SVENSK STANDARD SS-EN ISO :2017

Transcription

1 SVENSK STANDARD SS-EN ISO :2017 Fastställd/Approved: Publicerad/Published: Utgåva/Edition: 3 Språk/Language: engelska/english ICS: ; Biologisk värdering av medicintekniska produkter Del 6: Prövning för lokala reaktioner efter implantation (ISO :2016) Biological evaluation of medical devices Part 6: Tests for local effects after implantation (ISO :2016)

2 Standarder får världen att fungera SIS (Swedish Standards Institute) är en fristående ideell förening med medlemmar från både privat och offentlig sektor. Vi är en del av det europeiska och globala nätverk som utarbetar internationella standarder. Standarder är dokumenterad kunskap utvecklad av framstående aktörer inom industri, näringsliv och samhälle och befrämjar handel över gränser, bidrar till att processer och produkter blir säkrare samt effektiviserar din verksamhet. Delta och påverka Som medlem i SIS har du möjlighet att påverka framtida standarder inom ditt område på nationell, europeisk och global nivå. Du får samtidigt tillgång till tidig information om utvecklingen inom din bransch. Ta del av det färdiga arbetet Vi erbjuder våra kunder allt som rör standarder och deras tillämpning. Hos oss kan du köpa alla publikationer du behöver allt från enskilda standarder, tekniska rapporter och standardpaket till handböcker och onlinetjänster. Genom vår webbtjänst e-nav får du tillgång till ett lättnavigerat bibliotek där alla standarder som är aktuella för ditt företag finns tillgängliga. Standarder och handböcker är källor till kunskap. Vi säljer dem. Utveckla din kompetens och lyckas bättre i ditt arbete Hos SIS kan du gå öppna eller företagsinterna utbildningar kring innehåll och tillämpning av standarder. Genom vår närhet till den internationella utvecklingen och ISO får du rätt kunskap i rätt tid, direkt från källan. Med vår kunskap om standarders möjligheter hjälper vi våra kunder att skapa verklig nytta och lönsamhet i sina verksamheter. Vill du veta mer om SIS eller hur standarder kan effektivisera din verksamhet är du välkommen in på eller ta kontakt med oss på tel Standards make the world go round SIS (Swedish Standards Institute) is an independent non-profit organisation with members from both the private and public sectors. We are part of the European and global network that draws up international standards. Standards consist of documented knowledge developed by prominent actors within the industry, business world and society. They promote cross-border trade, they help to make processes and products safer and they streamline your organisation. Take part and have influence As a member of SIS you will have the possibility to participate in standardization activities on national, European and global level. The membership in SIS will give you the opportunity to influence future standards and gain access to early stage information about developments within your field. Get to know the finished work We offer our customers everything in connection with standards and their application. You can purchase all the publications you need from us - everything from individual standards, technical reports and standard packages through to manuals and online services. Our web service e-nav gives you access to an easy-to-navigate library where all standards that are relevant to your company are available. Standards and manuals are sources of knowledge. We sell them. Increase understanding and improve perception With SIS you can undergo either shared or in-house training in the content and application of standards. Thanks to our proximity to international development and ISO you receive the right knowledge at the right time, direct from the source. With our knowledge about the potential of standards, we assist our customers in creating tangible benefit and profitability in their organisations. If you want to know more about SIS, or how standards can streamline your organisation, please visit or contact us on phone +46 (0)

3 Europastandarden EN ISO :2016 gäller som svensk standard. Detta dokument innehåller den officiella engelska versionen av EN ISO :2016. Denna standard ersätter SS-EN ISO :2009, utgåva 2. The European Standard EN ISO :2016 has the status of a Swedish Standard. This document contains the official English version of EN ISO :2016. This standard supersedes the Swedish Standard SS-EN ISO :2009, edition 2. Copyright / Upphovsrätten till denna produkt tillhör SIS, Swedish Standards Institute, Stockholm, Sverige. Användningen av denna produkt regleras av slutanvändarlicensen som återfinns i denna produkt, se standardens sista sidor. Copyright SIS, Swedish Standards Institute, Stockholm, Sweden. All rights reserved. The use of this product is governed by the end-user licence for this product. You will find the licence in the end of this document. Upplysningar om sakinnehållet i standarden lämnas av SIS, Swedish Standards Institute, telefon Standarder kan beställas hos SIS Förlag AB som även lämnar allmänna upplysningar om svensk och utländsk standard. Information about the content of the standard is available from the Swedish Standards Institute (SIS), telephone Standards may be ordered from SIS Förlag AB, who can also provide general information about Swedish and foreign standards. Denna standard är framtagen av kommittén för Biologisk säkerhet, SIS / TK 340 / AG b. Har du synpunkter på innehållet i den här standarden, vill du delta i ett kommande revideringsarbete eller vara med och ta fram andra standarder inom området? Gå in på - där hittar du mer information.

