BS ISO 14949-2001 Implants for surgery - Two-part addition-cure silicone elastomers《外科植入物 双件式附加治疗的硅弹性体》.pdf

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1、BRITISH STANDARD BS ISO 14949:2001 Implants for surgery Two-part addition-cure silicone elastomers ICS 11.040.40 NO COPYING WITHOUT BSI PERMISSION EXCEPT AS PERMITTED BY COPYRIGHT LAWBS ISO 14949:2001 This British Standard, having been prepared under the direction of the Health and Environment Secto

2、r Policy and Strategy Committee, was published under the authority of the Standards Policy and Strategy Committee on 20 November 2001 BSI 20 November 2001 ISBN 0 580 38705 4 National foreword This British Standard reproduces verbatim ISO 14949:2001 and implements it as the UK national standard. The

3、UK participation in its preparation was entrusted to Technical Committee CH/18, Surgical implant materials, which has the responsibility to: A list of organizations represented on this committee can be obtained on request to its secretary. Cross-references The British Standards which implement inter

4、national or European publications referred to in this document may be found in the BSI Standards Catalogue under the section entitled “International Standards Correspondence Index”, or by using the “Find” facility of the BSI Standards Electronic Catalogue. A British Standard does not purport to incl

5、ude all the necessary provisions of a contract. Users of British Standards are responsible for their correct application. Compliance with a British Standard does not of itself confer immunity from legal obligations. aid enquirers to understand the text; present to the responsible international/Europ

6、ean committee any enquiries on the interpretation, or proposals for change, and keep the UK interests informed; monitor related international and European developments and promulgate them in the UK. Summary of pages This document comprises a front cover, an inside front cover, ISO title page, pages

7、ii to v, a blank page, pages 1 to 14, an inside back cover and a back cover. The BSI copyright date displayed in this document indicates when the document was last issued. Amendments issued since publication Amd. No. Date Comments Reference number ISO 14949:2001(E)INTERNATIONAL STANDARD ISO 14949 Fi

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13、1 11 xaF0 947 22 14 + 9 74 E-mail coirypthgiso.c h Web ww.wiso.ch Prinetdni wSizterland ii ISO 14949:2001(E) iiiContents Page Foreword.iv Introduction.v 1 Scope 1 2 Normative references1 3 Terms and definitions .1 4 Formulation 4 4.1 Composition.4 4.2 Raw materials assessment.4 5 Biocompatibility.5

14、6 Characterization and testing 5 6.1 Test slab preparation 5 6.2 Identification 5 6.3 Purity testing5 6.4 Cure rate .6 6.5 Physicomechanical properties and characterization 7 7 Documentation.7 7.1 Data sheet.7 7.2 Certificate of analysis7 Annex A (normative) Determination of substances soluble in he

15、xane .8 Annex B (normative) Determination of volatile matter 12 Bibliography14 ISO 14949:2001(E) iv 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

16、carried out through ISO technical committees. Each member 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 wo

17、rk. ISO collaborates closely with the International Electrotechnical 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. Draft International Standards adopted by the technical c

18、ommittees 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 International Standard may be the subject of patent right

19、s. ISO shall not be held responsible for identifying any or all such patent rights. International Standard ISO 14949 was prepared by Technical Committee ISO/TC 150, Implants for surgery, Subcommittee SC 1, Materials. Annexes A and B form a normative part of this International Standard. ISO 14949:200

20、1(E) vIntroduction Silicones are commercially available in a variety of physical forms and formulations. Silicone-cure products often employ cure mechanisms that utilize metals, free radicals and/or atmospheric moisture. This International Standard was undertaken to describe a subset of silicones wi

21、th a successful history of use in implant applications; namely, those utilizing two-part addition-cure (platinum-based) chemistry. It was developed in response to a need to standardize the raw materials, formulation, processing, characterization testing and documentation of two-part addition-cure si

