BS ISO 13781-2017 Implants for surgery Homopolymers copolymers and blends on poly(lactide) In vitro degradation testing《外科植入物 聚丙交酯上的均聚物、共聚物和共混物 体外降解试验》.pdf

1、Implants for surgery Homopolymers, copolymers and blends on poly(lactide) In vitro degradation testingBS ISO 13781:2017BSI Standards PublicationWB11885_BSI_StandardCovs_2013_AW.indd 1 15/05/2013 15:06National forewordThis British Standard is the UK implementation of ISO 13781:2017. The UK participat

2、ion in its preparation was entrusted to Technical Committee CH/150/1, Materials for surgical implants.A list of organizations 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 r

3、esponsible for its correct application. The British Standards Institution 2017 Published by BSI Standards Limited 2017ISBN 978 0 580 85741 6ICS 11.040.40Compliance with a British Standard cannot confer immunity from legal obligations. This British Standard was published under the authority of the St

4、andards Policy and Strategy Committee on 31 July 2017.Amendments/corrigenda issued since publicationDate Text affectedBRITISH STANDARDBS ISO 13781:2017 ISO 2017Implants for surgery Homopolymers, copolymers and blends on poly(lactide) In vitro degradation testingImplants chirurgicaux Homopolymres, co

5、polymres et mlanges sur poly(lactide) Essais de dgradation in vitroINTERNATIONAL STANDARDISO13781Second edition2017-07-15Reference numberISO 13781:2017(E)BS ISO 13781:2017ISO 13781:2017(E)ii ISO 2017 All rights reservedCOPYRIGHT PROTECTED DOCUMENT ISO 2017, Published in SwitzerlandAll rights reserve

6、d. Unless otherwise specified, no part of this publication may be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting on the internet or an intranet, without prior written permission. Permission can be requested from either ISO a

7、t the address below or ISOs member body in the country of the requester.ISO copyright officeCh. de Blandonnet 8 CP 401CH-1214 Vernier, Geneva, SwitzerlandTel. +41 22 749 01 11Fax +41 22 749 09 47copyrightiso.orgwww.iso.orgBS ISO 13781:2017ISO 13781:2017(E)Foreword ivIntroduction v1 Scope . 12 Normat

8、ive references 13 Terms and definitions . 24 Degradation evaluation . 34.1 General . 34.2 Apparatus and reagents 44.2.1 Soaking solution . 44.2.2 Sample container . 44.2.3 Constant-temperature bath or oven . 44.2.4 pH-meter . 54.2.5 Balance . 54.3 Real-time degradation Sample conditioning procedure

9、54.3.1 Sample loading and placement 54.3.2 Control of temperature . 54.3.3 Control of buffer solution . 54.3.4 Sample retrieval 65 Physical, chemical and mechanical tests . 65.1 General . 65.2 Loss of sample mass . 65.2.1 Apparatus . 65.2.2 Number of test samples . 75.2.3 Procedure . 75.2.4 Reusabil

10、ity of test specimens 85.3 Evaluation of molar mass . 85.3.1 Via inherent viscosity 85.3.2 Via gel permeation chromatography/size exclusion chromatography 85.4 Mechanical tests . 85.4.1 General 85.4.2 Conditioning of test samples . 95.4.3 Test methods . 95.5 Additional evaluation methods for conside

11、ration .106 Test termination 107 Test report 10Annex A (informative) Nomenclature of absorb, degrade and related terms 13Annex B (informative) Additional analytic methods for consideration 14Bibliography .15 ISO 2017 All rights reserved iiiContents PageBS ISO 13781:2017ISO 13781:2017(E)ForewordISO (

12、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 which a technical commi

13、ttee 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 matters of electrotec

14、hnical standardization.The procedures used to develop this document and those intended for its further maintenance are described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the different types of ISO documents should be noted. This document was drafted

15、 in accordance with the editorial rules of the ISO/IEC Directives, Part 2 (see www.iso.org/directives).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 rights

16、 Details of any patent rights identified during the development of the document will be in the Introduction and/or on the ISO list of patent declarations received (see www.iso.org/patents).Any trade name used in this document is information given for the convenience of users and does not constitute

17、 an endorsement.For an explanation on the voluntary nature of standards, the meaning of ISO specific terms and expressions related to conformity assessment, as well as information about ISOs adherence to the World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT) see the f

