工藝驗證方案

1、*制藥廠*Factor、86(300mg)工乙驗證方案86(300mg)PROCESSVALIDATIONPROTOCOL文件編號File#V-0382(P)共35頁第1頁86(300mg)86(300mg)工藝驗證方案PROCESSVALIDATIONPROTOCOL文件編號FilecodeV-0382(P)版本VersionV01頁數(shù)Page共35頁修訂記錄History修訂本Version修訂日期Date修訂/更改要求的原因Reason修訂者By*公司86(300mg)工乙驗證方案86(300mg)PROCESSVALIDATIONPROTOCOL文件編號File#V-0382(P)共3

2、5頁第2頁作者簽名Signatureofthauthoro您的簽名表明這份文件的準(zhǔn)備(編制/修訂)符合企業(yè)驗證主計劃、工藝驗證主計劃、GMP規(guī)范和企業(yè)生產(chǎn)的要求，并且充分反映了工藝驗證全過程中應(yīng)完成的必要任務(wù)，可以付諸對86工藝驗證的實施。Thesignaturemeansthedrafting/revisingconfirmstovalidationmasterplan,processvalidationmasterplan,GMP,andin-housespecifications.Itincludesallthecontentsneedtobevalidatedthatcanbeappl

3、iedtotheprocessvalidation審核簽名Checkingatureof86tablets.姓名Name職稱/職務(wù)Title部門Department簽名Signature日期Date驗證主管ValidationsupervisorQA您的簽名表明您已經(jīng)仔細(xì)審閱了本文件，確認(rèn)它正確并已全面反映了驗證任務(wù)，可以付諸對86工藝驗證的實施。Thesignaturemeanstheprotocolischeckedthoroughlyandcarefully.Itincludesallthecontentsneedtobevalidatedthatcanbeappliedtothepro

4、cessvalidationof86tablets.姓名Name職稱/職務(wù)Title部門Department簽名Signature日期Date*部長ManagerQA*部長Manager生產(chǎn)部ManufactureDepartment*部長ManagerQC批準(zhǔn)簽名ApprovaSignatwrer您的簽名表明這份文件符合企業(yè)驗證主計劃、工藝驗證主計劃、企業(yè)生產(chǎn)檢驗標(biāo)準(zhǔn)以及現(xiàn)行的GMP規(guī)范，并且在此包含的文件和信息是充分的，并可直接應(yīng)用。Thesignaturemeansthedrafting/revisingconfirmstovalidationmasterplan,processvali

5、dationmasterplan,GMP,andin-housespecifications.Itincludesallthecontentsneedtobevalidatedthatcanbeapplieddirectly.姓名Name職稱/職務(wù)Title部門Department簽名Signature日期Date*質(zhì)量廠長Quality-director廠部DirectorsOffice*廠長Director廠部DirectorsOffice86(300mg)工乙驗證方案86(300mg)PROCESSVALIDATIONPROTOCOL文件編號File#V-0382(P)共35頁第3頁目錄

6、TABLEOFCONTENTSTOC o 1-5 h z HYPERLINK l bookmark12 1目的OBJECTIVES32驗證范圍SCOPE33方案審查PROTOCOLREVIEWING34組織與責(zé)任RESPONSIBILITIES4 HYPERLINK l bookmark14 5概述INTRODUCTION46處方、工藝流程和驗證關(guān)鍵控制項目FORMULATION/PROCESS/CRITICALPARAMETERSINVALIDATION處方FORMULATION5工藝流程PROCESS66.3驗證關(guān)鍵控制項目CRITICALPARAMETERSINVALIDATION77驗