22、licone elastomers targeted as implants for surgery. Two-part addition-cure silicone elastomer is a thermoset elastomer and is commercialized as a two-part (non- crosslinked) product. The two parts should be thoroughly mixed in a fixed ratio before shaping by extrusion, press- or injection-moulding a

23、nd crosslinking at elevated temperatures. INTERNATIONAL STANDARD ISO 14949:2001(E)Implants for surgery Two-part addition-cure silicone elastomers 1 Scope This International Standard specifies the characteristics of, and corresponding test methods for, the two-part addition-cure high consistency or l

24、iquid silicone elastomer for use in the manufacture (partially or totally) of surgical implants. 2 Normative references The following normative documents contain provisions which, through reference in this text, constitute provisions of this International Standard. For dated references, subsequent a

25、mendments to, or revisions of, any of these publications do not apply. However, parties to agreements based on this International Standard are encouraged to investigate the possibility of applying the most recent editions of the normative documents indicated below. For undated references, the latest

26、 edition of the normative document referred to applies. Members of ISO and IEC maintain registers of currently valid International Standards. ISO 34-1:1994, Rubber, vulcanized or thermoplastic Determination of tear strength Part 1: Trouser, angle and crescent test pieces ISO 48:1994, Rubber, vulcani

27、zed or thermoplastic Determination of hardness (hardness between 10 IRHD and 100 IRHD) ISO 527-2:1993, Plastics Determination of tensile properties Part 2: Test conditions for moulding and extrusion plastics ISO 3417:1991, Rubber Measurement of vulcanization characteristics with the oscillating disc

28、 curemeter ISO 6502:1999, Rubber Guide to the use of curemeters ISO 10993-1:1997, Biological evaluation of medical devices Part 1: Evaluation and testing ISO 10993-5:1999, Biological evaluation of medical devices Part 5: Tests for in vitro cytotoxicity 3 Terms and definitions For the purposes of thi

29、s International Standard, the following terms and definitions apply. 3.1 catalyst organometallic complex, typically containing platinum substituted by ligands made of any suitable combination of the elements carbon, hydrogen, oxygen, chlorine or silicon (with the exclusion of aromatic rings), which

30、initiates a chemical reaction between a polymer and crosslinking agent NOTE The catalyst may be dispersed in a silicone oligomer, polymer or mixture of these, such as RMe 2 SiO(SiMe 2 O) x (SiMeRO) y SiMe 2 R where R and R are methyl or vinyl groups. 1ISO 14949:2001(E) 3.2 crosslinking agent monomer

31、, polymer, silicate or any combination of these, typically of the structure RM e 2 SiO(SiMe 2 O) x (SiRMeO) y SiMe 2 R where R is typically a methyl group or hydrogen, that on curing provides a crosswise connection to parallel polymer chains NOTE Excess SiH is recommended (not required) before curin

32、g to ensure that the cure is total and that no residual Si-vinyl reactive entities exist, thus providing better elastomer stability. 3.3 filler reinforcing agent for the purposes of this International Standard silicate or high purity amorphous silica NOTE 1 Such agents are commercially known as fume

33、d or precipitated silica. NOTE 2 Silica can be treated with silylating agents, for example, those of the formula Me 3 SiX or Me 2 SiX 2where X is a hydrolysable group, or polysiloxane oligomer of the formula HOMe 2 SiO(SiMe 2 O) p (SiMeRO) q SiMe 2 OH where R is a methyl or a vinyl group. NOTE 3 Age

34、nts that impart radiopacity to the elastomer (e.g. BaSO 4 ) may have reinforcing properties. 3.4 inhibitor compound or material that has the effect of slowing down or stopping a chemical reaction such as crosslinking 3.5 lot batch defined quantity of material manufactured in a single or multi-step p

35、rocess such that the material obtained can be considered as homogeneous NOTE in the case of a continuous process, the term corresponds to a defined fraction of the production, characterized by its intended homogeneity. 3.6 manufacturer company who manufactures the final medical device in question 3.

