ISO INTERNATIONAL STANDARD 13408-7 First edition 2012-08-01 Asepticprocessingofhealthcare products- Part 7: Alternativeprocessesformedicaldevices andcombinationproducts Traitementaseptiquedesproduitsdesante- Partie7:Procedesalternatifspourlesdispositifsmedicauxetles produitsdecombinaison Referencenumber ISO13408-7:2012(E) Iso ISO2012 ISO13408-7:2012(E) COPYRIGHTPROTECTEDDOCUMENT ISO2012 All rights reserved.Unless otherwise specified,no part of this publication maybe reproduced or utilized in any form or by anymeans, electronicormechanical, including photocopying andmicrofilm,withoutpermission in writingfromeitherISOattheaddress beloworISO's memberbodyinthecountryoftherequester. ISO copyright office Casepostale56·CH-1211Geneva20 Tel.+41227490111 Fax+41227490947 [email protected] Webwww.iso.org Published in Switzerland ISO2012-Allrightsreserved Cepyigt rovidedbylHSunderlicensewithISo NotforResale ISO13408-7:2012(E) Contents Page Foreword .iv Introduction V 1 Scope.. 2 Normativereferences. 3 Terms and definitions.. 4 Qualitysystemelements 2 5 Asepticprocessdefinition 2 5.1 General... 2 5.2 Riskmanagement. 2 6 Manufacturing environment .3 7 Equipment. 3 8 Personnel.. .3 9 Manufacture oftheproduct 10 Process simulation. 3 10.1 General.. 3 10.2 Media selectionand growth support. 3 10.3 Simulationprocedures... 3 10.4 Incubationandinspectionofprocesssimulationunits 6 10.5 Initialperformancequalification.. 10.6 Periodicperformancerequalification 6 10.7 Repeatofinitialperformancequalification. 10.8 Documentation ofprocess simulations 10.9 Dispositionoffilledproduct. 11 Testforsterility 11.1 General 11.2 Investigationofpositiveunitsfromtestsforsterility AnnexA(informative)Riskassessmentforasepticprocessing-Qualityriskmanagementmethod....8 AnnexB(informative)Selectionofasamplefortestingformicrobialcontamination. .15 AnnexC(informative)Testingoptionsforprocesssimulation 16 Bibliography... .19 alonghtsreserved ili Providedby IHSunder license with ISO ISO13408-7:2012(E) Foreword establishedhastherighttoberepresentedonthatcommittee.Internationalorganizations,governmentaland non-governmental,in liaisonwithisO,alsotakepartinthework.IsO collaboratescloselywiththeInternational ElectrotechnicalCommission (IEC)onall mattersofelectrotechnical standardization. International Standardsaredrafted inaccordancewiththerulesgiven intheISO/lEDirectives,Part2 Attention isdrawntothepossibilitythat someoftheelements of this document maybethesubjectof patent rights.isOshall notbeheldresponsibleforidentifyinganyorall suchpatentrights. ISO13408-7waspreparedbyTechnicalCommitteeISO/TC198,Sterilizationofhealthcareproducts. IsO13408consistsofthefollowingparts,underthegeneraltitleAsepticprocessingofhealthcareproducts: Part1:Generalrequirements Part2:Filtration Part3:Lyophilization Part4:Clean-in-placetechnologies Part5:Sterilizationinplace Part6:Isolatorsystems - Part7:Alternativeprocessesformedicaldevicesandcombinationproducts ISO2012-All rightsreserved ISO13408-7:2012(E) Introduction products.Historically,sterile health care productsthat areaseptically producedhave typicallybeen liquids, powdersorsuspensionsthat cannotbeterminallysterilized.Morerecently,medical devices andhealthcare productshavebeendevelopedthatarecombinedwithmedicinal products,includingbiologicalandviablecells, thatcannotbeterminally sterilized. TheapplicationofiSO13408-1tothesemedicaldevicesandcombinationproductscanrequirethedevelopment simulationofmedicaldevices andcombinationproductsthatmeettherequirements ofisO13408-1. ISO13408-1:2008,10.1.2permitstheuseofalternativeprocesssimulationapproaches,basedonparticularmedical devicesorcombinationproducts,wherethesubstitutioninfull withsterile liquidmediamightnotbepossible thefollowing. Medical devicesthatcannotbeterminallysterilizedandwheretheprocess simulation approachaccording a) toISO13408-1cannotbeapplied: bioprostheses (e.g.heartvalves,vascularimplants); biodegradable implants (e.g.herniameshes); artificial and/ornon-viable biologically based