CTD制剂部分学习之——骨架篇

CTD格式申报资料提交要求（药学部分：制剂——骨架篇）目录内容CCTD(China)CTD(ICH)3.2.P.1剂型及产品组成DescriptionandCompositionoftheDrugProduct(name,dosageform)3.2.P.2产品开发PharmaceuticalDevelopment3.2.P.2.1处方组成ComponentsoftheDrugProduct3.2.P.2.1.1原料药DrugSubstance3.2.P.2.1.2辅料Excipients3.2.P.2.2制剂DrugProduct3.2.P.2.2.1处方开发过程FormulationDevelopment3.2.P.2.2.2制剂相关特性Overages3.2.P.2.2.3PhysicochemicalandBiologicalProperties3.2.P.2.3生产工艺开发ManufacturingProcessDevelopment3.2.P.2.4包装材料容器ContainerClosureSystem3.2.P.2.5相容性Microbiologicalattributes3.2.P.2.6Compatibility3.2.P.3生产Manufacture3.2.P.3.1生产商Manufacturer(s)3.2.P.3.2批处方BatchFormula3.2.P.3.3生产工艺和工艺控制DescriptionofManufacturingProcessandProcessControls3.2.P.3.4关键步骤和中间体的控制ControlsofCriticalStepsandIntermediates3.2.P.3.5工艺验证和评价ProcessValidationand/orEvaluation3.2.P.4辅料控制ControlofExcipients3.2.P.4.1Specifications3.2.P.4.2Analyticalprocedures3.2.P.4.3Validationofanalyticalprocedures3.2.P.4.4Justificationofspecifications3.2.P.4.5Excipientsofhumanoranimalorigin3.2.P.4.6Novelexcipients(reftoA3)3.2.P.5制剂控制ControlofDrugProduct3.2.P.5.1质量标准Specifications3.2.P.5.2分析方法Analyticalprocedures3.2.P.5.3分析方法验证Validationofanalyticalprocedures3.2.P.5.4批检验报告Justificationofspecifications3.2.P.5.5杂质分析CharacterisationofImpurities3.2.P.5.6质量标准依据JustificationofSpecification(s)3.2.P.6对照品ReferenceStandardsorMaterials3.2.P.7Containerclosuresystem3.2.P.8稳定性Stability3.2.P.8.1稳定性总结StabilitySummaryandConclusion3.2.P.8.2上市后稳定性研究方案和承诺Post-approvalStabilityProtocolandStability3.2.P.8.3稳定性数据StabilityData个人定义CTD：ICH的要求，英文水平所限，仅罗列上，没有核对。CCTD：中国式CTD，主要来自CDE发布的讨论稿模板，和重庆培训的相关内容。申报资料正文及撰写要求3.2.P.1剂型及产品组成CTDAdescriptionofthedrugproductanditscompositionshouldbeprovided.Theinformationprovidedshouldinclude,forexample:Description1ofthedosageform;Composition,i.e.,listofallcomponentsofthedosageform,andtheiramountonaper-unitbasis(includingoverages,ifany)thefunctionofthecomponents,andareferencetotheirqualitystandards(e.g.,compendialmonographsormanufacturer’sspecifications)Descriptionofaccompanyingreconstitutiondiluent(s);andTypeofcontainerandclosureusedforthedosageformandaccompanyingreconstitutiondiluent,ifapplicable.ReferenceICHGuidelines:Q6AandQ6BCCTD：(1)说明具体的剂型，并以表格的方式列出单位剂量产品的处方组成，列明各成份在处方中的作用，执行的标准。如有过量加入的情况需给予说明。对于处方中用到但最终需去除的溶剂也应列出。1Foradrugproductsuppliedwithreconstitutiondiluent(s),theinformationonthediluent(s)shouldbeprovidedinaseparatepart“P”,asappropriate成份用量过量加入作用执行标准工艺中使用到并最终去除的溶剂(2)如附带专用溶剂，参照以上表格方式列出专用溶剂的处方。(3)说明产品所使用的包装材料及容器。