SIST EN 13503-5:2002

2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.Ophthalmische Implantate - Intraokularlinsen - Teil 5: Biokompatibilität (ISO 11979-5:1999, modifiziert)Implants ophtalmiques - Lentilles intraoculaires - Partie 5: Biocompatibilité (ISO 11979-5:1999, modifié)Ophthalmic implants - Intraocular lenses - Part 5: Biocompatibility (ISO 11979-5:1999, modified)11.100.20Biological evaluation of medical devices11.040.70Oftalmološka opremaOphthalmic equipmentICS:Ta slovenski standard je istoveten z:EN 13503-5:2001SIST EN 13503-5:2002en01-maj-2002SIST EN 13503-5:2002SLOVENSKI
STANDARD



SIST EN 13503-5:2002



EUROPEAN STANDARDNORME EUROPÉENNEEUROPÄISCHE NORMEN 13503-5March 2001ICS 11.040.70; 11.100English versionOphthalmic implants - Intraocular lenses - Part 5:Biocompatibility (ISO 11979-5:1999, modified)Implants ophtalmiques - Lentilles intraoculaires - Partie 5:Biocompatibilité (ISO 11979-5:1999, modifié)Ophthalmische Implantate - Intraokularlinsen - Teil 5:Biokompatibilität (ISO 11979-5:1999, modifiziert)This European Standard was approved by CEN on 4 February 2001.CEN members are bound to comply with the CEN/CENELEC Internal Regulations which 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 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 translationunder the responsibility of a CEN member into its own language and notified to the Management Centre has the same status as the officialversions.CEN members are the national standards bodies of Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Greece,Iceland, Ireland, Italy, Luxembourg, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and United Kingdom.EUROPEAN COMMITTEE FOR STANDARDIZATIONCOMITÉ EUROPÉEN DE NORMALISATIONEUROPÄISCHES KOMITEE FÜR NORMUNGManagement Centre: rue de Stassart, 36
B-1050 Brussels© 2001 CENAll rights of exploitation in any form and by any means reservedworldwide for CEN national Members.Ref. No. EN 13503-5:2001 ESIST EN 13503-5:2002



Page 2EN 13503-5:2001Contents1Scope.52Normative references.53Terms and definitions.54General requirements applying to the biological evaluation of intraocular lenses.55Physicochemical tests.65.1General.65.2Test for extractables and hydrolytic stability.65.3Degradation tests.6Annex A (normative)
Test for extractables and hydrolytic stability.8Annex B (normative)
Test of photostability.12Annex C (normative)
Nd-YAG laser exposure test.14Annex D (normative)
Ocular implantation test.15Annex E (informative)
Selected definitions.18Annex ZA (informative)
A-deviations.19Bibliography.20SIST EN 13503-5:2002



Page 3EN 13503-5:2001ForewordThis document has been prepared by Technical Committee CEN /TC 170, "Ophthalmic optics" the secretariat ofwhich is held by DIN.This European Standard shall be given the status of a national standard, either by publication of an identical text orby endorsement, at the latest by September 2001, and conflicting national standards shall be withdrawn at thelatest by September 2001.EN 13503 was developed by CEN/TC 170, Ophthalmic optics, in cooperation with ISO/TC 172/SC 7, Ophthalmicoptics and instruments, and is published in several parts under the general title Ophthalmic implants - Intraocularlenses:Part 1: VocabularyPart 2: Optical properties and test methodsPart 3: Mechanical properties and test methodsPart 4: Labelling and informationPart 5: BiocompatibilityPart 6: Shelf-life and transport stabilityPart 7: Clinical investigationsPart 8: Fundamental requirementsEN 13503 is the modified ISO 11979. The main difference between both series of standards is that ISO 11979 isbased on the reference to ISO 14155 Clinical investigation of medical devices while EN 13503 is based on thereference to EN 540 Clinical investigation of medical devices for human subjects.Modifications of this part of EN 13503 compared with ISO 11979-5 are indicated as follows:- text which has been deleted is striked out;- text which has been changed or added is underlined.This Part 5 of EN 13503 contains four normative annexes, A to D, and one informative annex, Annex E.According to the CEN/CENELEC Internal Regulations, the national standards organizations of the followingcountries are bound to implement this European Standard: Austria, Belgium, Czech Republic, Denmark, Finland,France, Germany, Greece, Iceland, Ireland, Italy, Luxembourg, Netherlands, Norway, Portugal, Spain, Sweden,Switzerland and the United Kingdom.Endorsement noticeThe text of the International Standard ISO 11979-5:1999 was approved by CEN as a European Standard withagreed commun modifications as given in the Foreword and indicated in the text by strike-out and underlining.NOTEA-deviations are given in Annex ZA (informative).SIST EN 13503-5:2002



