無源醫(yī)療器械CE技術(shù)文檔和CE設(shè)計檔案材料指南(中英文-也是極好的)

無源醫(yī)療器械技術(shù)文件和設(shè)計文檔指南Whereastheterm“TechnicalFile“isusedforMedicalDevicesofclassI,classIIaandclassIIb,theterm“DesignDossier“isusedfortheclassIIIproducts.標(biāo)題中的“技術(shù)文件”適用于I類，IIa類,IIb類醫(yī)療器械，“設(shè)計文檔”適用于III類醫(yī)療器械。TechnicalFilesareretainedinthepremisesofthemanufacturerortheAuthorizedRepresentativeforpotentialreviewofCompetentAuthoritiesandNotifiedBody.PartBoftheTechnicalFilemaybeavailableatthemanufactureronly.技術(shù)文件是保存在制造商或授權(quán)代表單位的主管部門和認(rèn)證機構(gòu)。局部技術(shù)文件B局部只保存在制造商處。WhereasDesignDossiershavetobesubmittedtotheNotifiedBodyforreviewpriortoCE-Markingoftheproduct(useformApplicationforCEConformityAssessment(Product)MED_F_03.03).Wewillassignaprojectmanagerwhowillentrustoneormorefurtherexpertswiththereviewofparticularmodules.Allexpertsareatyourdisposaldirectlyorindirectlythroughtheprojectmanager.Aftersuccessfulreview,theNotifiedBodyissuesadesignexaminationcertificateaccordingtoAnnexII.4oftheCouncilDirectivecertifyingcompliancewiththerelevantprovisionsofAnnexIoftheMDD.設(shè)計檔案材料已被提交到公告機構(gòu)用于需要CE認(rèn)證前的產(chǎn)品審查〔用CE合格評定〔產(chǎn)品〕規(guī)定的格式〕。我們將委派一個工程經(jīng)理，他將委托一個或多個資深專家審查特定的模塊。所有專家會直接或通過工程經(jīng)理間接與你接觸，在成功的審查后，公告機構(gòu)會按照MDD法規(guī)附件I和附件相關(guān)規(guī)定簽發(fā)檢驗證書。Article5oftheCouncilDirectivedescribesconsiderationoftheEuropeanharmonizedstandardsbythemanufacturerinordertodemonstratecompliancewiththeEssentialRequirements.ThisaspectisevenmoreimportantasInternationalStandardOrganizationshaveadoptedEuropeanNorms(andviceversa)anddemonstratingcompliancewiththesestandardscouldbeveryhelpfulininternationalmutualrecognitionoftheCE-Markingprocess.理事會指令5描述了制造商要遵守的歐洲統(tǒng)一標(biāo)準(zhǔn)，以證明附合根本要求，這方面更重要的是為國際標(biāo)準(zhǔn)組織已經(jīng)通過了歐洲標(biāo)準(zhǔn)〔反之亦然〕，并且遵守這些標(biāo)準(zhǔn)可能非常有助于國際的相互成認(rèn)在CE認(rèn)證過程中。ItisnotnecessarytoincludealldocumentsintheDesignDossierwhichhavealreadybeensubjecttoanISO/EN/MDDAuditbytheNotifiedBody.ExamplesofdocumentsnotnecessarytobeincludedareQualityManualsandrelatedlowerleveldocuments.設(shè)計檔案材料不必一定包括那些已經(jīng)提交給ISO/EN/MDD審查公告機構(gòu)的所有的文檔，例如文檔不必包括質(zhì)量手冊和一些相關(guān)更下層文檔。IfthemanufacturerofaclassIIIdeviceprovidesdetailedinformationaccordingtothechecklistdescribedbelow,therequirementsoftheDirectiveareappropriatelyaddressed.如果一個類III器件制造商提供詳細(xì)的資料按下述清單，該指令的要求得到適當(dāng)處理ThisisevenmoreimportantincaseaCompetentAuthorityoranotherNotifiedBodywishestoreviewthedocumentation.這樣很重要如果主管部門或其他認(rèn)證機構(gòu)要審查文件Generally,theinformationshouldbeprovidedasconclusions,summaries,reports,tablesorflowcharts(withreferencetothefulldocumentationintheEssentialRequirementchecklist).一般的，提供的信息應(yīng)包括結(jié)論，摘要，報告，表或流程圖〔參照完整文檔在根本要求檢查表中〕SpecialcareshouldbetakentoensurethatanyinformationisconsistentthroughouttheDesignDossier(e.g.descriptionandvariantsofthedeviceindifferentdocuments;adverseeventsasstatedintheIFUandhazardsinnormalconditionaswellasinfaultconditionintheRiskManagement).特別應(yīng)注意確保任何信息在整個卷中是一致的〔例如：在不同的文檔中器械的規(guī)格描述；說明書中不良事件的聲明和在正常情況下的危害，以及在故障情況下的風(fēng)險管理〕AcompletepaginationoftheDesignDossieroranothertypeofcontrolmechanismisnecessary,e.g.revisioncontrolofeachsection.Twocopiesofthedocumentationandanelectronicversion,ifpossiblearerequiredtoachieveanappropriatereviewtime.設(shè)計檔案材料必須有完整的頁碼控制或者另外形式的控制機制，例如，每個章節(jié)的版本控制。兩份拷貝和一個電子版本，如果可能還需要一個審查時間。