7、證用物料及主要設(shè)備RAWMATERIALSANDEQUIPMENTS97.1原輔料和包衣材料進(jìn)行確認(rèn)RAWMATERIALSCHECK97.2主要設(shè)備進(jìn)行確認(rèn)EQUIPMENTSCHECK98驗證程序及內(nèi)容VALIDATIONPROCEDUREANDCONTENT98.1配料DISPENSING10 HYPERLINK l bookmark42 8.2漿液的配制GRANULATIONSOLUTIONPREPARATION108.3干粉混合DRYMIXING118.4制粒GRANULATION118.5濕顆粒整粒WETMILLING12沸騰干燥FLUIDBEDDRYING12干顆粒整粒DRYMI

8、LLING14總混MIXING16壓片COMPRESSION20包衣COATING249偏差分析與說明DEVIATIONANALYSISANDEXPLANATION32 HYPERLINK l bookmark64 10驗證結(jié)果分析和結(jié)論VALIDATIONRESULTSANDCONCLUSION33參考文獻(xiàn)REFERENCE34附件APPENDICES34名稱：偏差清單DEVIATIONLIST3586(300mg)工乙驗證方案86(300mg)PROCESSVALIDATIONPROTOCOL文件編號File#V-0382(P)共35頁第4頁1目的OBJECTIVES為了驗證86(300m

9、g)的生產(chǎn)工藝規(guī)程，確保大生產(chǎn)的穩(wěn)定性，在本廠現(xiàn)有的設(shè)備和環(huán)境條件下連續(xù)驗證生產(chǎn)三批的86，批量為100萬片，對生產(chǎn)中的關(guān)鍵步驟和工藝參數(shù)進(jìn)行確認(rèn)。批號待定。Inordertoconfirmthemanufacturingprocessof86tablets(300mg),3consecutivebatchesof1.00million86tabletswillbeproducedonthearrangedequipmentsunderthecurrentenvironmentcondition.Thecriticalstageandparameterswillbefinalizedinthe

10、processtoensuretherobustnessoftheregularproduction.Thebatchnumberwillbearrangedinvalidating.驗證范圍SCOPE本方案適用于生產(chǎn)潔凈區(qū)一線設(shè)備的86的工藝驗證。Theprotocolisappliedtotheprocessvalidationof86tablets(300mg)thatproducedinworkline1.方案審查PROTOCOLREVIEWING下列時機(jī)應(yīng)對本方案進(jìn)行審查以確保方案的適宜性Reviewtheprotocolinthefollowingcondition產(chǎn)品處方發(fā)生變更

11、；Changingformulation產(chǎn)品的工藝步驟、工藝參數(shù)和批量發(fā)生變更；Changingprocess,parametersandbatchsize產(chǎn)品所使用的原料供應(yīng)商發(fā)生變更；Changingrawmaterialssupplier產(chǎn)品所使用的原料的生產(chǎn)工藝發(fā)生變更；Changingrawmaterialsmanufacturingprocess產(chǎn)品所涉及的設(shè)施設(shè)備發(fā)生變更；Changingequipments產(chǎn)品的生產(chǎn)環(huán)境發(fā)生變更；Changingmanufacturingenvironment86(300mg)工乙驗證方案86(300mg)PROCESSVALIDATIONPR

12、OTOCOL文件編號File#V-0382(P)共35頁第5頁4組織與責(zé)任RESPONSIBILITIES這些任務(wù)和責(zé)任可以適當(dāng)定義，按照他們的分工具體定義每項任務(wù)和責(zé)任Properl、definetheresponsibilitiesaccordingtothetasks.姓名職稱/職務(wù)Title部門職責(zé)ResponsibilitiesName*Title部長ManagerQA對工藝驗證提供全面的指導(dǎo)，以符合廠驗證方針Guidesthevalidationandensurestheconfirmationofin-housevalidationpolicv監(jiān)督方案的執(zhí)行，確定方案中要求的測試

