中美两国药典药品分析方法和方法验证

如何保障企业通过FDA常规年检并与
世界接轨
2012 Trends in 2012年GMP符合性

GMP Compliance: 的趋势：
With a focus on 专注于药品，而不是

pharmaceuticals rather than
medical devices to serve as 医疗设备，为中小型
a useful reference and 企业（SMB）的制药
management guide for the
Small and Medium Business
业在新兴市场作为一
(SMB) pharmaceutical sector 个有用的参考和管理
in emerging markets. 指南。
1
世界接轨
What Are Trends In GMP GMP认证的发展趋势是什么？
Compliance?
一个趋势被定义为方向或运动三年或以上
A trend is defined as direction or
的与高概率增加。在制药行业自2006年以
movement over 3 or more years with high
probability for increasing. The trends with 来的最大的潜在影响的趋势，优先顺序是：
the greatest potential impact in the
pharmaceutical sector since 2006 in
priority order are: 1 越来越多的检查
1. Increasing Number of Inspections 2 越来越多的警告信
2. Increasing Number of Warning
Letters 3 提高执法处罚
3. Increasing Enforcement Penalties 4 增加监管机构之间的协调
4. Increasing Harmonization between 5 越来越多地使用科技
Regulatory Agencies
6 越来越多地使用主题专家
5. Increasing Use of Science and
Technology
6. Increasing Use of Subject Matter
Experts
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世界接轨
Why identify GMP 为什么要识别GMP认证的趋势？
Compliance Trends?
Knowledge of GMP Compliance Trends can be GMP合规性趋势的知识可以用在制
useful in the pharmaceutical sector to guide 药业中，以指导日常工作，领导和管
daily work, lead and manage operational control,
and to develop and execute strategic planning. 理的操作控制，并制定和执行战略规
划。
GMP trends are applicable to:
 Construction and commissioning of a
major pharmaceutical manufacturing site GMP的趋势是适用于：
 Start-up and operation of an active
 建设和调试的主要药品生产基地
pharmaceutical ingredient complex
 Validation of a state-of-the-art steriles  启动和操作活性药物的复合体
manufacturing complex  验证一个最先进的无菌制造复合体
 Training and development of employees  从各个层次，学科药品的研究，开发，
and project teams from all levels and
制造，销售和销售员工和项目团队的
disciplines in pharmaceutical research,
development, manufacturing , marketing, 培训和发展
and sales
3
世界接轨
How to Identify and Use 如何识别和使用GMP合规性趋
GMP Compliance Trends 势
Go to the websites of pharmaceutical regulators, 药品监管机构，医药期刊和出版商，

pharmaceutical periodicals and publishers,
pharmaceutical associations and conferences, 医药协会和会议，医药顾问，药品
pharmaceutical consultants, pharmaceutical 供应商，制药承包商，和企业的制
vendors, pharmaceutical contractors, and 药公司的网站。
corporate pharmaceutical companies .
GMP知识的合规性的趋势，以帮助：
Used knowledge of the GMP Compliance
Trends to aid in: strategic planning and 战略规划和业务控制，财务规划，
operational control, financial planning, employee 员工招聘和发展，发展的政策和程
recruitment and development, development of 序，发展的绩效管理系统和文件，
policies and procedures, development of
performance management systems and 开发，执行，和评估内部和外部审
documents, and development, execution, and 计。
evaluation of internal and external audits.
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世界接轨
Increasing Number of 越来越多的检查--趋势 1
Inspections-Trend 1
GMP符合性认证驱动力是2012年的
The driver of the GMP Compliance 2012 trends.
 Be prepared for the GMP inspection. 趋势。
 Know your primary regulatory agency and  为GMP检查做好准备。
GMP inspection process  了解你的主要监管机构和GMP检查过程
 Be prepared by ensuring GMP compliance  虽然你的质量体系做好了准备，确保GMP
though-out your quality system. 达标。
 Communicate successful inspections are a  在检查中成功的沟通是重要要求。
requirement.
Why the increase in the number of inspections?
 the industry history (globally) of non- 为什么要增加检查的次数？
compliance to GMPs  行业历史（全球）不遵守GMPs 规则
 In the United States there are nearly two  在美国，仅在5年前才有近200更多检查人
hundred more inspectors than just 5 years 员。
ago.
 美国国会以回应公民的压力以强化行业规
 The U.S. Congress has responded to citizen
定，支持扩大监管部门的监督和联邦资金
pressure for stronger regulations of the
需求，增加检查
industry by supporting expansion of regulatory
oversight and the federal funding
requirements for increased inspections.
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世界接轨
How to Insure a 如何确保一个成功的检
Successful Inspection 验
Build an Integrated Quality System 建立完整的质量体系
Embrace the GMP Quality Systems

Approach 接纳GMP质量体系的方式
Prove the GMP Capability and 证明GMP的能力和控制周期

Control Cycle
应用GMP的过程分析技术
Apply GMP Process Analytical
Technology
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世界接轨
Increasing Number of 越来越多的警告信-趋势 2
Warning Letters-Trend 2
当FDA发现制造商已明显违反
When FDA finds that a manufacturer has FDA规定，FDA会通知制造商。
significantly violated FDA regulations, FDA
notifies the manufacturer. This notification is 这往往是在警告信的形式通知。
often in the form of a Warning Letter. The 警告信标识的违规行为，如恶
Warning Letter identifies the violation, such as 劣的生产实践，产品说明不对
poor manufacturing practices, problems with
claims for what a product can do, or incorrect 或误导使用。信中还明确指出，
directions for use. The letter also makes clear 该公司必须解决的问题，并提
that the company must correct the problem and 供了方向和时间表，公司要告
provides directions and a timeframe for the
company to inform FDA of its plans for 知FDA校正的计划。 FDA然后
correction. FDA then checks to ensure that the 检查，以确保该公司的修正是
company’s corrections are adequate.” 足够的。“
http://www.fda.gov/downloads/ICECI/EnforcementActions/U
CM285781.pdf
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世界接轨
Increasing Enforcement 提高执法处罚-趋势3
Penalties-Trend 3
Administrative actions include product
recalls, debarment of individuals or
行政行为包括产品召回，被
companies who have been convicted of 取消资格的个人或公司，已
felonies, withdrawals of product 被定罪重罪，产品撤回，许
approvals, license revocations, and 可的撤销，取消资格的临床
disqualification of clinical investigators.
研究。
Increasing Enforcement Penalties
Judicial actions include seizures of
violative products, injunctions, criminal 提高执法处罚
prosecutions, and certain civil money
penalties.
司法行动，包括抓住违规的
http://www.fda.gov/AboutFDA/Transparency/Transparency 产品，强制令，刑事检察工
Initiative/ucm254426.htm
作，和某些民事罚款。
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世界接轨
Increasing Harmonization 增加监管机构之间的协调-
between Regulatory 趋势4
Agencies-Trend 4
The International Conference on Harmonisation 国际协调会议（ICH），药品检查
(ICH), the Pharmaceutical Inspection
Convention and the Pharmaceutical Inspection 公约“和药品检查合作计划（PIC
Co-operation Scheme (PIC/S), and the World / S），世界卫生组织的全球性组
Health Organization are global organizations 织，促进全球GMP监管机构之间
promoting global harmonization between GMP
regulatory agencies. 的协调。
FDA Commissioner Margaret Hamburg supports FDA专员玛格丽特汉堡支持并谈统

