化学方法：GC, HPLC, GC-MS, GC-MS-MS, LC-MS, LC-MS-MS 免疫学方法 微生物学方法
动物用药品
BA， BE和PK研究 只适用于血样和尿样
绪言
分析方法验证的定义和种类
定义
生物样品分析方法验证是一个有计划系统性收集验证 资料的综合过程，以确保某一特定分析方法可靠，重 现性好，适用于其所指定的生物样品定量分析。
机构和人员
58.29 Personnel
(a)―Each individual engaged in the conduct of or responsible for the supervision of a nonclinical laboratory study shall have education, training, and experience, or combination thereof, to enable that individual to perform the assigned functions.‖
(b)―Each testing facility shall maintain a current summary of training and experience and job description for each individual engaged in or supervising the conduct of a nonclinical laboratory study.‖
The bioanalytical method for human BA, BE, PK, and drug interaction studies must meet the criteria in 21 CFR 320.29.
绪言
GLP/GCP/GMP
绪言: 美国《联邦法规典集》
（Code of Federal Regulations，CFR）
生物样品分析方法验证 工业指南的解读
杨永胜 博士
声明：本讲座只代表个人意见， 不代表官方立场。
6/22/2011
1
Guidance for Industry
Bioanalytical Method Validation
U.S. Department of Health and Human Services Food and Drug Administration
机构和人员
58.33 Study Director
―For each nonclinical laboratory study, a scientist or other professional of appropriate education, training, and experience, or combination thereof, shall be identified as the study director. The study director has overall responsibility for the technical conduct of the study, as well as for the interpretation, analysis, documentation, and reporting of results, and represents the single point of study control.‖
生物样本分析方法验证的主要参数与合格标准 选择性 线性范围 准确度 精密度 提取回收率 稳定性
报告的主要内容
小结
6/22/2011
3
绪言
指南覆盖的范畴
人用药品
试验用新药申请 (INDs), 新药上市申请(NDAs)以及仿制药上市申请 (ANDAs)的BA/BE研究
临床前安全评价的PK/TK研究 生物样品：全血、血浆、血清、尿样及皮肤和其他组织 分析方法
绪言
分析方法验证的种类—交叉验证
Comparison validation parameters of two bioanalytical methods Two or more bioanalytical methods for the same study or across
different studies : an original validated bioanalytical method and the revised bioanalytical method. Sample from a single study, but analysis at more than one site or more than one laboratory, cross-validation with spiked matrix standards and subject samples should be conducted at each site or laboratory to establish inter laboratory reliability. Data generated using different analytical techniques (e.g., LC-MSMS vs. ELISA) in different studies are included in a regulatory submission. All modifications should be assessed to determine the recommended degree of validation.
绪言
药品非临床研究质量管理规范 (GLP)
The analytical laboratory conducting pharmacology/toxicology and other preclinical studies for regulatory submissions should adhere to FDA Good Laboratory Practices (GLPs) (21 CFR 58).
机构和人员
58.35 Quality Assurance Unit
―A testing facility shall have a quality assurance unit which shall be responsible for monitoring each study to assure management that the facilities, equipment, personnel, methods, practices, records, and controls are in conformance with the regulations in this part. For any given study, the quality assurance unit shall be entirely separate from and independent of the personnel engaged in the direction and conduct of that study.‖
美国《联邦规章典集》第21篇“食品与药品” （Title 21―Food and Drugs） 9卷（Volume） 3章（Chapter） 1499部（Parts)
其中：第1―8卷第1章第1―1299部，为健康与 人类服务部食品与药品管理局（DHHS/FDA） 的规章
GLPs (21 CFR 58)
设施
58.41 General
―Each testing facility shall be of suitable size and construction to facilitate the proper conduct of nonclinical laboratory studies. It shall be designed so that there is a degree of separation that will prevent any function or activity from having an adverse effect on the study.‖
assay for quantification
绪言
分析方法验证的种类—部分验证
Partial validations are modifications of already validated bioanalytical methods.
Bioanalytical method transfers between laboratories or analysts Change in analytical methodology (e.g., change in detection systems) Change in anticoagulant in harvesting biological fluid Change in matrix within species (e.g., human plasma to human urine) Change in sample processing procedures Change in species within matrix (e.g., rat plasma to mouse plasma) Change in relevant concentration range Changes in instruments and/or software platforms Limited sample volume (e.g., pediatric study) Rare matrices Selectivity demonstration of an analyte in the presence of concomitant medications Selectivity demonstration of an analyte in the presence of specific metabolites