純化水的檢測

1、STANDARDOPERATINGPROCEDURE題目：純化水系統(tǒng)的質(zhì)量監(jiān)測TitleMONITORINGTHEPURIFIEDWATERSYSTEM起草/修訂人：日期:AuthorDate部門主管審查：日期:Dept.HeadApprovalDateQA批準(zhǔn)：日期:ApprovedbyQADate分發(fā)：QA、QC、工程Distribution:QA,QC,Engineering目的：制訂純化水系統(tǒng)的日常質(zhì)量監(jiān)測及偏差處理規(guī)程，確保純化水的質(zhì)量符合要求。PURPOSE:Thisdocumentdefinestheprocedureforroutinequalitymonitoringandd

2、eviationdispositiononpurifiedwatersystemtoensurethepurifiedwaterqualitymeetstherequirement.范圍：適用于公司內(nèi)純化水系統(tǒng)（包括純化水制備系統(tǒng)、純化水使用點(diǎn)及取樣點(diǎn)）的日常質(zhì)量監(jiān)測。在非日常監(jiān)測(如驗(yàn)證、再驗(yàn)證以及要求的研究)期間，根據(jù)具體的監(jiān)測方案進(jìn)行；在此期間相關(guān)的日常監(jiān)測暫停。SCOPE:ThisSOPisapplicabletotheroutinemonitoringonpurifiedwatersystem(includingpurifiedwatergeneratorsystem,usepoin

3、tsandsamplingpoints)Duringthenon-routinemonitoringperiod(suchasvalidation,re-validationandspecialstudies),themonitoringwillbeconductedinaccordancewiththespecificprotocol.Theroutinemonitoringcanbepausedduringsuchnon-routinemonitoringperiod.REFERENCEANDATTACHMENT:SOP/題目SOP/TITLE1-3002偏差調(diào)查DeviationInve

4、stigations參考文件：記錄/附件/題目FORMS/ATTACHMENTS/TITLE附件1:純化水系統(tǒng)中的使用點(diǎn)和取樣點(diǎn)Attachment1:Point-of-useandsamplingpointlocationsinthepurifiedwatersystemF-02-014純化水系統(tǒng)取樣記錄Purifiedwatersystemsamplinglogbook定義：N/ADEFINITIONS:規(guī)程：PROCEDURE:STANDARDOPERATINGPROCEDURE題目：純化水系統(tǒng)的質(zhì)量監(jiān)測TitleMONITORINGTHEPURIFIEDWATERSYSTEM責(zé)任人操作

5、RESPONSIBILITYACTION1. 系統(tǒng)描述SYSTEMDESCRIPTION1.1 純化水系統(tǒng)由2部分組成：Purifiedwatersystemconsistsof2portions:1.1.1 制備系統(tǒng)：包括相應(yīng)的設(shè)備單元和管路。Generatorsystem:Elementsincludetheappropriateequipmentunitandthepipes.1.1.2 循環(huán)管路系統(tǒng)：純化水的循環(huán)分配管路。Pipeloop:Distributionloop.1.2 純化水系統(tǒng)中的使用點(diǎn)和取樣點(diǎn)，見附件1。Thepoint-of-useandsamplingpointlo

6、cationsinthepurifiedwatersystempleaseseeAttachment1.2. 日常監(jiān)測ROUTINEMONITORING2.1 監(jiān)測點(diǎn)及監(jiān)測頻率Monitoringpointsandsamplingfrequency2.1.1 循環(huán)管路Pipeloop2.1.1.1 對于有4至7天的正常工作周，每周(至少每隔23天1次)取木¥監(jiān)測2次。如果工作周為3天或更少，則每次取樣1次。如果由于停產(chǎn)而不使用水，日常取樣可不進(jìn)行。Collectwatersamplestwiceperweek(atleastonceeverytwoorthreedays)fornor

7、malworkweeksoffourtosevendays.Iftheworkweekisthreedaysorless,collectsamplesonceperweek.Ifthewaterisnotbeingusedduetoashutdown,routinesamplingmaynotbeperformed.2.1.2.1.1 純化水貯罐、循環(huán)管路紫外燈后出水、總回水：每次均取樣。Storagetank,samplingpointafterUVsterilizerinthecirculatingsystem,loopreturn:shouldbesampledeachtime.2.1.

