药物使用期间稳定性试验的技术要求探讨

©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(3)1842010193[],,,,:(010)685855662633,E2mail:chenhf@cde1org1cn(,100038)[],,,3,[];;[]R927111[]B[]1003-3734(2010)03-0184-06Techniquerequirementsforin2usestabilitytestingofdrugproductsCHENHai2feng(DrugEvaluationCenterofStateFoodandDrugAdministration,Beijing100038,China)[Abstract]Theconceptofin2usestabilitytestingisintroducedinthispaper.Theimportanceofin2usesta2bilitytestingformultidosedrugproductsand/orproductswhichneedsconstitutionordilutionbeforeuseisempha2sized.Basedonsystemicanalysisforthevariouskeyelementsinrequirementsofin2usestabilitytesting,weputforwardEMEAandICHguidelines.Themaintechniquerequirementsarefurtherexplainedwiththeexamplesofthreedrugproducts.[Keywords]in2usestabilitytesting;multidosedrugproducts;in2useperiod,,ICHWHO,,,,[1],,,,,1,(),5%,,,,,,,,,,2,3%©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(3)18520101935%,20g(,)10g018g014g3mL115mL70%,,(in2usesta2bilitytesting):,,WHO212110[2]:,,,EMEA[3-4]:,ICH[5]:(in2useperiod),,:/2,,:,,,,,,,,,[4],,,,,,,,,,(),,3,FDAEMEAICHWHO,WHO[2],,:,,,,ICHQ1A(R)[5]:,,,,,,,,12EMEA1998[3]©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(3)1862010193,,,:y,X(h/d),,,tzdxyzt,z28dEMEA2001[4],,[4],,,,,,4ICHWHO,,,,,,,,,411EMEAWHO[3]:2,ICH,,,2,,,EMEA:,,,,412,,,,,WHOEMEA:(),ICH:(T=0)(24),12,ICHWHOEMEA,,,(),,413,EMEAWHO:,,,:,,2,2©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(3)1872010193,14d,,,,,,,(28),,414(in2useduration),,,,,24h,24h,,30d,30d,,,,,,,24h,0,4,8,16,24h,,,,,,415,,,,,,,,5,,,(PVC),2(22)(DEHP),,[7]:DEHP,,,PVC,0122m,,DE2HP,,,,,,,,,,416,,,,,,,DEHP,,,©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(3)1882010193,417,,,,,,,418,EMEA,:2,[]:,,,[]:,(4)353,511()30mg(5mL)/100mg(1617mL)/,1mL6mg,527mg4917%[]:019%,5%,5%019%(USP)5%,013112mgmL-1,:(),,,25,:(25)27h27h015,1,2,4,8,16,24,30h,5DEHP():,,(0122m),512():,1,34,4mL2mg,,,,,,,(),1,34,,,,,,,,,:,,,:,:1,,,15d,10d,20d,30d©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(3)1892010193,pH:,,,,5132[6],,:,,1,,:,,,,,,1,:(4),3,3,,,3,(0)12(3),,4,,,94070%,,,,,,,,,,,,,,,[][1]1[S].20051[2]WHO1GuidelinesforStabilityofPharmaceuticalProductsContai2ningWellEstablishedDrugSubstancesinConventionalDosageForms:StabilityTestingofActivePharmaceuticalIngredientsandPharmaceuticalProducts(Draft)(2007)1[3]EMEA1NoteforGuidanceonIn2useStabilityTestingofHumanMedicalProducts[S].20011[4]EMEA1MaximumShelf2LifeforSterileProductsforHumanUseafterFirstOpeningorFollowingReconstitution[S].19981[5]ICH1Q1A(R2)StabilityTestingofNewDrugSubstancesandProducts[S].20031:/:2009-03-26NipponShinyakuErizasÓ400g(dexamethasonecipecilate)ErizasÓ1ErizasÓ3()ErizasÓ(),200910(NipponShinyaku)