欧盟清洁验证方案(带风险分析)

1、Abcd上海勃林格殷格翰药业有限公司 Boehringer Ingelheim Shanghai Pharmaceuticals Co., Ltd.Cleaning Validation 清 洁 验 证 方 案ProtocolSystem Name / 设备名：气 雾 剂 生 产 线MDI Production Line Document No. /文件号： CV-04-P.01Page / 页数: PAGE 9 of 15Attachments / 附件:7Responsible Department/ 负责部门：Responsible Person/负责人：Start Date/起始日期：

2、Production Dept./生产部Mr. XL. Yin/殷雪林Subjeect/主题Lovasstattin Tabbletts 220mgg Clleanningg Vaaliddatiion Prootoccol鲨鱼软骨片片清洁验验证方案案文件编号：Tablee off coonteentss目录1. Reespoonsiibillityy职责2. Puurpoose 目的3. Frrequuenccy 周期4. Reelevvantt SOOPss 相关的 SOPPs5. Eqquippmennt 设备6. Teest Metthodd 测试方法法7. Acccepptannce

3、 Criiterria 接受限度度8. Riisk Anaalyssis 风险分析析9. Saampllingg Pllan 抽样计划划10. AActiion takken wheen oout-of-limmit ressultt fooundd对不符合接接受限度度的测试试结果所所采取的的措施12. RRevaaliddatiion 再验证13. CCleaaninng VValiidattionn Exxecuutivve RRecoord清洁验证过过程记录录14. CConcclussionn结论Attacchmeentss附件 Writtten by: 制订者者：Date: 日期：R

4、evieewedd byy: 复复核者：Date: 日期：Approovedd byy: 批批准者：Date: 日期：Approovedd byy: 批批准者：Date: 日期：1. Reespoonsiibillityy 职责QA iss reespoonsiiblee foor pplann thhe ccleaaninng vvaliidattionn. QA负责整整个清洁洁验证的的安排QC iss reespoonsiiblee foor ssampplinng aand anaalyssis.QC 负责责抽样及及测试Produuctiion Depparttmennt iis rre

5、spponssiblle ffor perrforrminng ccleaaninng pprodducttionn eqquippmennt.生产部负负责设备备的清洁洁.2. Puurpoose目目的The ppurpposee off thhis cleeaniing vallidaatioon pprottocool iis tto ddemoonsttratte tthatt thhe ccleaaninng pprocceduure useed tto ccleaan JJHZ-2500B hhighh shhearr miixerr / graanullatoor, thrreed

6、immenssionnal mixxer，CCT-CC-2 Hott Aiir CCircculaatinng DDrieer， JZFF-4000 ggrannulaatorrs & miill Korrschh PHH3000-366 Taableet PPresss，BGDD-1550D higgh-eeffiicieencyy cooatiing macchinne andd DPPP-2250BB bllistter pacckaggingg maachiine cann efffecctivvelyy reemovve rresiiduees oof tthe prooduccts

7、 mannufaactuuredd inn ZSS-6550 VVorttex Osccilllatoor/CComppactt Siievee，JHHZ-2250BB hiigh sheear mixxer / ggrannulaatorr, tthreeeddimeensiionaal mmixeer，CCT-CC-2 Hott Aiir CCircculaatinng DDrieer， JZFF-4000 ggrannulaatorrs & miill Korrschh PHH3000-366 Taableet PPresss，BGDD-1550D higgh-eeffiicieency

8、y cooatiing macchinne andd DPPP-2250BB bllistter pacckaggingg maachiine to a ppreddeteermiinedd leevell thhat doees nnot raiise anyy saafetty cconccernns.清洗验证方方案的目目的是证证明JHHZ-2250BB高效湿湿法制粒粒机、 HLDD-10000BB型料斗斗式混合合机清洁洁操作规规程、CT-T-III型热热风循环环烘箱、JJZF-4000型整粒粒、粉碎碎机、Korrschh PHH-3000-336旋转转式压片片机、BBGD-1500D型高

