检品取样、检验及报告管理规程

文件名称/DocumentName文件编号：DocumentNo.SMP-09-001-1Theprocedureofsampling,test,reportofsample文件页码：Page11/12执行日期：Executivedate2013.01.01颁发部门：IssuedDept.化验室/QCDept.文件名称文件编号：GMP文件管理规程版本号：页码：1/12执行日期：一、目的：Purpose:为保证检验样品的取样代表性，检验结果的准确、报告的规范，特制定本管理规程。Toensurethesamplingisrespresent,thetestresultsarecorrectandthereportsarestandard,speciallymaketheprocedure.二、适用范围：Scope原料药成品、中间产品、原辅料的取样、检验及报告。Sampling,testandreportofAPIproducts,intermediatesandrawmeterials.三、职责：Responsibility取样员对本规程的执行负责。QA,QCandqualitativeinspectmembersinchargeofexecutionofthisprocedure.四、主题内容：Subjectcontent1、检品分类Classificationoftestsample:1.1、本规程所指的检品包括进厂原辅料、中间产品、待包装产品及成品。Testsampleofthisprocedureisincludingoutsourcingrawmeterials,intermediates,bulkproductsandfinishdproducts.1.2、进厂原辅料包括化工原料、药用原料、食用原料、辅料、试剂级原料或辅料（不包括检验用试剂）及内包装材料。注：内包材的取样数量和取样规则见包装材料相关检验操作规程。Outsourcingrawmeterialsincludingchemicalrawmaterials、officinalrawmaterials、ediblerawmaterials、auxiliarymaterials、reagentmaterialsorauxiliarymaterials(notcontainreagentsforanalysis)andpackingmaterials.Notes:RegulationofsamplingandthequantityofsamplingofpackingmaterialsseeSOPofpackingmaterial.1.3、中间产品系指完成部分加工步骤的产品，尚需进一步加工方可成为待包装产品。Intermediatesistheproductswhichiscompletedpartsjobstepsanditneedstobefurtherprocessingthenitcanbebulkproducts.1.4、待包装产品系指尚未进行包装但已完成所有其他加工工序的产品。Bulkproductsistheproductswhichiscompletedalljobsteps,butpackaging.1.5、成品系指已完成所有生产操作步骤和最终包装的产品。Finishedproductsistheproductswhichiscompletedallproductionoperationstepsandfinalpackaging.2、检品取样Sampling:2.1、定义Definition:取样系指从一批被检验的样品中，按取样规则抽取一定数量的具有代表性的样品。Samplingmeansextractquantitiesofrepresentativesamplefromonebatchsampleaccordingtoregulationofsampling.样品系指为了检验产品的质量，从整批被检验的样品检品中抽取的具有代表性的足够检验用量的部分样品。Samplemeansextractadequacyquantitiesofrepresentativesamplefromwholebatchsampletoensurequalityoftestsample.2.2、取样人员要求Requestsforsamplingperson:2.2.1、取样人员需要经过质量受权人授权，被授权的取样人员可以为各车间现场QA，质监员或者是公司QC人员。SamplingpersoncanbeQAoftheworkshop,qualityinspectororQCwhohaveauthorizedbyqualifiedperson.2.2.2、取样人员应了解产品及化学的一般知识，有良好的视力和对颜色分辨、识别的能力，具有一定安全防护措施。Samplingpersonshouldhaveaknowledgeofgeneralinformationoftheproductsandchemistry.andhaveagoodeye-sightandtheabilityofdistinguishandrecognitioncolor.Theyalsoshouldtakesafetyandpreventivemeasures.2.2.3、取样人员应由经过与取样相关的规程的培训的。Samplingpersonshouledacceptthetrainingofthesamplingprocedure.2.3、取样器具Samplingapparatus:2.3.1、取样器具选择：易于装入样品、易于倒出样品、容器表面不吸附样品、易于密封和存储、重量轻便于携带，如有需要还能避光。应根据所取样品性状选择合适的取样器具。取样器具一般包括固体取样器、液体取样器、取样勺、混样用烧杯、具塞碘量瓶、PE袋。