ISO11737初始污染菌翻译版(1)

word医疗器械的灭菌(mièjūn)微生物 方法 快递客服问题件处理详细方法山木方法pdf计算方法pdf华与华方法下载八字理论方法下载 第一局部(júbù)：产品(chǎnpǐn)上微生物总数的估计目次前言(qiányán)…………·…………………………………………·引言(yǐnyán)………………………………··……………………1范围………………………………………·…………2 标准 excel标准偏差excel标准偏差函数exl标准差函数国标检验抽样标准表免费下载红头文件格式标准下载 性引用文件……………………………………-3术语和定义…………………………··……………··4总如此…·……··………………………………………·5产品单元的选择……………………………………·6技术的选择…………………………………………·7技术选择……………………………………………·8技术的使用…………··……………………………··附录A(资料性附录)产品上微生物总量的估计指南附录B(资料性附录)微生物学技术确认方法指南-·附录c(资料性附录)参考文献………………···……医疗器械的灭菌微生物学方法第1局部：产品上微生物总数的估计1范围ISO11737的本局部说明了应用于估计医疗器械、半成品或包装上活的微生物总数的一般标准。这种估计包括两个方面：微生物的计算和定性。注1：微生物特性的本质和限度以生物负载的预期使用目的为根底。本局部没有 规定 关于下班后关闭电源的规定党章中关于入党时间的规定公务员考核规定下载规定办法文件下载宁波关于闷顶的规定 计算和鉴定病毒性或原生动物污染的要求。注2：此外，本局部不用于对海绵状脑病的起因进展切除或检测，如：疯牛病、羊搔痒症及CJD。本局部不适用于对生产医疗器械的环境中微生物的监控。2.标准性引用文件如下文件是应用本局部不可缺少的，中的条款通过GB／T19973的本局部的引用而成为本局部的条款。但凡注日期的引用文件，其现行版本版适用于本局部，但凡不注日期的引用文件，其最新版本适用于本局部。ISO10012,测量管理系统.测量方法和测量设备的要求ISO13485:2003,医疗器械质量管理体系用于法规的要求ISO/IEC17025:2005,检测和校准实验室资格的一般要求3术语和定义如下术语和定义适用于本局部。3．1生物负载bioburden一件产品和／或无菌阻隔系统上存活微生物的总数。[ISO/TS11139:2006,定义2.2]3.2纠正Correction消除已发现的不合格所采取的措施。注：纠正可连同纠正措施一起实施(3.4).[ISO9000:2005,定义3.6.6]3.3correctionfactor修正系数补尝从产品和/或培养基上无法完全洗脱的微生物的数值3.4纠正措施correctiveaction为消除已发现的不合格或其他不期望情况的原因所采取的措施。注1一个不合格可以有假设干个原因注2采取纠正措施是为了防止再发生，而采取预防措施(3.9)是为了防止发生。注3纠正(3.2)和纠正措施是有区别的[ISO/TS11139:2006,定义2.8]3.5培养条件cultureconditions促进微生物发芽、生长和/或繁殖所采用的生长培养基和培养方法的组合。注培养方法可包括温度、时间和其他规定用于培养的条件。[ISO/TS11139:2006,定义2.10]3.6设定establish通过(tōngguò)理论(lǐlùn)评价确定(quèdìng)，并经实验(shíyàn)工作(gōngzuò)证实。[ISO/TS11139:2006,定义2.17]3.7医疗器械medicaldevice制造商的预期用途是为如下一个或多个特定目的用于人类的，不管单独使用或组合使用的仪器、设备、器具、及其、用具、植入物、体外试剂或校准物、软件、材料或其他相似或相关物品。这些目的是：疾病的诊断、预防、监护、治疗或者缓解；损伤的诊断、监护、治疗、缓解或者补偿；解剖或生理过程的研究、替代、调节或者支持；支持或维持生命；妊娠控制；医疗器械的消毒通过对取自人体的样本进展体外检查的方式来提供医疗信息。其作用于人体体表或体内的主要设计作用不是用药理学、免疫学或代谢的手段获得，但有可能有这些手段参与并起一定辅助作用。注：本定义由全球协调工作组制定〔GHTF〕。[ISO13485:2003]3.8微生物表征microbialcharacterization把微生物归类成主要类型的一般方法。注：列如：可根据采用的选择性培养基、菌落或细胞结构形态，染色特性或其他特性，组合成各个类型。[ISO/TS11139:2006,定义2.25]3.9预防措施preventiveaction为消除潜在的不合格或其他潜在不期望情况的原因所采取的措施。注1一个潜在不合格可以有假设干个原因。.NOTE2采取预防措施是为了防止发生，采取纠正措施(3.4)是为了防止再发生。[ISO9000:2005,定义3.6.4]3.10产品product过程的结果注用于灭菌的产品是实际的，是指原材料、半成品、部件和医疗保健产品。[ISO9000:2005,定义3.4.2]3.11公认的菌种保存库recognizedculturecollection根据“国际公认微生物菌种保存专利与法规〞布达佩斯公约建立的国际菌种保存机构。[ISO/TS11139:2006,定义2.38]3.12回收率recoveryefficiency对某一特定的技术从产品或/和培养基上获取微生物的能力的测定值。3.13样品分额sampleitemportionSIP医疗器械用于试验的局部。3.14规定specify在批准件范围内详细约定的内容。[ISO/TS11139:2006,定义2.42]3.15确认validation为设定某可持续生产出符合预定技术规格的产品的工艺，获得、记录和整理结果的文件化程序。注5：在生物负载判定中，“过程〞是试验方法，“产品〞是试验结果。对生物判定技术确实认包括一系列调查，来测定试验方法的有效性和重现性。