9、高效包衣衣机和DPPP-2550B型型多功能能自动铝铝塑包装装所使用用的清洗洗程序能能够有效效地除去去产品残残留，达达到预先先确定的的限度，从从而达到到对下批批产品无无影响。 3. Frrequuenccy周期期The ccleaaninng vvaliidattionn sttudyy iss peerfoormeed aafteer tthreee cconssecuutivve mmajoor ccleaaninngs of ZS-6500 Voorteex OOsciillaatorr/Coompaact Sieeve，JJHZ-2500B hhighh shhearr miixerr

10、 / graanullatoor, thrreedimmenssionnal mixxer，CCT-CC-2 Hott Aiir CCircculaatinng DDrieer， JZFF-4000 ggrannulaatorrs & miill Korrschh PHH3000-366 Taableet PPresss，BGDD-1550D higgh-eeffiicieencyy cooatiing macchinne andd DPPP-2250BB bllistter pacckaggingg maachiine aftter thee maanuffactturee off Loov

11、asstattin Tabbletts.连续三批生生产后，进进行清洗洗验证研研究。4. Reelevvantt SOOPss相关的的 SOOPssSOP-PPD-3304-00Cleanningg prroceedurre fforHHLSGG-3000Hiigh Speeed Mixxer/GraanullatoorHLSG-3000型高效效湿法混混合制粒粒机清洁洁操作规程程SOP-PPD-3304-00Cleanningg prroceedurre fforLLF1220E-B airrpillloww-drry GraanullatoorLF1200E-BB型沸腾干干燥制粒粒机清洁洁操作

12、规规程SOP-PPD-3310-00Cleanningg prroceedurre ffor ZP443 Higgh SSpeeed rrotaary tabblett prresss高效ZP443旋转转式压片片机清洁洁操作规程程SOP-PPD-3307-000Cleanningg prroceedurre ffor HLDD-10000BB Hooppeer ttypee off bllendderHLD-110000B型料斗式式混合机清洁洁操作规程程SOP-PPD-3306-00Cleanningg prroceedurre ffor YK-1600 graanullatoors YK-1

13、660整粒粒机清洁洁操作规程程SOP-PPD-3311-00Cleanningg prroceedurre ffor BG-3000E hhighh-effficcienncy coaatinng mmachhineeBG-3000E型型高效包包衣机清清洁操作作规程SOP-PPD-3313-00Cleanningg prroceedurre fforDDPH-1300、 DDPP-2500B bblissterr paackaaginng mmachhinee DPH-1130、DPP-250型铝塑袍罩包装机清洁操作规程ESS-VVD0007Validdatiion guiidellinee

14、clleanningg验证指南清洁验验证ESS-VVD0111Surfaace sammpliing forr clleanningg vaaliddatiion清洗验证设设备表面面取样ESS-VVD0114Selecctioon oof tthe worrst casse iin ccleaaninng vvaliidattionn清洁验证中中最坏情情况的选选择SOP-QQC-110755检验操作规规程ESS-GGM0666Microobe Tesst 微生物限度度检测法法Equippmennts设设备No.序号Equippmennt NNo.设备编号Equippmennt NNamee设备

15、名称Produuct Conntacct SSurffacee Arrea与产品接触触面积(m2)1HLSG-3000 hiigh speeed mmixeer / grranuulattorHLSG-3000高效湿湿法混合合制粒机机2.81LF1200E-BB airrpillloww-drry GraanullatoorLF1200E-BB沸腾干干燥制粒粒机器5.903ZP43TTabllet PreessZP43旋旋转式压压片机64METALL DEETECCTORR金属探测仪仪0.35HLD-110000BHLLD-110000B HHoppper typpe oof bblennde

16、rrHLD-110000B型料斗式式混合机机5.256YK-1660grranuulattorss YK-1660型整整粒机0.377DPH-1130DPPP-2550bllistter pacckaggingg maachiineDPH-1130、DDPP-2500型多功功能自动动铝塑包包装机1.08BG-3000Ehhighh-effficcienncy coaatinng mmachhineeBG-3000E型型高效包包衣机8.43Totall Prroduuct Conntacct SSurffacee Arrea (m2)与产品接触触面积总总和(mm2)99.6225.1 LList