Theselectionoftheapparatus:theapparatuswhosesurfacedonotabsorbthesampleshoulebeeasytoputinandpouroutthesample,anditiscomveninenttosealandstockthesample,havingalightweighttocarry,italsocanprotectthesamplefromthelightifnessary.choosetheappropriateapparatusaccordingtothecharacterofthesample.samplingapparatusgenerallyincludessamplerforsolid,samplerforliquid,samplingspoon,beakerformixthesample,iodinenumberflaskwithstopperandPEbag.、固体检品用清洁、干燥的不锈钢空心管（探子）、不锈钢勺或其他适宜的取样器具取样。Solidtestsampleissampledbyclean、drystainlesssteelhollowpipe(earchingunit),stainlesssteelscooporothersuitablesamplingapparatus.、液体检品用清洁、干燥的玻璃管、瓶或胖肚移液管取样。取样后放入清洁的具塞烧瓶或玻璃瓶内。Liquidtestsampleissampledbyclean、dryglasspipe,bottleorfattransferpipe.Takeintocleanflaskorglassbottlewhichhaveplugaftersampling./对不同包装的检品应选用大小或长短相适宜的取样器具（管），以使所取的样品具有代表性。Inordertomaketheextractedsamplehaverepresentativeness,choosesuitablesamplingapparatusassizeandlengthfortestsamplewhichhasdifferentpackage.2.3.2、取样器具的清洁，消毒和灭菌thecleaning,fumigationandsterilizingofthesamplingapparatus、取样器具及样品盛装器皿在使用后应立即清洗。取样用的玻璃、不锈钢器皿一般洗涤方法是：用饮用水冲洗数次，然后用适宜的毛刷蘸洗涤剂反复刷洗，再用饮用水冲洗至无泡沫后用纯化水冲洗三次，清洗后的器具应不挂水珠。洗净后的器具应晾干或烘干，挂已清洁标志，标明清洁日期或有效期。在清洁干燥处保存，有效期3天。samplingapparatusandvesselsforsampleshouldbecleanedimmediatelyafteruse.thegenerallycleaningpricedureforglassandstainlesssteelvesselis:washthevesselusedrinkingwaterseveraltimes,brushitoverandoverwithappripiatebushsaturatedwithdetergent,thenrinseitusedtinkingwatertillnofoamexitandringitusepurewaterthreetimes,nodropletsofwatershoudadheretotheapparatusaftercleaning.thecleanedappratusshoudairdryorovendry,andmarkthesymbolofcleaned,markingthedateofcleaningortheexpirydate.Theapparatusshouldplacedinthecleandryness,theperiodofvalidityis3days.、对于供微生物限度，细菌内毒素和无菌项目检查的进厂原辅料取样所用取样器具，按照方法清洗后，必须先经置于不锈钢盒子内在180℃干热灭菌2小时或者250℃干热灭菌1小时处理，填写灭菌记录和有效期。已灭菌的工具应在灭菌后48小时之内使用，使用前不得打开盒子，超过48小时应重新灭菌。对于原料药成品，取样器具由车间洁净区人员负责在洁净区内清洁并保存于洁净区内，可以不经灭菌处理直接用于取样做包括微生物限度，对于细菌内毒素和无菌项目的样品，应采用灭菌后的取样器具Fortestmicroorganismlimititem,thesamplingapparatususedforincomingmaterialthatneedtotestbacterialendotoxinandsterileshouldbedrysterilizationat180℃for2hoursor250℃for1hoursinthestainlessboxaftercleaningaccordingto2.3.21procedure,thenwritethesterilerecordandvaliddate.Theinstrumentsshouldbeusedwithin48hoursaftersterilization,otherwiseitshouldbesterilizedagain.donotopentheboxunlessuse.theapparatususedforAPIproductshouldbecleanedandkeptinthecleanarea,sotheycanusedforsamplingthatneedtodomicrobiallimit.Forbacteriaendotoxinandsteriletestwithoutsterilization,shouldtakethesamplingapparatusthathavesterilized.、中间体和成品用的取样器具由各车间协助清洁后存放于各车间内，进厂原辅料的取样器具由原辅料取样人员负责清洁和消毒灭菌。sampleapparatususedforintermediatesandproductpreseveinworkshopaftercleaning,samplingpersontakeinchargeofthecleaningandsterilizingofthesampleapparatususedforincomingmaterial2.3.3、采样时应准备好相应的标签，并按照标签上的内容填写完整，粘贴到取样容器表面。