13、項目有完整和適當(dāng)?shù)臅鴗報告Monitorsthewholeexecutionandensurestheprocessisthoroughlydocumented在方案執(zhí)行的過程中對取樣工作提供人員幫助Supportssampling對檢驗數(shù)據(jù)及最終報告進(jìn)行復(fù)核及批準(zhǔn)Checksandapprovesthetestdataandfinalreport*部長Manager生產(chǎn)部ManufactureDepartment在方案執(zhí)行的過程中對產(chǎn)品的生產(chǎn)及設(shè)備的操作提供人員幫助Supportmanufacturingprocessandequipmentoperation對檢驗數(shù)據(jù)及最終報告進(jìn)行復(fù)核及批

14、準(zhǔn)Checksandapprovesthetestdataandfinalreport*部長ManagerQC在方案執(zhí)行過程中負(fù)責(zé)樣品的檢驗工作Supportlabanalysis對檢驗數(shù)據(jù)及最終報告進(jìn)行復(fù)核及批準(zhǔn)Checksandapprovesthetestdataandfinalreport*質(zhì)量廠長Qualitv-director廠部DirectorsOffice對檢驗數(shù)據(jù)及最終報告進(jìn)行復(fù)核及批準(zhǔn)Checksandapprovesthetestdataandfinalreport*廠長Director廠部DirectorsOffice對檢驗數(shù)據(jù)及最終報告進(jìn)行復(fù)核及批準(zhǔn)Checksand

15、approvesthetestdataandfinalreport概述INTRODUCTION86(86Tablets)*類藥，用于*等。在完成86實驗室小試及批量試生產(chǎn)的基礎(chǔ)上，86進(jìn)行工藝驗證(一線)，連續(xù)生產(chǎn)三批，規(guī)格為300mg，生產(chǎn)批量為100萬片，驗證關(guān)鍵工藝參數(shù)，并證明該生產(chǎn)線有能力生產(chǎn)出質(zhì)量均一、工藝穩(wěn)定可靠的86，且符合本廠內(nèi)控標(biāo)準(zhǔn)。Onthebaseof86(300mg)labandmanufacturetrial,the3consecutivebatcheswillbevalidatedonworkline1.Thebatchsizeis1.00milliontablet

16、s.Inthestage,thecriticalparameterswillbeconfirmedtoensuretherobustnessofthe86(300mg)工乙驗證方案86(300mg)PROCESSVALIDATIONPROTOCOL文件編號File#V-0382(P)共35頁第6頁processinregularproductionthatcansupplyin-houseandAsspecific-caotmiopnlied86tablets.處方、工藝流程和驗證關(guān)鍵控制項目FORMULATION/PROCESS/ESCRITICALAPARAMETERSINVALIDATI

17、ON6.1處方FORMULATION6.1.186生產(chǎn)處方（每100萬片為一批號，制漿液分2批，制粒分10料）Batchsizeis1.00milliontablets.Granulationsolutionisseparatedinto2sub-batches,granuleinto10異物檢測Foreignmatter生產(chǎn)部中間控制MDIn-processcontrol物料溫度Materialtemp.生產(chǎn)部中間控制MDIn-processcontrol0.3-0.7mm異oFm表3干顆粒整粒TABLE3DRYMILLINGDATA*制藥廠*Factor、*制藥廠*Factor、86(30

18、0mg)工乙驗證方案86(300mg)PROCESSVALIDATIONPROTOCOL文件編號File#V-0382(P)共35頁第17頁0.7mm*水分Moisture*物料溫度Materialtemp.C/可接受標(biāo)準(zhǔn)設(shè)定說明Specificationreferto：依據(jù)86制粒批生產(chǎn)記錄。manufacturerecord.物料溫度檢查項目無可接受標(biāo)準(zhǔn)，結(jié)果僅作為數(shù)據(jù)積累。Thereisnospecificationformaterialtemp.,foritisthedataaccumulation,檢驗人Analyzer：日期Date：復(fù)核人Checkedby：日期Date：8.8總