17、t off Eqquippmennt设备备清单The llistt off Eqquippmennt uusedd inn thhe mmanuufaccturre oof LLovaastaatinn Taableets:有关鲨鱼软软骨片生生产线的的所有机机器列出出如下：1HLSSG-3300 higgh sspeeed mmixeer / grranuulattor HLSSG-3300高高效湿法法混合制粒粒机 2. LF1220E-B airrpillloww-drry GGrannulaatorr LF1120EE-B沸沸腾干燥燥制粒机机器 3. ZP443Taableet PPres

18、ss ZZP433 Taableet PPresss ZZP433旋转式式压片机机 4. METTAL DETTECTTOR 金属探探测仪 5. HLDD-10000BBHLDD-10000BB Hooppeer ttypee off bllendder HLDD-10000BB 型料斗式式混合机机 66. YYK-1160ggrannulaatorrs YK-1600 型整整粒机7. DPPH-1130DPPP-2550bllistter pacckaggingg maachiine DPHH-1330、DDPP-2500型多功功能自动动铝塑包包装机8. BGG-3000Ehhighh-ef

19、fficcienncy coaatinng mmachhinee BG-3000E型高高效包衣衣机Tablee 1表表1:5.2 Vaaliddatiion Scoope验验证范围围 HLSG-3000 hiigh sheear mixxer / ggrannulaatorr HLSSG-3300高高效湿法法制粒机机LF1200E-BB airrpillloww-drry Grranuulattor LF1120EE-B沸沸腾干燥燥制粒机器ZP43TTabllet Preess ZP443旋转转式压片片机METALL DEETECCTORR 金金属探测测仪HLD-110000B grannul

20、ee mixxer HLD-10000BB型料斗式式混合机机YK-1660 graanullatoors YYK-1160型型整粒机机DPH-1130、DDPP-2500 bllistter pacckaggingg maachiine DPPH-1130、DDPP-2500型多功功能 自动铝铝塑包装装机BG-3000Ehhighh-effficcienncy coaatinng mmachhinee BG-3000E型高高效包衣衣机Test Metthodd测试方方法The ccleaaninng vvaliidattionn sttudiies aree baasedd onn thhe

21、sswabbbinng ttechhniqque andd riinsiing sammpliing. TThe sellectted swaabs shoouldd bee chharaacteerizzed forr thheirr suuitaabillityy annd aa reecovveryy teest shoouldd bee peerfoormeed pprioor tto tthe vallidaatioon sstuddiess. Thee vaaliddatiion stuudiees iinclludee swwabbbingg off thhe mmainn su

22、urfaace areea aas wwelll ass thhe hhardd-too-clleann loocattionns. Swwabbbingg annd rringgingg iss caarriied outt foor tthe acttivee inngreedieent.清洁验证研研究用擦擦拭取样样法和最终淋淋洗水取取样。验验证研究究之前，选选择的棉棉签的特特性应适适合并进进行回收收率研究究。验证证研究包包括主要要表面积积和难清清洁部位位的擦拭拭。对活活性成分分擦拭取取样和淋淋洗水取取样。Sampllingg Meethood抽样样方法Swab Sammpliing擦擦拭

23、法Ringiing sammpliing最最终淋洗洗水取样样法Accepptannce Criiterria 接受限度Visuaal IInsppecttionn目测检查Accepptannce Criiterria接受限度Theree iss noo viisibble ressiduue iin eequiipmeent surrfacce aafteer ccleaaninng.设备在清洁洁后，无无可见的的物质残残留在设设备表面面Accepptannce Criiterria of miccrobbe微生物测试试接受限限度For sswabb saamplles 对擦拭样品品：Micro

