化学合成原料药起始物料国内外相关要求的比较-王宏亮

ChineseJournalofNewDrugs20142399982014239。[e-mail]。。[e-mail]。··1211008502100038。20。ICHQ11ICH。。、、ICH、、。Ｒ95C1003－3734201409－0998－06ComparisonofdomesticandforeignrelatedrequirementsofstartingmaterialsforsyntheticdrugsubstancesWANGHong-liang1CHENZhen21NationalEngineeringＲesearchCenterforStrategicDrugsInstituteofPharmacologyandToxicologyAcademyofMilitaryMedicalSciencesBeijing100850China2CenterforDrugEvaluationChinaFoodandDrugAdministrationBeijing100038ChinaAbstractTheselectionandqualitycontrolofstartingmaterialsareanimportantpartofdrugsubstancede-velopment．Inthepast20yearsthistopicinvolvesinthetechnicalrequirementsfordrugsubstanceregistrationandgetsattentionquitealltime．AsthepublicationofICHQ11guidelineagreementongeneralselectionprinci-plesandqualitycontrolrequirementsofstartingmaterialshasbeenreachedinICHregions．Incomparisonwearestilllaggingbehindintheunderstandingofthistopic．InthisarticlewereviewedFDAEMAICHanddomesticrelatedrequirementsofstartingmaterialsforsyntheticdrugsubstances．Furthermoreweanalyzedourexistingprob-lemsfocusingontheregulatoryfunctionselectionprinciplesanddocumentsubmissionrequirementsforstartingmaterials．Wewanttoprovideareferencetoamendthedomesticrelatedrequirementsforstartingmaterials．Keywordsdrugsubstancestartingmaterialguidelinetechnicalrequirements“startingma-terial”“APIstartingmaterial”GMP1－5。ICHQ7“”①、。②。③、。ChineseJournalofNewDrugs20142399992014239FDA19876－7EMA4。20。2012ICHQ118ICH。2005《》9。、ICH。1。。GMP10－12。。EDQMCEP2112。FDAANDA13NDAFDAⅡINDEnd-of-Phase2meetingpre-NDAmeeting610。23“”60%。11。GMP、310－12。2Q11ICHICH。、、11。ICHQ11、ICHQ11。2．1FDACDEＲ19876200414。。2004FDACDEＲCBEＲCVM《》5。CDEＲCBEＲ200615ICHQ11。13FDA①5－6。②5－6。5。③、、6。、ChineseJournalofNewDrugs2014239100020142390．10%5。④513。FDA、、、513－14。FDA6。⑤5。FDA5－613－14、、、、、/DMFFDA。2．2EMAEDQM3ASMFactivesub-stancemasterfileCEPcertif-icateofsuitabilitytothemonographsoftheEuropeanPharmacopeia。412①。②。③。CEP1～2。④/。、412。2．3ICHICH68①。、。、、。②。、。C-XC-C。③。④。GMP。GMP。⑤。。⑥“”。“”、。。ICHQ11。ChineseJournalofNewDrugs201423910012014239①。②。③。Q11。32005“”9、、。、。。/。2008《》16、/、/。2012“-”17①。②。③、。④。。4。ICHQ11ICH。。4．1GMP。GMP112。ICHQ11GMP8。①GMP、GMP。②。“、”9。。③。ICHQ7。ChineseJournalofNewDrugs201423910022014239DMF。4．2。、17。。“”、“、”17。ICHQ1163。。。“”1～2/。ICHQ11。Ⅲ、。4．3。《》、/、/16。《CTD》、18。。。ICHQ11/。GMPGMP。①、。②。③、、。④、。⑤、。⑥。1ICH．HarmonizedtripartiteguidelineQ7goodmanufacturingpracticeguideforactivepharmaceuticalingredientsEB/OL．2000－11－102013－12－05．http//．ich．org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q7/Step4/Q7_Guideline．pdf．2ICH．HarmonizedtripartiteguidelineQ3AＲ2impuritiesinnewdrugsubstancesEB/OL．2006－10－262013－12－05．http//．ich．org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3A_Ｒ2/Step4/Q3A_Ｒ2__Guideline．pdf．3EGA．EGApositionpaperonthedefinitionofactivesubstancestartingmaterialsinactivesubstancemasterfilesASMFsandCEPapplicationsEB/OL．2010－122013－12－05．http//198．170．119．137/doc/ega-20101207-pos-pap-starting-ChineseJournalofNewDrugs201423910032014239materials-rev00-FINAL．pdf．4EMA．GuidelineonthechemistryofnewactivesubstancesEB/OL．2013－12－062003－12－17．http//．ema．europa．eu/ema/pages/includes/document/open_document．jspwebContentId=WC500002815．5FDA．Guidanceforindustrydrugsubstancechemistrymanufac-turingandcontrolsinformationdraftguidancewithdrawnEB/OL．2004－01－082013－12－06．http//．regulations．gov/#documentDetailD=FDA-2003-D-0243-0003．6FDA．GuidelineforsubmittingsupportingdocumentationindrugapplicationsforthemanufactureofdrugsubstancesEB/OL．1987－02－012013－12－05．http//．fda．gov/downloads/Drugs/GuidanceComplianceＲegulatoryInformation/Guidances/UCM070632．pdf．7HELGAMCHＲISO．TheactivepharmaceuticalingredientsstartingmaterialAPISMandothermaterialsinAPImanufac-turescientifically-basedprinciplesforthecommontechnicaldos-sierJ．DrugInformJ199933755－761．8ICH．HarmonizedtripartiteguidelineQ11developmentandman-ufactureofdrugsubstanceschemicalentitiesandbiotechnologi-cal/biologicalentitiesEB/OL．2012－05－012013－12－05．http//．ich．org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q11/Q11_Step_4．pdf．9．EB/OL．2005－03－182013－12－10．http//．sfda．gov．cn/directory/web/WS01/ima-ges/u6Ｒp9KpzuUrcHP0qnWxrG4us294bm5yLfWpNHQvr+1xLy-8yvXWuLW81K3U8i5wZGY=．pdf．10ＲOBEＲTHSWILLIAMFK．ＲegulatoryStrategyforStartingMaterialDesignationJ/OL．http//．pharmoutsourcing．com/Featured-Articles/37689-Ｒegulatory-Strategy-for-Starting-Material-Designation/．11GＲAHAMTＲOBEＲTJTLINDAB．DrugsubstancestartingmaterialselectionJ．PharmTechnol2008321252－57．12EDQM．Toptendeficienciesfoundafterfirstassessmentofnewapplicationsin2011EB/OL．2012－062013－12－05．https//．edqm．eu/site/paphcep_12_15pdf-en-30964-2．html．13BAＲBAＲAS．FDAperspectivesdesignationofregulatorystart-ingmaterialsinthemanufacturingofdrugsubstancesimpactonANDAreviewtimeJ．PharmTechnol201236163－66．14FDA．GuidanceforindustrychangestoanapprovedNDAorAN-DAEB/OL．2004－04－012013－12－05．http//．fda．gov/downloads/Drugs/GuidanceComplianceＲegulatory-Information/Guidances/UCM077097．pdf．15FDA．Guidanceforindustr