-固体制剂仿制药研发流程.doc

Generic Drug Product Development Stages 仿制药发展阶段 (Oral Solid Dosage Forms, Tablets) （口服固体制剂，片剂） Stage Chemistry, Manufacturing Controls in Oral Solid Dosage Form Development 口服固体制剂发展中的化学特性，生产和控制 CGMP Compliance to Meet Regulatory Requirements 满足法规要求的CGMP规范 1 Drug Packaging Insert Study to obtain basic information about RLD, such as 通过对对照药物的包材以内成分的分析，获取有关该对照药物的基本信息 Components in the formulation处方成份 BE information生物等效性信息 Etc.其它 2 Reverse Engineering Study, including evaluation of three different lots of RLD for: 根据前述研究采用倒推法研究制剂工艺，包括对叁批不同批次对照药物的评估 Potency/purity 效价/纯度 Impurity profile (related substances) 杂质分布曲线图（相关物质） Content uniformity 含量均匀度 Weight variation 重量差异 Dissolution profile 溶出曲线 Disintegration time 崩解时间 Hardness and Friability 硬度和脆碎度 System based CGMP auditing on manufacturing facility: ① Quality System ② Materials System ③ Facilities and Equipment System ④ Production System ⑤ Packaging and Labeling System ⑥ Laboratory Control System 对生产设施进行基于系统的CGMP审计 ① 质量系统 ② 物料系统 ③ 设施设备系统 ④ 生产系统 ⑤ 包装和标签系统 ⑥ 实验室控制系统 3 Pre-formulation Studies 处方前研究 Analytical method development分析方法发展 (Develop adequate analytical methods for API) 针对原料药发展合适的分析方法 Acquiring API and related impurity reference standards (USP or other sources)获得原料药和相关杂质参考标准（美国药典或其他来源） API characterization and qualification, including chemical and physical properties studies, such as solubility, density, particle size distribution, polymorphism (any attributes relevant to the formulation) 原料药的特性和认证，包括理化特征研究，如：溶出度，密度，颗粒粒径分布，多态现象（任何与处方相关的属性） Excipients specifications (acceptance criteria and testing methods to meet USP/NF standards), and excipients characterization and qualification, including compatibility studies with API. 辅料的技术规范（符合USP和NF标准的可接受标准和测试方法）辅料特性认证，包括与原料药的相容性研究 Qualification of API and excipients suppliers, including auditing and full testing on three different lots原料药和辅料供应商的资格认证，包括审计和对三种不同批次进行的全面测试。 Establish acceptance criteria for API and excipients and corresponding