关于化学药品注册批量问题的探讨_王宏亮

ChineseJournalofNewDrugs2016,25(18)204620162518。[e-mail]。。[e-mail]。··1211000382450001。“”、、、。Ｒ95C1003－3734201618－2046－06DiscussionontheissuesofbatchsizeforregistrationofchemicaldrugWANGHong-liang1CHENZhen21CenterforDrugEvaluationChinaFoodandDrugAdministrationBeijing100038China2SchoolofPharmaceuticalSciencesZhengzhouUniversityZhengzhou450001ChinaAbstractFortheregistrationofchemicaldrugbatchsizeandscale-uparethekeyconcernsofCMCreview．Inthisarticleweanalyzedthedefinitionof“batch”comparedthedomesticrequirementsforbatchsizeduringprocessdevelopmentwiththeforeignsummarizedtherequirementsforbatchsizeofthosebatchesusedinvalidationofanalyticalproceduresstabilitynon-clinicalandclinicalstudiesandputforwardsomesuggestionstofurtherimprovetherelevantdomesticmanagementandtechnicalrequirementsforbatchsize．Keywordsdrugsubstancedrugproductbatchsizetechnicalrequirementsguideline、1－2。。、、、。1－4。5－7。。。1“”ICH“batchlot”“、”8“”“batchsize”。“100kg”100kg“500L”“10”5mL500L10。“”、、、、。《》ChineseJournalofNewDrugs2016,25(18)204720162518、、、、、7。“”。1。11．1“”、3“”、9。labscalebatch。pilotscalebatchICH“1/1010”10。productionbatch10。。2550100。、scale-upbatch。1．2“”“”、、。clinicalbatchbiobatch、11。processvalida-tionbatch。commercialbatch。“primarybatch”“primarystabilitybatch”10《》“”12。《》“”6－7“”“”“”FDA“exhibitbatch”13－15、、“primarybatch”。。、“”、。“”“”“”。16。“”“”7。ChineseJournalofNewDrugs2016,25(18)2048201625182。NDAANDA。2．1ICH1－3。WHOWHO17。FDA14－1518－20。exhibitbatch。FDA。FDA、、、。FDA、。。1。1FDA123FDA、EMA91618－21。22－25。2．22005“”26－27。。。2008《》“”“、、”“”5。。2010CTD“”、“”6、。《》1、2、35．1ChineseJournalofNewDrugs2016,25(18)20492016251845．2“”。“”1/107。3、、、。3．1“”、、。“”“3”“”28。ICHFDAEMA“”“”、、、。、、、、。、。。、。/、NDAANDA29。3．2ICH3231012。45．27。FDA2310%25%30。WHO2、2500050000/17。712pilotscaleICH。ICH1/10100000“1/10”10。。3．3。。。。ChineseJournalofNewDrugs2016,25(18)2050201625183．4、Ⅲ。、31。。、1－3。。Ⅲ32－33。1/101034－35。4。、。、。“”。①“”。②、、“”。③、、、。1ICH．HarmonisedTripartiteGuidelineQ8Ｒ2PharmaceuticaldevelopmentEB/OL．2009－08－012016－05－11．http//．ich．org/fileadmin/Public_Web_Site/ICH_Prod-ucts/Guidelines/Quality/Q8_Ｒ1/Step4/Q8_Ｒ2_Guideline．pdf．2ICH．HarmonisedTripartiteGuidelineQ11Developmentandmanufactureofdrugsubstanceschemicalentitiesandbiotechno-logical/biologicalentitiesEB/OL．2012－05－012016－05－11．http//．ich．org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q11/Q11_Step_4．pdf．3ICH．HarmonisedTripartiteGuidelineM4QＲ1ThecommontechnicaldocumentfortheregistrationofpharmaceuticalshumanusequalityEB/OL．2002－09－122016－05－11．http//．ich．org/fileadmin/Public_Web_Site/ICH_Prod-ucts/CTD/M4_Ｒ1_Quality/M4Q__Ｒ1_．pdf．4FDA．ManualofpoliciesandproceduresChemistryＲeviewofQuestion-basedＲeviewQbＲSubmissionsEB/OL．2014－11－182016－04－17．http//．fda．gov/downloads/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/manualofpoliciesprocedures/ucm423752．pdf．5．EB/OL．2008－06－032016－04－21．http//．sda．gov．cn/WS01/CL0844/30470．html．6．CTDEB/OL．2010－09－252016－04－21．ht-tp//．sda．gov．cn/WS01/CL0844/54391．html．7．EB/OL．2016－05－042016－05－04．http//．sda．gov．cn/WS01/CL0087/151985．html．8ICH．HarmonisedTripartiteGuidelineQ7GoodmanufacturingChineseJournalofNewDrugs2016,25(18)205120162518practiceguideforactivepharmaceuticalingredientsEB/OL．2000－10－102016－04－15．http//．ich．org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q7/Step4/Q7_Guideline．pdf．9EMA．NoteforguidanceonprocessvalidationEB/OL．2001－03－012016－04－15．http//．ema．europa．eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002913．pdf．10ICH．HarmonisedTripartiteGuidelineQ1AＲ2Stabilitytes-tingofnewdrugsubstancesandproductsEB/OL．2003－02－062016－04－15．http//．ich．org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q1A_Ｒ2/Step4/Q1A_Ｒ2__Guideline．pdf．11EMA．GuidelineonqualityoforalmodifiedreleaseproductsEB/OL．2014－03－202016－04－21．http//119．90．25．46/．ema．europa．eu/docs/en_GB/document_librar-y/Scientific_guideline/2014/07/WC500170465．pdf．12．EB/OL．2015－02－052016－04－21．http//．sda．gov．cn/WS01/CL1616/114289．html．13FDA．GuidanceforIndustryPowderBlendsandFinishedDos-ageUnits—StratifiedIn-ProcessDosageUnitSamplingandAssess-mentDraftguidanceEB/OL．2003－10－012016－04－21．http//．fda．gov/ohrms/dockets/98fr/03d-0493-gdl0001．pdf．14FDA．QualitybyDesignforANDAsAnExampleforModifiedＲeleaseDosageFormsEB/OL．2011－12－012016－04－21．http//．fda．gov/downloads/Drugs/Developmen-tApprovalProcess/HowDrugsareDevelopedandApproved/Approv-alApplications/AbbreviatedNewDrugApplicationANDAGenerics/UCM286595．pdf．15FDA．QualitybyDesignforANDAsAnExampleforImmediate-ＲeleaseDosageFormsEB/OL．2012－04－012016－04－21．http//．fda．gov/downloads/Drugs/Developmen-tApprovalProcess/HowDrugsareDevelopedandApproved/Approv-alApplications/AbbreviatedNewDrugApplicationANDAGenerics/UCM304305．pdf．16EMA．Guidelineonprocessvalidationforfinishedproducts-infor-mationanddatatobeprovidedinregulatorysubmissionsEB/OL．2014－02－272016－04－21．http//．ema．europa．eu/docs/en_GB/document_library/Scientific_guideline/2014/02/WC500162136．pdf．17WHO．Guidelinesonsubmiss