and speaks about harmonization of global
regulatory agencies. Follow this link to view her
一的全球监管机构。请点击此链接
comments on harmonization and world health on 查看她的意见，在YouTube上的
YouTube: 统一和世界卫生：
http://www.youtube.com/watch?v=BZ9GL9oNBXI&fe
ature=related
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世界接轨
Increasing use of Science 越来越多地使用科学和技术发
and Technology-Trend 5 展-趋势5
The use of the internet by the pharmaceutical 使用互联网的制药行业的GMP监管机构

sector and the GMP regulators is a visible,
是的一个可见的，有声的和提醒意义的
vocal, and ever present reminder of advancing
science and technology. Vendors to the 推动科学和技术。卖方制药行业，越来
pharmaceutical sector, consultants, customers, 越多地使用科学和技术顾问，客户和员
and employees using social media hardware
and software to share information, knowledge, 工使用社交媒体的硬件和软件，共享信
and opinions are a dramatic demonstration of 息，知识和意见，是一个很好的示范。
the increasing use of science and technology.
Follow this link to hear FDA Commissioner 请点击此链接，听取FDA专员玛格丽特

Margaret Hamburg speak on the FDA's 汉堡发言FDA的科学和技术越来越多地
increasing use of science and technology. 使用。
http://www.youtube.com/watch?v=JAh-
kc0yxTY&feature=related
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世界接轨
Increasing use of Subject 增加使用主题专家-趋势 6
Matter Experts-Trend 6
The increasing number of former regulators now serving 现在越来越多的前监管机构工作人员作为医药
as consultants to the pharmaceutical industry is
increasing. The drain on intellectual capital at the FDA
行业的顾问。在FDA的智力资本的消耗已经增
has been increasing for many years. Many inspectors exit 加了很多年。许多督察退出FDA完成后，检查
FDA just after completing the inspector learning curve to 人员的学习曲线，成为行业顾问。这将创建的
become industry consultants. This creates as great a 用于制药行业的问题，因为它的FDA。 FDA
problem for the pharmaceutical sector as it does for the 失去智力资本和产业的双重使命的检查组。新
FDA. The FDA loses intellectual capital and the industry
is inspected by an inspection team on a dual mission. 视察员的积极性都很高，以保护公众健康和建
New inspectors are highly motivated by missionary zeal to 立GMP，检查员有使命般的热情。新视察员
protect the public health and to establish GMP inspector 是很聪明的，受过良好所需的学科教育，专业
credentials. New inspectors are intelligent, well educated 培训，在检查过程中，无论在技术上和行为，
in required disciplines, expertly trained on the inspection 都专注于保护消费者和进行详细的记录为质量
process both technically and behaviorally, and focused on
protecting the consumer by conducting and documenting
体系检查。
detailed quality systems inspections.
监管机构和制药行业学科专家作为科技进步的
The regulators and the pharmaceutical sector have an 需求日益增加。 “我们必须确保FDA的主题
increasing need for subject matter experts as science and 专家，我们需要为我们的重要决策，”11日
technology advance. “We have to be sure that FDA has 的FDA专员玛格丽特汉堡，告诉我们。通过以
subject-matter experts that we need for our important
decision making,”11 Margaret Hamburg, Commissioner of
下链接，了解更多关于FDA的科学的优先领域
the FDA tells us. Follow these links to learn more about 主题专家使用：
the FDA's use of Subject Matter Experts in Scientific
Priority Areas:
http://www.genengnews.com/keywordsandtools/print/3/26290/
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世界接轨
CGMP CGMP
Current Good Manufacturing Practices 现行良好生产规范是制药和生物技术
followed by the pharmaceutical and biotech
firms to ensure that the products produced
公司工作原则，以确保所生产的产品
meet specific requirements for identity, 符合特定的产物，强度，质量和纯度
strength, quality, and purity. 要求。
CGMP regulations: Laws which can incur
criminal penalties when they are CGMP规定：法律会招致刑事处罚的
not followed; for example:
时候都没有，例如：
21 CFR Part 210 - Current Good
Manufacturing Practice in Manufacturing, 21 CFR第210第部一分 -现行良好生
Processing, Packing, Or Holding Of Drugs; 产规范生产，加工，包装或保持药;
General Part 总则
21 CFR Part 211 - Current Good
Manufacturing Practice for Finished
21 CFR第211部分 -成品制药现行良
Pharmaceuticals 好生产规范
21 CFR Part 600 - Biological Products: 21 CFR 第600 - 生物制品, 通则
General
21 CFR第11部分 - 电子记录，电子
21 CFR Part 11 - Electronic Records;
Electronic Signatures
签名
12
世界接轨
Documents usually contain 文件通常包含了更多的细节GMP
much more detail—GMP
GMPs for Bulk Drugs: Q7A Good 原料药：Q7A优良制造规范指南活性药物
Manufacturing Practice Guidance for Active 成分的绿化总纲图
Pharmaceutical Ingredients
Stability Testing: Q1A(R) Stability Testing 稳定性测试：Q1A（R）新药物质和产品
of New Drug Substances and Products
的稳定性测试
Validation of Analytical Procedures
 Q2A Text on Validation of Analytical  分析方法的验证
Procedures
 Q2A分析方法验证上的文字
 Bioanalytical Method Validation
 生物分析方法验证
 Analytical Procedures and Methods
Validation  分析方法和方法验证
 Process Validation  工艺验证
 Monoclonal Antibody Products  单克隆抗体产品
 Validation Of Cleaning process  清洗过程验证
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如何保障企业通过FDA常规年检并与世界接轨
21CFR600-BIOLOGICAL PRODUCTS: 21CFR600生物制品：总则
GENERAL 分部A – 通则介绍
Subpart A--General Provisions  分段 600.2邮寄地址
 Sec. 600.2 Mailing addresses
 分段 600.3定义
 Sec. 600.3 Definitions
http://www.fda.gov/cder/biologics/default.htm
http://www.fda.gov/cder/biologics/default.htm
Subpart B—Establishment Standards
部分B-建立标准
 Sec. 600.10 Personnel.  分段 600.10人员
 Sec. 600.11 Physical establishment, equipment,  分段 600.11物理的建立，设备，动物，和
animals, and care. 照顾。
 Sec. 600.12 Records.  分段 600.12纪录。
 Sec. 600.13 Retention samples.  分段 600.13保留样品。
 Sec. 600.14 Reporting of biological product
 分段 600.14生物制品偏差的特许生产商的
deviations by licensed manufacturers.
报告。
 Sec. 600.15 Temperatures during shipment.
 Sec. 600.20 Inspectors.  分段600.15在运输过程中的温度。
 Sec. 600.21 Time of inspection  分段600.20督察。
 Sec. 600.22 Duties of inspector  分段600.21时间的检验
Subpart D--Reporting of Adverse Experiences  分段600.22督察的职责
 Sec. 600.80 Postmarketing reporting of adverse 分部D - 性不良反应的报告
experiences
 Sec. 600.81 Distribution reports  分段 600.80上市后的不良反应报告
 Sec. 600.90 Waivers 分段 600.81分发“报告
分段 600.90豁免
http://www.fda.gov/cber/pubinquire.htm
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世界接轨
WHO-TRS No. 822 Annex1: WHO TRS第822号附件1：
Good Manufacturing Practice for 生物制品生产的质量管理规范
Biological Products
The regulatory procedures necessary to 要控制生物制品的监管程序，这在很
control biological products are in large 大程度上取决于产品和制造方法的来
part determined by sources of products 源。
and methods of manufacture.
The scope of these guideline include:
这些指导方针的范围包括：
 Growth of strains of microorganisms &
eukaryotic cells  株微生物和真核细胞的生长的
 Extraction of substances from biological  提取的物质来自于生物组织，包括人
tissues, including human, animal and plant 类，动物和植物组织（过敏原）
tissues (allergens)
 Recombinant DNA (rDNA) techniques
 重组DNA（rDNA ）技术
 Hybridoma techniques  杂交瘤技术
 Propagation of microorganisms in  微生物的繁殖，胚胎或动物
embryos or animals
TRS: Technical Report Series rDNA：Recombinant DNA 15

