immunosuppression. 5 6.4 Immunostimulation. 7 6.5 Hypersensitivity 7 6.

11、6 Auto-immunity. 7 7 Extrapolation of data provided by pre-clinical assays . 7 Annex A (informative) Current state of knowledge. 8 Annex B (informative) Clinical experience with medical devices . 12 Annex C (informative) Flow chart for immunotoxicity testing. 14 Bibliography . 15 DD ISO/TS 10993-20:

12、2006iv Foreword 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 a subject for wh

13、ich 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 Commission (IEC) on all

14、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 committees are ci

15、rculated to the member bodies for voting. Publication as an International Standard requires approval by at least 75 % of the member bodies casting a vote. In other circumstances, particularly when there is an urgent market requirement for such documents, a technical committee may decide to publish o

16、ther types of normative document: an ISO Publicly Available Specification (ISO/PAS) represents an agreement between technical experts in an ISO working group and is accepted for publication if it is approved by more than 50 % of the members of the parent committee casting a vote; an ISO Technical Sp

17、ecification (ISO/TS) represents an agreement between the members of a technical committee and is accepted for publication if it is approved by 2/3 of the members of the committee casting a vote. An ISO/PAS or ISO/TS is reviewed after three years in order to decide whether it will be confirmed for a

18、further three years, revised to become an International Standard, or withdrawn. If the ISO/PAS or ISO/TS is confirmed, it is reviewed again after a further three years, at which time it must either be transformed into an International Standard or be withdrawn. Attention is drawn to the possibility t

19、hat some of the elements of this document may be the subject of patent rights. ISO shall not be held responsible for identifying any or all such patent rights. ISO/TS 10993-20 was prepared by Technical Committee ISO/TC 194, Biological evaluation of medical devices. ISO/TS 10993 consists of the follo

20、wing 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: Tests for in vitro

21、 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 DD ISO/TS 10993-20:2006v Part 10: Tests for irritation and delayed-type hypersensitivity Part 11:

22、Tests 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 quantificatio

23、n of degradation products from metals and alloys Part 16: Toxicokinetic study design for degradation products and leachables Part 17: Establishment of allowable limits for leachable substances Part 18: Chemical characterization of materials Part 19: Physico-chemical, morphological and topographical

24、characterization of materials Part 20: Principles and methods for immunotoxicology testing of medical devices DD ISO/TS 10993-20:2006vi Introduction International and European Standards are the main focus for demonstration of the safety and compliance of medical devices. There has been increasing at

25、tention over the past few years on the potential for medical devices to cause changes in the immune system. It was felt necessary to provide guidance on how to address adverse effects of medical devices on the immune system. As there are no standardized tests available, this document provides a fram

26、ework on how to approach the evaluation of immunotoxicity. The intention of this document is: to summarize the current state of knowledge in the area of immunotoxicology, including information on methods of assessment of immunotoxicity and their predictive value; to identify what the problems are an

27、d how they have been dealt with in the past. For clinical indications of immune alterations due to medical devices, an extensive literature review has been performed, primarily through Medline. The key areas which have been researched are: immunosuppression; immunostimulation; hypersensitivity; chro

28、nic inflammation; autoimmunity. These key words are linked with the following materials: plastics and other polymers; metals; ceramics, glasses and composites; biological materials. NOTE See also Table 1 for possibilities of interaction of materials with the immune system. DD ISO/TS 10993-20:20061Bi

29、ological evaluation of medical devices Part 20: Principles and methods for immunotoxicology testing of medical devices 1 Scope This part of ISO 10993 presents an overview of immunotoxicology with particular reference to the potential immunotoxicity of medical devices. It gives guidance on methods fo

30、r testing for immunotoxicity of various types of medical devices. This part of ISO 10993 is based on several publications written by various groups of immunotoxicologists over the last few decades in which the development of immunotoxicology as a separate entity within toxicology took place. The cur

31、rent state of knowledge with regard to immunotoxicity is described in Annex A. A summary of clinical experience to date with immunotoxicology associated with medical devices is given in Annex B. NOTE See also Bibliographic Reference 11. 2 Normative references The following referenced documents are i

32、ndispensable for the application of this document. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies. ISO 14971, Medical devices Application of risk management to medical devices ISO 10993-1,