Ingeneral,designchangesdescribedintheMDD(93/42/EEC),AnnexII.4.4shallbereportedtotheNotifiedBody(useformChangeNotificationMED_F_09.04)inordertoensureconformitywiththerequirementsdefinedintheAnnexII.4.4andinordertoensurethattheDesignDossiersretainedattheNotifiedBody’sarchivearecompleteandup-to-date.一般來說，設(shè)計更改在MDD(93/42/EEC),附肵有說明，應(yīng)向公告機構(gòu)報告確保更改適宜〔按更改通知書格式〕。Furthermoreatleastonesampleofthedeviceshouldbeprovided.此外，至少應(yīng)提供一個設(shè)備樣品ForalldataSIunitsofmeasurementshallbeused.對于所有SI單位的測量數(shù)據(jù)應(yīng)得到使用。Importanthint:DesignDossiersthataccuratelyconformtothebelowguidancecanbereviewedmoreefficiently!重要提示：設(shè)計檔案材料準(zhǔn)確地符合以下指導(dǎo)可以更有效地進(jìn)行審查InthisregarditisrecommendedtocompileaDesignDossierorTechnicalFileasfollows在這方面，建議編制設(shè)計檔案材料或技術(shù)文件如下(也可看NB-MED/2.5.1和GHTF文檔SG1(PD)/N011R20:STED):PARTA:TechnicalFileA局部技術(shù)文件1.TableofContent目錄2.Introduction介紹3.DesignDossier/TechnicalFileSummaryInformation設(shè)計檔案材料/技術(shù)文件摘要信息PARTB:AnnexesB局部附件1.EssentialRequirementsChecklist根本要求檢查表2.RiskAnalysis風(fēng)險分析3.Drawings,Design-,Product-Specifications圖紙，設(shè)計-產(chǎn)品-規(guī)格4.Chemical,PhysicalandBiologicalTests化學(xué)，物理和生物測試4.1InVitroTesting-PreclinicalStudies體外試驗-臨床前研究4.2InVivoTesting-PreclinicalStudies體內(nèi)試驗-臨床前研究4.3BiocompatibilityTests生物相容性測試4.4Bio-stabilityTests生物穩(wěn)定性試驗4.5MicrobiologicalSafety,AnimalOriginTissue微生物平安，動物保護組織4.6Drug/medicaldevicecombination藥物/醫(yī)療設(shè)備組合4.7BloodDerivates,HumanTissue/medicaldevicecombination血液衍生物，人體組織/醫(yī)療設(shè)備組合4.8CoatedMedicalDevices涂層醫(yī)療器械5.ClinicalData臨床資料6.LabelsandInstructionsforUse標(biāo)簽和使用說明7.Manufacturing制造8.PackageQualificationandShelflife包裝和保質(zhì)期9.Sterilization滅菌10.Conclusion結(jié)論11.DeclarationofConformity(Draft)符合性聲明〔草稿〕PARTA:TechnicalFileA局部技術(shù)文件1.TableofContent目錄ContentofbothPartsAandB目錄包括A局部和B局部2.Introduction介紹RevisionhistoryofDesignDossier:changenotifications,revisionnumbersandapprovalsofalldocumentsincludingallamendments.設(shè)計文檔案修訂歷史：更改通知，版本號和批準(zhǔn)的所有文件，包括所有的修訂RegulatoryInformation法規(guī)信息oName,postaladdress,NotifiedBody,certifications(validcopiesattached!)of:以下機構(gòu)的名稱，通訊地址，公告機構(gòu)，證書〔有效的復(fù)的復(fù)印件〕themanufacturer(incl.contactperson)制造商〔包括聯(lián)系人〕OEM,criticalsuppliers,subcontractors(e.g.contractsterilizer)OEM，關(guān)鍵供給商，外協(xié)商〔例如：合同滅菌商〕EuropeanRepresentative(ifapplicable)歐盟代表〔如果適用〕oProductandaccessoryclassification,ruleaccordingtoMDD,AnnexIXandaccordingtoISO10993-1Table1and2產(chǎn)品及配件分類：按照MDD規(guī)定的附錄9和ISO10993-1表1和表2oConformityAssessmentRoute合格評定路oUMDNS-/GMDS-codeUMDNS-/GMDS編號oProductHistory:approvals(e.g.FDA510(k)orPMAclearance),marketrelease,statusofanypendingrequestformarketclearance;itemssold上市銷售歷史，證書，時間，數(shù)量Briefdescriptionoftheproduct產(chǎn)品簡要描述oIntendeduse,modelnames,configurations,variants產(chǎn)品預(yù)期用途，型號規(guī)格名稱，配置和規(guī)格表oAccessoriesfortheproduct,integralpartsofpackage產(chǎn)品的附件,同一包裝的部件oAppliedstandards(listortableincludingthefulltitle,identifyingnumbers,date,andtheorganizationthatcreatedthestandard)適用標(biāo)準(zhǔn)〔全名的列標(biāo)，包括編號，日期和該標(biāo)準(zhǔn)的編制機構(gòu)〕特別協(xié)調(diào)標(biāo)準(zhǔn)Note:Pleasemakesuretousecurrentstandardsonlyorprovideagapanalysisandrationale注：請務(wù)必使用唯一最新標(biāo)準(zhǔn)或提供差距分析和理由oRationaleifapplicablestandardsorpartsthereofhavenotbeenconsidered如為何沒有采用當(dāng)前標(biāo)準(zhǔn)或局部標(biāo)準(zhǔn)的理由3.DesignDossier/TechnicalFileSummaryInformation(referencetosupportingdocumentsfiledinPartB)設(shè)計檔案材料/技術(shù)文件摘要信息〔參照B局部支持文檔〕Comprehensivedescriptionofthesystemandeachfunctionalcomponentofthedeviceandtherelatedaccessoriesincludingutilizedmaterialoringredient(animal/humanorigin,drugdevicecombination?),packaging,methodofsterilization,shelflife,combinationwithactivemedicaldevices.Thedescriptionshouldbesupportedbydiagrams,photographsordrawings,asappropriate.