19、混MIXING將外加的*kg、*kg分4次放入盛放干顆粒的容器中，做完整批10料顆粒經(jīng)安全篩網(wǎng)和磁力儀，全部進(jìn)入混合料斗中，加蓋，將料斗安放到HYD-2500自動提升料斗混合機(jī)上，按動上升鍵，使料斗固定，設(shè)定轉(zhuǎn)速為8轉(zhuǎn)/分鐘，混合10分鐘出料，分裝在3個600L周轉(zhuǎn)料車中，稱量、顆粒進(jìn)中間庫復(fù)核驗收。Totallyadd*and*intodrygranulecontainersby4times.Pass10sub-batchesthroughsafetysieveandmagneticsieveintomixingtote.Cover,installintoHYD-2500mixer.Swit

20、chonpower,securingthetote,andsettingmixingspeedat8rpm.Mixfor10minutes.Dischargeinto3600Lcompressiontote,weighandtransfertoin-processstorage.混合程序結(jié)束后，由QA現(xiàn)場人員按示意圖位置和取樣方法在3個600L周轉(zhuǎn)料車中取樣，各取樣點均平行取樣3份（1份檢驗、1份復(fù)測、1份留樣，樣品編號分別以A、B、C英文字母區(qū)分），正確填寫取樣標(biāo)簽（名稱、批號、取樣人、取樣時間和容器號等），送QC檢驗水分、異物、性狀、含量、篩分試驗和松密度。并將結(jié)果填寫表4和表5。（為減小

21、數(shù)據(jù)的差異性QC須在收到樣品后的一小時內(nèi)完成水分的檢測。）QAsitepersonalsampleparallel3timesfromeachcompressiontoteatsamplelocations（1fortest,1forre-test,1forsampleretentionwhichaddingsuffixA,B,Ctoidentify）.Filinsamplelabelcorrectly（material,batch#,sampledby,time,compressiontote#）andsendtoQClabfortestingmoisture,foreignmatter,d

22、escription,sievetest,andbulkdensity.Moisturetestisrequiredtobecompletedwithin1hourfromreceivingsample.RecordtheresultsTABLE486(300mg)工乙驗證方案86(300mg)PROCESSVALIDATIONPROTOCOL文件編號File#V-0382(P)共35頁第18頁andTABLE5.松密度檢查項目無可接受標(biāo)準(zhǔn)，結(jié)果僅作為數(shù)據(jù)積累。其測試方法說明如下Thereisnospecificationforbulkdensitytest,foritisthedataacc

23、umulation.Thetestmethodasfollows:稱量15g樣品于一個干燥的100ml量筒內(nèi)，讀取15g樣品所占體積值V(ml),計算松密度=15g/V。Weigh15gsamplesintoadrygraduatedflask(range:100ml).recordtheactualvolumevalueandcalculatethebulkdensity(=15g/volumevalue).取樣示意圖如下：Sampleasthefollowingfigure:層上層中-A角剖面水分、含量檢測示意圖:層下性狀、篩分試驗、松密度和異物檢測示意圖：86(

24、300mg)工乙驗證方案86(300mg)PROCESSVALIDATIONPROTOCOL文件編號File#V-0382(P)共35頁第19頁注：取樣點12、14、16、18、19、22取樣棒垂直方向取樣，其余取樣點取樣棒角度始終保持在60NOTE:kesamplethiefperpendicultthebottowhentakesampl12,1416,1618,1819,19andan22.22Keepsamplethief6totthethbottomowhentasamplpefromotherlocation批號Batch#樣品數(shù)Sample樣品號SampleID取樣量Sample

25、qty.檢測項目Testitem檢測部門Testedby10716各取6g1g含量AssayQC6geach5g水分Moisture61722各取250g250geach異物檢查Foreignmatter、師分試驗Sievetest、性狀description、松密度BulkdensityQC相對標(biāo)準(zhǔn)偏差RSD計算公式：2(XX)標(biāo)準(zhǔn)偏差S=i=1In-1相對標(biāo)準(zhǔn)偏差RSD=(S/X)xlOO%表4總混顆粒的性質(zhì)（1）TABLE4MIXEDGRANULEDATA(l)容器號Container#樣品號SampleID批號Batch#：可接受標(biāo)準(zhǔn)Specification含量Assay(%)水分M