24、obess微生物物含量: 2 CFUU/cmm2 ，即 500 CFFU / 255 cmm2For rrinssingg saamplles / 对对冲淋样样品：Microobess微生物物含量: 1000 CFUU/mllAccepptannce Criiterria of asssay化学测试接接受限度度 AActiive Inggreddiennt (seee Atttacchmeent 26)活活性成分分 (见附附件266)MMC (mg/swaab) = _0.008433_ (AActiive) Foor rrinssingg saamplles 对冲淋样样品：MC (mmg/L

25、L) = _00.0884_ (AActiive)Test freequeencyy检测次数The ccleaaninng vvaliidattionn sttudiies aree coonduucteed aafteer tthreee cconssecuutivve mmajoor ccleaaninngs of Nouurkrrin Tabbletts.三批鲨鱼软软骨片生生产结束束后进行行清洗验验证。Risk Anaalyssis风风险分析析 The rresiiduees oof tthe prooduccts aree noot ddisttribbuteed uunifformm

26、ityy, sso tthe rissk aanallysiis sshouuld be doone befforee clleanningg vaaliddatiion sammpliing. Thhe CCritticaal llocaatioon wwilll bee deeterrminned at rissk aanallysiis. Rissk aanallysees aare summmarrizeed iin AAttaachmmentt 1aand Atttachhmennt 118.由于上一产产品生产产对下一一产品的的污染并并不是均均匀分布布在整个个设备的的接触面面上，因因

27、此清洁洁验证的的活性成成分抽样样计划的的确定必必须先进进行风险险分析，且且在风险险分析中中确定清清洁验证证的关键键部位。风风险分析析见附件件1到附件件18：风风险分析析表Sampllingg Pllan抽样计划 For acttivee ingrrediientt活性成成分9.1 SSwabb saampllingg擦拭法The ffolllowiing loccatiion willl bbe ssamppledd ass riisk anaalyssis: 根据风风险分析析，在下下列抽样样部位取取样：9.1.11HLSSG-3300hhighh shhearr miixerr/grranu

28、ulattor HLSG-3000高效湿湿法混合合制粒机机Totall arre 77 saamplles:总共7个取取样点:Tablee 3表表3:Part Namme部件名称Sampllingg Loocattionn取样位置Sampllingg Noo.取样点Swab Areea SSs (cm22)取样面积Pan制粒锅Side侧侧面HLSG-3000-1200Underrsidde底面面HLSG-3000-2200出料口Innerr suurfaace内内表面HLSG-30003200腔盖Rim aareaa unnderr thhe sseall 盖的边缘 HLSG-3000-420

29、0内表面HLSG-3000-5200切粒切刀桨片HLSG-3000-6全部搅拌切刀下表面HLSG-3000-72009.1.33 ZPP43TTabllet Preess ZP43旋旋转式压压片机Totall arre 88 saamplles:总共8个取取样点:Tablee 5表表5:Part Namme部件名称Sampllingg Loocattionn取样位置Sampllingg Noo.取样点Swab Areea SSs (cm22)取样面积下料斗内表面PG16、ZZP433-1200饲料靴表面PG16、ZZP433-2200孔PG16、ZZP433-3200出片器内表面PG16、ZZ

30、P433-4200除粉器内表面PG16、ZZP433-5200转盘侧面PG16、ZZP433-6200底面PG16、ZZP433-7200模孔内表面PG16、ZZP433-8200HLD-110000BHLLD-110000B HHoppper typpe oof bblennderr HLD-110000料斗式式混合机机Totall arre 33 saamplles:总共3个取取样点:Tablee 6表6:Part Namme部件名称Sampllingg Loocattionn取样位置Sampllingg Noo.取样点Swab Areea SSs (cm22)取样面积加料口内表面JSH-

31、6600-1200边缘JSH-6600-2200出料口内表面JSH-6600-32009.1.66 JZFF-4000 graanullatoors & mmilllJZF-4400型型整粒、粉粉碎机Totall arre 66 saamplles:总共6个取取样点:Tablee 8表8:Part Namme部件名称Sampllingg Loocattionn取样位置Sampllingg Noo.取样点Swab Areea SSs (cm22)取样面积盖子内表面JZF-4400-1200内表面JZF-4400-2200容器内侧面JZF-4400-3200内底部JZF-4400-4200出料口表