綜合描述：整個系統(tǒng)的〔包括包裝〕，產(chǎn)品的每個功能部件和相關(guān)的附件包括關(guān)鍵材料或組成局部〔動物/人類,藥物組合裝置〕,包裝,滅菌方法,有效期,配合使用的有源醫(yī)療器械,描述應(yīng)有適用的簡圖,照片或工程圖.Basicscientificconceptsthatformthefundamentalsforthedeviceincludingmedical,biological,chemical,andphysicalbackgroundinformation產(chǎn)品依據(jù)的根本的科學(xué)概念,包括材料,生物,化學(xué)和物理背景資料.IncaseofaChangeNotification:descriptionofallchangesincomparisonwiththepreviousdesignormanufacturingprocess(e.g.tabularformat)更改通知:所有的變化描述與先前的設(shè)計或制造過程中的比擬(例如:列表的格式)SummaryoftheessentialdataandresultsasdetailedinPartBB局部中關(guān)鍵數(shù)據(jù)和結(jié)果摘要InformationasprovidedintheInstructions/DirectionsforUse(detailedinsectionB):IntendedUse,Indication,Contraindications,Warnings,Adverseevents,Operationanduseofaccessories使用說明提供的信息:使用指導(dǎo)(詳細(xì)見B局部),用途,標(biāo)志,禁忌,警告,不良反響,操作和使用的配件Plannedchanges方案中的改變〔規(guī)格型號〕Summarydescriptionofmanufacturingprocess簡要介紹制造過程Anyotherimportantsafety/performancerelatedinformation.任何其他重要的平安特性:性能相關(guān)的信息Thisstructureenablesefficientprojectplanningandmanagement.PartAcanbeusedforapre-reviewinordertoinstantlynotifythemanufacturerofopenissuesorincaseparticularaspectsarenotcoveredintheDesignDossier.這種結(jié)構(gòu)應(yīng)該能夠有效的工程規(guī)劃和管理。A局部可用于預(yù)先審查，以便即時通知制造商顯爾易見的問題或某些具體方面沒有包括在設(shè)計開發(fā)資料中的問題PARTB:AnnexesB局部附件1.EssentialRequirementsChecklist根本要求檢查表Example:例:E.R.根本要求applicabilityallapplied是否適用standards(withdateofissue)標(biāo)準(zhǔn)(帶有效發(fā)布時間)compliancedemonstratedby(referenceddocuments)證明材料(參考文檔)location–section所在章節(jié)(text)內(nèi)容Yes是/否ENISO10993-1:2003-5:1999等EN62336=IEC62336laboratorytestreports:-cytotoxicity(reportnumberanddate)實驗室測試報告-細(xì)胞毒性(報告編號和日期)Sectionb)c)節(jié)SeealsoAttachmentI:EuropeanNormsandStandardsandotherDocumentssupportingTechnicalFilesandDesignDossiers.另見附件I:歐洲的標(biāo)準(zhǔn)和標(biāo)準(zhǔn)及配套技術(shù)文件和其他設(shè)計檔案材料2.RiskAnalysis風(fēng)險分析Thedocument(RiskManagementFile)whichdescribestheresultoftheriskmanagement(includingriskanalysis,evaluation,mitigationandoverallresidualriskevaluationandproduction/postproductioninformationseeISO14971fig.B1foranoverview)processshouldcontainatleastthefollowinginformation:風(fēng)險管理文檔描述了風(fēng)險管理的結(jié)果(包括風(fēng)險分析,風(fēng)險評估,風(fēng)險降低和剩余風(fēng)險評價以及按照ISO14971fig.B1進(jìn)行的生產(chǎn)/生產(chǎn)后信息評價),風(fēng)險分析程序到少包括下面和信息;Generalinformation簡要信息oSummary概要oPurposeofthedocumentincludingprojectphase(s)/lifecyclephase(s)forwhichtheriskanalysiswasperformedandreviewedScope(e.g.design/product,manufacturingprocess,user/operation);productidentificationanddescription;intendeduse,shelflife.文件的目的包括工程階段〔第〕/風(fēng)險分析進(jìn)行的生命周期階段〔s〕和審查范圍(例:設(shè)計／生產(chǎn)制造程序，使用者／操作)；產(chǎn)品標(biāo)識和說明，用途，有效期。oReferenceto:RiskManagementSOPandPlan,RiskManagementPolicy,standards(ENISO14971,ISO22442part1-3andMEDDEV2.5-8stronglyrecommended),specificationdocuments,designdocuments,procedures,protocols,reports,manufacturingandproductionprocessinformation參考：風(fēng)險管理標(biāo)準(zhǔn)操作程序和方案，風(fēng)險管理政策，標(biāo)準(zhǔn)〔ENISO14971,ISO22442第1-3和強制執(zhí)行〕，標(biāo)準(zhǔn)文件，設(shè)計文檔，規(guī)程，協(xié)議，報告，制造和生產(chǎn)過程的信息oDefinitionofterms,abbreviationsandacronyms術(shù)語定義，縮略語oParticipantsoftheriskanalysisteam(personsandorganisations),theirqualification,responsibilityandauthority.