世界接轨
Contents in WHO-TRS No. 在WHO-TRS 822号内容，附
822, Annex 1 件1
(1). Scope of these guideline （1）这些指导原则的适用范围
(2). Principles
（2）原则
（3）人员
(3). Personnel
（4）物业及设备
(4). Premises and equipment
（5）动物宿舍及护理
(5). Animal quarters and care
（6）生产
(6). Production （7）标签
(7). Labeling （8）批次处理记录（协议）和
(8). Lot processing record (protocol) 销售记录
and distribution records （9）质量保证和质量控制
(9). Quality assurance and quality
control
16
ROBERT T DEAN 05/24/2012
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18
19
20
21
22
23
24
Type of Analytical 分析实验室类型

Laboratories
 内部设施：
Internal Facilities:
R&D or other labs within the R＆D或其他实验室内制
manufacturing company that 造公司执行所有内部分析
perform all internal analyses
 对外设施：
External Facilities:
Contract laboratories that perform 合同实验室, 为客户进行分析
analyses for customers
学术/政府实验室除了执行其
Academic/Government laboratories 资助的研究项目分析
that perform analyses in addition to
their sponsored research projects
25
Continued
FDA cGMP Compliance in FDA的cGMP符合性
an Analytical Laboratory
分析实验室
 Organization/Personnel
 组织/个人
 Facilities
 设施
 Equipment
 仪器/设备
 Laboratory control- Build  实验室控制--建设质量到运

Quality into Operations 营中
 Laboratory record and  实验室记录和文件存档

documentation
26
Continued
FDA cGMP Compliance in an FDA的cGMP符合性分析实

Analytical Laboratory 验室
Organization/Personnel 组织/个人
 Can differ by functional  不同职能部门会不同
department
 Excipients/ Raw Materials  辅料/原材料
 Finished Product/Stability
 成品/稳定性
 APIs
 Specific Techniques  原料药
 Supervisor /Analyst Ratio
 具体技术
 Independent Peer Review  监管领班/分析员比率
 Quality Unit/Operational
Employee Ratio  独立的同行审查
 质量部门/操作人员比率
27
Continued
FDA cGMP Compliance in FDA的cGMP符合性分析实验室

培训模块
Training Modules
 Technique Based  基于技术的
 Core Modules  基于核心模块
 Electives Based on Job
Duties  基于对工作职责的选修培训
 Proficiency Assessments
 计能水平评估
Method Specific Modules
 Technique Department 具体的方法模块
Methods
 Client Required  技术部方法
 客户端需要
28
Continued
FDA cGMP Compliance in an FDA的cGMP符合性分析实验室

Analytical Laboratory
建筑及设施
Building and Facilities
 安全
 Security
 Controlled/Limited Access  控制/限制接近
 Employee/Visitor Identification  雇员/访客身分识别
 Disaster Recovery Plan
 Disaster recovery team with  灾难恢复计划
predefined plan for: Electrical
failures, Fire, HVAC failures,  灾难恢复小组的预定计划与电气故障，
Computer Failures, Injury, 消防，空调故障，电脑故障，损伤，
HAZ/MAT spills 危险物料泄漏
 Water Systems
 USP/EP Grade Water Supply  水系统
 Tested/ Monitored weekly
 USP / EP级供水
 测试/每周监测
HVAC：Heating, ventilation and air-conditioning systems

HAZ/MAT：Hazardous Materials 29
Continued

Building and Facilities 建筑及设施

 Cleaning/Housekeeping
 Procedures and Controls in  清洁/管理
place  程序和控制措施到位
 Insect/Rodent Control  昆虫/灭鼠
 Routine and Ongoing  常规和持续监测
Monitoring
 应急电源
 Emergency Power
 短期：使用UPS用来关键
 Short Term-Example UPS 操作
used for Critical Operation
 长期-柴油/天然燃气发生
 Long term-Diesel/Natural Gas 器
generator
UPS：Uninterruptible Power Supply 30

Continued

建筑及设施
Building and Facilities
 Environmental monitoring for  微型实验室的环境监测
micro labs
 Temperature & humidity  温度和湿度控制/监测实验室和
control/monitoring of lab and 样品储存区
sample storage areas
 System capable of alerting on  能够游览警报系统
Excursions  系统必须提供即时的温度/湿度
 System must provide an 条件下的持续记录/跟踪
ongoing record/trace of
temperature/humidity
 变化控制--设施
conditions
 Change control-Facilities  查出变化对整体运作的影响
 Access impact of change on
overall operations
31
Continued

Equipment 设备
 Validation for new instruments/  验证新的仪器/设备
Equipment
 Validation plan  验证计划
 Vendor Evaluation  供应商评估
 User Functional Requirements  用户的功能需求
 IQ/OQ/PQ-Test plans and
 IQ / OQ/ PQ—测试计划和存档
Documentation
 验证摘要
 Validation Summary
 系统验收和质量保证审批
 System Acceptance and QA
Approval  系统维护：
重资格化，变化控制，标准操
 System Maintenance:
作程序
Re-qualification, Change
control, SOPs
32
Continued

Equipment 设备
 遗留系统的回顾性验证项
 Legacy System-Retrospective
Validation Project Plans
目计划
 Validation plan  验证计划

 Gather Historical Data to  收集历史数据，以支持过去
support past operation and to 的操作，并证明继续使用
justify continued use
 Validation summary
 验证摘要
 System acceptance and QA  系统验收和质量保证批准
approval  系统维护
 System maintenance
33
Continued
FDA cGMP Compliance in FDA的cGMP符合性分析实验室

设备
Equipment
 Instrument/Equipment
Calibration & Maintenance  仪器/设备校准和维护
 M&C program—Metrology  M＆C的程序--计量组
group
 Operation/Maintenance/
 操作/维护/校准/资格程序
Calibration/Qualification
procedures
 Intervals Established based  建立间隔基于使用，
on use, internal 内部需求和供应商的建议
requirements and vendor
recommendations
 Calibration traceable to  校准可溯源到国家标准局
national standards (NIST) （NIST）尽可能
whenever possible
 Detailed Documentation in  在M＆C记录本中详细的存档
M&C logbooks
34
Continued