8、2.1.2 其余使用點(diǎn)/取樣點(diǎn)：每次從其中隨機(jī)抽取一點(diǎn)。Otherpoints-of-useandsamplingpoints:onepointwillbesampledrandomeachtime.STANDARDOPERATINGPROCEDURE題目：純化水系統(tǒng)的質(zhì)量監(jiān)測TitleMONITORINGTHEPURIFIEDWATERSYSTEM責(zé)任人操作RESPONSIBILITYACTION2.1.2制備系統(tǒng)（僅供參考）Generatorsystem（forinformationonly）2.2.2.1 每月（一般為每月的第一個(gè)工作周）取樣監(jiān)測1次。Collectwatersample

9、sonceamonth（normally,thefirstweekeverymonth）.2 純化水系統(tǒng)的原水（注：每年至少送衛(wèi)生防疫部門檢驗(yàn)一次）Sourcewaterofthegeneratorsystem（note:suchwatersamplewillbesenttothelocalgovernmentdepartmentofhygieneandepidemicfortestingannually,asaminimum.2 保安過濾器出水OutputwateraftertheSafetyfilter2.2.2.2 每2周取樣監(jiān)測1次。Collectwatersamplesonceper

10、twoweeks2.1.2.1.2精密過濾器出水Outputwaterafterthefinefilter2.2監(jiān)測項(xiàng)目Testitems3.3.1.0 微生物限度Microbiallimittest3 細(xì)菌、霉菌、酵母菌：“2.1”中的所有監(jiān)測點(diǎn)Bacteria,MildewandMicrozyme:Allmonitoringpointsdescribedin2.1”.3 大腸桿菌：純化水貯罐、總回水、精密過濾器出水，每季度檢測一次。E.Coli:Storagetank,loopreturnandOutputwaterafterthefinefiltershouldbetestedoncea

11、quarter.2.2.2理化指標(biāo)Chemicaltestitems4 總回水、精密過濾器出水：每2周檢測一次。Loopreturn,Outputwaterafterfinefilterwillbetestedoncepertwoweeks.QC3.取樣、檢驗(yàn)SAMPLINGANDTESTING通則General菌檢操作員3.1.1遵循取樣區(qū)域的最低衣著要求，或穿潔凈的化驗(yàn)室工作服。Microbiologist3.1.2Followtheminimumgowningrequirementsfortheareabeingsampledorwearacleanlabcoat.在取水樣時(shí)，應(yīng)遵循無菌

12、操作方法。Followaseptictechniquewhencollectingwatersamples.STANDARDOPERATINGPROCEDURE題目：純化水系統(tǒng)的質(zhì)量監(jiān)測TitleMONITORINGTHEPURIFIEDWATERSYSTEM責(zé)任人操作RESPONSIBILITYACTION菌檢操作員Microbiologist3.1.33.1.4在取水樣時(shí)，應(yīng)肉眼檢查是否有水滴泄漏，或有可見的破損。Whencollectingwatersamples,visuallyinspectthewaterdropsforleakingorvisibledamage.將理化檢驗(yàn)樣品送

13、至化驗(yàn)室檢驗(yàn)；將菌檢樣品送至菌檢室檢驗(yàn)。Takechemistrysamplestothelaboratoryfortesting,andSendmicrobiologysamplestomicrobiologicallaboratoryfortesting.3.1.4.1微生物限度檢查的樣品不能立即檢驗(yàn)的，應(yīng)存放于冰箱中冷藏，并于取樣后24小時(shí)內(nèi)完成檢驗(yàn)。Ifthesamplesformicrobiologicaltestingcannotbetestedimmediately,thesesamplesmustbestoredintherefrigeratorandmustbetestedw

14、ithin24hoursaftersampling.理化檢驗(yàn)樣品的取樣。SamplesforChemicalsTesting.Followthesesteps.在取樣前，不需用75%乙醇擦拭取樣口。Donotneedtosanitizethesamplingportwith75%ethanolpriortocollectingthewatersample.用兩個(gè)潔凈的500ml帶蓋三角瓶。Usetwoclean500mlflaskswithcap.在三角瓶上作好標(biāo)記，注明日期、樣品描述(如，建筑物、房間等)Labeltheflaskwithdate,sampledescription(such

15、asbuilding,room,etc).取樣前，將三角瓶至少淋洗3次。Rinsetheflaskatleastthreetimesbeforecollectingthesample.取至少550ml水，以確保檢驗(yàn)所需的足夠體積。Collectatleast550mlofwatertoensureanadequatesamplevolumefortesting.微生物檢驗(yàn)樣品的取樣。SamplesforMicrobiologicalTesting.Followthesesteps.使用潔凈的，已滅菌的帶蓋250ml三角瓶或25ml試管。Useaclean,sterilized250mlflas

