Example QbD MR Tablet Module 3 Quality 3.2.P.2 Pharmaceutical Development
实例QbD MR 片剂 模块3 质量3.2.P.2 药物开发

2011 年11 月 1Quality by Design for ANDAs: ANDAs的质量源于设计:
An Example forModified Release Dosage Forms 缓释制剂的实例
Introduction to the Example 实例简介

This is an example pharmaceutical development report illustrating how ANDA applicants can
move toward implementation of Quality by Design (QbD).
The purpose of the example is to illustrate the types of pharmaceutical development studies
ANDA applicants may use as they implement QbD in their development process and to promote
discussion on how OGD would use this information in review.

Although we have tried to make the example as realistic as possible, the development of a real
product may differ from this example. The example is for illustrative purposes and, depending on
applicants’ experience and knowledge, the degree of experimentation for a particular product may
vary. The impact of experience and knowledge should be thoroughly explained in the submission.
The risk assessment process is one avenue for this explanation. At many places in this example
alternative pharmaceutical development approaches would also be appropriate.


Notes to the reader are included in italics throughout the text. Questions and comments may be
sent to GenericDrugs@fda.hhs.gov
整篇文章的斜体内容为致读者的内容。如有任何问题和意见, 请发送至

Table of Contents 目录表

1.1 Executive Summary/概述
1.2 Analysis of the Reference Listed Drug Product/分析参考列表药品
1.2.1 Clinica/l临床
1.2.2 Pharmacokinetics/药动学
1.2.3 Drug Release/药物释放
1.2.4 Physicochemical Characterization/理化性质
1.2.5 Composition/成分
1.3 Quality Target Product Profile for the ANDA Product/ANDA药品的目标药品质量概述
1.4 Dissolution Method Development and Bioequivalence Studies
1.4.1 Development of a Predictive Dissolution Method/溶出预测方法开发
1.4.3 Pivotal Bioequivalence Study/关键生物等效性研究
2.1 Components of Drug Product/制剂成分
2.1.1 Drug Substance/原料药 Physical Properties/物理性质 Chemical Properties/化学性质 Biological Properties/生物学性质 Risk Assessment of Drug Substance Attributes/原料药属性风险评估
2.1.2 Excipients/辅料 Excipients in the IR Granules/IR颗粒中的辅料 Excipients in the ER Coated Beads/ ER包衣微丸中的辅料 Excipients in Example MR Tablets, 10 mg/实例10 mg MR片剂中的辅料
2.2 Drug Product/制剂
2.2.1 Formulation Development/处方开发 Initial Risk Assessment of the Formulation Components/处方成分的初始风险评估 IR Granule Formulation Development./IR颗粒处方开发 ER Bead Formulation Development/ER微丸处方开发 Prototype Tablet Formulation Development./原型片剂处方开发 Prototype Tablet Formulations and Trial BE Studies/原型片剂处方和试验性BE研究 Updated Risk Assessment of the Formulation Components/更新的处方成分风险评估
2.2.2 Overages/过量投料
2.2.3 Physicochemical and Biological Properties/理化和生物学性质
2.3 Manufacturing Process Development/生产工艺开发
2.3.1 Initial Risk Assessment of the Drug Product Manufacturing Process
2.3.2 IR Granule Process Development/IR颗粒工艺开发
2.3.3 ER Bead Process Development/ER微丸工艺开发 Drug Layering Process Development/层积上药工艺开发 ER Polymer Coating Process Development/ER聚合物包衣工艺开发

Drug Layering and Polymer Coating
ER层积上药微丸和聚合物包衣的放大 Scale-up of Blending and Compression/混合和压制的放大
2.3.8 Updated Risk Assessment of the Drug Product Manufacturing Process
2.4 Container Closure System/容器密封系统
2.5 Microbiological Attributes/微生物属性
2.6 Compatibility/相容性
2.7 Control Strategy/控制策略
2.7.1 Control Strategy for IR Granules/IR颗粒的控制策略
2.7.2 Control Strategy for ER Coated Beads/ER包衣微丸的控制策略
2.7.3 Control Strategy for Example MR Tablets, 10 mg/实例10 mg MR片剂的控制策略
2.7.4 Product Lifecycle Management and Continual Improvement
A.1 Appendix I/附录I

List of Abbreviations 缩略语表

ANDA: Abbreviated New Drug Application 简明新药申请
ANOVA: Analysis of Variance 方差分析
AUC: Area Under the Curve 曲线下面积
AV: Acceptance Value 合格判断值
BE: Bioequivalence 生物等效性
BU: Blend Uniformity 混合均匀度
CCF: Central Composite Face-centered 中心复合表面
CFR: Code of Federal Regulations 美国联邦法规
CMA: Critical Material Attribute 关键物质属性
Cmax: Concentration Maximum 最大浓度
CPP: Critical Process Parameter 关键工艺参数
CQA: Critical Quality Attribute 关键质量属性
CU: Content Uniformity 含量均匀度
df: degrees of freedom 自由度
DOE: Design of Experiments
DS: Drug Substance 实验设计
ER: Extended Release 延迟释放
f2: Similarity factor 相似因子

HPC: Hydroxypropyl Cellulose 羟丙基纤维素
HPMC: Hydroxypropyl Methylcellulose 羟丙甲纤维素
ICH: International Conference on Harmonization 国际协调会议
IR: Immediate Release 速释
IVIVC: In Vitro-In Vivo Correlation 体内外相关性
IVIVR: In Vitro-In Vivo Relationship 体内外相关性
LOD: Loss on Drying 干燥失重
MCC: Microcrystalline Cellulose 微晶纤维素
MFT: Minimum Film-forming Temperature 最低成膜温度
MR: Modified Release 缓释
NIR: Near-infrared 近红外
No.: Number 数字
Nrev: Number of revolutions 转速
PEG: Polyethylene Glycol 聚乙二醇
PG: Propylene Glycol 丙二醇
PSD: Particle Size Distribution 粒度分布
PVAc: Polyvinyl Acetate 聚乙酸乙烯酯
PVP: Polyvinylpyrrolidone, Povidone 聚乙烯吡咯烷酮,聚维酮
QTPP: Quality Target Product Profile 目标药品的质量概况
R2: Coefficient of Determination 决定系数
RLD: Reference Listed Drug 参考目录药品
RSD: Relative Standard Deviation 相对标准偏差
RT: Room Temperature 室温
SLS: Sodium Lauryl Sulfate 十二烷基硫酸钠
SSG: Sodium Starch Glycolate 羧甲基淀粉钠
TEC: Triethyl Citrate 柠檬酸三乙酯
Tmax: Time for achieving Maximum Plasma Concentration 血药浓度达峰时间
TPI: Terahertz Pulse Imaging 太赫兹脉冲反射成像技术
XRPD: X-Ray Powder Diffraction X 射线粉末衍射


有机化合物的波谱解析(第七版)药明康德 译