设备
Equipment
有效的“标签”的系统
Effective “Tag Out” system  保证不使用非验证/没维修仪器
 Insure non-validated
/Maintained Instruments not  变化控制--设备
used
 Change Control- Equipment  接近验证的影响
 设备运行-PQ到IQ / PQ途径方
 Access validation impact 法
 Equipment moves- PQ to
IQ/PQ approach  退休计划，关闭了的PQ
 Retirement plans- Close out
PQ
35
Continued

Building Quality into Operations 建设质量到操作运营中

 Quality Policy  质量方针
 Based on overall business and  基于整体业务和管理理念，

Management philosophies, 使命和目标
mission and goals
 Detailed overview of quality
 质量体系的详细概述
systems
 Provides employees clear
guidance for production of  为员工提供明确的指导生产
analytical data 分析数据
36
Continued

建设质量到操作运营中
Building Quality into Operations  文件控制
 Document Control
 SOPs/ Methods/Specifications  容易获得SOPs/方法/规格
readily accessible
 Expiration of printed
 如果使用LIMS,印刷的SOP/方
SOPs/Methods/Specifications if
using LIMs 法/规格过期
 Contract lab specific
challenges: Additional  合同实验室的具体挑战：其他
instruction not included in 指令不包括在方法里;实验室需
method; lab needs mechanism 要捕捉到这一信息的机制
to capture this information
 Control of Samples  样品控制
 Assigned to controlled location
 Tracked by individual (Chain of  分配到控制位置
Custody)
 每人都可追查（监管链）
37
Continued
FDA cGMP Compliance in an FDA的cGMP符合性分

析实验室
Building Quality into Operations
建设质量到操作运营中
 Routine Quality Control Checks
 Key to building quality into  常规质量控制检查

operations
 Help to prevent need for

 质量建设到运营的关键
historical evaluation of data
 帮助防止数据的历史评价的
 Need to balance cost vs. 需要
benefit/risk
 要平衡成本与效益/风险
38
Continued
FDA cGMP Compliance in an FDA的cGMP符合性分

Analytical Laboratory 析实验室
Routine QC Checks 常规质量控制检查

 Balance qualification/daily checks
 平衡资格/日常检查
 Yearly service by vendor
 Bi-annual USP accurate weight
 每年由供应商服务
qualification  双年度USP准确的重量
 Daily S class weight check 资格
 FTIR Daily Quality Control Check  每天S级重量检测
 Daily scan of NIST traceable  红外每日质量控制检查
polystyrene
 pH meter and auto-pipettes
 每日扫描NIST可追踪的
聚苯乙烯
 Calibrated at each point of use
 pH计和自动移液器
 在每个使用点校准
NIST：National Institute of Standard and Technology 39

Continued

Routine QC Checks-Example 常规质量控制检查为例

 Chromatographic Analysis—
Beyond System Suitability  色谱分析—超出系统适用性
 Blanks-Filtered sample &  空白--过滤了样品和标准溶剂

standard solvents
 Check standards  检查标准
 Continuing system suitability
(every 6hrs)
 持续系统的适用性（每6小时）
 Impurity marker/ resolution
solutions: Injected every 24 hrs
for extended runs  杂质标记/解决方案：每24小时
 Dosage form weighted prior to 注入，延长运行
testing
 Ability to query data based on  测试前加权的剂型
instrument, column, method,
client and analyst.
 基于仪器，柱，方法，客户和
分析师有能力查询数据。
40
Continued

实验室记录/文档
Laboratory Records/ Documentation
 记录实验数据
 Recording laboratory data
 Establish standards for free form  为自由形式的文档建立标准
documentation
 Advantage of pre-formatted  预格式化的工作表有优势
worksheet
 Documentation error codes  文档中的错误代码
 Electronic records
 Audit trail and ability to lock down  电子记录
 Back-up
 Archival and restore  审计途径和锁定的能力
 备份
 归档和恢复查寻
41
Continued
实验室记录/文档
Laboratory Records/ Documentation
 明确定义在程序中的原始数据
 Clearly define raw data in
procedures
 第一个电子信号被数据采集系
统捕获
 First electronic signal captured by
the data acquisition system
 Printout from Karl Ficsher Titrator  从Karl Ficsher滴定的打印
 Sample weight documented in
analyst notebook  分析师笔记本记录样品重量
 Unused data– needs to be explained  未使用的数据--加以解释，并详细记

and documented in detail 录：
 失败的QC
 Failed QC
 Analyst Error
 分析师错误
42
Continued
Regulatory Compliance for Analytical Laboratories
43
Continued
How to pass FDA Inspection 如何通过FDA检查
Get Practical Inspection 得到实践检验的知识：

Knowledge:
 What inspectors are looking for  什么检查员要寻找
 Successful preparation and management  成功的准备和管理巡查过程

of inspections
 Typical compliance issues and proactive  典型的合规性问题，并积极遵守

compliance
 执行模拟检查
 Perform a Mock-inspection
 The psychology of inspection  心理检查
44
Continued
How to pass FDA Inspection/如何通过FDA检查
GMP Compliance: FDA CFR Regulations
21 CFR Parts 110, 111 - Food GMP

These cGMP regulations effects the food industry and complements the HACCP (Hazard
Analysis Critical Control Points) program. 21 CFR Part 110 deals largely with food
sanitation, food handling and food preparation issues.
21 CFR Part 111 effects the dietary supplement industry and deals with the manufacturing,
processing and holding of these substances. Although dietary supplements are regulated by
the FDA as foods, they are regulated differently from other foods and from drugs.
21 CFR Parts 210, 211, 212 - Drug Pharmaceutical GMP

These cGMP regulations effect the drug and pharmaceutical industry. CFR Part 210 deals
with the manufacturing, processing and holding of drugs. CFR Part 211 deals with finished
pharmaceuticals. 21 CFR Part 212 deals with radioactive drugs used in medical imaging
tests.
45
Continued
FDA Inspection Guides: FDA检查指南：

Pharmaceutical Quality Control Labs
(7/93) 药品质量控制实验室（7/93）
 The pharmaceutical quality control laboratory  药品质量控制实验室提供在药品生产和控

serves one of the most important functions in
pharmaceutical production and control. A 制的最重要职能之一。一个CGMP法规的
significant portion of the CGMP regulations (21 重要部分（21 CFR211）涉及到的质量控
CFR 211) pertain to the quality control laboratory
and product testing 制实验室和产品检测
FDA Inspection Objective:
FDA检查目的：
 As a minimum, each pharmaceutical quality control
laboratory should receive a comprehensive GMP
evaluation each two years as part of the statutory
inspection obligation.  作为最低要求，各药品质量控制实验室应
接受一个全面的GMP评估，每一两年法定
检验义务的一部分。
Inspections may include:
 the specific methodology which will be
used to test a new product 检查可能包括：
 a complete assessment of laboratory's
conformance with GMP's  具体的方法，将用于测试新产品
 a specific aspect of laboratory operations 符合GMP的一个实验室的一致性评估
具体方面的实验室操作
46
Continued