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5 EUROPEAN STANDARD NORME EUROPÉENNE EUROPÄISCHE NORM Provläsningsexemplar / Preview EN ISO December 2016 ICS Supersedes EN ISO :2009 English Version Biological evaluation of medical devices - Part 6: Tests for local effects after implantation (ISO :2016) Évaluation biologique des dispositifs médicaux - Partie 6: Essais concernant les effets locaux après implantation (ISO :2016) Biologische Beurteilung von Medizinprodukten - Teil 6: Prüfungen auf lokale Effekte nach Implantationen (ISO :2016) This European Standard was approved by CEN on 4 November CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this European Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references concerning such national standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN member. This European Standard exists in three official versions (English, French, German). A version in any other language made by translation under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management Centre has the same status as the official versions. CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and United Kingdom. EUROPEAN COMMITTEE FOR STANDARDIZATION COMITÉ EUROPÉEN DE NORMALISATION EUROPÄISCHES KOMITEE FÜR NORMUNG CEN-CENELEC Management Centre: Avenue Marnix 17, B-1000 Brussels 2016 CEN All rights of exploitation in any form and by any means reserved worldwide for CEN national Members. Ref. No. EN ISO :2016 E

6 SS-EN ISO :2017 (E) Provläsningsexemplar / Preview Contents Page European foreword... iv 1 Scope Normative references Terms and definitions Common provisions for implantation test methods Test methods, general aspects Test report General Test laboratory Implant samples Animals and implantation Retrieval and histological procedure Macroscopic and microscopic evaluation Final evaluation...10 Annex A (normative) Test methods for implantation in subcutaneous tissue...11 Annex B (normative) Test method for implantation in muscle...13 Annex C (normative) Test method for implantation in bone...15 Annex D (normative) Test method for implantation in brain tissue...18 Annex E (informative) Examples of evaluation of local biological effects after implantation...23 Annex ZA (informative) Relationship between this European Standard and the essential requirements of Directive 93/42/EEC [OJ L 169] aimed to be covered Annex ZB (informative) Relationship between this European Standard and the essential requirements of Directive 90/385/EEC [OJ L 189] aimed to be covered Bibliography...31 iii

7 SS-EN ISO :2017 (E) European foreword This document (EN ISO :2016) has been prepared by Technical Committee ISO/TC 194 "Biological and clinical evaluation of medical devices" in collaboration with Technical Committee CEN/TC 206 Biological and clinical evaluation of medical devices the secretariat of which is held by DIN. 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 June 2017, and conflicting national standards shall be withdrawn at the latest by June 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 :2009. This document has been prepared under a mandate given to CEN by the European Commission and the European Free Trade Association, and supports essential requirements of EU Directives. For relationship with EU Directives, see informative Annex ZA and ZB, which are integral parts 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, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the United Kingdom. Endorsement notice The text of ISO :2016 has been approved by CEN as EN ISO :2016 without any modification. The following referenced documents are indispensable for the application of this document. For undated references, the latest edition of the referenced document (including any amendments) applies. For dated references, only the edition cited applies. However, for any use of this standard within the meaning of Annex ZA, the user should always check that any referenced document has not been superseded and that its relevant contents can still be considered the generally acknowledged state-ofart. When an IEC or ISO standard is referred to in the ISO standard text, this shall be understood as a normative reference to the corresponding EN standard, if available, and otherwise to the dated version of the ISO or IEC standard, as listed below. NOTE The way in which these referenced documents are cited in normative requirements determines the extent (in whole or in part) to which they apply. iv

8 SS-EN ISO :2017 (E) Provläsningsexemplar / Preview Table 1 Correlations between undated normative references and dated EN and ISO standards Normative references as listed in Clause 2 of the ISO standard Equivalent dated standard EN ISO or IEC ISO EN ISO :2009 ISO :2009 ISO EN ISO :2006 ISO :2006 ISO EN ISO :2009 ISO :2002 ISO EN ISO :2012 ISO :2012 ISO EN ISO :2010 ISO :2010 NOTE This part of EN ISO refers to ISO which itself refers to ISO In Europe, it should be assumed that the reference to ISO is to EN ISO 14971:2012. v

9 SS-EN ISO :2017 (E) Biological evaluation of medical devices Part 6: Tests for local effects after implantation 1 Scope This part of ISO specifies test methods for the assessment of the local effects after implantation of biomaterials intended for use in medical devices. This part of ISO applies to materials that are solid and non-absorbable, non-solid, such as porous materials, liquids, gels, pastes, and particulates, and degradable and/or absorbable, which may be solid or non-solid. The test sample is implanted into a site and animal species appropriate for the evaluation of the biological safety of the material. These implantation tests are not intended to evaluate or determine the performance of the test sample in terms of mechanical or functional loading. This part of ISO can also be applied to medical devices that are intended to be used topically in clinical indications where the surface or lining might have been breached, in order to evaluate local tissue responses. The local effects are evaluated by a comparison of the tissue response caused by a test sample to that caused by control materials used in medical devices whose clinical acceptability and biocompatibility characteristics have been established. The objective of the test methods is to characterize the history and evolution of the tissue response after implantation of a medical device/biomaterial including final integration or absorption/degradation of the material. In particular for degradable/absorbable materials, the degradation characteristics of the material and the resulting tissue response should be determined. This part of ISO does not deal with systemic toxicity, carcinogenicity, teratogenicity or mutagenicity. However, the long-term implantation studies intended for evaluation of local biological effects might provide insight into some of these properties. Systemic toxicity studies conducted by implantation might satisfy the requirements of this part of ISO When conducting combined studies for evaluating local effects and systemic effects, the requirements of both standards is to be fulfilled. 2 Normative references The following documents, in whole or in part, are normatively referenced in this document and are indispensable for its application. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies. ISO , Biological evaluation of medical devices Part 1: Evaluation and testing within a risk management process ISO , Biological evaluation of medical devices Part 2: Animal welfare requirements ISO , Biological evaluation of medical devices Part 4: Selection of tests for interactions with blood ISO , Biological evaluation of medical devices Part 12: Sample preparation and reference materials 1