Samplingpersonshouldpreparesamples’labelswhilesampling,accordingtothecontentofthelabelfilledoutcompletely,andstickthelabelonthesurfaceofsample’scontainers.2.4、取样环境Samplingenvironment:2.4.1、原料药的原辅料取样在一般区的取样室内进行。Theaircleannesslimitofsamplingenvironmentofrawmaterialsshouldbethesameascleannesslevelforusingtestsample.2.4.2、原料药成品、中间产品在生产现场或中间站取样。API,intermediateproductsandshouldbesampledinmanufacturingsite.2.4.3、退货的原料药成品在D级环境下取样。SamplingofthereturningrentsintheenvionmentoflevelD.2.5、取样操作要求Requestofoperationofsampling:2.5.1、取样时应先与请检单核对和检查检品的品名、规格、批号、数量、生产单位及包装情况等。经检查无误和符合要求后方可取样。当发现异常现象例如：包装被污染或破损，取样人员则可拒绝采样，在取样记录备注栏中记录异常现象并立即报告化验室和品管部。Checkthetestapplicationformandcheckthename、specification、batch、quantity、manufacturingfactory、packagestatusetc.beforesampling.Samplingshouldbetakenaftermakesurealltheinformationiserrorfreeandcomplywiththerequirements.Iffoundanyabnormalphenomena,suchasthepackageiscontaminatedordamaged,samplingpersonshouldrefusetosample,recordtheabnormalphenomenaontheremarkscolumnofsamplingrecordandreporttoQCandQApromptly.2.5.2、固体物料用取样器从各被抽件检品的上、中、下各部位取样。注意绝对不允许同时打开两个物料的包装以防止物料的交叉污染。Solidmaterialissampledfromabove、middle、belowandaroundofextractedtestsample,thenmixwell.Noteneverallowedtoopentwopackagesofmaterialsatthesametimetopreventcrosscontamination.2.5.3、液体物料（包括乳剂、混悬剂）应混匀后再取样；如体积过大（如铁桶装），无法混匀的，则应用不同长度的玻璃吸管从各被抽件检品的上、中、下三层取样，然后混匀。Liquidmaterial(containemulsion,suspension)shouldbesampledafteritismixwell;Ifthevolumeistobig(exampleassteeltub),can’tmixwell,theglasspipeofdifferentlengthisusedtoextractfromthreefloorasabove、middle、belowofsample,thenmixwell.2.5.4、如遇同一批号检品外观质量不一致时，可拒绝取样并报告化验室和品管部，得到品管部批准和要求按件分别取样和分别检验。此时应在物料外包装和样品包装上同时注明取样顺序号。Iftheappearanceofsamebatchsampleisnotidentical,rejectingtosample,atthesametimereporttoQCandQA.AftergettheapprovalandrequirementsbyQA,samplingthentestrespectivelybypackagingcanbedone.Atthistimesamplingpersonshouldmarktheserialnumberontheouterpackingofbothmaterialandsample.2.5.5、进厂原辅料取样时，取样人员需要佩戴护袖，必要时佩戴一次性手套。取样后应对容器进行密封（如塑料袋用扎带扎紧或用封口机融封）以防止污染。在同一天换品种取样时，一般按照包装材料，辅料，原料药的顺序进行取样，同时取样人员应更换护袖及手套，更换取样器具，避免交叉污染。Whenextracttheoutsourcingrawmaterials,samplingpersonshouldtakeapairofsleeveandglovesifnessary.Thecontainershouldbesealedtopreventfromcontaminationaftersampling(forexample:plasticbagcanbefrapbyribbonorcanbemeltssealingbysealingmachine).Whensamplingdifferentvarietiesonthesamedata,samplingpersonshouldchangesleeve,glovesandsamplingtoolstopreventcrosscontamination.2.5.7、取样完成后或同一工作日取不同的物料之间需要对取样间做适当的清洁。合成原辅料取样室的清洁详见化工原料取样室管理规程。