26、oisture（%）7含量Assay：90.0%110.0%水刀Moisture:1.5%-2.2%8910111213141516平均值XAverageRSD(%)3.0%86(300mg)工乙驗證方案86(300mg)PROCESSVALIDATIONPROTOCOL文件編號File#V-0382(P)共35頁第20頁可接受標(biāo)準(zhǔn)設(shè)定說明Specificationreferto:日期Date:日期Date含量檢測Assay:依據(jù)86測試標(biāo)準(zhǔn)操作程序水分檢測Moisture:依據(jù)86中間體測試標(biāo)準(zhǔn)操作程序檢驗人Analyzer:復(fù)核人Checkedby：結(jié)論Comments:可接受標(biāo)準(zhǔn)設(shè)定說明

27、表5總混顆粒的性質(zhì)（2）參數(shù)批號Batch#:可接受標(biāo)準(zhǔn)Specification樣Sam品號pleID171819202122er07mm*物oF性狀*彳檢Description松密度/Bulkdensity(g/cm3)平均值)%st驗tv(.ieSVVIug,V12冃mesh*20冃mesh*80冃mesh*底盤pan*總量Total/篩分TABLE5MIXEDGRANULEDATA(2)Specificationreferto：可接受標(biāo)準(zhǔn)Specification:依據(jù)86中間體測試標(biāo)準(zhǔn)操作程序檢驗人Analyzer：日期Date:復(fù)核人Checkedby：日期-Date：結(jié)論Comm

28、ents:8.9壓片COMPRESSION86(300mg)工乙驗證方案86(300mg)PROCESSVALIDATIONPROTOCOL文件編號File#V-0382(P)共35頁第21頁顆粒在壓片機(jī)上壓片，按以下方法取樣，將結(jié)果填入表6、表7。TakesamplesasperfollowingplanandrecordresultintoTABLE6andTABLE7.外觀、硬度、片重、平均片重：每30分鐘取樣檢測。Tabletdefects,hardness,tabletweight,averagetabletweight:sampleandtestper30minutes.平均厚度、

29、脆碎度：每2小時取樣檢測。Averagethickness,friability:sampleandtestper2hours.金屬片檢測:每2小時校驗一次,在批號結(jié)束時,記錄不合格金屬污染的產(chǎn)品數(shù)量Themetaldetectortest:thechallengetestshouldbedoneatevery2hours.Attheendofthebatch,collecttherejected,metalcontaminatedtablets,recordthenumber.壓片機(jī)轉(zhuǎn)速：每2小時檢測Pressrotationspeed:testper2hours.溶出：開車正常、壓片過程中

30、和壓片結(jié)束時取樣，共3次。次10片。Dissolution:start-upchecking,regularcompression,andendingtime,totally3times.含量：開車穩(wěn)定后，根據(jù)壓片機(jī)轉(zhuǎn)速和壓片批量計算壓片時間，在壓片時間段內(nèi)平均取樣30次，每Assay:sample10tablets30timeswhenpresssmoothly.計算公式：壓片時間（min）=批量片數(shù)/C43x轉(zhuǎn)速rpm）=1.00 x10/（43x50）=781min壓片間隔（min）=壓片時間/（取樣次數(shù)-1）=781/29=27min1.00 x10/(43x50)781minForm

31、ula:Compressiontime(min)=batchsize/(43Xrotationspeedrpm)=Sampleinterval(min)=Compressiontime/(sampletimes-1)=781/2927min批號Batch#樣品號SampleID取樣量Sampleqty.檢測項目Item檢測部門Testedby5片/次平均厚度Averagethickness、硬度Hardness生產(chǎn)部中間控制MDIn-processcontrol200片/次外觀tabletdefects6.5g/次脆碎度Friability10片/次片重Tabletweight、平均片重Ave