Page 4EN 13503-5:2001IntroductionEN ISO 10993-1 indicates the fundamental principles governing the biological evaluation of medical devices, thedefinition of categories based on the nature and duration of contact with the body, and selection of appropriatetests. Other parts of EN ISO 10993 present biological test methods, tests for ethylene oxide residues, tests fordegradation and principles for sample preparation.NOTE
It always was and still is the intention of the Technical Committees ISO/TC 172/SC 7 and CEN/TC 170 to prepareidentical ISO and CEN (European Committee for Standardization) Standards on intraocular lenses. However, during thepreparation of part 7 of this series, problems were encountered with normative references to the existing ISO 14155 and EN 540horizontal standards on clinical investigation of medical devices, which are similar but not identical.ISO and CEN principles concerning normative references made it impossible to continue the preparation of identicalInternational and European Standards on the clinical investigation of intraocular lenses. As a result, two different standardsseries have had to be prepared. It is the intention of ISO/TC 172/SC 7 and CEN/TC 170 to revise these standards with the goalto end up with identical ones as soon as identical ISO and CEN horizontal standards on clinical investigations become available.SIST EN 13503-5:2002



Page 5EN 13503-5:20011 ScopeThis part of EN 13503 ISO 11979 specifies particular requirements for the the biological evaluation of intraocularlenses (IOLs) which are in addition to the requirements outlined in the relevant parts of EN ISO 10993. It also givesguidance on conducting an ocular implantation test.2 Normative referencesThis European Standard incorporates by dated or undated references, provisions from other publications. Thesenormative references are cited at the appropriate places in the text and the publications are listed hereafter. Fordated references, subsequent amendments to or revisions of any of these publications apply to this European Stan-dard only when incorporated in it by amendment or revision. For undated references the latest edition of thepublication referred to applies (including amendments).EN 1441 : 1997, Medical devices – Risk analysis
ISO 14971-1:1998, Medical devices - Risk management - Part 1:Application of risk analysis.EN ISO 10993-1: 1997, Biological evaluation of medical devices - Part 1: Evaluation and testing:EN 30993-6 ISO 10993-6 : 1994, Biological evaluation of medical devices - Part 6: Tests for local effects afterimplantation.EN ISO 11979-1: 1999, Ophthalmic implants - Intraocular lenses - Part 1: Vocabulary.EN ISO 11979-2 : 1999, Ophthalmic implants - Intraocular lenses - Part 2: Optical properties and test methods.EN 13503-3 ISO 11979-3: 1999 Ophthalmic implants - Intraocular lenses - Part 3: Mechanical properties and testmethods.3 Terms and definitionsFor the purposes of this part of EN 13503 ISO 11979, the terms and definitions given in
EN ISO 11979-1 apply.NOTE
Some definitions from EN ISO 11979-1 are reproduced for information in Annex E.4 General requirements applying to the biological evaluation of intraocular lensesAn evaluation of biological safety shall be undertaken in accordance with the principles and requirements ofEN ISO 10993-1. The evaluation of the biological safety of the test material shall include an assessment for risk inaccordance with EN 1441 ISO 14971-1. The results of the tests described in clause 5 shall be included in the riskassessment.The material shall be either the final product or representative sample material which has undergone the sameprocessing steps, including sterilization. Where representative sample material is used, the shape and size shall bejustified.In addition, for each test material the results of the following physicochemical evaluations (see clause 5) shall beavailable. All extractions shall be performed using an aqueous solvent and a lipophilic solvent, unless otherwisestated in the test method:a) extractables and hydrolytic stability;b) photostability against ultraviolet/visible (UV/Vis) irradiation; andc) stability against Nd-YAG laser exposure.Consideration of the need for an ocular implantation test shall be documented and justified. Where necessary, anocular implantation test shall be conducted in line with the general principles in EN 30993-6 ISO 10993-6,supplemented as described in annex D.SIST EN 13503-5:2002