Samplingroomshouldbecleanedaftersamplingorbetweentakedifferentmaterialsatthesameworkingday.CleaningofthesamplingroomforoutsourcingrawmaterialsofAPIproductsseeManagemenrprocedureofsamplingroominwarehouseforoutsourcingrawmaterialsofAPI.2.6、取样规则与取样量Regulationofsamplingandthequantityofsampling:2.6.1、对进厂原辅料，由取样人员以下规则取样：同一次进厂原辅料按批号（或件数）随机取样。若进厂原辅料总件数为n，则当n≤3时，每件取样；当3<n≤300时，按取样；当n>300时，按取样。取出的样品在混合用的烧杯内混匀，对于只有化学检测的品种，分成两份保存于PE袋内，一份作为留样，另一份作检验样品；对于有微生物限度检验项目的品种，分成三份，一份保存于灭菌后的具塞锥形瓶中，用于微生物限度检测，另两份保存于PE袋中，一份做化学检测，一份用于留样。Samplingregulationofoutsourcingrawmaterialsisasfollows:Samplerandomlyaccordingtobatch(quantity)forrawmaterialsreceivedatthesametime.Iftheoverallquantitiesofreceivedrawmaterialsisn,whenn≤3,samplingforeverysample;when3<n≤300,samplingaccordington1/2+1;whenn>300,samplingaccordingto(n1/2)/2+1.Parallelsamplingtwice,mixandsealupseparatly,oneofthesampleasretentionsampleandtheotheroneastestingsample2.6.2、对原料药成品，由取样人员按批次（均质产品）随机取样。取样两份，一份作为留样，另一份作检验样品。APIproducta:Samplingbyworkshopqualitativeinspectmembersrandomlyaccordingtobatch(uniformityproducts).Parallelsamplingtwice,mixoneofthesampleasreservedsampleandmixtheotheroneastestingsample2.6.3、取样量：对于进厂原辅料和原料药成品，取样量一般为40~50g（检验和留样各约20g）；对于稳定性留样量参考各品种稳定性考核方案中规定量执行。Thequantityofsampling:ReceivedrawmaterialsandAPIproductsalwaysextract40~50gexceptsomevaluablesampleasreserpineorenalaprilatandsoonextract20g.ThequantityofStabilityretentionsamplesrefertotheprovisionofeachvarietie’sStabilityevaluationscheme.2.7、取样记录Recordofsampling:2.7.1、取样后必须填写取样记录，对于进厂原辅料，在备注栏中写明“取样件数”。Samplingrecordmustbefilledwhilethesamplingisfinished.Foroutsourcingrawmeterials,"samplingnumber"shouldbewrittenintheremarkscolumn.2.7.2、对于进厂原辅料，被取样检品包装上都应由取样人员贴上“取样证”。（注明名称、批号、进厂编号、取样人和取样日期）取样证应贴在原包装标签附近处，不得对原品名、批号、生产厂家等主要内容的可视性有影响。Fortheoutsourcingrawmaterials,the“samplingsticker”shouldbestickedonthepackageofextractedsamplebysamplingperson.(includingname、batch、receivedNo.、samplingperson、samplingdate).Thesamplingstickershouldbestickedneartheformerpackage,thereshouldnoteffectonthevisibilityofmaincontentexampleassamplename、batch、manufacturingfactoryandsoon.3、检品的接收、登记编号和发放Receive,registrationofnumberandextendoftestsample:3.1、取样后，由各取样人员将样品交到化验室检品管理人员处，化验室检品管理人员负责样品接收、填写取样发放登记卡(附件2~4)并给予检品编号，并将检验样品、请检和取样记录(附件1)及检验操作原始记录纸一起发给各组组长，再由各小组组长负责安排主检人和协检人。检验报告书使用的编号应与检验操作原始记录一致。Thetestsamplemanagerisresponsibleforreceivesample,fillthedistributionregistrationform(seeattachmentsNo.2~4)andnumberedforcategoryrespectively,thensendthetestingsample,recordoftestrequestandsampling(seeattachmentsNo.1)andrecordformtoteamleaderwhoisresponsibleforarrangedirectanalystandassistanalyst.Thenumberintheanalysisreportmustinaccordancewithrecordform.3.2、原料药成品按产品分别登记编号，编号xx-xxxxxx，“-”前为各产品的代码，“-”后的前2位为年号，后4位为流水号。