風(fēng)險分析團隊〔個人和組織〕，他們的證書，職責(zé)和權(quán)力。oNote:theRiskAnalysisshallincludeamedicalknowledgeableandexperiencedexpertinthecorrespondingfieldofapplication.注：風(fēng)險分析應(yīng)有一個具有醫(yī)療知識和相關(guān)領(lǐng)域應(yīng)用經(jīng)驗的專家oNote:TheRiskManagementPlanaccordingtoISO14971-especiallyinrelationtoriskacceptancecriteria-hastobedefinedbythetopmanagementunderconsiderationoftheestimatedproductionvolumetobesoldperyearandunderconsiderationofregulatoryrequirements.注：風(fēng)險管理方案根據(jù)ISO14971－尤其是有關(guān)風(fēng)險接受準(zhǔn)那么－已被高層管理人員定義〔考慮預(yù)計每年的產(chǎn)量和銷售量以及監(jiān)管規(guī)定〕oIdentificationofmedicaldevicecharacteristicsthatcouldimpactonsafety,e.g.accordingtoISO14971.識別可能影響平安的醫(yī)療設(shè)備的特征，例：參照ISO14971oIfapplicableconsiderationofdataobtainedfromliteraturereview,usabilitytesting,marketsurveillanceofsimilardevices,postmarketsurveillanceorpostmarketclinicalfollow-up(alsorelatedtoe.g.changenotifications,predicateorotherwisecomparabledevices):complainthistory,incidentspernumberofdevicessold,analysisofunderlyingcausesandfinaloutcome,correctiveandpreventiveactionincludingproofofeffectiveness如果適用性審議的數(shù)據(jù)來自文獻(xiàn)回憶，可用性測試，市場類似產(chǎn)品比照，產(chǎn)品售后信息和售后臨床隨訪〔其他相關(guān)的如：更改通知，其他方式類似裝置〕投訴歷史，事故占銷售設(shè)備的數(shù)量，分析事故原因及最終結(jié)果，糾正和預(yù)防措施，包括有效的證明。oRevisionhistory修訂歷史Methodology評估方法oHazards/hazardoussituationsinnormalcondition:HazardAnalysis;patient/userrelated(top-downapproach),e.g.FaultTreeAnalysis,tableformat在正常狀態(tài)下的危害/危害性情況;危害分析;病人/相關(guān)使用者(自上而下方法),例如:失效的樹形分析,表格格式Clinicalexperienceandclinicalrisks臨床經(jīng)驗和臨床風(fēng)險Methodforidentificationofapplicablehazards;sourcesofinformationused識別可適用性危害的方法;所用信息的來源Methodfordeterminationofthepotentialcausesofhazards;sourcesofinformationused判定危害的潛在原因的方法;所用信息的來源Systemusedforcategorizationofseveritylevels(e.g.examples);descriptionofconsequencestopatients,usersandotherpersons嚴(yán)重程度的分類系統(tǒng)(例如:舉例);對病人,用戶和其它人產(chǎn)生的后果描述Systemusedforcategorizationofoccurrenceofeachhazardcause(probabilityestimate,frequencyexpressedase.g.‘eventsperdeviceandtime’)每種危害原因產(chǎn)生的分類系統(tǒng)(可能性估計,頻率表述為”根據(jù)器械和次數(shù)的事件”)Methodforcombinationofseverityandoccurrencetorisklevel(e.g.diagram,graph,formula)風(fēng)險水平的嚴(yán)重和發(fā)生的組合方法(例如:圖表,圖形,公式)Criteriaforriskacceptance(e.g.acceptable,ALARP,unacceptable)underconsiderationoftheriskmanagementplanandaccumulatedrisks考慮到風(fēng)險管理方案和累計風(fēng)險情況下的風(fēng)險可接受性標(biāo)準(zhǔn)(例如:可接受,可操作又合理的最低情況,不可接受)Note:IfresidualrisksremaininALARPregionarationalshouldbereadytosubstantiatethatnofurthermitigationwaspossibleaccordingtoriskcontroloptionanalysis.注意:如果剩余風(fēng)險是在”可操作又合理的最低情況”的范圍內(nèi),應(yīng)該根據(jù)風(fēng)險控制選擇分析合理地證實沒有其它的緩解措施.oHazards/hazardoussituationsinfaultcondition:e.g.FMEA;devicerelated(bottom-upapproach)在失效狀況下的危害/危害性情況:例如:潛在失效模式及后果分析;相關(guān)器械(自下而上方法)Methodforidentificationofapplicablefailuremodes;sourcesofinformationUsed適用的失效模式識別方法;所用信息來源Methodfordeterminationofthepotentialcausesoffailuremodes;sourcesofinformationused失效模式的潛在原因的判定方法;所用信息來源Systemusedforcategorizationofseveritylevels;descriptionofconsequencestopatients,usersandotherpersons嚴(yán)重程度分類系統(tǒng);對病人,用戶和其它人所產(chǎn)生的后果描述Systemusedforcategorizationofoccurrenceofeachfailuremode(probabilityestimate,frequencyexpressedase.g.