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Description and Composition of the Drug Product (name, dosage form)
3.2.P.2 产品开发Pharmaceutical Development
3.2.P.2.1 处⽅组成Components of the Drug Product
长城历史3.2.P.2.1.1 原料药Drug Substance
3.2.P.2.1.2 辅料Excipients
3.2.P.2.2 制剂Drug Product
3.2.P.2.2.1 处⽅开发过程Formulation Development
3.2.P.2.2.2 制剂相关特性Overages
3.2.P.2.2.3 Physicochemical and Biological Properties
3.2.P.2.3 ⽣产⼯艺开发Manufacturing Process Development
3.2.P.2.4 包装材料容器Container Closure System
3.2.P.2.5 相容性Microbiological attributes
3.2.P.2.6 Compatibility
3.2.P.3 ⽣产Manufacture
3.2.P.3.1 ⽣产商Manufacturer(s)
3.2.P.3.2 批处⽅Batch Formula
3.2.P.3.3 ⽣产⼯艺和⼯艺控制Description of Manufacturing Process and Process Controls
3.2.P.3.4 关键步骤和中间体的
控制
Controls of Critical Steps and Intermediates
3.2.P.3.5 ⼯艺验证和评价Process Validation and/or Evaluation 3.2.P.4 辅料控制Control of Excipients
3.2.P.
4.1 Specifications
3.2.P.
4.2 Analytical procedures
3.2.P.
4.3 Validation of analytical procedures
3.2.P.
4.4 Justification of specifications
3.2.P.
4.5 Excipients of human or animal origin
3.2.P.
4.6 Novel excipients(ref to A 3)
3.2.P.5 制剂控制Control of Drug Product
3.2.P.5.1 质量标准Specifications
3.2.P.5.2 分析⽅法Analytical procedures
3.2.P.5.3 分析⽅法验证Validation of analytical procedures
3.2.P.5.4 批检验报告Justification of specifications
3.2.P.5.5 杂质分析Characterisation of Impurities
3.2.P.5.6 质量标准依据Justification of Specification(s)
3.2.P.6 对照品Reference Standards or Materials 3.2.P.7 Container closure system
3.2.P.8 稳定性Stability
3.2.P.8.1 稳定性总结Stability Summary and Conclusion
3.2.P.8.2 上市后稳定性研究⽅
案和承诺
Post-approval Stability Protocol and
阳光课堂
Stability
3.2.P.8.3 稳定性数据Stability Data
个⼈定义
CTD：ICH的要求，英⽂⽔平所限，仅罗列上，没有核对。
把你锁在床上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
CTD
A description of the drug product and its composition should be provided. The information provided should include, for example:
Description1of the dosage form;
Composition, i.e., list of all components of the dosage form, and their amount on a per-unit basis (including overages, if any) the function of the components, and a reference to their quality standards (e.g., compendial monographs or manufacturer’s specification s)
Description of accompanying reconstitution diluent(s); and
Type of container and closure ud for the dosage form and accompanying reconstitution diluent, if applicable. Reference ICH Guidelines: Q6A and Q6B
CCTD：
(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。
1For a drug product supplied with reconstitution diluent(s), the information on the diluent(s) should be provided in a parate part “P”, as appropriate
(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：
The Pharmaceutical Development ction should contain information on the development studies co
nducted to establish that the dosage form, the formulation, manufacturing process, container closure system, microbiological attributes and usage instructions are appropriate for the purpo specified in the application. The studies described here are distinguished from routine control tests conducted according to specifications. Additionally, this ction should identify and describe the formulation and process attributes (critical parameters) that can influence batch reproducibility, product performance and drug product quality. Supportive data and results from specific studies or published literature can be included within or attached to the Pharmaceutical Development ction. Additional supportive data can be referenced to the relevant nonclinical or clinical ctions of the application.
Reference ICH Guidelines: Q6A and Q6B
CCTD
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：
子道The compatibility of the drug substance with excipients listed in 3.2.P.1 should be discusd. Additionally, key physicochemical characteristics (e.g., water content, solubility, particle size distribution, polymorphic or solid state form) of the drug substance that can influence the performance of the drug product should be discusd.
For combination products, the compatibility of drug substances with each other should be discusd.
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
南梁精神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：
The choice of excipients listed in 3.2.P.1, their concentration, their characteristics that can influence the drug product performance should be discusd relative to their respective functions. 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：
A brief summary describing the development of the drug product should be provided, taking into consideration the propod route of administration and usage. The differences between clinical formulations and the formulation (i.e. composition) described in 3.2.P.1 should be discusd. Results
from comparative in vitro studies (e.g., dissolution) or comparative in vivo studies (e.g., bioequivalence) should be discusd when appropriate.