10 SS-EN ISO :2017 (E) Provläsningsexemplar / Preview ISO , Biological evaluation of medical devices Part 16: Toxicokinetic study design for degradation products and leachables 3 Terms and definitions For the purposes of this document, the terms and definitions given in ISO , ISO , ISO , ISO and the following apply. 3.1 absorb/absorption action of a non-endogenous (foreign) material or substance, or its decomposition products passing through or being assimilated by cells and/or tissue over time 3.2 degradation decomposition of a material [SOURCE: ISO :2009, 3.1] 3.3 degradation product any intermediate or final by-product which results from the physical, metabolic, and/or chemical decomposition of a material or substance [SOURCE: ISO/TR 37137:2014, 2.2, modified] 3.4 degrade to physically, metabolically, and/or chemically decompose a material or substance [SOURCE: ISO/TR 37137:2014, 2.3] 3.5 biomaterial material or substance intended to interface with biological systems to evaluate, treat, augment or replace any tissue, organ or function of the body. [SOURCE: European Society Biomaterials Conference II] 4 Common provisions for implantation test methods 4.1 General It is important that the study be planned in sufficient detail such that all relevant information can be extracted from the use of each animal and each study (see ISO , ISO and ISO ). All animal studies shall be performed in a facility approved by a nationally recognized organization and in accordance with all appropriate regulations dealing with laboratory animal welfare to comply with the requirements of ISO These studies shall be performed under good laboratory practices or other recognized, quality assurance systems. The provisions of this Clause shall apply to the test methods specified in Annex A, Annex B, Annex C, and Annex D. 4.2 Preparation of samples for implantation Test sample and reference or control material preparation shall be in accordance with ISO The implant size and shape shall be documented and justified. Test samples for various implant sites are described in Annex A, Annex B, Annex C, and Annex D. Physical characteristics (such as form, density, 2

11 SS-EN ISO :2017 (E) hardness, surface) can influence the character of the tissue response to the test material and shall be recorded and taken into account when the response is characterized. Control articles should be matched as closely as reasonably possible for physical characteristics Each implant shall be manufactured, processed, cleaned of contaminants, and sterilized by the method intended for the final product and this shall be confirmed in the study documentation. After final preparation and sterilization, the implant samples shall be handled aseptically and in such a way as to ensure that they are not damaged or contaminated in any way prior to or during implantation For materials used as scaffolds for tissue-engineered medical products, it may be appropriate not to use the final preparation pre-populated with cells and/or proteins, as the immune reaction of the animal to the cellular/protein components of such products and the reaction of the cells to the animal may interfere with the resulting local tissue response, making it difficult to interpret For composite materials (e.g. bone cements, dental materials), the components may be mixed before use and allowed to set before implantation. For multicomponent materials designed to be cured prior to placement, the components may be mixed before use and allowed to set before implantation. However, materials that are designed to polymerize in situ (e.g. bone cements, many dental materials) shall be introduced in a manner such that in situ polymerization occurs. The procedure used shall be documented and justified Non-solid materials (including powders) may be contained in open-ended cylindrical tubes for the purpose of testing for local effects after implantation (see ISO for the selection of materials for tubes). Prepare the test material according to the manufacturer s instructions and insert the material into the tube until level with the end, taking care not to contaminate the outer surface of the tube with the test material. If contamination occurs, the sample shall not be implanted. Avoid entrapment of air in the tube and ensure that the end surfaces of the inserted material in the tube and the tube ends are smooth. Polyethylene (PE), polypropylene (PP), or polytetrafluoroethylene (PTFE) tubes are commonly used for this purpose. PE tubes can be deformed by autoclaving Evaluation shall be performed by comparing the tissue reaction to that of a similar sample/material whose clinical acceptability and biocompatibility characteristics have been established. NOTE For further guidance, see ISO The physical characteristics such as shape, and especially the surface condition of the control(s), shall be as similar to that of the implant test samples as is practical, with any deviations being explained and justified. When the test material is contained in a tube, the control shall be of the same material as the tube and have the same diameter as the outer diameter of the tube. The choice of the control rod or tube shall be documented and justified For implantation studies, the amount or size of the test and control article shall be documented. 4.3 Study design For devices comprising/composed of two or more different materials, the test articles should be of similar composition or multiple implants may be needed, e.g. if a device is made of HDPE and titanium then the test article should be made of HDPE and titanium. 3