[ISO/TS11139:2006,定义2.55]4质量管理体系根底4.1文件4.1.1应规定生物负载(fùzài)的判定程序。ISO11737本局部(júbù)使用的文件和记录(jìlù)应经制定人员审核及批准(see)。文件(wénjiàn)和记录应按ISO13485或ISO/IEC17025要求(yāoqiú)进展受控.应保存原始观察的记录、导出数据和最终报告。记录应包括取样、制备和试验人员的识别。计算和数据转化应进展适当的校核。4.2管理 职责 岗位职责下载项目部各岗位职责下载项目部各岗位职责下载建筑公司岗位职责下载社工督导职责.docx ISO11737本局部描述的贯彻和执行的职责和职权应该规定。按照ISO13485或ISO/IEC17025要求将责任分派给能胜任的人员。如果ISO11737的这局部的要求由几个独立的质量管理系统组织承当，应规定每局部的职责和职权。应具备规定试验的校核和测量所需设备的所有工程。4.3产品的实现应规定采购程序。这些程序应符合ISO13485或ISO/IEC17025要求。符合ISO13485或ISO/IEC17025或ISO10012的要求建立的文件体系，应规定按照ISO11737本局部的要求所使用的设备，包括用于检测的仪器的校核。应规定生物负载判定(包括适宜的质量试验)所用的材料制备和灭菌方法。4.4测量、分析和改良－不合格品控制应规定检验不合格结果调查、纠正、纠正措施和玉兔方措施的程序，这些程序应符合ISO13485或ISO/IEC1702要求。5.产品的选择5.1总如此应建立选择和处理判定生物负载产品的程序，以保证这些产品包括包装材料和过程对常规生产具有代表性。如果确定生物负载所用产品是成组的，在一组中产品内含物的根本原理应该被记录(见4.1.2)，根本原理包括确认的标准来自某一组群中选择的一个产品确实定的生物负载，这一组群在整个组群中是有代表性的应考虑做生物负载判定的采样时间，因为生物负载判定会随时间而改变。5．2样品份额(SIP)假设生物负载被证明均匀地分布在产品上或/和产品内，SIP可以从产品的任意局部挑选。否如此SIP应由产品的多局部组成，随便地选择，其制成产品的每种材料适当的代表。如果生物负载的分布，那么SIP可以选择产品的一局部，该局部对灭菌过程具有挑战性，SIP能以长度、质量、体积或外表积计算出。表1—SIP计算举例BasisforSIP产品Surfacearea外表积Implants(non-absorbable)植入〔非吸收的〕Mass质量Powders粉末GownsImplants(absorbable)植入〔可吸收的〕Length长度Tubing(consistentdiameter)管〔外径一致〕Volume体积Fluidinwatercup在水杯中的液体〕注：如适用，规定灭菌过程确实认和常规控制要求的标准应提供样品份额的适宜性指标。Removalofmicroorganisms微生物的消除6.1.2.1Foranidentifiedproductwhereremovalofviablemicroorganismsispartofthemethod,theefficiencyofremovalshallbeconsideredandtheoutcomesofthisconsiderationrecorded(see4.1.3).Considerationshall,atleast,begivento:对于确定的产品消除存活的微生物是一局部方法，应考滤消除的效率和记录的考虑的结果，至少应考虑：a)abilityofthetechniquetoremovemicroorganisms;〔见4。1。3〕，消除微生物技术的能力b)possibletype(s)ofmicroorganismandtheirlocation(s)onproduct;微生物的可能类型和在产品上的位置c)effect(s)oftheremovaltechniqueontheviabilityofmicroorganisms;对于存活微生物消除技术的效果d)thephysicalorchemicalnatureofproductundertest.在试验状态下产品的物理和化学性质6.1.2.2Foranidentifiedproductforwhichremovalofviablemicroorganismsisnotpartofthemethod,theefficiencyofenumerationofmicroorganismsshallbeconsideredandtheoutcomesofthisconsiderationrecorded(see4.1.3).Considerationshall,atleast,begivento:对于确定的产品消除产品上的存活微生物的方法不包括在本局部中，列举微生物的效率应考虑，并且记录考虑的结果〔见4。1。3〕至少应考虑以下方面：a)possibletype(s)ofmicroorganismandtheirlocation(s)onproduct;微生物的类型和在产品(chǎnpǐn)上的位置b)thephysicalorchemicalnatureoftheproducttobetested;试验产品的物理(wùlǐ)、化学性能c)aggregatesofcellsformingsinglecoloniesduetoin-situculturing.在原处(yuánchǔ)培养的单克隆细胞合计6.1.2.3Ifthephysicalorchemicalnatureofproductissuchthatsubstancescanbereleasedthatadverselyaffecteitherthenumberorthetypesofmicroorganismfound,thenasystemshallbeusedtoneutralize,removeor,ifthisisnotpossible,minimizetheeffectofanysuchreleasedsubstance.Theeffectivenessofsuchasystemshallbedemonstrated.