BS EN ISO 10993-7-2008 Biological evaluation of medical devices - Ethylene oxide sterilization residuals《医疗器械的生物学评估 环氧乙烷灭菌残留量》.pdf

1、 ! ()*+ ,)- !“#$%residuals IncorporatingcorrigendumNovember 2009National forewordThis British Standard is the UK implementation of EN ISO 10993-7:2008. It is identical to ISO 10993-7:2008, incorporating corrigendum November 2009. It supersedes BS EN ISO 10993-7:1996 which is withdrawn.The start and

2、finish of text introduced or altered by corrigendum is indicated in the text by tags. Text altered by ISO corrigendum November 2009 is indicated in the text by .The UK participation in its preparation was entrusted to Technical Committee CH/194, Biological evaluation of medical devices.A list of org

3、anizations represented on this committee can be obtained on request to its secretary.This publication does not purport to include all the necessary provisions of a contract. Users are responsible for its correct application.Compliance with a British Standard cannot confer immunity from legal obligat

4、ions.BS EN ISO 10993-7:2008This British Standard was published under the authority of the Standards Policy and Strategy Committee on 31 December 2008 BSI 2010Amendments/corrigenda issued since publicationDate Comments 31 July 2010 Implementation of ISO corrigendum November 2009ISBN 978 0 580 70145 0

5、EUROPEAN STANDARDNORME EUROPENNEEUROPISCHE NORMEN ISO 10993-7October 2008ICS 11.100.20 Supersedes EN ISO 10993-7:1995 English VersionBiological evaluation of medical devices - Part 7: Ethylene oxidesterilization residuals (ISO 10993-7:2008)valuation biologique des dispositifs mdicaux - Partie 7:Rsid

6、us de strilisation loxyde dthylne (ISO 10993-7:2008)Biologische Beurteilung von Medizinprodukten - Teil 7:Ethylenoxid- Sterilisationsrckstnde (ISO 10993-7:2008)This European Standard was approved by CEN on 23 September 2008.CEN members are bound to comply with the CEN/CENELEC Internal Regulations wh

7、ich stipulate the conditions for giving 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 Sta

8、ndard exists in three official versions (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 stan

9、dards bodies of Austria, Belgium, Bulgaria, 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 King

10、dom.EUROPEAN COMMITTEE FOR STANDARDIZATIONCOMIT EUROPEN DE NORMALISATIONEUROPISCHES KOMITEE FR NORMUNGManagement Centre: rue de Stassart, 36 B-1050 Brussels 2008 CEN All rights of exploitation in any form and by any means reservedworldwide for CEN national Members.Ref. No. EN ISO 10993-7:2008: E3 Fo

11、reword This document (EN ISO 10993-7:2008) has been prepared by Technical Committee ISO/TC 194 “Biological evaluation of medical devices“ in collaboration with Technical Committee CEN/TC 206 “Biological evaluation of medical devices” the secretariat of which is held by NEN. This European Standard sh

12、all be given the status of a national standard, either by publication of an identical text or by endorsement, at the latest by April 2009, and conflicting national standards shall be withdrawn at the latest by October 2011. Attention is drawn to the possibility that some of the elements of this docu

13、ment 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 10993-7:1995. This document has been prepared under a mandate given to CEN by the European Commission and the European Free Trade

14、Association, and supports essential requirements of EC Directives. For relationship with EC Directives, see informative Annexes ZA and ZB, which are an integral part of this document. NOTE : The Essential Requirements of the Medical Devices Directives require that risks be reduced or eliminated as f

15、ar as possible and, specifically, that risks posed by residues be minimized and risks posed by substances leaking from a device be reduced to a minimum. It is inherent in these Essential Requirements that, within the maximum limits specified by this standard, exposure to a genotoxic carcinogen shoul

16、d be reduced to levels as low as reasonably practicable, taking account of the generally acknowledged state of the art, the technological level existing at the time of design and technical and economic considerations compatible with a high level of health and safety. According to the CEN/CENELEC Int

17、ernal Regulations, the national standards organizations of the following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, M

18、alta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and the United Kingdom. Endorsement notice The text of ISO 10993-7:2008 has been approved by CEN as a EN ISO 10993-7:2008 without any modification. BS EN ISO 10993-7:2008EN ISO 10993-7:2008 (E)4 Anne

19、x ZA (informative) Relationship between this International Standard and the Essential Requirements of EU Directive 93/42/EEC Medical devices This International Standard has been prepared under a mandate given to CEN by the European Commission and the European Free Trade Association to provide a mean

20、s 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 has been implemented as a national standard in at least one Member State, compliance with the

21、 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 associated EFTA regulations. Table ZA Correspondence between this International Standard and Directive

22、 93/42/EEC on medical devices Clause(s)/sub-clause(s) of this International Standard Essential Requirements (ERs) of Directive 93/42/EEC Qualifying remarks/Note 4, 5 Annex I, 7.2 and 7.5 For presumption of conformity, the standard needs to be interpreted as explained in the European Foreword. WARNIN

23、G Other requirements and other EU Directives may be applicable to the product(s) falling within the scope of this International standard. BS EN ISO 10993-7:2008EN ISO 10993-7:2008 (E)5 Annex ZB (informative) Relationship between this International Standard and the Essential Requirements of EU Direct

