EN ISO 10993-17-2009 en Biological evaluation of medical devices - Part 17 Establishment of allowable limits for leachable substances《医疗器械的生物学评定 第17部分 可浸出物质容许限值的确定》.pdf

1、BS EN ISO10993-17:2009ICS 11.100.20NO COPYING WITHOUT BSI PERMISSION EXCEPT AS PERMITTED BY COPYRIGHT LAWBRITISH STANDARDBiological evaluationof medical devicesPart 17: Establishment of allowablelimits for leachable substances (ISO10993-17:2002)This British Standardwas published under theauthority o

2、f the StandardsPolicy and StrategyCommittee on 30 June2009. BSI 2009ISBN 978 0 580 65823 5Amendments/corrigenda issued since publicationDate CommentsBS EN ISO 10993-17:2009National forewordThis British Standard is the UK implementation of EN ISO10993-17:2009. It is identical to ISO 10993-17:2002. It

3、 supersedes BS ENISO 10993-17:2002 which is withdrawn.The UK participation in its preparation was entrusted to TechnicalCommittee CH/194, Biological evaluation of medical devices.A list of organizations represented on this committee can be obtained onrequest to its secretary.This publication does no

4、t purport to include all the necessary provisionsof a contract. Users are responsible for its correct application.Compliance with a British Standard cannot confer immunityfrom legal obligations.EUROPEAN STANDARDNORME EUROPENNEEUROPISCHE NORMEN ISO 10993-17April 2009ICS 11.100.20 Supersedes EN ISO 10

5、993-17:2002 English VersionBiological evaluation of medical devices - Part 17: Establishmentof allowable limits for leachable substances (ISO 10993-17:2002)valuation biologique des dispositifs mdicaux - Partie 17:tablissement des limites admissibles des substancesrelargables (ISO 10993-17:2002)Biolo

6、gische Beurteilung von Medizinprodukten - Teil 17:Nachweis zulssiger Grenzwerte fr herauslsbareBestandteile (ISO 10993-17:2002)This European Standard was approved by CEN on 12 April 2009.CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for givi

7、ng this EuropeanStandard the status of a national standard without any alteration. Up-to-date lists and bibliographical references concerning such nationalstandards may be obtained on application to the CEN Management Centre or to any CEN member.This European Standard exists in three official versio

8、ns (English, French, German). A version in any other language made by translationunder the responsibility of a CEN member into its own language and notified to the CEN Management Centre has the same status as theofficial versions.CEN members are the national standards bodies of Austria, Belgium, Bul

9、garia, Cyprus, Czech Republic, Denmark, Estonia, Finland,France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal,Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom.EUROPEAN COMMITTEE FOR STANDARDIZ

10、ATIONCOMIT EUROPEN DE NORMALISATIONEUROPISCHES KOMITEE FR NORMUNGManagement Centre: Avenue Marnix 17, B-1000 Brussels 2009 CEN All rights of exploitation in any form and by any means reservedworldwide for CEN national Members.Ref. No. EN ISO 10993-17:2009: EBS EN ISO 10993-17:2009EN ISO 10993-17:200

11、9 (E) 3 Foreword The text of ISO 10993-17:2002 has been prepared by Technical Committee ISO/TC 194 “Biological evaluation of medical devices” of the International Organization for Standardization (ISO) and has been taken over as EN ISO 10993-17:2009 by Technical Committee CEN/TC 206 “Biological eval

12、uation of medical devices” the secretariat of which is held by NEN. This European Standard shall be given the status of a national standard, either by publication of an identical text or by endorsement, at the latest by October 2009, and conflicting national standards shall be withdrawn at the lates

13、t by March 2010. Attention is drawn to the possibility that some of the elements of this document may be the subject of patent rights. CEN and/or CENELEC shall not be held responsible for identifying any or all such patent rights. This document supersedes EN ISO 10993-17:2002. This document has been

14、 prepared under a mandate given to CEN by the European Commission and the European Free Trade Association, and supports essential requirements of EU Directives 93/42/EEC on Medical Devices and 90/385/EEC on Active Implantable Medical Devices. For relationship with the EU Directives, see informative