Typical cGMP Compliance Issues 典型的cGMP符合性问题
 质量体系
 Quality System
 Material System  教材体系
 Production System  生产系统
 Laboratory system  实验室系统
 Facility & equipment system  设施及设备系统
 Packing and labeling system
 包装和标签系统
Organization and Personnel/
Records and reports are checked in 检查会深入到检查每一个部门，个人
each system /记录与报告
FDA inspect system instead of
specific product to make sure firm is
working properly and producing safe FDA 检查不是检查个别产品而是要
medicine.
确认药厂操作适当，生产安全药品
47
Continued
Core Knowledge 核心知识

 GxPs  GxPs
 Orientation to GMP Compliance
 Biotechnology: An overview of  浏览GMP符合规则
Compliance Considerations  生物技术：遵守注意事项概述
 GMPs for API bulk Manufacturers  API批量制造厂遵守的GMPs
 GMP principles for SOPs  标准操作规程的GMP原则
 Principles of good documentation
 Electronic records and electronic  良好的文档的原则
signatures  电子记录和电子签名
 Key concepts of process validation  工艺验证的关键概念
 Change control  变更控制
 Awareness of FDA Inspections for
pharmaceutical Manufacturers  FDA的检查药品生产企业的意识
 Understanding Post-Approval  了解批准后变更
changes
48
Continued
FDA Inspection Preparation FDA检验的准备

FDA expects that complex, highly technical and
specialized testing equipment, procedures and FDA希望复杂的，高度的技术和专门的检
data manipulations, as well as scientific
laboratory operations will be evaluated by an 测设备，操作程序和数据处理，以及科学
experienced laboratory analyst with specialized 实验室操作将评估等事项的专门知识与经
knowledge in such matters. 验的实验室分析师。
FDA expects investigators, analysts and others
to work as teams and to advise management FDA希望调查员，分析员和其他人员一起
when additional expertise is required to 工作，并建议管理部门，当需要额外的专
complete a meaningful inspection. 业知识来完成一个有意义的检查。
FDA team members participating in a pre-
approval inspection must read and be familiar 参加在批准前检查FDA小组成员必须阅读
with Compliance Program 7346.832, Pre- 和熟悉GMP合规计划7346.832，前置审批
Approval Inspections/Investigations. 的检查/调查。
CDER may have issued deficiency letters listing
problems that the sponsor must correct prior to CDER可能已发出警告信，赞助商必须纠
the approval of NDA/ANDA's and supplements. 正之前批准NDA/ANDA和补充。视察组预
The inspection team is expected to review such 计在民政事务处审查这些文件，他们预计
letters on file at the district office, and they are
expected to ask the plant for access to such 将要求公司获得这些信件。该小组应评估
letters. The team should evaluate the replies to 这些信件的答复，以确保数据的准确和真
these letters to assure that the data are accurate
and authentic. 实的。
49
Continued
FDA Inspection Approach FDA检验方法

General Approach: 一般方法：
inspection of a laboratory requires the use of
observations of the laboratory in operation and 实验室检查需要观察实验室在操作和使用
of the raw laboratory data to evaluate 的原料实验室数据评估与CGMP的遵守，
compliance with CGMP's and to specifically
carry out the commitments in an application or 并专门开展在应用程序中的承诺或DMF。
DMF. When conducting a comprehensive 在进行全面检查的实验室，实验室操作的
inspection of a laboratory, all aspects of the 所有方面进行评估。
laboratory operations will be evaluated.
Laboratory records and logs represent a vital 实验室记录和操作记录代表信息的重要来
source of information that allows a complete 源，使工作人员和技术能力的整体质量控
overview of the technical ability of the staff and
of overall quality control procedures. SOPs 制程序得到一个完整的概述。标准操作程
should be complete and adequate and the 序应该是完整的和适当的，并应符合实验
operations of the laboratories should conform to 室操作的书面记录。
the written procedures. Specifications and
analytical procedures should be suitable 评估实验室的原始数据，实验程序和方法，
Evaluate raw laboratory data, laboratory 包括维护和校准实验室设备和分析方法验
procedures and methods, laboratory equipment
including maintenance and calibration, and 证数据，以确定在实验室操作的整体素质
methods validation data to determine the overall 和能力，符合CGMP法规。
quality of the laboratory operation and the ability
to comply with CGMP regulations. 要求看已无法满足规范和审查产品的分析
Ask to see results of analyses for lots of product 结果，审查复检，拒绝的批次分析，或返
that have failed to meet specifications and 工的分析。
review the analysis of lots that have been
retested, rejected, or reworked.
50
Continued
FDA Inspection Approach FDA检验方法
Pre-Approval 预先核准
Documents relating to the formulation of the
product, synthesis of the bulk drug substance, 审查有关文件的产品配方，大量原料药的
product specifications, analysis of the product, 合成，产品规格，产品的分析，以及其他
and others are examined during the review
process in headquarters. 项目。
Determine if the data submitted in an application 确定是否申请提交的数据是真实的和准确
are authentic and accurate and if the procedures
listed in the application were actually used to 的，是否申请实际上用来产生所包含的数
produce the data contained in the application. 据。
The inspection team must decide if there is valid 视察组必须确定是否有有效的和科学的理
and scientific justification for the failure to report
data which demonstrates the product failed to 由，不能报告数据，缺乏这些数据表明该
meet its predetermined specifications. 产品未能满足其预定规格。
Investigators and analysts may contact the
review chemist (with appropriate supervisory 有关规范和标准的问题出现时，调查员和
concurrence) when questions concerning 分析员可联络审评化学家适当的监督同意。
specifications and standards arise.
Inspections should compare the results of
analyses submitted with results of analysis of 检查应该比较可能已产生的其它批次的分
other batches that may have been produced. 析结果。分析师预计评估实验室测试批次
The analyst is expected to evaluate raw
laboratory data for tests performed on the test （生物和临床批次），进行测试的原始数
batches (biobatches and clinical batches) and to 据和应用程序中提交的数据与原始数据比
compare this raw data to the data filed in the 较。
application.
51
Continued
Inspections on Failures 检查故障（OOS）
(OOS) 结果
Results 评估该公司的系统研究实验室的测试
Evaluate the company's system to 失败
investigate laboratory test failures.
这是一个关键问题，在决定产品是否
It’s a key issue in deciding whether
可以发布或拒绝，并形成复检和重新
a product may be released or
rejected and form the basis for 取样。
retesting, and resampling. -- 实验室错误
-- laboratory error 分析师可以犯分析方法上的错误，使
analysts make mistakes in following the 用不正确的标准，和/或只是误判的
method of analysis, use incorrect 数据。
standards, and/or simply miscalculate the
data. Laboratory errors must be 必须鉴定实验室的错误，通过故障调
determined through a failure investigation 查，以确定不合格的原因。
to identify the cause of the OOS.
-- non-process related or operator
error -- 非过程相关或操作错误
-- process related or manufacturing -- 过程或相关制造过程中出现错误
process error
52
Continued
Inspections on Failures (OOS) 检查故障（OOS）