‘eventsperdeviceandtime’)每種失效模式發(fā)生的分類系統(tǒng)(可能性估計,頻率表述為”根據(jù)器械和次數(shù)的事件”)Systemusedforcategorizationofdetectabilityofeachfailuremode(criteriafordetectability,frequencyofin-processtesting:100%,sampling,ornotestingi.e.validatedprocess)每種失效模式的可檢測性分類系統(tǒng)(可檢測性標(biāo)準(zhǔn),進(jìn)程內(nèi)測試頻率:100%,抽樣,或者無測試,也就是經(jīng)驗證的過程)Methodforcombinationofseverity,occurrenceanddetectabilitytorisklevelunderconsiderationoftheriskdefinition(seeISO149712.16)(e.g.diagram,graph,formula)在考慮風(fēng)險定義(參見)(例如:圖表,圖形,公式)情況下,風(fēng)險程度的嚴(yán)重,發(fā)生和可檢測的組合方法Criteriaforriskacceptability(e.g.acceptable,ALARP,unacceptable)underconsiderationoftheriskmanagementplanandunderconsiderationofaccumulatedrisks在考慮風(fēng)險管理方案和累計風(fēng)險情況下,風(fēng)險可接受性的標(biāo)準(zhǔn)(例如:可接受,可操作又合理的最低情況,不可接受)Note:IfresidualrisksremaininALARPregionarationalshouldbereadytosubstantiatethatnofurthermitigationwaspossibleaccordingtoriskcontroloptionanalysis.注意:如果剩余風(fēng)險是在”可操作又合理的最低情況”的范圍內(nèi),應(yīng)該根據(jù)風(fēng)險控制選擇分析合理地證實沒有其它的緩解措施.Result(signedanddateddocuments):RiskManagementReport結(jié)果(文件上有簽字和日期):風(fēng)險管理報告oHazards/hazardoussituationsinnormalcondition正常狀態(tài)下的危害/危害性狀況:listofapplicablehazards列出適用危害;foreachhazard(tableformatinhierarchicalstructure,ifapplicable)對于每一種危害(層級結(jié)構(gòu)的表格形式,如果適用的話)Listofpotentialworstcaseeffects(descriptionofconsequencestopatients,usersandotherpersons列出潛在的最壞情況的影響(對病人,使用者和其他人所產(chǎn)生的后果描述)Listofpotentialcausesofhazardsasappropriate適當(dāng)列出危害的可能原因Estimationofriskbeforemitigation(severity,occurrence,risk)includingdecisiononacceptability緩解措施前的風(fēng)險評估(嚴(yán)重,發(fā)生,危險),包括可接受性的判定Definitionofriskreductionmeasuresincludingreferencetomethods(e.g.design,testing,manufacturing)andresultsofverification(implementationandeffectiveness)風(fēng)險降低措施的定義,包括方法(例如:設(shè)計,測試,制造),確認(rèn)結(jié)果(實施和有效性)Estimationofriskaftermitigation(severity,occurrence,risk)includingdecisiononacceptabilityunderconsiderationoftheriskmanagementplanandunderconsiderationofaccumulatedrisks在考慮風(fēng)險管理方案和累計風(fēng)險情況下,緩解措施后的風(fēng)險評估((嚴(yán)重,發(fā)生,危險),包括可接受性的判定Risk/benefitweightingunderconsiderationofthestateoftheart在考慮工藝狀態(tài)情況下的風(fēng)險/獲益權(quán)衡oHazards/hazardoussituationsinfaultcondition:listofapplicablefailuremodes;foreachfailuremode(tableformatinhierarchicalstructure,ifapplicable):在失效情況下的危害/危害性情況:列出適用的實失效模式;對于每種失效模式(層級結(jié)構(gòu)的表格形式,如果適用的話):Listofpotentialfailuremodes列出可能的失效模式Listofpotentialworstcaseeffects(descriptionofconsequencestopatients,usersandother)列出潛在的最壞情況的影響對病人,使用者和其他人所產(chǎn)生的后果描述)Listofpotentialcausesoffailures(asappropriate)適當(dāng)列出危害的可能原因Estimationofriskbeforemitigation(severity,occurrence,detectability,risk)includingdecisiononacceptability緩解措施前的風(fēng)險評估(嚴(yán)重,發(fā)生,可接受性,危險),包括可接受性的判定Definitionofriskreductionmeasuresincludingreferencetomethods(e.g.design,testing,manufacturing)andresultsofverification(implementationandeffectiveness)風(fēng)險降低措施的定義,包括方法(例如:設(shè)計,測試,制造)和驗證結(jié)果(實施和有效性)Estimationofriskaftermitigation(severity,occurrence,detectability,risk)includingdecisiononacceptability緩解措施之后的風(fēng)險估計(嚴(yán)重,發(fā)生,可檢測,危險),包括有關(guān)于可接受性的決定.Risk/benefitweightingunderconsiderationofthestateoftheart在考慮工藝水平情況下的風(fēng)險/獲益權(quán)衡oNewhazards:Assessmentofrisksassociatedwithnewhazardsinnormalandfaultconditiongeneratedbyriskmitigationmeasures.Correspondingriskreduction,ifapplicable新危害:評估與在正常和失效狀態(tài)下由風(fēng)險緩解措施所產(chǎn)生的新危害有關(guān)聯(lián)的危害.