举例：3.2.P.2产品开发CTD：ThePharmaceuticalDevelopmentsectionshouldcontaininformationonthedevelopmentstudiesconductedtoestablishthatthedosageform,theformulation,manufacturingprocess,containerclosuresystem,microbiologicalattributesandusageinstructionsareappropriateforthepurposespecifiedintheapplication.Thestudiesdescribedherearedistinguishedfromroutinecontroltestsconductedaccordingtospecifications.Additionally,thissectionshouldidentifyanddescribetheformulationandprocessattributes(criticalparameters)thatcaninfluencebatchreproducibility,productperformanceanddrugproductquality.SupportivedataandresultsfromspecificstudiesorpublishedliteraturecanbeincludedwithinorattachedtothePharmaceuticalDevelopmentsection.Additionalsupportivedatacanbereferencedtotherelevantnonclinicalorclinicalsectionsoftheapplication.ReferenceICHGuidelines:Q6AandQ6BCCTD提供相关的研究资料或文献资料来论证剂型、处方组成、生产工艺、包装材料选择和确定的合理性，具体为：应包含为了确定剂型、处方、生产工艺、直接接触药品的包装容器而开展的研究工作；应确定并描述可影响批次可重复性、产品性能和药品质量的处方和工艺特性（关键参数）；特定研究或已发表文献的支持性数据和结果可列入此章节内或附于此章节；其他支持性数据可参考申报资料相关非临床或临床章节。3.2.P.2.1处方组成3.2.P.2.1.1原料药CTD：Thecompatibilityofthedrugsubstancewithexcipientslistedin3.2.P.1shouldbediscussed.Additionally,keyphysicochemicalcharacteristics(e.g.,watercontent,solubility,particlesizedistribution,polymorphicorsolidstateform)ofthedrugsubstancethatcaninfluencetheperformanceofthedrugproductshouldbediscussed.Forcombinationproducts,thecompatibilityofdrugsubstanceswitheachothershouldbediscussed.CCTD：参照《化学药物制剂研究的技术指导原则》，提供资料说明原料药和辅料的相容性，根据药物稳定性、拟考察的制备工艺，选择可靠的分析方法，有针对性的进行研究。复方制剂还要说明两种成分的相容性，根据药物特性，剂型特点选择工艺制备方法，如混合制粒还是分开制粒。分析与制剂生产及制剂性能相关的原料药的关键理化特性晶型溶解性：不同pH、不同溶剂；结合渗透性了解药物的生物药剂学分类（BCS）吸湿性粒度分布粒度与制剂工艺、溶出或释放行为、生物利用度，进行批汇总分析。尤其是难溶性药物。3.2.P.2.1.2辅料CTD：Thechoiceofexcipientslistedin3.2.P.1,theirconcentration,theircharacteristicsthatcaninfluencethedrugproductperformanceshouldbediscussedrelativetotheirrespectivefunctions.CCTD：说明辅料种类和用量选择的依据，分析辅料用量是否在常规用量范围内，是否适合所用的给药途径，并结合辅料在处方中的作用分析辅料的哪些性质会影响制剂特性。辅料选择：符合药用要求，注射剂辅料应符合注射用要求；不应与主药发生不良相互作用；根据制剂需要选择必要的辅料。3.2.P.2.2制剂研究3.2.P.2.2.1处方开发过程CTD：Abriefsummarydescribingthedevelopmentofthedrugproductshouldbeprovided,takingintoconsiderationtheproposedrouteofadministrationandusage.Thedifferencesbetweenclinicalformulationsandtheformulation(i.e.composition)describedin3.2.P.1shouldbediscussed.Resultsfromcomparativeinvitrostudies(e.g.,dissolution)orcomparativeinvivostudies(e.g.,bioequivalence)shouldbediscussedwhenappropriate.CCTD：参照《化学药物制剂研究的技术指导原则》，提供处方的研究开发过程和确定依据，包括文献信息（如对照药品的处方信息）、研究信息（包括处方设计，处方筛选和优化、处方确定等研究内容）以及与对照药品的质量特性对比研究结果（需说明对照药品的来源、批次和有效期，自研样品批次，对比项目、采用方法），并重点说明在药品开发阶段中处方组