18、ollowing URL: www.iso.org/iso/foreword.html.This document was prepared by Technical Committee ISO/TC 150, Implants for surgery, Subcommittee SC 1, Materials. This second edition cancels and replaces the first edition (ISO 13781:1997) and ISO 15814, which have been technically revised. The main chang

19、e compared to the previous edition is as follows: the principle contents of ISO 15814 are incorporated into this document.iv ISO 2017 All rights reservedBS ISO 13781:2017ISO 13781:2017(E)IntroductionWith the development of absorbable polymers for use in implantable devices, there is a need to define

20、 standard test methods to evaluate the behaviour of bulk material or devices under simulated physiological environments. On the other hand, the behaviour of absorbable materials and devices in situ depends on the conditions in which the material is implanted. These conditions differ, so that the sit

21、e-specific behaviour of the material or device can differ. The interpretation of in vitro test results therefore needs to be considered carefully, taking into account any correlation of test results under in vitro and in vivo conditions. Only functional in vivo tests with the final product can answe

22、r actual degradation behaviour in situ. ISO 2017 All rights reserved vBS ISO 13781:2017This page deliberately left blankImplants for surgery Homopolymers, copolymers and blends on poly(lactide) In vitro degradation testing1 ScopeThis document describes methods for the determination of chemical and m

23、echanical changes in poly(lactide)-based homopolymers, copolymers and/or blends induced under in vitro degradation testing conditions. This document covers polymers based on L-lactide, D-lactide, and/or D, L-lactide monomeric units.The purpose of this document is to compare and/or evaluate materials

24、 or processing conditions. This document also describes the fundamental physical and mechanical evaluations needed for an in vitro degradation characterization of an absorbable poly(lactide) or other hydrolysable material or device.This document is applicable to poly(lactide)-based homopolymers, cop

25、olymers and/or blends in bulk or processed forms and used for the manufacture of surgical implants, including finished products (packaged and sterilized implants).The test methods specified in this document are also intended to determine the in vitro degradation rate and related changes in material

26、properties of polylactide-based copolymers and/or blends with various other comonomers, such as glycolid, trimethylene, carbonate and/or -caprolactone. Unless otherwise validated for a specific device, these in vitro methods cannot be used to definitively predict device behaviour under in vivo condi

27、tions.2 Normative referencesThe following documents are referred to in the text in such a way that some or all of their content constitutes requirements of this document. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (incl

28、uding any amendments) applies.ISO 178, Plastics Determination of flexural propertiesISO 180, Plastics Determination of Izod impact strengthISO 527-1, Plastics Determination of tensile properties Part 1: General principlesISO 527-2, Plastics Determination of tensile properties Part 2: Test conditions

29、 for moulding and extrusion plasticsISO 527-3, Plastics Determination of tensile properties Part 3: Test conditions for films and sheetsISO 604,Plastics Determination of compressive propertiesISO 1628-1, Plastics Determination of the viscosity of polymers in dilute solution using capillary viscomete

30、rs Part 1: General principlesISO 1805, Fishing nets Determination of breaking force and knot breaking force of netting yarnsISO 2062, Textiles Yarns from packages Determination of single-end breaking force and elongation at break using constant rate of extension (CRE) testerISO 6721-2, Plastics Dete

31、rmination of dynamic mechanical properties Part 2: Torsion-pendulum methodISO 13934-1,Textiles Tensile properties of fabrics Part 1: Determination of maximum force and elongation at maximum force using the strip methodINTERNATIONAL STANDARD ISO 13781:2017(E) ISO 2017 All rights reserved 1BS ISO 1378

32、1:2017ISO 13781:2017(E)ISO 14130, Fibre-reinforced plastic composites Determination of apparent interlaminar shear strength by short-beam methodISO 16014-1, Plastics Determination of average molecular mass and molecular mass distribution of polymers using size-exclusion chromatography Part 1: Genera

33、l principlesISO 16014-2, Plastics Determination of average molecular mass and molecular mass distribution of polymers using size-exclusion chromatography Part 2: Universal calibration methodISO 16014-3, Plastics Determination of average molecular mass and molecular mass distribution of polymers usin