32、面JZF-4400-5200表面JZF-4400-62009.1.77 DPPP-2550B bliisteer ppackkagiing macchinneDPP-2250BB型多功功能自动动铝塑包包装机Totall arre 44 saamplles:总共4个取取样点:Tablee 9表9:Part Namme部件名称Sampllingg Loocattionn取样位置Sampllingg Noo.取样点Swab Areea SSs (cm22)取样面积加料斗侧面DPP-2250BB-1200底部DPP-2250BB-2200分料刷表面DPP-2250BB-3200滚刷表面DPP-2250

33、BB-42009.1.88 METTAL DETTECTTOR金属探测仪仪Totall arre 44 saamplles:总共4个取取样点:Tablee 100表10:Part Namme部件名称Sampllingg Loocattionn取样位置Sampllingg Noo.取样点Swab Areea SSs (cm22)取样面积加料斗上侧面M-1200下侧面M-2200出料斗内表面M-3200废片出口内表面M-42009.1.99 BGGD-1150DD hiigh-effficiienccy ccoattingg maachiine包衣机Totall arre 88 saamplles

34、:总共8个取取样点:Tablee 111表11:Part Namme部件名称Sampllingg Loocattionn取样位置Sampllingg Noo.取样点Swab Areea SSs (cm22)取样面积配料锅顶部BGD-1150DD-1200侧面BGD-1150DD-2200底部BGD-1150DD-3200包衣锅侧面BGD-1150DD-4200底部BGD-1150DD-5200顶部BGD-1150DD-6200接缝处BGD-1150DD-7200边缘BGD-1150DD-82009.2 RRinggingg saampllingg淋洗水水取样BGD-1150DD hiigh-e

35、ffficiienccy ccoattingg maachiine包包衣机Sampllingg loocattionn取样部部位：硅硅胶管、喷喷枪Threeedimmenssionnal mixxer HLDD-10000BB型料斗斗式混合合机清洁洁操作规规程Sampllingg loocattionn取样部部位：腔腔体For MMicrrobees微生物取样样点9.3.11 JHHZ-2250BB hiigh sheear mixxer/graanullatoor JHZ-2250BB高效湿湿法制粒粒机Totall arre 77 saamplles:总共7个取取样点:Tablee 122表

36、12:Part Namme部件名称Sampllingg Loocattionn取样位置Sampllingg Noo.取样点Swab Areea SSs (cm22)取样面积Pan制粒锅Side侧侧面JHZ-2250BB-A25Underrsidde底面面JHZ-2250BB-B25出料口Innerr suurfaace内内表面JHZ-2250BB-C25腔盖Rim aareaa unnderr thhe sseall 盖的边缘 JHZ-2250BB-D25内表面JHZ-2250BB-E25切粒切刀桨片JHZ-2250BB-F25搅拌切刀下表面JHZ-2250BB-G259.3.22 ZSS-6

37、550 VVorttex Osccilllatoor/CComppactt Siievee ZS-6550漩涡涡振荡筛筛Totall arre 55 saamplles:总共5个取取样点:Tablee 133表13:Part Namme部件名称Sampllingg Loocattionn取样位置Sampllingg Noo.取样点Swab Areea SSs (cm22)取样面积上盖内表面ZS-6550-AA25筛网上表面ZS-6550-BB25出料口内表面ZS-6550-CC25密封圈内表面ZS-6550-DD25容器内表面ZS-6550-EE259.3.33 Korrschh PHH300

38、0-366 Taableet PPresss KORSCCH PPH-3300-36旋旋转式压压片机Totall arre 88 saamplles:总共8个取取样点:Tablee 144表14:Part Namme部件名称Sampllingg Loocattionn取样位置Sampllingg Noo.取样点Swab Areea SSs (cm22)取样面积下料斗内表面PH-3000-336-AA25饲料靴表面PH-3000-336-BB25孔PH-3000-336-CC25出片器内表面PH-3000-336-DD25除粉器内表面PH-3000-336-EE25转盘侧面PH-3000-336