15、Annexes ZA and ZB, which is an integral part of this document. According to the CEN/CENELEC Internal Regulations, the national standards organizations of the following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finla

16、nd, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and the United Kingdom. Endorsement notice The text of ISO 10993-17:2002 has been approved by CEN as a E

17、N ISO 10993-17:2009 without any modification. BS EN ISO 10993-17:2009EN ISO 10993-17:2009 (E) 4 Annex ZA (informative) Relationship between this European Standard and the Essential Requirements of EU Directive 93/42/EEC on Medical Devices This European Standard has been prepared under a mandate give

18、n to CEN by the European Commission and the European Free Trade Association to provide a means of conforming to Essential Requirements of the New Approach Directive 93/42/EEC on medical devices. Once this standard is cited in the Official Journal of the European Communities under that Directive and

19、has been implemented as a national standard in at least one Member State, compliance with the clauses of this standard given in table ZA confers, within the limits of the scope of this standard, a presumption of conformity with the corresponding Essential Requirements of that Directive and associate

20、d EFTA regulations. Table ZA Correspondence between this European Standard and Directive 93/42/EEC on medical devices Clause(s)/sub-clause(s) of this EN Essential Requirements (ERs) of Directive 93/42/EEC Qualifying remarks/Notes 4, 5, 6, 7, 8, 9, 10 Annex I: 7.1, 7.2, 7.5 WARNING Other requirements

21、 and other EU Directives may be applicable to the product(s) falling within the scope of this standard. BS EN ISO 10993-17:2009EN ISO 10993-17:2009 (E) 5 Annex ZB (informative) Relationship between this European Standard and the Essential Requirements of EU Directive 90/385/EEC on Active Implantable

22、 Medical Devices This European Standard has been prepared under a mandate given to CEN by the European Commission and the European Free Trade Association to provide a means of conforming to Essential Requirements of the New Approach Directive 90/385/EEC on active implantable medical devices. Once th

23、is standard is cited in the Official Journal of the European Communities under that Directive and has been implemented as a national standard in at least one Member State, compliance with the clauses of this standard given in table ZB confers, within the limits of the scope of this standard, a presu

24、mption of conformity with the corresponding Essential Requirements of that Directive and associated EFTA regulations. Table ZB Correspondence between this European Standard and Directive 90/385/EEC on active implantable medical devices Clause(s)/sub-clause(s) of this EN Essential Requirements (ERs)

25、of Directive 90/385/EEC Qualifying remarks/Notes 4, 5, 6, 7, 8, 9, 10 Annex I : 9 WARNING Other requirements and other EU Directives may be applicable to the product(s) falling within the scope of this standard. BS EN ISO 10993-17:2009ISO 10993-17:2002(E) ISO 2002 All rights reserved iiiContents Pag

26、e Foreword iv Introduction vi 1 Scope 1 2 Normative reference 1 3 Terms and definitions. 1 4 General principles for establishing allowable limits . 4 5 Establishment of tolerable intake (TI) for specific leachable substances 5 5.1 General . 5 5.2 Exposure considerations for TI calculation . 7 5.3 Co

27、llection and evaluation of data 7 5.4 Set TI for noncancer endpoints . 8 5.5 Set TI for cancer endpoints 10 5.6 Establishment of tolerable contact levels (TCLs) 11 5.7 Risk assessment of mixtures. 13 6 Calculation of tolerable exposure (TE) . 13 6.1 General . 13 6.2 Exposure population. 14 6.3 Calcu

28、lation of utilization factor from intended use pattern 14 6.4 Tolerable exposure . 15 7 Feasibility evaluation 16 8 Benefit evaluation . 16 9 Allowable limits . 17 10 Reporting requirements 17 Annex A (informative) Some typical assumptions for biological parameters 18 Annex B (informative) Risk asse

29、ssment for mixtures of leachable substances 20 Annex C (informative) Conversion of allowable limits for systemic exposure and for body surface contact to maximum dose to patient from a medical device 21 Annex D (informative) Risk analysis report . 23 Bibliography 24 BS EN ISO 10993-17:2009ISO 10993-

30、17:2002(E) iv ISO 2002 All rights reservedForeword 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