32、ragetabletweight金屬片檢測、壓片機(jī)轉(zhuǎn)速M(fèi)etaltest,rotationspeedofcompressor86(300mg)工乙驗證方案86(300mg)PROCESSVALIDATIONPROTOCOL文件編號File#V-0382(P)共35頁第22頁B、M、E6片/次溶出DissolutionQC23、245210片/次含量Assay注NOTE：B：表示開車穩(wěn)定后抽取樣SampleafterpreirunningnnsmoothlyM：表示開車到一半批量時抽取樣Samplewhenpre50finished(Alitablets)E：表示開車即將結(jié)束前

33、抽取樣Samplebeforecompletepress溶出、含量檢驗的各取樣點均平行取樣3份(1份檢驗、1份復(fù)測、1份留樣，樣品編號分別以A、B、C英文字母區(qū)分)，正確填寫取樣標(biāo)簽(名稱、批號、取樣人、取樣時間和容器號等)，送QC檢驗Sampleparallele3timesefromeachatsampllocationsfordissolutioinassay(1fotest,1forfore-test,fosampleretentionwhichaddingsuffixA,BCtotidentify).Fillinsamplelabelcorrectl(material,lbatch#

34、,sampledpeby,bytime,ecompressionsotote#)#andansendtQClabfotest.表6片子性質(zhì)（1）TABLE6TABLETANALYSISDATA(1)項目測試序號批號Batch#：實際結(jié)果可接收標(biāo)準(zhǔn)Item厚度、硬度ThicknessHardnessSer.numberTestresultSpecification平均厚度Thickness：*mm平均硬度Hardness：*scu取大和取小硬度差值Max.-Min.*SCU厚度Thickness硬度Hardness12345平均值A(chǔ)vg.外觀Max.-Min./缺陷數(shù)量合格Defectedtab

35、letsqtycompliestherequirement平均片重，Averagetabletweight*平均片重Averagetabletweight：*g最大和最小片重差值123456Max.-Min.:78*g86(300mg)工乙驗證方案86(300mg)PROCESSVALIDATIONPROTOCOL文件編號File#V-0382(P)共35頁第23頁日期Date：復(fù)核人Checkedby：結(jié)論Comments:表7片子性質(zhì)（2）TABLE7TABLETANALYSISDATA(2)主批號De仆Z：項目樣品編號實際結(jié)果可接收標(biāo)準(zhǔn)溶出()DissolutionomiijjicJLJ

36、-xB1CSlICSUllOJJCvlllvclllUli90%M86(300mg)工乙驗證方案86(300mg)PROCESSVALIDATIONPROTOCOL文件編號File#V-0382(P)共35頁第24頁E含量（）Assay樣品編號SampleID實際結(jié)果Testresult232425262728293031323334353637可接受標(biāo)準(zhǔn)設(shè)定說明Specificationreferto：溶出檢驗Dissolution:依據(jù)86中間體測試標(biāo)含量檢驗Assay:依據(jù)86測試標(biāo)準(zhǔn)操作程序樣品編號SampleID實際結(jié)果Testresult90.0-110.0%38394041424

37、3444546474849505152準(zhǔn)操作程序檢驗人Anal、zer：復(fù)核人Checkedby：結(jié)論Comments:日期Date：日期Date8.10包衣COATING工序Process原輔料名稱Materialname實際量(Kg)Actualqty.配料(Kg)Dispensing*8.10.1包衣液配料COATINGSOLUTION注:本批產(chǎn)品分2鍋進(jìn)行包衣。NOTE:thwholebatchiseparatedtbebcoated.d86(300mg)工乙驗證方案86(300mg)PROCESSVALIDATIONPROTOCOL文件編號File#V-0382(P)共35頁第25頁