LABORATORY INVESTIGATIONS: 实验室调查：
The exact cause of analyst error or
mistake can be difficult to determine 分析师错误或错误的确切原因可能
specifically. 是难以具体确定。
Laboratory investigation consists of more 无法识别错误的原因，会影响有信
than a retest. The inability to identify an 心进行复检，不是初步结果不合格
error's cause with confidence affects 的调查询问。
retesting procedures, not the
期望实验室测试数据直接被记录在
investigation inquiry required for the initial 笔记本。
OOS result.
调查产品故障，要审查和评价实验
Expect laboratory test data to be 室的SOP。
recorded directly in notebooks. 单个和多个OOS结果调查时，必须
Review and evaluate the laboratory SOP 遵循特定的程序。
for product failure investigations.
Specific procedures must be followed
when single and multiple OOS results are
investigated.
53
Continued
Inspections on 检查故障（OOS）
Failures (OOS)
LABORATORY 实验室调查：
INVESTIGATIONS：
For the single OOS result the 单个OOS的结果，调查应包括以下几个步
investigation should include the 骤。在进行一个样品的复检之前，必须进
following steps and these inquiries 行这些查询：
must be conducted before there is a
retest of the sample:
 the analyst conducting the test 进行测试的分析师，应报告主管OOS结果
should report the OOS result to the 分析师和主管应该进行一次非正式的实验
supervisor 室调查，其中涉及以下几个方面：
 the analyst and the supervisor
should conduct an informal
laboratory investigation which 1 讨论测试程序
addresses the following areas: 2 讨论计算
 1. discuss the testing procedure 3 检查仪器
 2. discuss the calculation 4 审查包含OOS结果的笔记本
 3. examine the instruments
 4. review the notebooks containing
the OOS result
54
Continued
Inspections on Failures
(OOS) 检查故障（OOS）
LABORATORY INVESTIGATIONS：
Determine that a full scale inquiry has 实验室调查：
been made for multiple OOS results. This
inquiry involves quality control and quality 已为多个不合格结果，要确定一个完整规
assurance personnel in addition to 模的调查。该调查涉及除实验室工作人员
laboratory workers to identify exact 确定确切的过程或者非过程相关的错误外，
process or non process related errors. 质量控制和质量保证人员也要参与。
When the laboratory investigation is 当实验室的调查尚无定论（错误的原因是

inconclusive (reason for the error is not 没有确定）公司：
identified) the firm:
1。不能进行两个复检，基于三次测试的
1. Cannot conduct 2 retests and base 平均释放
release on average of three tests 2。在化学测中不能使用边缘测试
2. Cannot use outlier test in chemical 3。不能使用重取样，承担取样或制备错
tests
误
3. Cannot use a re-sample to assume a 4。可从不同药片同一样品进行复验，复
sampling or preparation error
验时被认为是适当的（见其他地方的标准）
4. Can conduct a retest of different
tablets from the same sample when a
retest is considered appropriate (see
criteria elsewhere)
55
Continued
Inspections on Failures (OOS) 检查故障（OOS）

FORMAL INVESTIGATIONS
Formal investigations extending beyond 正式调查
the laboratory must follow an outline with
particular attention to corrective action.
The company must: 扩大超出了实验室的正式调查必须遵循大
纲，特别注意纠正行动。该公司必须：
1. State the reason for the investigation
2. Provide summation of the process sequences 1。说明调查的原因
that may have caused the problem 2。提供过程序列可能造成问题的总结
3. Outline corrective actions necessary to save 3。概述必要的纠正措施保存批次，并防止类似
the batch and prevent similar recurrence 的复发
4. List other batches and products possibly 4。列出可能受影响的其他批次的产品，这些批
affected, the results of investigation of these 次和产品的调查结果，以及任何纠正行动。具体
batches and products, and any corrective action.
Specifically: 做法是：
examine other batches of product made by the 检查出错的雇员或机器制成的其他产品批次

errant employee or machine 检查所犯错误的过程或操作产生的其他产品
examine other products produced by the errant
process or operation 5。保留所有进行了调查的生产和质量控制人员
的意见和签名，额外的测试后并批准任何再加工
5. Preserve the comments and signatures of all 的材料。
production and quality control personnel who
conducted the investigation and approved any
reprocessed material after additional testing
56
Continued
Inspections on Failures 检查故障（OOS）

(OOS)
调查文档
INVESTIGATION DOCUMENTATION
Analyst's mistakes, such as undetected

分析师的失误，例如，未被发现的计
calculation errors, should be specified with 算错误，应指定具有特殊性和证据支
particularity and supported by evidence. 持。调查得出的结论，必须保留书面
Investigations along with conclusions reached 文件，列举了调查的每一步。评价，
must be preserved with written documentation
that enumerates each step of the investigation.
结论和采取纠正措施，如有，应予以
The evaluation, conclusion and corrective action, 保留在调查或失败的报告中。
if any, should be preserved in an investigation or
failure report and placed into a central
调查时间框架
INVESTIGATION TIME FRAMES
问题的发生，在20个工作日内，和所
All failure investigations should be performed
within 20 business days of the problem's
有失败的调查应进行记录并写入失败
occurrence and recorded and written into a 或调查报告。
failure or investigation report.
57
Continued
FDA Inspections FDA的检查
PRODUCT FAILURES 产品故障

RETESTING 复检
 The court ruled that retesting:
 must be done on the same, not a different 法院裁定，复验：
sample
 必须做相同的，而不是不同的样本
 may be done on a second aliquot from the
same portion of the sample that was the  可以做第二个等分样品相同的部分是
source of the first aliquot 第一等分源
 may be done on a portion of the same  可完成的部分相同较大先前收集的样
larger sample previously collected for 本实验室的目的
laboratory purposes
RESAMPLING 重采样
To release a product that has failed testing and  释放失败测试和复验产品，除非事故
retesting unless the failure investigation 调查披露的证据原始样品不具代表性
discloses evidence that the original sample is
或有不当失败准备。
not representative or was improperly prepared.
Evaluate each resampling activity for  评估每个重采样活动遵守本指导意见。

compliance with this guidance.
58
Continued
AVERAGING RESULTS OF ANALYSIS 平均分析结果

Averaging can be a rational and valid approach
when the object under consideration is total
product assay, but as a general rule this practice 如果考虑的对象是总的产品检测，平均可以是一个合
should be avoided because averages hide the 理和有效的方法。但作为一般规则，这种做法应该避
variability among individual test results.
免，因为平均数掩盖了个别测试结果之间的变异。
Content uniformity and dissolution results never should be
averaged to obtain a passing value. 含量均匀度和溶出度结果不应该取平均获得值。
In the case of microbiological turbidimetric and USP建议微生物浊度和板块分析的情况下取平均值。
plate assays an average is preferred by the USP.
混合取样和试验
BLEND SAMPLING AND TESTING
The laboratory serves a vital function in blend
testing which is necessary to increase the 该实验室提供一个混合测试的重要功能，这是必要的
likelihood of detecting inferior batches. Blend 检测伪劣批次的可能性增加。混合均匀度测试不能放
uniformity testing cannot be waived in favor of 弃赞成完全依赖成品检验，成品检验，因为是有限的。
total reliance on finished product testing 必须通过验证证明，他们的抽样技术是代表所有部分
because finished product testing is limited.
的混合浓度。这意味着，样品必须是代表这些网站可
Must demonstrate through validation that their 能有问题，例如弱混合或有热点。
sampling technique is representative of all
portions and concentrations of the blend. This
means that the samples must be representative
of those sites that might be problems; e.g. weak
or hot spots in the blend.
59
Continued