16、kor25mltubewithclosure.在三角瓶/試管上作好標(biāo)記，注明日期、樣品描述(如，建筑物、房間等)Labeltheflask/tubewithdate,sampledescription(suchasbuilding,room,etc).保持樣品收集三角瓶密閉直至裝樣。Keepthesamplecollectionflask/tubecloseduntilitistobefilled.在取樣前，用75%乙醇擦拭消毒取樣口。Sanitizethesamplingportwith75%ethanolpriortocollectingthewatersample.如果是通過水系統(tǒng)上的軟

17、管取樣的：Ifasampleiscollectedusingawatersystemhose:STANDARDOPERATINGPROCEDURE題目：純化水系統(tǒng)的質(zhì)量監(jiān)測TitleMONITORINGTHEPURIFIEDWATERSYSTEM責(zé)任人操作RESPONSIBILITYACTION當(dāng)軟管是附在使用點(diǎn)上時(shí)，用連接在上面的軟管進(jìn)行取樣。Whenahoseisattachedtothedrop,usetheattachedhosetoperformthesampling.當(dāng)沒有軟管連接在使用點(diǎn)上時(shí)，使用一潔凈專用的軟管。當(dāng)沒有軟管連接在使用點(diǎn)上時(shí)，在同一天，同一根軟管可用于同一區(qū)域中的

18、多個(gè)使用點(diǎn)/管路。Whennohoseisattachedtothedrop,useacleananddedicatedhose.Thesamehosecanbeusedformultipledrops/loopswithinthesameareaonthesamedaywhennohoseisattachedtothedrop.用75%乙醇擦拭消毒將要連接到水系統(tǒng)上的軟管尾部。將軟管連接到使用點(diǎn)上并可靠連接。用75%乙醇擦拭消毒軟管尾部。Sanitizetheendofthehosetobeattachedtothewatersystemwith75%ethanol.Attachthehos

19、etothewaterdropandsecuretheconnection.Sanitizetheendofthehosewith75%ethanol.打開水，沖洗使用點(diǎn)，當(dāng)使用點(diǎn)放出一部分水（將閥門與循環(huán)管路之間的水放凈）后，取樣；如取樣時(shí)使用到軟管，則軟管應(yīng)用純化水沖洗至少3次（確保軟管的內(nèi)壁被徹底沖洗到）。Beforesampling,openthevalvetoflushtheuseofpoint,onlyacertainquantityofpurifiedwater(thewaterbetweenthevalveandthemaindistributionloopshouldbedr

20、oppedoff)hasbeendischarged,thenthepurifiedwatercansampled;ifahoseisused,thehoseshouldbeflushedatleast3timeswithpurifiedwater(toensurethattheinsidewallhasbeencompletelyrinsed).將水流速減小，以使裝水時(shí)不潑灑(若需要)。Reducethewaterflowtopermitfillingwithoutsplashing(ifnecessary).打開取樣三角瓶/試管，用無菌操作方法收集水樣。Openthesampleflask

21、/tubeandcollectthewatersampleusingaseptictechnique.取至少20ml水，以確保檢驗(yàn)所需的足夠體積。Collectatleast20mlofwatertoensureanadequatesamplevolumefortesting.在取樣容器上注明取樣時(shí)間。Labelthesamplecontainerwiththetimeofsampling.作好取樣記錄。Recordthesamplingeventsinthewatersamplingform.STANDARDOPERATINGPROCEDURE題目：純化水系統(tǒng)的質(zhì)量監(jiān)測TitleMONITO

22、RINGTHEPURIFIEDWATERSYSTEM責(zé)任人操作RESPONSIBILITYACTION4.結(jié)果報(bào)告和評價(jià)TESTRESULTSREPORTINGANDEVALUATINGQC主管或其4.1指定人員QCSupervisororDesigneeQC主管或其指定人員QCSupervisororDesignee化驗(yàn)室主管或其指定人員對檢驗(yàn)結(jié)果進(jìn)行審核，確定數(shù)據(jù)是否超出下列的任何一項(xiàng)：Reviewthetestresultsanddetermineifdataexceedanyofthefollowing:4.1.1大腸桿菌檢測1個(gè)/mlE.Colitest=1Coliform/ml細(xì)菌