38、8.10.2包衣液的配制COATINGSOLUTIONPREPARATION包衣液：稱量純化水*kg放入一潔凈、去皮的帶攪拌器的不銹鋼容器，用攪拌器緩慢攪拌形成漩渦，但不得起泡，邊攪拌邊加入*，繼續(xù)攪拌溶液1至少60分鐘，直至無塊狀物存在，保持漿桶密封。Coatingsolution:weigh*kgpurifiedwaterintoaclean,taredstainlesssteelcontainerwithmixer.Switchonthemixertoswirlthepurifiedwaterandadd1*.Continuemixingforatleast60minutestoavoi

39、dlumping.Keepthecontainertightl、closed.8.10.3包衣1（第1鍋）COATING1（1SPAN）將1/2批量的片子加入包衣鍋后，用專用管子連接溶液的配漿桶與蠕動泵，使用包衣液1對片子進(jìn)行噴漿。包衣1程序設(shè)置如下：Loadhalfbatchtabletsintocoatingpan.Connectthededicatedlinesfromthesolutiontanktotheconstantflowpump.Spra、coatingsolution1usingthefollowingparameters.包衣時段Coatingprocess包衣周期數(shù)Co

40、atingcycles參數(shù)設(shè)置Parameter1*2*3*4*5*注：包衣開始前確認(rèn)包衣液1距離失效時間至少5小時以上，包衣1結(jié)束時要確保包衣液1在有效期內(nèi)(從攪拌開始起24小時內(nèi))。NOTE:confircoatingsolution1isiataleasthourfromexpirytime,ebeforestartingcoating.Confircoatingnsolutiono1isiiniexpirydateaftercoatinhexpirationoperiodoisi242hoursfrompreparation.n由生產(chǎn)部每隔15分鐘記錄包衣1的噴包衣階段的出風(fēng)溫度、空氣

41、流量、噴量、片床和噴嘴完好性，檢測結(jié)果填寫表8。Manufacturedepartmentshallrecordtheoutletairtemp.,airflow,spra、speed,tabletbedandnozzleintegrit、ofcoating1inTABLE8atapproximatel、15minutesintervals.由生產(chǎn)部每隔15分鐘記錄包衣2的噴包衣階段的出風(fēng)溫度、空氣流量、噴量和片床和噴嘴完好性檢查。包衣結(jié)束后生產(chǎn)部取約*g樣品（約*片）進(jìn)行外觀檢查。結(jié)果匯總于表8。86(300mg)工乙驗證方案86(300mg)PROCESSVALIDATIONPROTOCO

42、L文件編號File#V-0382(P)共35頁第26頁Manufacturedepartmentshallrecordtheoutletairtemp.,airflow,sprayspeed,tabletbedandnozzleintegrityofcoating2atapproximately15minutesintervals.Manufacturedepartmentcollectacompositesampleofapproximate*g(approximate*tabs),andinspectfordefects.GathertheresultsinTABLE886(300mg)工

43、乙驗證方案86(300mg)PROCESSVALIDATIONPROTOCOL文件編號File#V-0382(P)共35頁第27頁表8包衣時段性能TABLE8COATINGPROCESSDATA批號Batch#記錄時間minRecordTime參數(shù)Parameter可接受標(biāo)準(zhǔn)Specification出風(fēng)溫度COutletAirTemp.空氣流量m3hAirflow噴量ml/minSprayspeed片床和噴嘴完好性Tabletbedandnozzleintegrity包衣0出風(fēng)溫度OutletAirTemp.*目標(biāo)值Target：*C進(jìn)風(fēng)量：InterAirQty：*m3h噴量FlowRat

44、e:*ml/min153045607590105120135150165180195210225240153045607590105120135150165180測試項目TestItems測試結(jié)果Results可接受標(biāo)準(zhǔn)Specification外觀tabletdefects*86(300mg)工乙驗證方案86(300mg)PROCESSVALIDATIONPROTOCOL文件編號File#V-0382(P)共35頁第28頁可接受標(biāo)準(zhǔn)設(shè)定說明Specificationreferto：所有項目Allitem:依據(jù)86包衣批記錄。manufacturingcard檢驗人Analyst：日期date