34、g size-exclusion chromatography Part 3: Low-temperature methodISO 16014-4, Plastics Determination of average molecular mass and molecular mass distribution of polymers using size-exclusion chromatography Part 4: High-temperature methodISO 16014-5, Plastics Determination of average molecular mass and

35、 molecular mass distribution of polymers using size-exclusion chromatography Part 5: Method using light-scattering detectionASTM D2990,Standard test methods for tensile, compressive, and flexural creep and creep-rupture of plasticsASTM D5296, Test method for molecular weight averages and molecular w

36、eight distribution of polystyrene by high performance size-exclusion chromatographyASTM F1635-16, Standard test method for in vitro degradation testing of hydrolytically degradable polymer resins and fabricated forms for surgical implantsASTM F2902-16, Standard guide for assessment of absorbable pol

37、ymeric implants3 Terms and definitionsFor the purposes of this document, the following terms and definitions apply.ISO and IEC maintain terminological databases for use in standardization at the following addresses: IEC Electropedia: available at http:/www.electropedia.org/ ISO Online browsing platf

38、orm: available at http:/www.iso.org/obp NOTE A discussion regarding the basis for some of the terms and definitions in this clause is available in Annex A.3.1absorbable polymernon-endogenous (foreign) polymeric material that is capable of passing through or being assimilated by cells and/or tissue o

39、ver time3.2absorptionact of a non-endogenous (foreign) material or substance passing through or being assimilated by cells and/or tissue over time3.3blendphysical mixture of two or more different thermoplastic polymers and/or copolymers (3.4) 3.4copolymerpolymer synthesized by polymerizing two or mo

40、re monomer units together2 ISO 2017 All rights reservedBS ISO 13781:2017ISO 13781:2017(E)3.5in vitro degradationloss of mechanical properties and/or chemical integrity through chemical changes induced by a simulated physiological environment3.6poly(D,L-lactide)polymer synthesized with approximately

41、equimolar concentrations of D-lactide and L-lactide monomeric units3.7poly(L-lactide)polymer synthesized exclusively from L-lactide monomeric units3.8samplefinite subset, object or individual of a group, class or population whose properties or characteristics are studied to gain information regardin

42、g the whole3.9specimenspecific portion or quantity of a sample utilized to obtain a single measurement of a property or characteristic4 Degradation evaluation4.1 GeneralAppropriate in vitro characterization of the degradation of an absorbable polymeric material monitors the progressive loss of both

43、sample mass and molar mass (i.e. molecular weight) from ongoing exposure to a physiologically relevant environment. Such an environment provides fluid and thermal conditions that generate an in vitro degradation rate that approximates the rate observed in vivo. Such an in vitro degradation character

44、ization also monitors the loss of device-relevant mechanical properties over time. Thus, unless justified otherwise, such a material or device degradation characterization shall include a systematic monitoring of the loss of sample mass (see 5.2), molar mass (via inherent viscosity and/or GPC/SEC, s

45、ee 5.3) and at least one mechanical property that can be considered relevant to the characteristics and intended use of the device (see 5.4).The degradation rate of an absorbable material or device can be affected by sample dimensions and other manufacturing/processing parameters (e.g. fibre draw ra

46、tio). As the shape and the structure of the test sample can have a strong influence on the degradation kinetics, where applicable, the initial test sample should be comparable to the intended product in shape and structure (i.e. fibre, film, plate, rod, bulk material or other relevant form, as appro

47、priate). The test sample may be a finished product or a test coupon fabricated to emulate the relevant physical and/or mechanical properties of the intended product.Evaluation of samples representative of the finished product shall be conducted following terminal sterilization at a level that meets

48、or exceeds anticipated commercial exposure.While the described general degradation evaluations and related tests can be useful toward characterizing a finished product, they are not necessarily adequate to address all device-specific issues. For example, a device that undergoes in vivo loading can d

49、egrade significantly faster than an identical device implanted in an unloaded application. Thus, a device that is intended to undergo in vivo loading should be additionally evaluated in vitro under real-time degradation conditions that approximate the anticipated mechanical loading, including, if applicable, cyclic loading, shear, creep loading, with further guidance available in ASTM F2902-16, 6.2.2.2. ISO 2017 All rights reserved 3BS ISO 13781:2017ISO 13781:2017(E)The init