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成的主要变更、原因以及⽀持变化的验证研究。
如⽣产中存在过量投料的问题，应说明并分析过量投料的必要性和合理性，并提供⽀持性资料，如重复批次验证，数据验证。
关注点：
处⽅设计思路及预期达到⽬标
处⽅筛选、优化及处⽅确定，与对照药品进⾏质量对⽐研究：基于前期对药物、辅料考察有针对性设计，系统设计各种处⽅进⾏筛选研究；进⾏制剂基本性能评价和稳定性评价（考察影响质量和稳定性
的关键项⽬，关注制剂的个性化指标考察）；确定影响制剂质量的关键因素。
处⽅筛选可以是实验室⼩规模，但要注意⼩试、中试放⼤、处⽅转移研究开发阶段的处⽅变化情况，重点讨论临床试验⽤处⽅和3.2.P.1中处⽅之间的差异，进⾏⽀持变化的验证研究。
3.2.P.2.2.2 overages
CTD:
Any overages in the formulation(s) described in 3.2.P.1 should be justified.
3.2.P.2.2.3 制剂相关特性
CTD ：
Parameters relevant to the performance of the drug product, such as pH, ionic strength, dissolution, redispersion, reconstitution, particle size distribution, aggregation, polymorphism, rheological properties, biological activity or potency, and/or immunological activity, should be addresd. CCTD
对与制剂性能相关的理化性质，如pH，离⼦强度，溶出度，再分散性，复溶、粒径分布、聚合、多晶型、流变学等进⾏分析。
提供⾃研产品与对照药品在处⽅开发过程中进⾏的质量特性对⽐研究结果，例如有关物质等。
红豆莲子汤
炒黄豆如为⼝服固体制剂，需提供详细的⾃研产品与对照药品在不同溶出条件下的溶出曲线⽐较研究结果，推荐采⽤f2相似因⼦的⽐较⽅式。
3.2.P.2.3 ⽣产⼯艺的开发
CTD：
The lection and optimisation of the manufacturing process described in 3.2.P.3.3, in particular its critical aspects, should be explained. Where relevant, the method of sterilisation should be explained and justified.
Differences between the manufacturing process(es) ud to produce pivotal clinical batches and the process described in 3.2.P.3.3 that can influence the performance of the product should be discusd.
CCTD：
简述⽣产⼯艺的选择和优化过程，⽣产⼯艺的选择优化，特别是⽣产过程的关键⽅⾯：结合剂型特点、药物及辅料的理化性质、拟达到的质量指标设计和选择⼯艺，如遇湿热不稳定，⼯艺应避免⽔分、热的影响；制剂⼯艺设计和选择应充分考虑⼯业化放⼤⽣产的可⾏性；注意考察⼯艺各环节对产品质量的影响，确定制备⼯艺关键环节，建⽴相应质控参数。
重点描述⼯艺研究的主要变更（包括批量、设备、⼯艺参数等的变化）及相关的⽀持性验证研究：技术转移、产地转移；设备变更、参数变化。
汇总研发过程中代表性批次（应包括但不限于临床研究批、中试放⼤批、⽣产现场检查批、⼯艺验证批等）的样品情况，包括：批号、⽣产时间及地点、批规模、⽤途（如⽤于稳定性试验，⽤于⽣物等效性试验等）、分析结果（例如有关物质、溶出度以及其他主要质量指标）。
举例
批分析汇总
3.2.P.2.4 包装材料/容器
CTD
The suitability of the container closure system (described in 3.2.P.7) ud for the storage, transportation (shipping) and u of the drug product should be discusd. This discussion should consider, e.g., choice of materials, protection from moisture and light, compatibility of the materials of construction with the dosage form (including sorption to container and leaching) safety of materials of construction, and performance (such as reproducibility of the do delivery from the device when prented as part of the drug product).
CCTD：
（1）、包材类型、来源及相关证明⽂件，提供包材的检验报告（可来⾃包材⽣产商或供应商）：
大米发糕配方
注1：关于包材类型，需写明结构材料、规格等。
例如，五层共挤膜输液袋，规格为内层：改性⼄烯/丙烯聚合物，第⼆层：聚⼄烯，第三层：聚⼄烯，第四层：⼄烯甲基丙烯酸酯聚合物，第五层：多酯共聚物；聚丙烯输液瓶，规格为250ml；
铝塑泡罩包装，组成为：3.2.PVC/铝、3.2.PVC/3.2.PE/3.2.PVDC/铝、3.2.PVC/3.2.PVDC/铝；
复合膜袋包装，组成为：聚酯/铝/聚⼄烯复合膜袋、聚酯/低密度聚⼄烯复合膜袋。
注2：表中的配件⼀栏应包括所有使⽤的直接接触药品的包材配件。如：塑料输液容器⽤组合盖、塑料输液容器⽤接⼝等。
（2）阐述包材的选择依据
（3）描述针对所选⽤包材进⾏的⽀持性研究