39、-FF25底面PH-3000-336-GG25模孔内表面PH-3000-336-HH259.3.44 Thrreedimmenssionnal mixxerHLD-110000B型料料斗式混混合机清清洁操作作规程Totall arre 33 saamplles:总共3个取取样点:Tablee 155表15:Part Namme部件名称Sampllingg Loocattionn取样位置Sampllingg Noo.取样点Swab Areea SSs (cm22)取样面积加料口内表面JSH-6600-A25边缘JSH-6600-B25出料口内表面JSH-6600-C259.3.55 CT-C-2

40、2 Hott Aiir CCircculaatinng DDrieerCT-C-2型热热风循环环烘箱Totall arre 110 saamplles:总共10个个取样点点:Tablee 166表16:Part Namme部件名称Sampllingg Loocattionn取样位置Sampllingg Noo.取样点Swab Areea SSs (cm22)取样面积烘盘表面CT-C-2-AA25内侧面CT-C-2-BB25箱体左侧CT-C-2-CC25右侧CT-C-2-DD25顶部CT-C-2-EE25接缝处CT-C-2-FF25台车托架CT-C-2-GG25边缘CT-C-2-HH25箱门内表

41、面CT-C-2-II25密封条CT-C-2-JJ259.3.66 JZFF-4000 graanullatoors & mmilllJZF-4400型型整粒、粉粉碎机Totall arre 66 saamplles:总共6个取取样点:Tablee 177表17:Part Namme部件名称Sampllingg Loocattionn取样位置Sampllingg Noo.取样点Swab Areea SSs (cm22)取样面积盖子内表面JZF-4400-A25内表面JZF-4400-B25容器内侧面JZF-4400-C25内底部JZF-4400-D25出料口表面JZF-4400-E25表面JZF

42、-4400-F259.3.77 DPPP-2550B bliisteer ppackkagiing macchinneDPP-2250BB型多功功能自动动铝塑包包装机Totall arre 44 saamplles:总共4个取取样点:Tablee 188表18:Part Namme部件名称Sampllingg Loocattionn取样位置Sampllingg Noo.取样点Swab Areea SSs (cm22)取样面积加料斗侧面DPP-2250BB-125底部DPP-2250BB-225分料刷表面DPP-2250BB-325滚刷表面DPP-2250BB-4259.3.88 METTAL

43、DETTECTTOR金属探测仪仪Totall arre 44 saamplles:总共4个取取样点:Tablee 199表19:Part Namme部件名称Sampllingg Loocattionn取样位置Sampllingg Noo.取样点Swab Areea SSs (cm22)取样面积加料斗上侧面M-A25下侧面M-B25出料斗内表面M-C25废片出口内表面M-D259.3.99 BGGD-1150DD hiigh-effficiienccy ccoattingg maachiine包衣机Totall arre 88 saamplles:总共8个取取样点:Tablee 200表20:P

44、art Namme部件名称Sampllingg Loocattionn取样位置Sampllingg Noo.取样点Swab Areea SSs (cm22)取样面积配料锅顶部BGD-1150DD-A25侧面BGD-1150DD-B25底部BGD-1150DD-C25包衣锅侧面BGD-1150DD-D25底部BGD-1150DD-E25顶部BGD-1150DD-F25接缝处BGD-1150DD-G25边缘BGD-1150DD-H259.4 RRinggingg saampllingg淋洗水水取样BGD-1150DD hiigh-effficiienccy ccoattingg maachiine

45、包包衣机Sampllingg loocattionn取样部部位：硅硅胶管、喷喷枪Threeedimmenssionnal mixxer HLDD-10000BB型料斗斗式混合合机清洁洁操作规规程Sampllingg loocattionn取样部部位：腔腔体Actioon ttakeen wwhenn ouut-oof-llimiit rresuult fouund对不符合接接受限度度的测试试结果所所采取的的措施Inspeect thee prroceess of opeerattionn检查测试过过程Inspeect thee eqquippmennt oof aassaay检查查分析所所用的

