应用TOC进行清洁验证


TOC 

TOC

 TOC
TOC TOC
GEAI/CleaningValidation©2009GeneralElectricCompany.Allrightsreserved:2
!,#TOC$%RTR(&!'()*)+,
 GEAI/CleaningValidation©2009GeneralElectricCompany.Allrightsreserved:3CV( )USACodeofFederalRegulations(CFRs) USAGuidancedocumentsGEAI/CleaningValidation©2009GeneralElectricCompany.Allrightsreserved:4USAGuidancedocuments InternationalstandardsCFRs,CurrentGoodManufacturingPractices(cGMPs),International(
)1)1963USAFDAGMPs2)1978USAcGMPModernization(
):21CFR211.673)1992UnitedStatesvs.BarrLabs1992BarrLabs 4)1993USAFDAMid-AtlanticInspectionGuide:CleaningValidation5)1993USAFDAGuideForInspections:CleaningValidation6)1996UnitedStatesPharmacopeia(USP)643compendialTOCGEAI/CleaningValidation©2009GeneralElectricCompany.Allrightsreserved:56)1996UnitedStatesPharmacopeia(USP)643compendialTOCwaterspecification(USP)643TOC7)1999EuropeanAPICGuidetoCleaningValidationatAPIPlants1999/APICAPI8)2000ICHQ7:ProcessValidation(InternationalConferenceonHarmonisation)2000ICHQ7(!)9)2004cGMPsforthe21stCentury10)2008ProposednewUSAFDAProcessValidationGuidance2008#USAFDAUSCodeofFederalRegulations210-211
210-211-./0•
: •GEAI/CleaningValidation©2009GeneralElectricCompany.Allrightsreserved:6••cGMPs•!#,$%&',()*,+, - CV:CFR211.67
“!##$%,&'()*+,-./012
34GEAI/CleaningValidation©2009GeneralElectricCompany.Allrightsreserved:7/012
345/67/&89,:;=?@ABCDEF/G/HI/JK/LIMN/OPQ.UnitedStatesvs.BarrLabsBarrLabs1992R, STUVWXYZ
[\]^_,`abOP&01cd.eb^fghi,jk.U)*lmngh.WolinU-WX:o)*?pqrs&tGEAI/CleaningValidation©2009GeneralElectricCompany.Allrightsreserved:8h.WolinU-WX:o)*?pqrs&tuCD.!rsgtv,[\)*^wmxyz.U{|}~tvB.CGMP’sCurrentGoodMfgPracticesLegalPDAISPEAPICIndustryStandardsUSP,JPCP,FP,DAB,ASTMFDAUSPICHGuidanceHealthCanada,WHO,USFDA,EU/EMEA,ChineseFDARegulatorsFDA’s483’sPracticePharmaRegulatoryFramework1 GEAI/CleaningValidation©2009GeneralElectricCompany.Allrightsreserved:9PharmaIndustry
FDAIndustryOrganizations
StandardsOrganizationsGuidanceOrganizations Regulators483’sGuidetoInspections483Uncertainty =Risk(Overcompensate )Regulators
,,,, :!#$%;&'()*+,-./012345(6789GEAI/CleaningValidation©2009GeneralElectricCompany.Allrightsreserved:10-./012345(678934:;=?@A.USFDA
ü23üüü4567(3Q)ü.89:;GEAI/CleaningValidation©2009GeneralElectricCompany.Allrightsreserved:11ü.89:;ü
9:;ü=?@ü?@ü?@
GEAI/CleaningValidation©2009GeneralElectricCompany.Allrightsreserved:12 
-gyz.U€�‚&�ƒ„,wm…�†x.-USP1226andICHQ2(R1)‡ˆbyz.wmUSP1226ICHQ2(R1)
GEAI/CleaningValidation©2009GeneralElectricCompany.Allrightsreserved:13Q2(R1)‡ˆbyz.Uwm‰
 ICHQ2(R1)ü(%)ü–5ü–!#$%&'()ü*+(,-.)GEAI/CleaningValidation©2009GeneralElectricCompany.Allrightsreserved:14ü*+(,-.)ü/+–%RSD01*23ü!4(LOD)&!5(LOQ)ü67–89:%;=--Š‹–“Š‹€?Œ�pŽp3��l‘BJQ–ICHQ2(R1)-’?“”BJ45p3K|‘–g•GEAI/CleaningValidation©2009GeneralElectricCompany.Allrightsreserved:15-’?“”BJ45p3K|‘–g•–,—˜™`~yz.U“g•–(gŠ‹.~�†x|‘(gšYg•B.�jY›gœ–�ž�Ÿ: ¡¢g•B.£’,›g¤�¥�¦/§g•B.CurrentEnforcement
:“Yourfirmfailedtoestablishandfollowwrittenprocedurestoassurethecleaningandmaintenanceofequipmentusedinthemanufacturingofdrugproducts.Forexample,cleaningvalidationfortheCIPprocessvessel,whichisutilizedintheasepticformulationofGEAI/CleaningValidation©2009GeneralElectricCompany.Allrightsreserved:16vessel,whichisutilizedintheasepticformulationoftrivalentbulkinfluenzavaccine…Thestudydidnotincludeswabsamplingoftheproducttransferlines.”ABCD=EFGHIJ?,1KLMN
OP%.QR,STUVCIPW?X
,CYZ$[\#]^_`&.
 TOCGEAI/CleaningValidation©2009GeneralElectricCompany.Allrightsreserved:17 TOC (CV)TOC1.e¨©B
ª«^TOC–CV?2.
ªwm¬­GEAI/CleaningValidation©2009GeneralElectricCompany.Allrightsreserved:182.
ªwm¬­«,TOC†�®¯HPLC.3.’°CV«wmTOCBC(DE+FGHTOC?ü
 TOCCV.ü,!#$%&'()*,+,-..ü/0)1:23-.45(Verification),6789:;ü)1=?@A,”B@”CD=E):9FGHIJK(.GEAI/CleaningValidation©2009GeneralElectricCompany.Allrightsreserved:19üLHPLCM,CNOP.üTOC!QRGSTUVW23$XY&'(.üZ[\](^_:1ppbasCarbon)ü`abPNO,Mc-.,,defgh.ü`ZQRijkl.!#$%&'():IHJK-.BCLMNGEAI/CleaningValidation©2009GeneralElectricCompany.Allrightsreserved:20BCLMNO=PQRSHTUVWG3±²Bvs.g•–G3.U•ab;caDdefghgij•klmcDn8eokklipqdersklitu.
:
:GEAI/CleaningValidation©2009GeneralElectricCompany.Allrightsreserved:21
:•HPLC(UVandMS)•NIR•IMS•ELISA
:•TOC•NPOC
R&D&
,,.HPLC&TOC*+,-.HPLC•$fvtklab;wkcxy$z•HPLC{.fvghv&W?TOC•cxy$z|$okkl;•vgTOC$}ok&W?.GEAI/CleaningValidation©2009GeneralElectricCompany.Allrightsreserved:22v&W?•~ (€