24、ive 90/385/EEC on Active Implantable Medical Devices This International 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 ac

25、tive implantable medical devices. Once this 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 limi

26、ts of the scope of this standard, a presumption of conformity with the corresponding Essential Requirements of that Directive and associated EFTA regulations. Table ZB Correspondence between this International Standard and Directive 90/385/EEC on active implantable medical devices Clause(s)/sub-clau

27、se(s) of this International Standard Essential Requirements (ERs) of Directive 90/385/EEC Qualifying remarks/Note 4, 5 Annex I, 9 For presumption of conformity, the standard needs to be interpreted as explained in the European Foreword. WARNING Other requirements and other EU Directives may be appli

28、cable to the product(s) falling within the scope of this International standard. BS EN ISO 10993-7:2008EN ISO 10993-7:2008 (E)iiiContents Page Foreword iv Introduction . vi 1 Scope 1 2 Normative references 1 3 Terms and definitions .1 4 Requirements.2 4.1 General2 4.2 Categorization of devices .2 4.

29、3 Allowable limits3 4.4 Determination of EO and ECH residuals .5 5 Product release10 5.1 General10 5.2 Release of products without dissipation curve data .10 5.3 Procedure for product release using residue dissipation curves 10 Annex A (normative) Evaluation of gas chromatograms12 Annex B (informati

30、ve) Gas chromatographic determination for EO and ECH15 Annex C (informative) Flowchart and guidance for the application of this part of ISO 10993 series of standards to the determination of EO and ECH residuals in medical devices.19 Annex D (informative) Factors influencing product residual26 Annex

31、E (informative) Extraction conditions for determination of residual EO .28 Annex F (informative) Rationale for the provisions of this part of ISO 10993 29 Annex G (informative) Establishment of allowable limits for EO .33 Annex H (informative) Establishment of allowable limits for ECH.50 Annex I (in

32、formative) Establishment of allowable limits for EG.59 Annex J (informative) Preparation of EO and ECH standards63 Annex K (informative) Ethylene oxide residue measuring methods .67 Bibliography 74 BS EN ISO 10993-7:2008EN ISO 10993-7:2008 (E) ISO 2010 iv Foreword ISO (the International Organization

33、 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 which a technical committee has been established has

34、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 matters of electrotechnical standardization. Intern

35、ational 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 circulated to the member bodies for voting. Publicati

36、on 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 document may be the subject of patent rights. ISO shall not be held responsible for identifying any or all such patent right

37、s. ISO 10993-7 was prepared by Technical Committee ISO/TC 194, Biological evaluation of medical devices. This second edition cancels and replaces the first edition (ISO 10993-7:1995) which has been technically revised. ISO 10993 consists of the following parts, under the general title Biological eva

38、luation of medical devices: 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 Part 7: Ethylene

39、 oxide sterilization residuals Part 9: Framework for identification and quantification of potential degradation products Part 10: Tests for irritation and skin sensitization Part 11: Tests for systemic toxicity Part 12: Sample preparation and reference materials Part 13: Identification and quantific

40、ation of degradation products from polymeric medical devices Part 14: Identification and quantification of degradation products from ceramics Part 15: Identification and quantification of degradation products from metals and alloys Part 1: Evaluation and testing within a risk management process BS E

41、N ISO 10993-7:2008EN ISO 10993-7:2008 (E) ISO 2010v 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 topographic

42、al characterization of materials Technical Specification Part 20: Principles and methods for immunotoxicology testing of medical devices Technical SpecificationBS EN ISO 10993-7:2008EN ISO 10993-7:2008 (E) ISO 2010vi Introduction Requirements for the development, validation and routine control of an

43、 ethylene oxide sterilization process for medical devices are given in International Standards developed by ISO/TC 198. Certain requirements relating to medical devices for biological testing, selection of tests, and the allocation of devices to categories are dealt with in a variety of Internationa

44、l Standards developed by ISO/TC 194. The specific requirement for ethylene oxide and other sterilization process residuals was referred to ISO/TC 194. Other International Standards delineate particular requirements for biological testing for specific products. As noted in the introduction to ISO 111

45、35-1:2007, when determining the suitability of ethylene oxide (EO) for sterilization of medical devices, it is important to ensure that the levels of residual EO, ethylene chlorohydrin (ECH) and ethylene glycol (EG) pose a minimal risk to the patient in normal product use. Therefore, it is important

46、 that the use of alternative materials and sterilization processes be considered during product design and development. EO is known to exhibit a number of biological effects. In the development of this part of ISO 10993, consideration was given to these effects, which include irritation, organ damag

47、e, mutagenicity and carcinogenicity in humans and animals, and reproductive effects in animals. Similar consideration was given to the harmful effects of ECH and EG. In practice, for most devices, exposure to EO and ECH is considerably lower than the maximum values specified in this part of ISO 1099

48、3. Moreover, when the choice for EO sterilization has been made, irrespective of the provisions of this part of ISO 10993, exposure to EO residues should be minimized. Requirements herein are in addition to the biological evaluation and testing requirements for each individually designed medical device as indi