46、仪仪器 Inspeect thee sttep of opeerattionn检查实实验步骤骤Inspeect thee prroceess of sammpliing检检查抽样样过程QA，QCC annd tthe prooducctioon ddepaartmmentt caalcuulatte wwithh thhe rresuultss off innspeect.QA，QCC及生产产部对检检查结果果进行讨讨论Modiffy tthe vallidaatioon pplann; rrevaaliddatee thhe iitemms, whiich aree noot aappllic

47、aablee beeforre.修改验证计计划，对对不符合合的项目目进行重重验证。Revallidaatioon再验证Revallidaatioon sshouuld be connsiddereed uundeer tthe folllowwingg ciircuumsttancces:在下列情况况发生时时，必须须考虑是是否要进进行重验验证：Cleanningg meethood cchanngedd/清洁洁程序变变化时Cleanningg deeterrgennts chaangeed/清清洁剂变变化时Produuct chaangeed/产产品变化化时Cleanningg Vaalidd

48、atiion Exeecuttivee Reecorrd清洁验证过过程记录录 附件1-118Rissk AAnallysiis TTablle风险险分析表表附件19Vissuall Innspeectiion andd Saampllingg foor AActiive Inggreddiennt目检检和取样样附件20Vissuall Innspeectiion andd Saampllingg foor MMicrrobees目检检和取样样附件21Anaalytticaal RResuultss foor AActiive Inggreddiennt分析析结果附件22Anaalytticaa

49、l RResuultss foor MMicrrobees分析析结果附件23 Sammpliing Reccoveery Tesst取样样回收率率试验附件24 Swaab CChaccterrizaatioon ffor Cleeaniing Vallidaatioon清洗验证棉棉签特性性研究附件25 Swaab SSampplinng ffor Cleeaniing Vallidaatioon清洗洗验证棉棉签取样样附件26 Callcullatiion forr Acccepttancce CCritteriia接受受限度的的计算 14. COONCLLUSIION结论The ressult

50、ts oobtaaineed sshouuld nott exxceeed tthe callcullateed cconttamiinattionn liimitt. Thee clleanningg prroceedurre ffor alll piiecees oof pprodducttionn eqquippmennt eeffeectiivelly rremoovess reesidduess off Loovasstattin Tabbletts mmanuufaccturred in thiis eequiipmeent andd iss thhereeforre ddeemm

51、ed vallidaatedd. Microobess liimitt coomplly wwithh thhe rrequuireemennt.测试结果果不得大大于计算算出的检检测限.设备的的清洁程程序可以以有效清清除产品品残留，认认为验证证有效。 微微生物限限度符合合要求。Attacchmeent附附件1: Riisk Anaalyssis Tabble forr acctivve iingrrediientt风险分分析表:FormatA+B Equuipmmentt Naame 设备名名称: JHZZ-2550B Higgh SSheaar MMixeer / Grranuulattor

52、 Daate日日期: FormatA+BJHZ-2250BB高效湿湿法制粒粒机12341.11.2*2.1Critiicall关键3.1Risk forr Prroceess Steep风险 3.2Eval.of riisk风险评估3.3Folloow-uupof riisk是否确认为为有风险险4.1Possiiblee caausee可能的原因因4.2Validdatiion meaasurr验证措施4.3Validdatiion plaan验证计划4.4Date日期4.5Respoonsiiblee peersoon负责人No.序号CompoonenntName部件名称Sam. No.取样

53、部位Contaact Areea药品接触表表面Yes是No否Yes是No否12345制粒锅出料口腔盖切粒切刀搅拌切刀Innerr suurfaace内表面内表面内表面表面表面XXXXPossiibillityy off coontaaminnatiion witth pprevviouus pprodductt与前批产品品交叉污污染的可可能性Dittoo同上Dittoo同上 Dittoo同上MMMHHXxxxXCleanningg prroceedurre oof SSOP is nott effficciennt清洁方法不不足够有有效Dittoo同上Dittoo同上Dittoo同上 Chec