31、body interested in a subject for which 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 Electr

32、otechnical Commission (IEC) on all matters of electrotechnical standardization. International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 3. The main task of technical committees is to prepare International Standards. Draft International Standards adopted

33、 by the technical committees are circulated to the member bodies for voting. Publication as an International Standard requires approval by at least 75 % of the member bodies casting a vote. Attention is drawn to the possibility that some of the elements of this part of ISO 10993 may be the subject o

34、f patent rights. ISO shall not be held responsible for identifying any or all such patent rights. ISO 10993-17 was prepared by Technical Committee ISO/TC 194, Biological evaluation of medical devices. ISO 10993 consists of the following parts, under the general title Biological evaluation of medical

35、 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 cytotoxicity Part 6: Tests for local effects after implantation Par

36、t 7: Ethylene oxide sterilization residuals Part 8: Selection and qualification of reference materials for biological tests Part 9: Framework for identification and quantification of potential degradation products Part 10: Tests for irritation and delayed-type hypersensitivity Part 11: Tests for sys

37、temic 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 quantification of degradat

38、ion products from metals and alloys Part 16: Toxicokinetic study design for degradation products and leachables BS EN ISO 10993-17:2009ISO 10993-17:2002(E) ISO 2002 All rights reserved v Part 17: Establishment of allowable limits for leachable substances Part 18: Chemical characterization of materia

39、ls Future parts will deal with other relevant aspects of biological testing. For the purposes of this part of ISO 10993, the CEN annex regarding fulfilment of European Council Directives has been removed. BS EN ISO 10993-17:2009ISO 10993-17:2002(E) vi ISO 2002 All rights reservedIntroduction The det

40、ermination of the suitability of a medical device for a particular use involves balancing any identified risks with the clinical benefit to the patient associated with its use. Among the risks to be considered are those arising from exposure to leachable substances arising from medical devices. Risk

41、s associated with exposure to hazardous leachable substances are managed by identifying the leachable substances, quantifying the associated risks and limiting exposure within tolerable levels. This part of ISO 10993 provides a method by which maximum tolerable levels can be calculated from availabl

42、e data on health risks. Allowable limits may be based upon health risks that can be systemic or local, immediate or delayed, and range in severity from minor localized adverse effects to life-threatening risks. These allowable limits are intended to be derived, using this part of ISO 10993, by toxic

43、ologists or other knowledgeable and experienced individuals, capable of making informed decisions based upon scientific data and a knowledge of medical devices. The allowable limits derived may be used by anyone. In addition to use by ISO, other standards-developing organizations, government agencie

44、s, regulatory bodies, and other users for setting allowable limits as standards or regulations, manufacturers and processors may use the allowable limits derived to optimize processes and aid in the choice of materials in order to protect patient health. Where risks associated with exposure to parti

45、cular leachable substances are unacceptable, this part of ISO 10993 can be used to qualify alternative materials or processes. BS EN ISO 10993-17:2009INTERNATIONAL STANDARD ISO 10993-17:2002(E) ISO 2002 All rights reserved 1Biological evaluation of medical devices Part 17: Establishment of allowable

46、 limits for leachable substances 1 Scope This part of ISO 10993 specifies a method for the determination of allowable limits for substances leachable from medical devices. It is intended for use in deriving standards and estimating appropriate limits where standards do not exist. It describes a syst

47、ematic process through which identified risks arising from toxicologically hazardous substances present in medical devices can be quantified. This part of ISO 10993 is not applicable to devices that have no patient contact (e.g. in vitro diagnostic devices). Exposure to a particular chemical substan

48、ce may arise from sources other than the device, such as food, water or air. This part of ISO 10993 does not address the potential for exposure from such sources. 2 Normative reference The following normative document contains provisions which, through reference in this text, constitute provisions o

49、f this part of ISO 10993. For dated references, subsequent amendments to, or revisions of, any of these publications do not apply. However, parties to agreements based on this part of ISO 10993 are encouraged to investigate the possibility of applying the most recent edition of the normative document indicated below. For undated references, the latest edition of the normative document referred to applies. Members of ISO and IEC maintain registers of currently valid International Standards. ISO 10993-1, Biologic