如果产品的物理和化学状态其物质能被释放出来，反作用在发现的一个或一种(yīzhǒnɡ)类型的微生物上，那么使用中和、消除系统，如果这些是不可能的，那么这种释放的物质的作用应降低到最小化NOTEAnnexBdescribestechniquesthatmaybeusedtoassessthereleaseofmicrobicidalormicrobiostaticsubstances.附录(fùlù)B描述了用于评定微生物或微生物物质释放的技术Culturingofmicroorganisms微生物的培养Cultureconditionsshallbeselectedafterconsiderationofthetypesofmicroorganismlikelytobepresent.Theresultsofthisconsiderationandtherationaleforthedecisionsreachedshallberecorded(see4.1.2).选择培养条件然后考虑微生物可能存在的类型，考虑的结果和到达结果的根本原理应该纪录〔见4.1.2).Enumerationofmicroorganisms微生物列举Thetechniqueforenumerationshallbeselectedafterconsiderationofthetypesofmicroorganismlikelytobepresent.Theresultsofthisconsiderationandtherationaleforthedecisionsreachedshallberecorded(see4.1.2).选择列举的技术然后考虑微生物的类型。考虑的结果和到达结果的根本原理应该纪录〔见4.1.2).6.2Microbialcharacterizationofbioburden生物负载的微生物特征Appropriatetechniquesformicrobialcharacterizationofbioburdenshallbeselected.选择生物负载的微生物描述的适当的技术NOTEMicrobialcharacterizationisnecessarytodetectachangetoproductmicroflorathatmightaffectsomeaspectoftheuseofthebioburdendata(e.g.establishingasterilizationprocess).微生物的描述是必要的对于发现产品的一个变化的微生物群，那可能影响一些外表的生物负载资料的使用〔建立一个灭菌过程〕Microbialcharacterizationshallbeaccomplishedusingoneormoreofthefollowing:微生物描述应用一下一个或更多个完成a)stainingproperties;着色性b)cellmorphology;细胞形态c)colonymorphology;群体形态d)useofselectiveculturing;使用的培养方法e)biochemicalproperties;生物化学性质f)geneticsequencedataforwhichthereisanadequatedatabase.遗传序列资料，对此有适当的资料库7Validationofmethodfordeterminingbioburden确定生物负载方法确实认7.1Themethodfordeterminingofbioburdenshallbevalidatedanddocumented.生物负载确实定方法应被确认和文件化7.2Validationshallconsistofthefollowing:确认有以下内容组成a)assessmentoftheadequacyofthetechniqueforremovalofmicroorganismsfromproduct,ifremovalispartofthemethod;从产品上消除微生物的适当的技术评估，如果消除是方法的一局部。。b)determinationoftherecoveryefficiencyinorderthatacorrectionfactorbederived;回收率的测定以便于推断纠正因子c)assessmentoftheadequacyoftheenumerationofmicroorganisms,includingcultureconditionsandmicrobiologicalcountingtechniques;适当的微生物列举(lièjǔ)评估，包括培养条件和微生物计算技术。d)assessmentofthesuitabilityofthetechnique(s)ofmicrobialcharacterization.微生物表述(biǎoshù)技术的适宜性评估8Routinedeterminationofbioburdenandinterpretationofdata生物(shēngwù)负载确实(quèshí)定程序(chéngxù)和数据资料8.1Routinedeterminationofbioburdenshallbeperformedemployingdocumentedsamplingplan(s)definingsamplesizeandsamplingfrequency.生物负载确实定程序应文件规定采样 方案 气瓶 现场处置方案 .pdf气瓶 现场处置方案 .doc见习基地管理方案.doc关于群访事件的化解方案建筑工地扬尘治理专项方案下载 ，定义样品规格和采样频率。