相應(yīng)的風(fēng)險降低,如果適用的話.Finaljudgment,statementof對以下內(nèi)容的最終判斷,陳述:oCompletenessofriskevaluation風(fēng)險分析的完整性oEffectivenessofmitigationmeasuresincludingalinktotheverificationdocuments緩解措施的有效性,包括連接到驗證文件oOverallacceptabilityofresidualrisk剩余風(fēng)險的整體可接受性oSignedanddatedbytheteamleaderorresponsibleperson團隊領(lǐng)導(dǎo)或負(fù)責(zé)人簽字并署上日期3.Drawings,Design-,Product-Specifications圖紙,設(shè)計和產(chǎn)品規(guī)格Comprehensivedescriptionoftheproduct產(chǎn)品的綜合描述Componentsandmaterials:completechemical,biologicalandphysicalcharacterization部件和材料:完整的化學(xué),生物和物理性特性描述Photographs,Blueprints照片,圖紙Functionalcharacteristicsandtechnicalperformancespecificationssuchasmechanical,physical,electrical,biological,chemical,sterility,stability,packaging,transport,storage,combinationwithothermedicaldevices,accuracy,sensitivity,specificityofmeasuringanddiagnosticdevices,reliability功能性特征和技術(shù)性能指標(biāo),例如機械的,物理性的,電氣的,生物的,化學(xué)的,無菌性,穩(wěn)定性,包裝,運輸,存儲,也其他醫(yī)療器械的組合,精確性,敏感性,測量和診斷器械的特異性,可靠性.Otherimportantdescriptivecharacteristicsnotdetailedabove以上未詳述的其他重要的描述性特征DesignControl(briefdescription)設(shè)計控制(簡單描述)QM(ISO13485)Certificateofdesignfacility質(zhì)量管理(ISO13485)設(shè)計設(shè)施證書Finalproductreleasecriteriaincludingreferencetoverificationtest/validation4.Chemical,PhysicalandBiologicalTests化學(xué),物理和生物測試4.1InVitroTesting-PreclinicalStudies體內(nèi)測試-臨床前研究Ingeneraltestingmustbeconductedtopredicttheadequacyofdeviceresponsetophysiologicalandpathologicalstresses,undesirableconditionsandforces,long-termuseandallknownandpossibleorforeseeablefailuremodes一般來說,測試必須能預(yù)測器械應(yīng)對生理和病理應(yīng)力,不利因素和外力,長期使用和所有的和可能的或可預(yù)見的失效模式的妥善性Testing:e.g.visual,chemical,biological,physical/mechanicaltesting(i.e.tensilestrength,durability,corrosion,fatigue,longtermstability),efficacy/performancetesting,simulateduse測試:例如視覺性,化學(xué)性的,生物性的,物理性的/機械性的測試(也就是拉力,持久性,腐蝕性,疲勞,長期穩(wěn)定性),效能/性能測試,模擬使用.FiniteElementAnalysisifapplicable如果適用的話,有限元分析Testingshallbeperformedonfinishedproduct(devicesfromthenormalmanufacturingandaftersterilization)應(yīng)對成品進(jìn)行測試(成品指正常生產(chǎn)的并經(jīng)過滅菌的)Otherwise,useofsemi-finisheddevices,components,orrawmaterialsmustbecharacterizedandjustified否那么,使用半成品,部件或原材料必須是并合法化的.DrugCompatibility:Interactionbetweendruganddevice(e.g.adsorption)藥物相容性;藥物和器械之間的交互作用(例如:吸附作用)Testprotocols測試協(xié)議oPurposeandobjectiveoftesting測試實物和目的oStandardapplicabilitymatrix標(biāo)準(zhǔn)適用性模型Listortableincludingthefulltitle,identifyingnumbers,date,andtheorganizationthatcreatedthestandard包括全稱,識別號,日期和編制標(biāo)準(zhǔn)的機構(gòu)的清單或表格Listofallsections列出所有的章節(jié)Justificationifparticularsectionsarenotapplicable如果特殊章節(jié)不適用的話,進(jìn)行證實Referencetoverificationtest/validation參考驗證測試/確認(rèn)oJustificationifapplicablestandardsorpartsthereofarenotconsidered如果可適用標(biāo)準(zhǔn)或局部標(biāo)準(zhǔn)沒被考慮的話,進(jìn)行證實Ifothermethods,suchasinternalstandardsareused,thesemethodsshallbedescribedindetail如果使用其他的方法,例如內(nèi)部標(biāo)準(zhǔn),這些方法要詳細(xì)的進(jìn)行描述.oAcceleratedandrealtimeageingandsimulateddistribution(packagetesting)priortotesting.Otherwiseajustificationisrequired測試前的加速和實時老化以及模擬分配(包裝測試).