固体制剂仿制药研发流程

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
① Components in the formulation 处方成份
② BE information 生物等效性信息
Hale Waihona Puke Baidu
② Establish acceptance criteria for
和相关杂质参考标准（美国药典或其他来源）
API and excipients and
③ API characterization and qualification, including chemical and physical properties
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
同批次对照药物的评估
① Potency/purity 效价 /纯度
② Impurity profile (related substances)
③ 杂质分布曲线图（相关物质）
④ Content uniformity 含量均匀度
⑤ Weight variation 重量差异
⑥ Dissolution profile 溶出曲线
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） ④ 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
analytical methods 这些分析方法的 验证和确认。 ④ Preparation of pre-formulation study report or summary from CGMP perspective 从现行 GMP 的 角度，准备处方前研究报告或概括 总结
4
Formulation Development
③ Etc. 其它
CGMP Compliance to Meet
Regulatory Requirements 满足法规要求的 CGMP 规范
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
处方开发 ① Formulation selection (components and composition) based on RLD formulation and
1） Properly document study results and preparation of DP formulation development report or summary to
⑦ Disintegration time 崩解时间
⑧ 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
corresponding analytical methods 建立可接受的原料药及辅料标准和
studies, such as solubility, density, particle
相应的分析方法
size distribution, polymorphism (any attributes
③ Validation or verification of these
(Develop adequate analytical methods for API)
料药和辅料供应商的资格认证，包
针对原料药发展合适的分析方法
括审计和对三种不同批次进行的全
② Acquiring API and related impurity reference
面测试。
standards (USP or other sources) 获得原料药
3
Pre-formulation Studies
① Qualification of API and excipients
处方前研究
suppliers, including auditing and
① Analytical method development 分析方法发展
full testing on three different lots 原
in-house study. 处方筛选（组成成份）以对照 药物配方和室内研究为基础） ② Define initial process (platform) for preparation of prototype generic drug product