8.2Determinationofbioburdenshallbeperformedusingamethodspecifiedforaproductorgroupofproducts(see5.1.2).对于一个产品或一组产品使用规定的方法进展生物负载确实定。8.3Microbialcharacterizationofbioburdenshallbeperformedtoadegreedependentonthepurposeforwhichthedataderivedfromthedeterminationofbioburdenaretobeused(see6.2).进展生物负载的微生物描述度量依赖于来源于使用生物负载确实定的推断数据If,onmicrobialcharacterization,isolatesarerecoveredthatarenotpartofthenormalmicroflora,considerationshouldbegiventoassessingthepropertiesoftheseisolates.假设，涉及微生物描述，隔离种群被恢复，那不是普通的生物群，应考虑这些隔离种群的性质评估。8.4Ifbioburdendataaretobeusedtoestablishtheextentoftreatmentofasterilizationprocess,anyrequirementsapplicabletotheuseofbioburdendata,specifiedintheappropriatestandardforthedevelopment,validationandroutinecontrolofthesterilizationprocess,shallbemet.假设生物负载的资料用于建立灭菌程序涉及的程度，一些必要的条件应用于使用的生物负载数据，在适当的标准中规定灭菌过程的开展、确认和常规控制，应满足.8.5Acceptablelimitsforbioburdenonorinamedicaldeviceshallbespecified.Thisspecificationshallbebasedonpreviouslygenerateddata.Iftheselimitsareexceeded,actionshallbetaken(see4.4).可承受的在医疗器械上或内的生物负载的限度应规定，这个规定基于前期产生的资料。如果这些限度超标，应采取措施〔见4.4〕8.6Dataderivedfromdeterminationofbioburdenobtainedoveraperiodoftimeshallbeusedtoidentifytrends.Acceptablelimitsshallbereviewedandrevisedasnecessary.通过前期获得的生物负载测定的推断资料被应用于确定趋势，观察可承受的界限并进展必要的修正。word8.7Theapplicationofstatisticalmethodstodefinesamplesize,samplingfrequencyand/oracceptablelimitsshallconformtoISO13485.应用(yìngyòng)统计方法说明样品大小，取样频度或/和承受(chéngshòu)限度(xiàndù)符合ISO13485.。9Maintenanceofthemethodofdeterminationofbioburden生物(shēngwù)负载确定方法的维护9.1Changestotheproductand/ormanufacturingprocess产品(chǎnpǐn)和/或生产流程的改变Changestoproductand/ormanufacturingprocessesshallbereviewedtodeterminewhethertheyarelikelytoalterbioburden.Theresultsofthereviewshallberecorded(see4.1.2).Ifthereispotentialforalterationofbioburden,specificdeterminationsofbioburdenshallbeperformedtoevaluatetheextentandnatureofanychange.评价产品和/或生产流程的改变，确定是否可能是变化的生物负载。评价的结果应记录〔见4.1.2〕，如果有可能改变生物负载，进展明确的生物负载确定，并估计变化的程度和种类。9.2Changestothemethodofdeterminationofbioburden生物负载确定方法的变化Anychangetoaroutinemethodofbioburdendeterminationshallbeassessed.Thisassessmentshallinclude:生物负载确定的常规方法的任何改变应评定，这种评定包括：a)evaluationoftheeffectofthechangeontheoutcomeofdetermination;评价于确定结果的改变的影响b)establishmentoftherecoveryefficiencyofthemethodfollowingthechange.建立以下变化方法的回收率NOTETheassessmentofthechangecouldindicatethatthepreviousvalidationandrecoveryefficiencyarestillapplicable.变化的评价指出先前确实认和回收率仍然适用。