LABORATORY RECORDS AND
DOCUMENTATION
LABORATORY STANDARD 实验室记录和文件
SOLUTIONS
Ascertain that suitable standards are being used
(i.e. in-date, stored properly). Check for the 实验室的标准溶液
reuse of stock solutions without assuring their 确定合适的标准正在使用的（没过期，储
stability. Stock solutions are frequently stored in 存得当）。检查不保证其稳定性的储存溶
the laboratory refrigerator.
液再使用。标准溶液经常在实验室冰箱储
存。
METHODS VALIDATION
Methods can be validated in a number of 方法验证
ways. Methods appearing in the USP are
considered validated and they are 方法可以在许多方面进行验证。出现在
considered validated if part of an USP方法认为已验证。在ANDA已批准的
approved ANDA. Also a company can 部分也认为验证了。公司可以对他们的方
conduct a validation study on their 法进行验证研究。系统适应性数据不构成
method. System suitability data alone is 方法验证。
insufficient for and does not constitute
method validation.
60
Continued

EQUIPMENT 设备
RAW MATERIAL TESTING
IN PROCESS CONTROLS AND 原材料测试
SPECIFICATIONS 在过程控制和规范
A product with a 90.0%-110.0% assay release，与190.0％〜110.0％释放法，规范的产品可能有
specification may have a limit of 95.%-105.0%
限制的95％〜105.0％的混合进程。
for the in-process blend.
STABILITY
COMPUTERIZED LABORATORY
稳定性
DATA ACQUISITION SYSTEMS
LABORATORY MANAGEMENT 电脑实验室
Overall management of the laboratory work, its 数据采集系统
staff, and the evaluation of the results of
analysis are important elements in the
evaluation of a control laboratory. Span of
supervisory control, personnel qualifications, 实验室管理
turnover of analysts, and scope of the 实验室工作和人员管理，评价分析结果是整体管
laboratory's responsibility are important issues to 理控制实验室评估中的重要组成部分。跨度监控，
examine when determining the quality of overall
management and supervision of work. 人员资格，分析家使用，和实验室的责任范围是
Individually or collectively, these factors are the 很重要的问题在确定的整体管理和监督工作的质
basis for an objection only when they are shown 量检查。单独或总体这些因素都是反对的基础，
to result in inadequate performance of 只有当它们显示不足的CGMPs所需的职责。
responsibilities required by the CGMPs.
61
Continued
How to Pass FDA 如何通过FDA的检查

Inspections
Be Prepared 做好准备
Are you ready to demonstrable 你准备好了论证控制吗？
control? 确保遵守与cGMP规则
Ensure Compliance with cGMP
用预知结局的方式开始
Start with the end in sight 符合cGMP的，联邦法规（CFRS），质
Compliant to cGMP, Code of 量管理体系要求（QSRs），以及ISO及
Federal Regulations (CFRs), Quality GHTF
System Requirements (QSRs), as
well as ISO & GHTF
检查前的准备：
Pre-Inspection Preparation:
DO NOT:
DO NOT （不要）：
Wait for letter informing you of an 采取行动之前等待通知检查你的信。
inspection before taking actions. It’s 这是为时已晚。
too late.
62
Continued
How to Pass FDA Inspections 如何通过FDA的检查

DO: 做：
 Make a quality plan not just reference to the
quality manual and regular management 不仅使质量计划引用质量手册和定期的管理层会议
meetings
 Ensure a thorough study and review of all the 所有适当的指导性文件的审查，确保了深入研究，并已采
appropriate guidance documents has been 取行动项目，所以可以很容易识别
undertaken so action items can be readily
identifies 符合ISO13485:2003和CGPM/ QSRs
 Comply with ISO 13485:2003 and
cGPM/QSRs
有一个检查程序/计划
 Have an inspection procedure/ plan
 Ensure all training needs have been
identified—action plan to address them 确保所有的培训需求，已确定的行动计划，以解决他们同
agreed, budgeted and completed in a timely 意，预算和及时完成
manner
 Review your own history and that of any FDA 检讨自己的历史和任何美国FDA的调查，派出检查您的设
investigator sent to inspect your facility 备
 Undertake mock FDA factory inspections
 Provide ,if asked, copies of the firm’s quality 进行模拟FDA工厂视察
policy and high level quality system
procedures (including management review 提供，如果问，公司的质量方针和高层次的质量体系程序
procedures), quality manual, quality plan, or （包括管理审查程序），质量手册，质量计划，或同等文
equivalent documents to preview prior to 件的副本之前预览检查
inspection
 Remember importance of corrective actions 记得纠正措施和预防措施（CAPA）等的重要性，并努力实
and preventive actions (CAPA) and try to 现一些真正的预防措施，可以显示检查员。
achieve some truly preventive measures that
you can show the inspector.
63
Continued
How to Pass FDA Inspections
64
Continued

Managing the inspection
 It’s important that all managers know why 管理检查
the inspection is taking place  这一点很重要，所有的管理者都知道
 Manufacturers are well advised to treat all 为什么检查正在发生
FDA inspectors as if they were for cause
 建议厂商把所有FDA检查员他们来是
and that the FDA are indeed investigating
and not just auditing. Routine inspection 有原因的，并指出，FDA确实调查并
using the QSIT approach can turn on full 不仅仅是审计。如果制造商的准备工
detailed investigations of troublesome 作一直不佳，例行常规检查使用
area if the manufacturer’s preparation has QSIT方法很容易打开麻烦地区的全
been poor. 面细致的调查。
Suggested Factory Inspection
Procedure/ Plan
 Post-inspection work needs to be
建议工厂检查程序/计划
agreed and budgeted and actions  同意的后检查工作需要，预算和
given with the full authority of top 行动给予充分的权力与高层管理
management backing. 人员支持。
65
Continued
Factory Inspection Procedure/Plan 出厂检验程序/计划

 Quality Manager shall ensure in routine quality  质量经理应确保所有监管要求已得到满足
system audits that all regulatory requirements have 和记录日常质量体系审核
been met and documented
 All staff shall be informed of an inspection by
 所有工作人员应以书面通知告知检查
written notice
 Quality manager is responsible for ensuring all  质量经理是负责确保所有管理人员适当的
managers are appropriately trained and briefed on 培训，并介绍要求
requirements
 Receptionist will first inform the quality manager
when FDA investors arrive, then senior executive  接待员会第一时间告知质量经理当FDA检
on site and senior officers on site 查者到达时，然后在现场高级行政人员和
 Quality manager is responsible for checking 高级管理人员
inspecting official’s credentials on their arrival and
obtaining business cards. Quality manager will  质量经理是负责检查他们的到来视察官方
receive any formal notification of inspection
provided (if any) and inform management team. 的凭据，并取得名片。质量经理将接受检
 An initial reception to introduce management team 查的任何正式通知，规定（如有），并告
to the investigators will undertaken before 知管理团队。
investigators tour any part of the facility. Senior
executive gives overview of the business and
products  一个初始接待是介绍管理团队。带调查人
 Quality manager will review the company quality
员进行调查游览设施的任何部分。高级行
policy. This include the positive aspects of 政人员提供的业务和产品概述
continuous improvement and the changes
introduced since last inspection  质量经理将介绍该公司的质量方针。这包
括持续改进的积极方面和自上次检查后的
改变
66
Continued