33、 Biological evaluation of medical devices Part 1: Evaluation and testing ISO 10993-2, Biological evaluation of medical devices Part 2: Animal welfare requirements ISO 10993-6, Biological evaluation of medical devices Part 6: Tests for local effects after implantation ISO 10993-10, Biological evaluat

34、ion of medical devices Part 10: Tests for irritation and delayed-type hypersensitivity ISO 10993-11:2006, Biological evaluation of medical devices Part 11: Test for systemic toxicity 3 Terms and definitions For the purposes of this document, the following terms and definitions apply. 3.1 immunotoxic

35、ology study of the adverse health effects that result, directly or indirectly, from the interaction of xenobiotics with the immune system DD ISO/TS 10993-20:20062 3.2 medical device any instrument, apparatus, appliance, material or other article, including software, whether used alone or in combinat

36、ion, intended by the manufacturer to be used on human beings solely or principally for the purpose of: diagnosis, prevention, monitoring, treatment or alleviation of disease; diagnosis, monitoring, treatment, alleviation of, or compensation for an injury or handicap; investigation, replacement or mo

37、dification of the anatomy or of a physiological process; control of conception and which does not achieve its principal intended action in or on the human body by pharmacological, immunological or metabolic means, but which can be assisted in its function by such means. NOTE 1 Devices are different

38、from drugs and their biological evaluation requires a different approach. NOTE 2 Use of the term “medical device“ includes dental devices. 3.3 xenobiotic substance foreign to the human body or living organisms 3.4 immunogenic able to stimulate cells of the immune system resulting in an antigen speci

39、fic immune response 4 Risk assessment and risk management Risk assessment includes hazard identification, dose response assessment and exposure assessment, which together allow characterization of the risk. Based on this risk characterization, risk management shall be applied. Because of the difficu

40、lties in predicting immunotoxicity of new chemicals and materials, effort and interest need to be focused on the assessment and management of risks arising from known immunotoxic chemicals contained in medical devices. Application of risk management to medical devices shall be performed in accordanc

41、e with ISO 14971. Possible immunotoxic hazards of the chemicals contained in the medical device shall be identified first by an extensive literature search. Examples of such hazards are the production of anaphylactic shock by chlorohexidine in medicines and by proteins in latex rubber. Subsequently

42、the overall risk management/reduction procedures shall be considered, together with the various possible actions that could be taken to further reduce remaining risks such as indicating contra-indications on the label, product recall, design-change and restrictions of use or application. 5 Identific

43、ation of hazards Immunological hazards should be identified by assessing exposure to medical device materials to identify the presence of (potentially) immunotoxic agents. There are many sources from which information on immunological hazards can be obtained. These sources include but are not limite

44、d to: material characterization; residue characterization; characterization of the leachable materials; DD ISO/TS 10993-20:20063 characterization of drugs and other substances added to the medical device; characterization of exposure duration and route; observations made during previous exposure to

45、chemicals, drugs or materials; toxicity testing. Most immunological reactions identified to date relate to the additives to materials. Therefore exposure assessment for these chemicals is important in order to identify the immunological hazard. Details of potential outcomes with various materials fr

46、om different types of medical devices are given in Table 1. Table 1 Potential responses of the immune system Medical device categorization by Immune system responses Nature of body contact Contact duration Category Contact A:limited (u 24 h) B:prolonged ( 24 h to 30 d) C:permanent ( 30 d) Irritation

47、/ acute inflammationChronic inflammation Immunosuppression Immunostimulation HypersensitivityAutoimmunity A B Skin C A B Mucosal membrane C A B Surface device Breached or compromised surfaceC A B Blood path, indirect C A B External communicating device Tissue, bone, dentin communicating implant devi

48、ces C A B Implant device Tissue, bone and other body fluids C NOTE This table is a framework for consideration of the potential interaction of materials from different types of medical devices with various parts of the immune system, and is not a checklist for testing. DD ISO/TS 10993-20:20064 Effects on the immune system (immunotoxicity) occur due to an encounter of immunologically competent cells with foreign substances that are toxic and kill the cells, or result from foreign substances that interact with the early events of the immune response and alter subsequ