另外需要證實oConditionsofacceleratedageing加速老化的條件oForeachtest對于每個測試:Parameterstobemeasuredandtestdescriptionincludingreferencetotestprocedureifapplicable測量參數(shù)和測試描述,如適用的話,包括測試程序Measuringandtestingequipment測量和測試設(shè)備Calibrationarrangements校準(zhǔn)安排Acceptancecriteria驗收準(zhǔn)那么Numberoftestsamplesincludingsamplesizerationale被測樣品數(shù)量,包括樣品尺寸根本原理Testreports測試報告oDeviationsandamendmentstotheprotocolsandjustification偏差,協(xié)議和證實的修正oReferencetorawdataincludingdate,laboratory,location,engineer,testingequipment(devicenumberandcalibrationdate)參考原始數(shù)據(jù),包括日期,實驗室,位置,工程師,測試設(shè)備(設(shè)備號和效準(zhǔn)日期)oStatisticalanalysis統(tǒng)計分析oInterpretationofdataandconclusion(s)數(shù)據(jù)和結(jié)論闡述oApprovalsignature(s)批準(zhǔn)簽字4.2InVivoTesting-PreclinicalStudies體外測試-臨床前研究Pre-clinicalanimalstudiesusedtosupporttheprobabilityofeffectivenessinhumans用于支持對人體的有效性的概率的臨床前動物研究Goodlaboratorypractice良好實驗室研究標(biāo)準(zhǔn)Objectives,methodology,rationaleforselectingtheparticularanimalmodelincludingtransferabilitytohumansandlimitations用于選擇特殊的動物模型包括對人類的轉(zhuǎn)移性和局限性的目的,方法和根本原理Results,analysis(alsostatistical)ofthefunctionaleffectivenessandthedevice'sinteractionswithanimalfluidsandtissues功能性效果的結(jié)果和分析,器械與動物流體和組織之間的交互作用的結(jié)果和分析(也是統(tǒng)計性的)Pharmacological/pharmacokinetical/toxicologicalstudiesi.e.purity,toxicity,ADME(adsorption,distribution,metabolism,eliminationstudies,LD50)藥理學(xué)/藥動學(xué)/毒理學(xué)研究,也就是純度,毒性,ADME(即吸收、分布、代謝、排泄研究,LD50)Manufacturer'sconclusions生產(chǎn)商的結(jié)論4.3BiocompatibilityTests生物相容性測試Thedocumentationinsupportofbiocompatibilityshallcomprisethefollowing:Biocompatibilitytestingplan生物相容性測試方案oPurposeofthedocument,allappliedstandards文件的目的,所有適用的標(biāo)準(zhǔn)oScope,Descriptionofthemedicaldevice適用范圍,醫(yī)療器械的描述Intendeduse預(yù)期用途Listofcomponents/materialshavingdirectorindirectbodycontact列出有直接或間接的人體接觸的部件/材料Propertiesandcharacteristicsofthefinishedproduct成品的性能和特性Allmaterialsusedinthemanufacture,includingauxiliarymaterials,additives,processcontaminantsandresidues,leachables,degradationproducts,othercomponentsthatdointeractwiththefinalproduct,etc.,orrefertotheapplicablesectionoftheDesignDossier在生產(chǎn)中使用的所有的材料,包括輔助材料,添加劑,過程污染和殘留物,濾除物,降解產(chǎn)物,其它與成品有交互作用的部件等等,或者參見設(shè)計檔案材料的適用章節(jié).WhereappropriatedefinetotalsurfaceareacontactingthebodyorbodyFluids在適用的地方定義出與人體或人體流體有接觸的整個外表區(qū)域CategorizationofthemedicaldevicebasedonISO10993-1:Tables1and2accordingto:根據(jù)以下內(nèi)容以ISO10993-1為根底的醫(yī)療器械分類::表1和表2:Natureofbodycontact人體接觸的性質(zhì)Contactduration接觸持續(xù)時間Thecategorydefineswhicheffectsneedtobeconsideredatleast分類定義至少哪些效果需要考慮oDescriptionoftesteditem(s)(finisheddevice,partofdevice,rawmaterial)測試工程描述(成品,器械部件,原材料)Testingshallbeperformedonthefinalproductorrepresentativesamplestakenfromthefinalproductorfrommaterialsprocessedinthesamemannerasthefinalproduct(ifapplicableprovideLOT/REF.No.,etc.)對從成品中或從以同樣的方式進(jìn)行處理的材料中抽出的成品或代表性樣品驚醒測試(如果適用,提供批號/參考編號等等)Rationalefortheselectionofthesampletested被測樣品選擇的根本原理Statementonthesterilestateofthetestsample.Ifthetestsamplewasnotsterilized,arationaleshallbegivenwhysterilizationhasnoinfluenceonbiocompatibilityofthefinaldevice關(guān)于被測樣品無菌狀態(tài)的陳述．如果測試樣品不是無菌，應(yīng)給出滅菌對成品的生物相容性不起作用的原因的根本原理．Assignappropriateteststothebiologicaleffects.(Onlysuchtestsshallbeperformedwhichleadtoevidentresults)指定適當(dāng)?shù)臏y試來測試生物性效應(yīng)〔只進(jìn)行此類能產(chǎn)生明顯結(jié)果的測試〕oOverviewofteststobeperformedinbiologicalevaluation在生物學(xué)評價中所進(jìn)行的測試的概觀Theselectionandevaluationofanymaterialordeviceintendedforuseinhumansrequiresastructuredprogrammeofassessment(refertoISO10993-1AnnexB)用于人體的任何材料或器械的選擇和評估需要結(jié)構(gòu)化的評估程序〔參見ISO10993-1中附錄Ｂ〕oJustificationfortestsnotperformed未進(jìn)行的測試的證實Thequalityandtheextentofdocumentationaswellastheassessmentinregardtotheintendedusedeterminewhetherornotbiologicaltestsshallbeperformedwiththefinalproductandtowhatextent關(guān)于預(yù)期用途的文件材料的質(zhì)量和范圍以及評估決定了是否對成品進(jìn)行生物測試，以及進(jìn)行到什么程度．