各产品代码见《产品批号编制规程》中的各产品代码。APIproductsisnumberedbyeachworkshop,numberingxxxxxx,thefirst2numberisyearandthelast4numberisserialnumber.SeethecodesoftheproductsonCY-08-0053.3、进厂原辅料按照使用车间分别登记编号，编号xxxxxx，前2位为年号，后4位为流水号；Outsourcingrawmaterialsisnumberedbyeachend-user(workshop),numberingxxxxxx,thefirst2numberisyearandthelast4numberisserialnumber.4、检品的检验Testofsample:4.1、检品应由具有检验上岗证的专业人员检验，见习期人员或实习人员可在带教人员指导下承担一定的检验工作，但不得独立出具检验报告书。Thesampleshouldbetestedbyprofessionalpersonwhohascertificateofanalysisonjob,thepersoninnovitiateandtrainingpersoncantakeonsomeanalysisjobunderdirectionoftutor,butcan’tfinishtheanalysisreportindependently.4.2、检验应依据现行检验操作规程进行。若遇到客户额外增加的项目，参照客户标准执行。检验人员应对检验结果直接负责。TestshouldgoonaccordingtocurrentSOP.Ifthereareadditionalitemsbyclient,executethetestasspecificationofclient.Analystdirectlyaccountabletotheresultsoftest.4.3、检验过程中，应按要求做好检验记录，无论主检或协检的检验记录，均应经有资质第二个人员核对。核对人应查对检验依据是否正确，记录是否完整、规范、计算公式和数据处理是否正确，实验精度是否符合要求。检验人和核对人均应在检验原始记录上签字。Intheprocessofanalysis,recordshouldbedoneaccordingrequests.Whetherthetestrecordofdirectanalystorassistedanalyst,shouldbereviewedbyaqualifiedperson.Thepersonshouldcheckifthetestbasisisright,therecordiscomplete、normative,formulaofcalculationandprocessofdataareright,iftheprecisionofexperimentconformtorequests.Analystandthecheckershouldsignontheanalysisoriginalrecord.4.4、当检验结果出现异常结果时，应按照异常分析结果(OOS)处理要求进行处理。Whenthetestresultisoutofspecification,itshouldbetreatedaccordingtotreatedrequestsofOOS.4.5、当全部检验项目完成后，检验人员需将检验剩余样品去除包装后作为固体废物或废液，每3个月集中处理一次。Afterallthetestsarecomplete,analystshouldremovethepackageofremainingsamplesaswastesolidorwasteliquid,centralizedprocessingevery3months.5、检验报告书的形成Formtheanalysisreport:5.1、检验人员应根据检验结果，按要求填写检验操作原始记录纸和检验卡，连同图谱，一并移交组长。经组长核对后，将全部原始记录（应每页编号并说明总页数）及图谱，交化验室主任审核。Analystshouldfilltherecordformsandanalysiscard,delivertoteamleaderwithchromatograms.Aftercheckedbyteamleader,alltheoriginalrecord(numberoneverypageandillustratenumberofpages)andchromatogramsarehandedontoQCdirectortoreview.5.2、化验室主任审核同意后，填写打印份数（一般为4份），交给有关人员打印检验报告书。打印好的报告书经有资质第二个人员核对与原文无误后，方可加盖检验人、核对人，质量受权人章及检验章。AfteragreementofreviewbyQCdirector,compilethecodenumberofanalysisreportontheanalysiscard,fillinthenumberforprinting,anddelivertorelativepersontoprintanalysisreport.Aftertheprintedreportischeckedbyanotherqualifiedpersonandnoerrorisfound,itcanbestampedbyanalyst、checkperson、Qualitydirectorandstampedbyofficialseal.5.3、检验人、核对人、化验室主任、报告书打印人及核对人，均应在检验卡上签字。Analyst,checker,QCdirector,printerandreviewershouldallsignonanalysiscard.6、检验记录的存档Placetheanalysisrecordonfile:6.1、批检验记录按下列顺序：检验报