23、、霉菌和酵母菌總數(shù)20CFU/ml,警戒限TotalcountofBacteria,MildewandMicrozyme>20CFU/ml,AlertLimit細(xì)菌、霉菌和酵母菌總數(shù)30CFU/ml,行動(dòng)限TotalcountofBacteria,MildewandMicrozyme>20CFU/ml,ActionLimit細(xì)菌、霉菌和酵母菌總數(shù)100CFU/ml,標(biāo)準(zhǔn)規(guī)定TotalcountofBacteria,MildewandMicrozyme_100CFU/ml,Specification理化檢驗(yàn)結(jié)果不符合放行標(biāo)準(zhǔn)。Chemicalresultsthatdonotmeetr

24、eleasespecifications如果數(shù)據(jù)是可以接受的，將數(shù)據(jù)和記錄送QA歸檔。Ifdataareacceptable,sendthecompleteddataandrecordstoQAforfiling.QA4.3收集微生物檢驗(yàn)數(shù)據(jù)，以季度為基礎(chǔ)給出趨勢分析。將該趨勢分析抄送給菌檢室和QA主管/經(jīng)理。Collectdatafrommicrobiologicaltests.Performtrendingonaquarterlybasis.ForwardthetrendingtotheMicrobiologyLaboratoryandQASupervisor/Manager.QC如果數(shù)據(jù)

25、不可以接受，通知QA。Ifdataarenotacceptable,notifyQAManagement.QC4.4.1QC應(yīng)將所有>20CFU/ml的檢驗(yàn)結(jié)果立即通知QA,以便于采取適當(dāng)?shù)拇胧ㄈ粢螅?。QCwillpromptlyinformQAofallmicrobiologicalresultsthatareobtainedthatare20CFU/mlsothatappropriateactioncanbetakenifrequired.STANDARDOPERATINGPROCEDURE題目：純化水系統(tǒng)的質(zhì)量監(jiān)測TitleMONITORINGTHEPURIFIEDWATERS

26、YSTEM責(zé)任人操作RESPONSIBILITYACTIONQA4.4.2針對得到的微生物檢驗(yàn)結(jié)果，QA將根據(jù)下面的要求決定是否采取相應(yīng)的措施：Giventhemicrobialresults,QAwillconsideranyactiontotakeinthelightofthefollowing:對于任何單個(gè)點(diǎn)的微生物檢驗(yàn)結(jié)果>20CFU/ml,但V30CFU/ml,記錄結(jié)果，不需要采取措施。Foranysinglemicrobiologicalresultthatis>20CFU/mlbut<30CFU/ml,theresultwillberecordedbutnosp

27、ecificactiontaken.若所得連續(xù)3次的檢驗(yàn)結(jié)果20CFU/ml,則純化水系統(tǒng)應(yīng)停止用于生產(chǎn)：If3consecutiveresultsareobtainedthatare>20CFU/ml,thentheuseofthepurifiedwaterforpharmaceuticalmanufacturingwillstop.QAQA填寫偏差報(bào)告，并進(jìn)行偏差調(diào)查以找出最有可能的根本原因(參見SOP1-3002)。QAwillraiseaDeviationReportandtheincidentinvestigatedtoidentifythemostprobablerootca

28、use(seeSOP1-3002).純化水系統(tǒng)應(yīng)用臭氧消毒后將水排空。Thepurifiedwatersystemwillbedrainedandsanitizedbyozone.純化水系統(tǒng)重新注入純化水，根據(jù)QA和QC菌檢的要求進(jìn)行取樣檢測。Thepurifiedwatersystemwillberefilled,sampledasspecifiedbyQAandQCMicrobiology.純化水系統(tǒng)循環(huán)，但不得使用，直至菌檢結(jié)果顯示適于使用。ThePurifiedwatersystemwillbecirculatedwithoutuseuntilshowntobefitforusebyQ

29、CMicrobiology.同樣，若所得的檢驗(yàn)結(jié)果30CFU/ml,應(yīng)按上面的操作執(zhí)行。Assuch,ifthemicrobiologicalresultsthatare30CFU/ml,theaboveprocedureshouldbefollowed.注：對于僅用作淋癥之用的，微生物數(shù)較高的純化水；必須經(jīng)明確的證明，并表明并不給產(chǎn)品帶來風(fēng)險(xiǎn)；該批產(chǎn)品必須經(jīng)QA適當(dāng)?shù)脑u價(jià)后才能被放行。Note:UseofpurifiedwaterwithhighmicrobialcountsforrinsingpurposesonlymustbeclearlyjustifiedanddemonstratednottopresentarisktotheproductandsuchproductsexposedmustbeappropriatelyassessedbyQApriortorelease.STANDARDOPERATINGPROCEDURE題目：純化水系統(tǒng)的質(zhì)量監(jiān)測TitleMONITORINGTHEPURIFIEDWATERSYSTEMSUMMARYO