9.3Revalidationofthemethodofdeterminationofbioburden生物负载确定方法的再确认Theoriginalvalidationdata(see7.2)andanysubsequentrevalidationdatashallbereviewedatspecifiedintervalsinaccordancewithadocumentedprocedure.Theextenttowhichrevalidationistobeundertakenshallbedetermined.Theoutcomeofthereviewandanyrevalidationundertakenshallberecorded(see4.1.3).确认的原始资料〔见7.2)和一些后来再确认资料应按照文件规定的时间间隔再评价。进展再评价的范围应确定，评价的结果和进展得再确认应记录〔见4。1。3)AnnexA(informative)Guidanceondeterminationofapopulationofmicroorganismsonproduct确定产品上微生物数量的指南NOTEForeaseofreference,thenumberinginthisannexcorrespondstothatusedinthenormativepartofthispartofISO11737.为了参考简单，本附录的编号与ISO11737用于本局部的相符合A.1Scope概述ThisannexcontainsguidanceontheimplementationoftherequirementsspecifiedinthispartofISO11737.Theguidancegivenisnotintendedtobeexhaustive,buttohighlightimportantaspectstowhichattentionshouldbegiven.本附录包含ISO11737本局部规定要求的执行，所给指南没有规定是详尽的，但关心的最重要的方面应给出。Methodsotherthanthosegiveninthisannexmaybeused,butthesealternativemethodsshouldbedemonstratedasbeingeffectiveinachievingcompliancewiththerequirementsofthispartofISO11737.除了本附录给出的方法被使用外，对于其他可供选择的方法应被论证ThisannexisnotintendedasachecklistforassessingcompliancewiththerequirementsofthispartofISO11737.本附录不包含评价符合本局部ISO11737要求的清单。A.2Normativereferences参考标准TherequirementsofdocumentsincludedasnormativereferencesarerequirementsofthispartofISO11737onlytotheextentthattheyarecitedinanormativepartofthispartofISO11737;thecitationmaybetoanentirestandardorlimitedtospecificclauses.参考文件包含参考标准作为本局部ISO11737要求，只是本局部ISO11737标准引用的程度；该引用可能是标准的全部也可能限于规定的条款A.3Definitions定义Noguidanceoffered.没有指南提供A.4Qualitymanagementsystemelements质量管理体系要素NOTEItisnotarequirementofthispartofISO11737tohaveafullqualitymanagementsystem,buttheelementsofaqualitymanagementsystemthataretheminimumnecessarytocontrolthedeterminationofbioburdenasusedinthevalidationandmonitoringofmedicaldevicestobesterilizedarenormativelyreferencedatappropriateplacesinthetext(see,inparticular,Clause4).Attentionisdrawntothestandardsforqualitymanagementsystems(seeISO13485)thatcontrolallstagesofproductionorreprocessingofmedicaldevices.Nationaland/orregionalregulationsfortheprovisionofmedicaldevicesmightrequireacompleteimplementationofafullqualitymanagementsystemandtheassessmentofthatsystembyathirdparty.A.4.1Documentation文件(wénjiàn)InISO13485,therequirementsinthedocumentationsectionrelatetothegenerationandcontrolofdocumentation(includingspecificationsandprocedures)andrecords.Computersmaybeusedinlaboratoriesfordirectandindirectcollection,processingand/orstorageofdata.Boththehardwareandsoftwareusedforsuchapplicationsshouldbecontrolled.ISO11737-1:2006(E)Thecomputersysteminuseshouldbeidentified,bothintermsofhardwareandsoftware,andanychangesineitheroftheseaspectsshouldbedocumentedandsubjecttoappropriateapproval.Ifcalculationsareperformedbyelectronicdataprocessingtechniques,thesoftware(e.g.,spreadsheetcalculations)shouldbevalidatedpriortouseandrecordsofthisvalidationshouldberetained.Forsoftware,thereshouldbedocumentationdescribing:⎯applicationssoftwarerunonthecomputersystem;⎯operationssoftware;⎯datapackagesinuse.Allsoftwareshouldbeacceptancetestedbeforebeingputintoservice.Ifcomputersoftwareisdevelopedin-house,suitableproceduresshouldbedevelopedtoensurethat:⎯documentationondevelopment,includingthesourcecode,isretained;⎯recordsofacceptancetestingareretained;⎯modificationstoprogramsaredocumented;⎯changesinequipmentaredocumentedandformallytestedbeforebeingputintouse.Thesecontrolsshouldalsobeappliedtoanymodificationorcustomizingofcommercialsoftwarepackages.Thereshouldbeprocedurestodetectorpreventunauthorizedchangestosoftwareprograms.Softwareprogramsthatorganize,tabulateand/orsubjectdatatostatisticalorothermathematicalprocedures,orwhichotherwisemanipulateoranalysetheelectronicallystoreddata,shouldpermitretrievaloforiginaldataentries.Specialproceduresforarchivingcomputerdataarelikelytoberequiredandtheseproceduresshouldbedocumented.Requirementsforcontrolofdocumentsandrecordsarespecifiedin4.2.3and4.2.4ofISO13485:2003,or4.3and4.13ofISO/IEC17025:2005.Requirementsfortechnicalrecordsarespecifiedin4.13.2and5.4ofISO/IEC17025:2005.SeealsoISO90003forguidanceoftheapplicationofqualitymanagementsystemstocomputersoftware.A.4.2Managementresponsibility管理(guǎnlǐ)职责InISO13485,therequirementsinthemanagementresponsibilitysectionrelatetomanagementcommitment,customerfocus,qualitypolicy,planning,responsibility,authorityandcommunication,andmanagementreview.Inorderthatthedataobtainedfromperformingbioburdendeterminationsarereliableandreproducible,itisimportantthatthedeterminationsbeperformedundercontrolledconditions.Therefore,thelaboratoryfacilitiesusedforthedeterminations,whetheronthesiteofthemanufacturerofthemedicaldeviceorlocatedataremotelocationshouldbemanagedandoperatedinaccordancewithadocumentedqualitysystem.Thedeterminationofbioburdencaninvolveseparateparties,eachofwhomisresponsibleforcertainelementsofthemethodorprocedure.ThispartofISO11737requiresthatthepartyacceptingparticularresponsibilitiesbedefinedandthatthisdefinitionofresponsibilitiesbedocumented.Thisdefinitionofauthorityandresponsibilityisdocumentedwithinthequalitymanagementsystem(s)oftheidentifiedparties.Thepartyacceptingresponsibilitiesfordefinedelementsisrequiredtoassigntheseelementstocompetentpersonnel,withcompetencedemonstratedthroughappropriatetrainingandqualification.Ifbioburdendeterminationsareperformedinalaboratoryunderthedirectmanagementofthemanufacturerofthemedicaldevice,theoperationofthelaboratoryresideswithinthemanufacturer'squalitymanagementsystem.Ifanexternallaboratoryisused,thelaboratoryshouldbeformallycertifiedagainstanappropriateInternationalStandard(e.g.ISO/IEC17025).Anylaboratoryshouldbecommittedtoprovidingaqualityserviceandthiscommitmentshouldbedocumentedasaqualitypolicy.Thelinesofauthorityandresponsibilitywithinthelaboratoryorganizationshouldbeformallyestablishedanddocumented.Anindividualshouldbenominatedtoberesponsiblefortheestablishmentofthelaboratoryqualitysystemandshouldhavetheauthoritytoensurethatthesystemisimplemented.Theoperationofthelaboratoryshouldbesubjecttoregularinternalaudits.Theresultsoftheauditshouldbedocumentedandreviewedbythelaboratorymanagement.See4.14ofISO/IEC17025:2005.Requirementsforresponsibilityandauthorityarespecifiedin5.5ofISO13485:2003andrequirementsforhumanresourcesarespecifiedin6.2ofISO13485:2003.RequirementsforprovisionofresourcesarespecifiedinISO13485andrequirementsforequipmentarespecifiedin5.5ofISO/IEC17025:2005.A.4.3Productrealization产品(chǎnpǐn)实现InISO13485,therequirementsintheproductrealizationsectionrelatetotheproductlifecyclefromthedeterminationofcustomerrequirements,designanddevelopment,purchasing,controlofproduction,andcalibrationofmonitoringandmeasuringdevices.Thereshouldbeasystemforidentifyingthemaintenancerequirementsforeachpieceoflaboratoryequipment.Equipmentthatdoesnotrequirecalibrationshouldbeclearlyidentified.Anyequipment,orpartsthereof,thatcomesintocontactwithproduct,eluent,media,etc.,duringtestingshouldbesterile.Allmicrobiologicalmediaandeluentsusedtoremovemicroorganismsfromproductshouldbepreparedinamannerthatensurestheirsterility.Appropriatequalitytestsshouldincludegrowthpromotiontests.Generally,growthpromotiontestsareperformedoneachbatchofmediumusinganinoculumoflownumbers[between10and100colony-formingunits(CFUs)]ofselectedmicroorganisms.Growthpromotiontestsaredescribedinpharmacopoeialmonographsthatdetailsuitablemicroorganisms.Otherrecognisedquantitativeandsemi-quantitativemethodsformediaqualitycontrolarealsoacceptable.Requirementsforpurchasingarespecifiedin7.4ofISO13485:2003.Inparticular,itshouldbenotedthattherequirementsin7.4.3ofISO13485:2003forverificationofpurchasedproductapplytoallproductandservicesreceivedfromoutsidetheorganization.Requirementsforcalibrationofmonitoringandmeasuringdevicesarespecifiedin7