美国与药品标准相关的法律

USP:QualityStandardsforMedicinesUSP:药品质量标准,操洪欣CRM,USP-China,美国与药品标准相关的法律,USDrugLaw,FederalFood,Drug,andCosmeticAct(FFDCA)联邦食品药品化妆品法Basictextthatgovernsallpharmaceutical,medicaldevice,food,cosmetics,dietarysupplements管理药品、医疗器械、食品、化妆品和膳食补充剂的基本法律Includesrequirementsforapprovaltomarketadrug包括对药品上市批准的要求PortionsrelevanttoUSPalsoapplytobiologics涉及USP的部分同样适用于生物制品FDAregulationsFDA的法规DevelopedbyFDAunderauthoritygrantedbyFFDCA在FFDCA法律框架下由FDA建立FDAguidanceFDA指南Non-binding,butindicatesFDAsthinking非法规，但体现FDA的考虑,RecognitionofUSPinFFDCADocumentaryStandards,Section501(b):Adrugisadulterated“ifitpurportstobeorisrepresentedasadrugthenameofwhichisrecognizedinanofficialcompendium,anditsstrengthdiffersfrom,oritsqualityorpurityfallsbelow,thestandardsetforthinsuchcompendium.Suchdeterminationastostrength,quality,orpurityshallbemadeinaccordancewiththetestsormethodsofassaysetforthinsuchcompendium”以下情况判为假药“其声称为药典收录的药品名称，而其效力不同于、或其质量或纯度低于药典中所设定的标准。对效力、质量或纯度的判断应当根据药典中所设定的分析方法或测试而得到”Section501(a)(2)(B):AdrugisadulteratedifitisnotmanufacturedinaccordancewithcurrentGoodManufacturingPractices(cGMPs)若药品未按照cGMP规范生产视为假药cGMPregulationsrequiretestingofeachbatchoffinisheddrugproducttoensurethatitmeetsdefinedspecifications.cGMP法规要求最终产品每批检测，以保证产品符合既定的标准Section201(j):Theterm“officialcompendium”meanstheofficialUnitedStatesPharmacopeia.NationalFormulary,oranysupplement.”术语“officialcompendium”意思是法定美国药典国家处方集及其增补本,FFDCARequirementsforConformancetoUSPDocumentaryStandards,Ultimately,theproductmustconformtothecompendialstandard.最终，制剂产品必须符合药典标准。USP-NFmethodmustbeusedifthecompanyhascommittedtoFDAtouseit,orifitistheonlyappropriatetest以下情况必须使用USP-NF方法：如果生产商向FDA承诺使用，或者USP-NF的方法是唯一恰当的方法Inothercases,manufacturerscanuseanalternativetestmethodifitis:其他情况下生产商可以使用替代方法，如果（替代方法）：Atleastasstringentasthecompendialmethodand至少和药典方法一样严格，并且“Scientificallysound.”“科学合理.”ManufacturermustassureconformancetoUSPstandard“bysuitablemeans,includingadequatemanufacturingprocessvalidationandcontrol.”生产商必须“通过恰当的方式，包括充分的生产工艺验证和控制”保证符合USP标准。FDAwillalwaysusethecompendialmethodasthe“refereetest.”USPis“regulatoryanalyticalprocedure”FDA总是使用药典方法作为“仲裁方法”。USP是“法定分析方法”ORA,CPGSec.420.400PerformanceofTestsforCompendialRequirementsonCompendialProducts(CPG7132.05),FFDCA2000drugproductmonographs;360excipientmonographs,Example:PioglitazoneMonographinUSP34举例：吡格列酮各论,收录于USP34,USP标准建立流程,ScientificLiaisonperformstechnicalreviewanddraftsthemonograph(2-3months)科学联络人进行技术审核，草拟各论,Monographisreceived/developmentinitiated收到各论，启动流程,Monographispublishedforpublicreviewandcomment(3months)发布各论供公众评议,ScientificLiaisonsubmitsallcommentstoExpertCommittee科学联络人向专家委员会提交评议,ExpertCommitteeballots(1-2months)专家委员会投票,Monographispublishedinofficialpublication(USP-NF,FCC,etc)(3months)各论正式发布,Approved,Notapproved,StandardsAcquisition标准收集,WeidentifysponsorsthatcanproposemonographsandreferencematerialstoUSPfordevelopmentintostandards确定可以提供分析方法和样品的发起方，与USP合作开发制定标准Sponsorsarepharmaceutical,food,anddietarysupplementindustries,manufacturers,government,academia发起方可以是药品，食品，膳食补充剂生产企业，也可以是政府或科研机构Collaboratewiththesponsorstogettherightinformationtestmethods,validations,etc.requiredforstandarddevelopment与发起方合作获得标准开发所必需的信息，包括测试方法，验证数据等,WhereAretheMonographsComingFrom标准从何而来,USPwouldliketoworkwithmoremanufacturersfromChinaUSP希望与更多中国生产商合作建立标准,Example:PioglitazoneMonographinPF36（1）举例：吡格列酮各论,收录于PF36（1）,ReferenceStandardDevelopment标准品开发,Materialistestedandcharacterizedthroughcollaborativetestinginvolvingaminimumofthreelabsindustry,FDA,andUSP(3months)物料在至少3个实验室进行联合标定-企业，FDA和USP,Bulkmaterialisobtainedfromindustry从企业获取原料,DatafromthecollaborativestudyarereviewedbyUSPstaffscientists(1week)USP科学人员审核联合标定数据,CompilationofcollaborativestudyisreviewedandballotedbyUSPscientificteams(3weeks)USP科学小组审核联合标定汇总数据并投票,Onceapproved,materialsubdivided,labeled&QC(1-2months)批准后，分装、贴标及QC程序,USPExpertCommitteesreviewforsuitabilityforuseinUSPdocumentarystandards(2weeks)USP专家委员会审核标准品的适用性,SubmitaReferenceStandard提交标准品,USPreleasesabout360newlotsofofficialReferenceStandardsyearlyUSP每年正式发行约360个新批次的标准品Halfarebrandnewtoourcatalog,andhalfarereplacementlotsforexistingstandards其中半数为新加入的标准品，另有一半为现有标准品的更新批次USPappreciatesyoursupportonRScandidatesUSP欢迎国内企业提供标准品候选样品,BenefitsofParticipation参与对于企业的利益,DirectimpactinsettingtheUSPspecificationsforthedonatedmaterial/monograph通过提供样品和方法直接影响USP规格的制定Competitiveadvantage,becauseyourstandardisusedandenforcedbyregulatoryauthorities竞争优势，因为您的标准是官方标准并被强制执行PublicrecognitionbyUSPthroughitsDonorRecognitionProgram通过USP质量标准合作方认可（表彰）计划获得公众认可Enhancedcorporatecitizenshipimage有助于提高企业形象Copiesofthemulti-laboratorycollaborativetestingresultswithtraceabilitytoyourreferencestandard提供给企业标准品标定的多实验室联合标定结果和可追溯性说明,DonorRecognitionProgramUSP质量标准合作方认可计划,Freeworkshopregistrations专题学术讨论会免费注册FreeprintsubscriptiontoeitherUSP-NF,FCCorDSC免费印刷版USP-NF,FCC或DSCFreeon-siteUSPPharmacopeiaEducationcourse免费现场药典培训Oneyear,multipleuserlicenseofelectronicUSP-NF一年多用户电子版USP-NFUSPReferenceStandards免费USP标准品RecognitionontheUSPWebSiteUSP官方网站致谢RecognitionintheUSP-NFUSP-NF出版物致谢USPAnnualScienceMeetingRecognitionUSP年度科学大会致谢,ProvideRSCandidatestoUSP提供标准品给USP,DonorswillreceiveUSPssummarydatapackageandatraceabilitystatementafterlotrelease在批次放行之后，样品提供者会收到由USP颁发的样品联合检测数据汇总报告和可追溯性说明TraceabilityprovideslinkbetweenUSPstandardandin-housestandard可追溯性说明为生产厂家提供了USP标准和生产厂家内部标准之间的相关性,USPCertificateUSP证书,USPAppreciatesYourContributionUSP感谢您为公众健康的贡献,EvonikRexim(Nanning)Pharmaceutical南宁赢创美诗药业,陕西汉江制药,技源科技（中国）有限公司,StatusofRosidlitazoneMonograph罗格列酮标准开发状态,USP已经收到罗格列酮标准提案USP已经收到罗格列酮有关标准品物料的捐赠罗格列酮罗格列酮有关物质A富马酸马来酸计划在2011年公布提案,做好准备参与标准评价？,Identificationtests:鉴别测试Itispreferredtoincludetwoorthogonaltests(IRabsorptionandHPLCretentiontimecomparison)首选方法包括两个正交试验（红外光谱和液相色谱保留时间的比较）TLCproceduresandUV-visibleabsorptiontestsaremaynotalwaysbeorthogonaltoHPLCprocedures薄层色谱和紫外可见吸收法不一定是高效液相色谱法的正交试验Colorimetricandwetchemicaltestsarenotpreferredsincetheseofteninvolvehazardousreagentsorlackspecificity比色法和湿法测试并非首选，因为这些方法往往涉及到危险试剂或缺乏专属性,CurrentTrends标准发展趋势,TheinclusionoftestsforOrganicImpuritiesaddsvaluetomonographs有机杂质测试方法的收录将有助于提高各论的价值OrganicImpuritiesproceduresshouldbequantitative,selectiveandstability-indicating有机杂质测试方法应当是定量的，有选择性的，并且是具有稳定性指示的HPLCproceduresforOrganicImpuritiesarepreferredoverTLCorspectrophotometrictests有机杂质的高效液相色谱方法优于薄层色谱或光度法,CurrentTrends标准发展趋势,MonographModernization各论现代化,EffortsareinprocesstomodernizeUSPmonographswherenecessaryUSP正在努力实现各论的现代化Thefollowingchangesaretargeted:目标是完成如下的变化Replace*TLCprocedureswithHPLCprocedures用HPLC方法替代TLC方法Addtestsfororganicimpuritieswherethesearenotavailable目前没有有机杂质测试方法的地方需要增加该内容Replace*packedcolumnGCprocedureswithcapillaryGCprocedures用GC毛细管方法替代GC填充柱方法Replace*titrimetricprocedureswithHPLCprocedures用HPLC方法替代滴定法*Note:Needtodemonstratethatthenewprocedureis“equivalenttoorbetterthan”theexistingprocedure,USPGeneralChaptersGuide,USPGeneralChapters,OfficialArticles,GeneralApplicable,NoncomplexActiveDrugSubstances,Biotechnology-derivedDrugSubstances,Excipients,Noncom