45、：復(fù)核人reviewer：日期date：結(jié)論comments：包衣結(jié)束后，在包衣片從包衣鍋中出料前。由QA人員抽樣，各取樣點均平行取樣3份（1份檢驗、1份復(fù)測、1份留樣，樣品編號分別以A、B、C英文字母區(qū)分），正確填寫取樣標(biāo)簽（名稱、批號、取樣人、取樣時間和容器號等），送QC檢驗性狀、鑒別A、鑒別B、片重差異、溶出度、含量和微生物，檢測結(jié)果填寫表9。取樣圖如下：QApersonnelsamplebeforedischargingcoattablets.Sampleparallel3timesfromeachsamplelocations(1fortest,1forre-test,1forsam

46、pleretentionwhichaddingsuffixA,B,Ctoidentify).Fillinsamplelabelcorrectly(material,batch#,sampledby,time,compressiontote#)andsendtoQClabfordescription,identificationAandB,weightuniformity,dissolution,assay,andmicrobialtestsTestandrecordinTABLE9.Thesamplelocations包衣片上層包衣片中層包衣片下層53545a包衣片上層包衣片中層包衣片下層注：

47、取樣點54、57、58取樣棒垂直方向取樣，其余取樣點取樣棒角度始終保持在60NOTE:kesamplthiefperpendicultthethbottomowhentasampl54,57andan58.58Keepsamplethief686(300mg)工乙驗證方案86(300mg)PROCESSVALIDATIONPROTOCOL文件編號File#V-0382(P)共35頁第29頁tothbottomowhentasamplpefromotherlocation批號Batch#樣品數(shù)Sample樣品號SampleID取樣量Sampleqty.檢測項目Testitem檢測部門Tested

48、by6(1stPAN)53,54-58各取210片Sample210tabletsfromeachlocations性狀Description、片重差異Weighuniformity、溶出度Dissolution,含量AssayQC6(2ndPAN)61,62-661(1stPAN)59上述6個樣品各取10片做一份混合樣Sample10tabletsfromtheabove210tabletstoformacombined鑒別AIdentificationA、鑒別BIdentificationB、QC1QpAN)671(1stPAN)60sample上述6個樣品各取10片做一份混合樣Sampl

49、e10tabletsfromtheabove210tabletsto微生物MicrobialtestQC1QPAN)68formacombinedsample86(300mg)工乙驗證方案文件編號File#V-0382(P)86(300mg)PROCESSVALIDATIONPROTOCOL共35頁第30頁表9包衣片性質(zhì)TABLE9COATEDTABLETS批號Batch#：項目Item樣品號SampleID實測數(shù)據(jù)ActualData樣品號SampleID實測數(shù)據(jù)ActualData可接收標(biāo)準(zhǔn)Specification性狀Description5361*5462556356645765586

50、6含量Assay5361*54625563566457655866片重差異Weightuniformity5361*54625563566457655866溶出度Dissolution5361*54625563566457655866鑒別AIdentification5967*86(300mg)工乙驗證方案86(300mg)PROCESSVALIDATIONPROTOCOL文件編號File#V-0382(P)共35頁第31頁鑒別BIdentificationB5967*微生物Microbialtest6068*可接受標(biāo)準(zhǔn)設(shè)定說明Specificationreferto：微生物檢驗Microbialtest:依據(jù)*.其余項目Otheritems:依據(jù)86測試標(biāo)準(zhǔn)操作程序復(fù)核人reviewer：日期date：理化檢驗人Analyst:：_日期date：微生物檢驗人Microbialanalyst：日期date：復(fù)核人reviewer：日期date：8.10.包衣(第2鍋)COATING(2nPdAN)同上所述，將剩余1/2批量的片子投入包衣鍋中進(jìn)行包衣，并將檢驗結(jié)果填寫表8、表9中Loadhalfbatchtabletsintocoatingpan.Runtheprocesssameastheab