.6ofISO13485:2003.Requirementsforequipmentandmeasurementtraceabilityrequirementsarespecifiedin5.5and5.6ofISO/IEC17025:2005.A.4.4Measurement,analysisandimprovement—Controlofnonconformingproduct测量(cèliáng)、分析和改良(gǎiliáng)-不合格品的控制(kòngzhì)InISO13485,therequirementsinthemeasurement,analysisandimprovementsectionrelatetoin-processmonitoring,controlofnonconformingproduct,analysisofdataandimprovement(includingcorrectiveandpreventiveactions).Allbioburdenresultsthatexceedspecificationandthatindicateanadversetrendrequireinvestigation.Theinitialphaseoftheinvestigationshouldinvolveassessingiftheresultsareatruefindingorareinerror.Thefollowingcancontributetoanerrorandshouldbeaddressed:⎯inappropriatesamples(e.g.non-representative,non-homogeneousrejectedmaterials);⎯inappropriatesamplingmaterials(e.g.swabs,containers,packages);⎯unsuitableconditionsoftransport/handling/storage;⎯inappropriatetestmaterials(e.g.storage,pipettes,filtrationapparatus);⎯incorrecthandlingortestmethod(s);⎯inappropriatemediaordiluents;⎯inappropriatelaboratoryenvironment;⎯inappropriateincubationenvironment;⎯errorsofcalculationortranscription.Iftheresultsareduetoanerror,thebioburdenresultthatexceedsthespecifiedlimitshouldbeverifiedbytheperformanceofarepeatdeterminationemployingsamplesfromthesamebatchofproduct.Ifproductsupportsmicrobialgrowthorifthesamebatchisnolongeravailable,anewbatchmaybeused.Iftheoriginalresultisconfirmedasatruefinding,atleastthefollowingshouldbeconsideredinthesecondphaseoftheinvestigation:a)theimplicationoftheresultinrelationtotheeffectivenessofthesterilizationprocess;b)theneedtoincreasethesamplesizeand/orfrequency;c)theoutcomeofanassessmentofmanufacturingprocesses;insuchanassessment,thefollowingshouldbeaddressed:1)rawmaterials/components(vendors,changes);2)cleaning/lubrication/manufacturingliquid;3)transport/holdingcontainers;4)worksurfaces;5)personnelattire/hygiene/practices;6)handling/assembly;7)environmentalconditionsandmonitoringresults(includingseasonalfactors,ifany);8)packagingmaterialsandprocedures;9)storageconditions;d)microbialcharacterizationoforganism(s)recovered,including1)potentialsources;2)comparisonwithpreviousisolates.A.5产品(chǎnpǐn)的选择A.5.1总如此(rúcǐ)A.5.1.1取样和处理样品时应防止因疏忽而引起的污染和对样品中微生物数量和性质有较大改变。取样系统应具有一致性，以便在一段时间内具有可比性。取样进展生物负载判定时，无非有两种可能性：a)随机抽取样品；b)抽取不适于销售的产品，如废料或不合格品。I此类样品的选择取决于众多因素，但是先决条件是所选样品能尽可能地具有生物负载代表性。如果是用不合格品，如此宜选择那些已经过各个关键的生产过程阶段(包括清洗和包装过程)的产品。按以上a)抽取的产品是更为理想的样品。为判定生物负载取样时，产品应装在其标准包装之中A.5.1.2在为生物负载产品进展编组过程中，应考虑以下内容：a)微生物数量;b)微生物类型(lèixíng);c)产品规格;d)部件(bùjiàn)数量;e)产品(chǎnpǐn)复杂性;f)生产过程(guò