54、kk clleanningg reesullt aat ddefiinedd loocattionn在规定部位位检查清清洁结果果Dittoo同上Dittoo同上Dittoo同上 See vvaliidattionn prrotoocoll 见清洁验证证方案 1.2* Saamplle NNo. seee thhe sseveen ssampplinng ppoinnts on Tabble33. 取取样部位位： 共7个取样样点 见表3.Attacchmeent附附件2 : RRiskk Annalyysiss Taablee foor aactiive ingrrediientt风险分分析表:

55、FormatA+B Eqquippmennt NNamee设备名名称: ZSS-6550 VVorttex Osccilllatoor/CComppactt Siievee DDatee日期: FormatA+BZS-6550漩涡涡振荡筛筛12341.11.22.1Critiicall关键3.1Risk forr Prroceess Steep风险 3.2Eval.of riisk风险评估3.3Folloow-uupof riisk是否确认为为有风险险4.1Possiiblee caausee可能的原因因4.2Validdatiion meaasurre验证措施4.3Validdatiion

56、plaan验证计划4.4Date日期4.5Respoonsiiblee peersoon负责人No序号 CoompoonenntName部件名称*Sam.No.取样部位ContaactArea药品接触表表面 Yess 是No否Yes是No否12345上盖筛网出料口密封圈容器Innerr suurfaace内表面Surfaace表面Surfaace内表面内表面内表面xxxxxPossiibillityy off coontaaminnatiion witth pprevviouus pprodductt与前批产品品交叉污污染的可可能性Dittoo同上Dittoo同上Dittoo同上Dittoo同

57、上LHH MMxxxxXCleanningg prroceedurre oof SSOP is nott effficciennt清洁方法不不足够有有效 Dittto同上Dittoo同上Dittoo同上Dittoo同上Checkk clleanningg reesullt aat ddefiinedd loocattionn在规定部位位检查清清洁结果果Dittoo同上Dittoo同上Dittoo同上Dittoo同上See vvaliidattionn prrotoocoll 见清清洁验证证方案1.2 * Sammplee Noo. ssee fivve ssampplinng ppoinnts

58、 on Tabble 4. 取样部部位：共共5个取样样点见表表4.Attacchmeent附附件3: Riisk Anaalyssis Tabble forr acctivve iingrrediientt风险分分析表:FormatA+B Equuipmmentt Naame 设备名名称: Korrschh PHH3000-366 Taableet PPresss Datte日期期: FormatA+BKORSCCH PPH-3300-36旋旋转式压压片机12341.11.2*2.1Critiicall关键3.1Risk forr Prroceess Steep风险 3.2Eval.of ri

59、isk风险评估3.3Folloow-uupof riisk是否确认为为有风险险4.1Possiiblee caausee可能的原因因4.2Validdatiion meaasurr验证措施4.3Validdatiion plaan验证计划4.4Date日期4.5Respoonsiiblee peersoon负责人No.序号CompoonenntName部件名称Sam. No.取样部位Contaact Areea药品接触表表面Yes是No否Yes是No否12345678Hoppeer 下料斗饲料靴出片器除粉器压片室隔板板转盘冲头和冲模模模孔Innerr suurfaace内表面表面及孔表面内表面

60、表面表面内表面内表面XXXXXXXXPossiibillityy off coontaaminnatiion witth pprevviouus pprodductt与前批产品品交叉污污染的可可能性Dittoo同上Dittoo同上 Dittoo同上MHM MLMLHxxxxxxxxCleanningg prroceedurre oof SSOP is nott effficciennt清洁方法不不足够有有效Dittoo同上Dittoo同上Dittoo同上 Dittto同上 Checkk clleanningg reesullt aat ddefiinedd loocattionn在规定部位位检