Page 6EN 13503-5:2001NOTEAs the mass of an intraocular lens is typically only about 20 mg, in general no systemic or chronic toxicity testing isrequired.5 Physicochemical tests5.1 GeneralThe objectives of this group of tests are:a) to quantify possible residues of synthesis and additives or impurities from manufacturing;b) to quantify possible degradation products due to hydrolysis;c) to quantify leachable chemical components; andd) to facilitate an analysis of any risks introduced by toxic products which may result from processing, treatment inuse, or ageing of the test material.5.2 Test for extractables and hydrolytic stabilityThe material shall be tested for extractables and hydrolytic stability in accordance with annex A, which specifiesseveral different extraction conditions, including the extraction media, temperature and duration. For all conditionsthe following shall be observed. The manufacturer shall be required to justify and document the reasons for selecting each solvent. The extraction media shall be qualitatively and quantitatively analysed for possible extractable components ofthe material, such as process contaminants, residual monomers, additives of any kind, and other extractablecomponents. Before and after extraction, the test material shall be weighed and any change in mass shall be calculated.The test material underdoing hydrolysis testing shall be examined by light microscopy at 10x and by scanningelectron microscopy (SEM) at 500x before and after extraction. The test material shall be compared withnonhydrolysed material
and shall exhibit no difference in surface appearance (e.g. bubbles, dendrites, breaks andfissures).Optical transmittance curves of the test material in the ultraviolet and visible spectral regions (UV/Vis) shall berecorded before and after hydrolysis testing. By comparison of the spectra, assurance shall be obtained that nosignificant changes in spectral transmittance have occurred due to the testing.The results shall be evaluated to assess the risk for potentially harmful effects due to extractable components. Theresults of the tests described in annex A shall be recorded and included in the assessment for risk in accordancewith EN 1441 ISO 14971-1 as discussed in clause 4.5.3 Degradation tests5.3.1 Test for photostabilityThe test material shall be assessed for photostability in accordance with annex B.The saline solution surrounding the test material during exposure shall be analysed for migrated components.No significant change shall be detected between the UV/Vis spectra of the test material before and after the exposure.For anterior chamber IOLs, it shall in addition be shown that no significant change in mechanical properties of theirradiated test material has occurred, compared with non-irradiated test material.NOTEThe loops of implanted anterior chamber IOLs are exposed to radiation, hence the rationale for requiring mechanicaltesting after irradiation.SIST EN 13503-5:2002



Page 7EN 13503-5:20015.3.2 Nd-YAG laser exposure testThe effect of Nd-YAG laser exposure shall be tested in accordance with annex C.The physiological saline surrounding the IOLs shall be analysed for released additives and, also, shall show nocytotoxicity.The results of the tests described in annexes B and C shall be recorded and included in the assessment for risk asdescribed in clause 4.SIST EN 13503-5:2002



Page 8EN 13503-5:2001Annex A(normative)Test for extractables and hydrolytic stabilityA.1
PurposeThe purpose of these tests is to quantify extractable additives and other leachables, as well as possibledegradation products due to hydrolysis.A.2
General remarksThe selected analytical methods should be justified in terms of being well established and of sufficient sensitivity todetect significant concentrations.A.3
Test of extractablesA.3.1
Test materialsUse a total of 180 IOLs, if sterile finished IOLs are chosen as the test material.If representative sample material is chosen, cut it into pieces to give about the same ratio of mass to surface areaas would be obtained with finished IOLs.A.3.2
Control materialsUse untreated sterile finished IOLs or representative sample material as control material.Use solvent blanks that have undergone the same procedures as described in A.3.4, for comparison with extractsof test material.A.3.3
ApparatusA.3.3.1
Glass vials, of hydrolytic class I according to EP and USP.A.3.3.2
Laboratory glass ware.A.3.3.3
Syringes.A.3.3.4
Analytical balance.A.3.3.5
Shaker.A.3.3.6
Incubator.A.3.3.7
Centrifuge.A.3.3.8
High pressure liquid chromatograph (HPLC).A.3.3.9
Gas chromatograph (GC).A.3.3.10
UV/Visible spectrophotometer.SIST EN 13503-5:2002



Page 9EN 13503-5:2001NOTEThis list is advisory. Other suitable means may be used.A.3.4
Test procedureA.3.4.1
ExtractionExtract the test material at 37°C ± 2°C for 72 h ± 1 h using two different extraction media, one aqueous and onelipophilic solvent, selected with relevance to the test material.Divide the test material into two equal parts for incubation in the two extraction media. Determine the mass of eachpart.Incubate the test material in glass vials with a sufficient volume of medium to achieve a ratio of 10 g of test materialper 100 ml of medium. Use at least two vials for each medium. If necessary, use more vials and agitate to ensurethat all surfaces of the test material are available for extraction during the entire period of extraction.A.3.4.2
Analysis of extractsCarry out the analysis of the extract of each vial separately.Remove the vials from the incubator and allow to equilibrate at room temperature for 2 h ± 15 min. Then shake thevials and centrifuge at room temperature. Collect the clear supernatant with a syringe and transfer to a second vialfor qualitative and quantitative analyses for leachable substances such as UV-absorbers, additives, anddegradation products.Carry out corresponding qualitative and quantitative analyses on solvent blanks that have undergone the sameincubation procedures.Compare the results of the qualitative and quantitative analyses of the extracts of the test material to those of thesolvent blank, and interpret the findings in the context of possible material changes.A.3.4.3
Analysis of the test
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