公司检验程序/计划
Factory Inspection Procedure/Plan
 Investigators shall be accompanied at all times by  在任何时候公司经理和记录员都应陪同调查人员。
a company manager and a recording clerk. It is
vital that all discussion and observations made by 这是至关重要的，所有的讨论和调查人员提出的意
investigators are recorded and transferred to 见记录在案，并转移到收集和行动的质量经理。
quality manager for collection and action.
 Employees must be co-operative, avoid conflict.  员工必须合作，避免冲突。
 Employees shall not argue with mislead, threaten,
compromise or try to deceive any investigator.
 员工不得主张与误导，威胁，妥协或尝试欺骗任何
 Employees shall ensure they understand the
investigator’s questions before answering them. 调查。
 Quality manager shall delegate immediate
correction of any noted deficiency by investigators  员工应确保他们明白，然后回答他们的问题。
so that it can be discussed during the next
interview.
 质量管理人应当委托任何检测员指出不足，立即改
 Duplicate photocopies of any material given to 正，以便可以在接下来的采访中讨论。
investigators shall be kept and given to quality
manager for collection. 重复影印的调查材料，应保持和采集质量经理。
 If an investigator requires samples during
inspection, a form for receipt of samples is to be  如果检查员需要样品，要填写收到样品表并签署。
completed and signed.
 During close-out meeting, all managers shall be  在会议结束期间，所有管理人员应当到场，并确保
present and ensure that all non-conformances an
observations are adequately discussed. If there is a 所有不符合的意见，充分讨论。如果有异议，应当
disagreement, the relevant manager shall present 出示有关经理调查的所有信息，任何规章和支持经
to investigators all of the information, any 理人的案件的官方解释。
regulations and official interpretations that support
the manager’s case.
67
Continued
 Quality manager or senior executive 公司检验程序/计划
shall authorize and allocate work
required to correct any deficiency  质量经理或高级管理人员应当授权和分配
 Senior executive will write to thank 工作的要求，以纠正任何不足
the investigators and request a full
 高级行政人员会写感谢调查，并要求一份
report 完整的报告
 Quality manager will submit a
written reply to any non-  质量经理将提交一份书面答复对任何非一
conformance raised by inspection to 致性检查，在检查后15个工作日内提出，
the lead investigator at their office 快寄给他们的办公室首席检查员。
within 15 working days of inspection.
 所有非不合格和意见，应全面，系统地解
 All non-conformances and 决如下。
observations shall be full and
systematically addressed as follows.  找出根本原因
 Identify the root cause
 Determine the corrective action &  确定纠正措施及预防措施
preventive action
 Implement the corrective action,  实施纠正措施，包括预防复发。
including preventive reoccurrence.
 Prevent reoccurrence-monitoring  防止复发--监测产品，发展趋势，过
product, trends, process, procedures 程，程序和制度，以避免潜在的问题，
and systems to avoid potential 包括员工培训。
problems including employee
training.
68
Continued

 The format of reply shall be as follows.
 Findings-restated for ease of reference 公司检验程序/计划
 History-give the background to the  答复的格式应为如下:
problem and root cause
 Actions:  结果--重申为便于参考
 Corrective-action taken to correct  历史--背景的问题和根源
specific findings
 Preventive-action taken to prevent
行动：
reoccurrence of non-conformance  采取纠正行动，以纠正具体结果
and training staff to ensure  采取预防性行动，以防止非一致性,培
continued compliance
 Timeframe 训工作人员以防止再次发生，以确保
继续遵守
 Documentation
 时间表
 Time schedule for corrective action must  文档
be reasonable and achieved in a timely
manner.
 Quality manager is responsible for  纠正行动的时间安排必须合理，并及
producing a Post-Inspection Report that 时取得。
will be circulated to all managers and
relevant employees. It must be discussed  质量经理负责写后检验报告将分发给
at the next quality management review
meeting. 所有管理人员及有关雇员。它必须在
今后的质量管理审查会议讨论。
69
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Attention
多谢您的时间
Questions？？？
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如何保障企业通过FDA常规年检并与

2012 Trends in 2012年GMP符合性

With a focus on 专注于药品，而不是

Go to the websites of pharmaceutical regulators, 药品监管机构，医药期刊和出版商，

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The use of the internet by the pharmaceutical 使用互联网的制药行业的GMP监管机构

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TRS: Technical Report Series rDNA：Recombinant DNA 15

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 Laboratory record and  实验室记录和文件存档

FDA cGMP Compliance in an FDA的cGMP符合性分析实

FDA cGMP Compliance in FDA的cGMP符合性分析实验室

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HVAC：Heating, ventilation and air-conditioning systems

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 Validation plan  验证计划

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FDA cGMP Compliance in an FDA的cGMP符合性分析实验室

FDA cGMP Compliance in an FDA的cGMP符合性分析实验室

Building Quality into Operations 建设质量到操作运营中

 Based on overall business and  基于整体业务和管理理念，

FDA cGMP Compliance in an FDA的cGMP符合性分析实验室

FDA cGMP Compliance in an FDA的cGMP符合性分

 Key to building quality into  常规质量控制检查

 Help to prevent need for

FDA cGMP Compliance in an FDA的cGMP符合性分

Routine QC Checks 常规质量控制检查

NIST：National Institute of Standard and Technology 39

FDA cGMP Compliance in an FDA的cGMP符合性分析实验室

Routine QC Checks-Example 常规质量控制检查为例

 Blanks-Filtered sample &  空白--过滤了样品和标准溶剂

FDA cGMP Compliance in an FDA的cGMP符合性分析实验室

 Unused data– needs to be explained  未使用的数据--加以解释，并详细记

Regulatory Compliance for Analytical Laboratories

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Get Practical Inspection 得到实践检验的知识：

 What inspectors are looking for  什么检查员要寻找

 Successful preparation and management  成功的准备和管理巡查过程

 Typical compliance issues and proactive  典型的合规性问题，并积极遵守

 The psychology of inspection  心理检查

How to pass FDA Inspection/如何通过FDA检查

GMP Compliance: FDA CFR Regulations

21 CFR Parts 110, 111 - Food GMP

21 CFR Parts 210, 211, 212 - Drug Pharmaceutical GMP

How to pass FDA Inspection 如何通过FDA检查

FDA Inspection Guides: FDA检查指南：

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How to pass FDA Inspection 如何通过FDA检查

How to pass FDA Inspection 如何通过FDA检查

Core Knowledge 核心知识

FDA Inspection Preparation FDA检验的准备

FDA Inspection Approach FDA检验方法

Inspections on Failures (OOS) 检查故障（OOS）

When the laboratory investigation is 当实验室的调查尚无定论（错误的原因是

Inspections on Failures (OOS) 检查故障（OOS）

examine other batches of product made by the 检查出错的雇员或机器制成的其他产品批次