36、7 raw materials materials from which two-part addition-cure silicone elastomer is manufactured 3.8 silicone elastomer synthetic rubber obtained by the crosslinking of silicone polymer chains essentially made of repeat siloxane units EXAMPLE 2ISO 14949:2001(E) 3.9 silicone polymer any polymer or comb

37、ination of polymers of medium or high molecular mass of the structure RMe 2 SiO(SiMe 2 O) x (SiMeRO) y SiMe 2 R, where R is typically a methyl, vinyl or hydroxyl group but might also be a fluoro, phenyl or other group and where R is typically a methyl or vinyl group but might also be a fluoro, pheny

38、l or other group EXAMPLE 1 EXAMPLE 2 EXAMPLE 3 both R and R are methyl, phenyl, fluoro or other suitable organic groups. NOTE The definition of the polymer and its substituted groups is taken very broadly, as it is not the function of this International Standard to limit the number or the type of su

39、bstituent groups present; however, for the purposes of this International Standard the definition only relates to materials with available preclinical biocompatibility data (see clause 5) and a well-established history of safe international use in implant applications. 3.10 supplier company who manu

40、factures and/or supplies the two-part silicone elastomer used for the production of the medical device in question 3.11 treating agent monomer, oligomer or polymer used to coat the outer surface of silica to reduce the reactivity of the silica 3ISO 14949:2001(E) 3.12 two-part addition-cure silicone

41、elastomer elastomer formed by crosslinking silicone polymer chains via an addition reaction between the vinyl functional groups of a vinyl silicone polymer and the silicon hydride of a crosslinking agent containing SiH functions NOTE The reaction requires the presence of a catalyst, usually an organ

42、ometallic complex of platinum. EXAMPLE 4 Formulation 4.1 Composition The defined raw materials shall be used in a formulation as defined in Table 1. Table 1 General formulation for two-part addition-cure silicone elastomers Compound Percentage range (% mass fraction) Silicone polymer 60 to 80 Reinfo

43、rcing agent less than 40 Crosslinking agent 1 to 5 Catalyst 0,5 Inhibitor 1,0 4.2 Raw materials assessment Both during product development and on an audit basis (at least once a year or every tenth production lot), the supplier of the two-part addition-cure elastomer shall assess the raw materials (

44、see 3.8) as follows. a) Structure and functionality of polymer The structure and functionality of the polymer(s) used shall be determined by a suitable method such as nuclear magnetic resonance spectroscopic analysis (see 2 for further information). b) Purity of silica The purity of the silica used

45、shall be assessed by elemental analysis or any other suitable method, and the result should be expressed as (mg Si obtained/theoretical mass) 100 = % mass fraction Si. c) Structure and purity of treating agent(s) The structure and purity of the treating agent(s) used shall be determined by a suitabl

46、e method such as infrared spectroscopy (see 2 for further information). 4ISO 14949:2001(E) d) Structure of the crosslinking agent(s) The structure of the crosslinking agent(s) used shall be determined by a suitable method such as infrared spectroscopy (see 2 for further information). e) Purity of th

47、e inhibitor The purity of the inhibitor used shall be determined based on an appropriate analysis and shall be greater than 95 % mass fraction (see 2 for further information). f) Structure of the inhibitor The structure of the inhibitor used shall be determined by a suitable method such as infrared

48、spectroscopy (see 2 for further information). 5 Biocompatibility The biological and physical properties of the cured silicone elastomer depend largely on the formulation as contained in the two-part starting material. Processing conditions to produce silicone parts (extrusion or molding) can also im

49、pact biological and physical properties. The validation and consistency of production should be part of the quality system of the supplier. In order to ensure consistent final product properties, the manufacturer should ensure that the supplier has installed measures to control for processing and formulation parameters in accordance with ISO 9001, ISO 14969 and good manufacturing practice. In addition, process validation should include a biological assessment, since production could introduce contaminants, and the function