Biologicalevaluationmayincludebothastudyofrelevantexperienceandactualtesting.Suchanevaluationmayresultintheconclusionthatnotestingisneededifthematerialhasadocumentedhistoryofuseinaspecifiedrolethatisequivalenttothatofthedeviceunderdesign生物評估包括相關(guān)經(jīng)驗和實際測試的研究．這樣的評估可能導(dǎo)致以下的結(jié)論：如果材料有文件化的使用歷史并在指定的作用方面等同于正在設(shè)計中的器械的使用歷史，那么不需要測試．Eachdeviceshouldbeexaminedonitsownfeatures.Datamaybeavailablefromsuppliersorintheliterature.Inthiscasefulltransferabilityistobedemonstrated.Testsystems,testsensitivityandconcentrationsusedshouldbetakenintoconsideration每種器械應(yīng)根據(jù)其自身的特征進(jìn)行檢查．可從供給商或文獻(xiàn)中獲得數(shù)據(jù)．在此種情況下，將展示完全的可轉(zhuǎn)移性．應(yīng)考慮到用過的測試系統(tǒng)，測試敏感性和濃度．Waivingoftestsshallberecorded棄權(quán)的測試應(yīng)記錄Biocompatibilitytestprotocols(copies)生物相容性測試協(xié)議(復(fù)印件)oQualificationofthetestlaboratory,i.e.accreditation測試實驗室的資格驗證，即認(rèn)證oTestingshouldbeconductedaccordingtoappropriategoodlaboratorypracticesfollowedbyevaluationbycompetentinformedpersons測試應(yīng)按照適當(dāng)?shù)牧己脤嶒炇覙?biāo)準(zhǔn)進(jìn)行，然后由權(quán)威的知情人士進(jìn)行評估oForqualitativedata:acceptancecriteria對于定性數(shù)據(jù)：驗收準(zhǔn)那么Biocompatibilitytestreports(copies)生物相容性測試報告〔復(fù)印件〕oForqualitativedata/results:interpretation對于定性數(shù)據(jù)／結(jié)果：闡述oPositiveresults–Whattodo?陽性反響－要做什么？Verificationofresults結(jié)果確實認(rèn)Chemicalcharacterizationofleachables濾出物的化學(xué)特性O(shè)verallinterpretationofthebiologicalevaluationofthedevice器械的生物學(xué)評價的總體闡述Relevanceofclinicaluse臨床使用的相關(guān)性Biocompatibilityevaluationandsummaryreport生物相容性評價和總結(jié)報告oCompilationoftestsperformedintabularform以表格的形式編制測試Example例如:Test測試ProtocolNo.協(xié)議號ProjectNo./產(chǎn)品編號LaboratoryNo.實驗室編號Reportdate報告日期Result結(jié)果Conclusion結(jié)論Cytotoxicity細(xì)胞毒性Cytotoxicitytest/細(xì)胞毒性測試L929-proliferationL929-擴散XYyyyy-mm-dd年－月－日GrowthanalysisofcellsculturedwiththetestextractshowednorelevantgrowthinhibitionofL929cells.測試提取的培養(yǎng)細(xì)胞的生長分析未顯示相關(guān)的L929細(xì)胞的生長抑制Sensitization致敏性MurineLocalLymph鼠性局部淋巴NodeAssay節(jié)點化驗YZyyyy-mm-dd年－月－日Thestimulationindiceswerecalculatedtobelessthan3.0.刺激指數(shù)要少于3.0.oFurtherrelevantinformationonthetests有關(guān)測試的更多相關(guān)信息Testsample(parttested)e.g.cathetershaftortip,balloon,wholedevice試樣〔局部測試〕例如：管桿或?qū)Ч芗舛耍瑲饽?，整個器械Specification(polymertype,supplier,tradename,additives)e.g.PUR,Pellethane2363-90A,20%Ba2SO4規(guī)格〔聚合物類型，供給商，商品名，添加劑〕例如：PUR,Pellethane2363-90A,20%Ba2SO4Statusoftestmaterial(finalproduct,sterile)測試材料狀態(tài)〔成品，無菌〕Typeofbodycontacte.g.circulatingblood身體接觸類型例如：血液循環(huán)Contactduratione.g.limitedcontactduration(<24h)接觸持續(xù)時間例如：限定的接觸持續(xù)時間〔＜24小時)Standard/norme.g.ENISO10993-5:1999標(biāo)準(zhǔn)／標(biāo)準(zhǔn)例如：ENISO10993-5:1999Extractpreparation(medium,surface/masstovolumeratio,temperature,time)提取準(zhǔn)備〔媒介，外表／質(zhì)量體積比，溫度，時間〕Testlabqualificatione.g.competenceunderDINENISO/IEC17025,certificationacc.toGLP測試實驗室資格例如：DINENISO/IEC17025的資格認(rèn)證，依據(jù)GLP的認(rèn)證Actiontakenonpositiveresultsasdescribedabove上述的對陽性反響采取的措施oConclusion結(jié)論Biologicalevaluationshallbepartoftheriskmanagementprocess生物學(xué)評價應(yīng)是風(fēng)險管理過程的一局部．Afinalstatementofthemanufacturerisnecessary.Themanufacturermightconcludethatinhisopinion,basedo