FDA关于厂房和设施的条款翻译(青霉素和非青霉素)
美国FDA的GMP法规
美国FDA的GMP法规A部分——总则110.3 定义110.5 现行的良好生产规范110.10 人员110.19例外情况B部分——建筑物与设施110.30 厂房与场地110.35 卫生操作110.37 卫生设施及管理C部分——本节预留作将来补充110.40 设备与用具D部分——本节预留作将来补充E部分——生产及加工管理110.80 加工及控制110.93 仓贮与分销F部分——本节预留作将来补充G部分——缺陷行动水平（DEFECT ACTION LEVEL）110.110 食物中对人体健康无危害的天然的或不可避免的缺陷授权自：联邦食品、药物及化妆品法（21.U.S.C.342, 371, 374）第402, 701, 704节,公众健康服务法(42 U.S.C.264)第361节如不另作说明,皆出自51FR24475, 1986年6月19日版本。
A部分——总则110.3定义联邦食品、药物及化妆品法（以下简称该法）第201节中术语的定义和解释适用于本部分的同类术语。
下列定义亦同样适用：“酸性食品或酸化食品”是指平衡PH值为4.6或低于4.6的食品。
“适当的”指为达到良好的公共卫生规范的预期目的所需要满足的要求。
“面糊”是指一种半流体物质，通常含面粉和其它原料，要加工的主要食品可在其中浸下，或用它涂膜，或直接用它制烘烤食品。
“热烫”坚果和花生除外，指在包装前对食品进行充分时间和充分温度的热处理，以使天然形成的酶部分地或完全失活，并对该食品产生物理或生化方面的变化。
“关键控制点”是指食品加工过程中的一个点，在这个点上控制不好就可能造成或引发危害，或使成品受到杂质污染，或使成品分解。
“食品”指该法201（F）节所定义的食品，包括各种原料的配料。
“食品接触面”指接触人类食品那些表面以及在正常加工过程中会将污水滴溅在食品上或与食品接触的表面上的那些表面。
“食品接触面”包括用具及接触食品的设备的表面。
“批”指在某一自段时间生产的，由具体的代号标记的食品。
GMP规范中英文对照
GMP规范中英文对照Chapter 1: General Provisions第一章总则Article 1: This Regulation is enacted in accordance with the "Drug Administration Law of The People's Republic of China".第一条根据《中华人民共和国药品管理法》规定，制定本规范。
Article 2: This Regulation is promulgated as the basic guideline for manufacturing and quality control of pharmaceutical products. This Regulation shall be applicable to all the manufacturing processes of drug preparations and to the key manufacturing processes of raw materials which may cause variation in the quality of finished products.第二条本规范是药品生产和质量管理的基本准则。
适用于药品制剂生产的全过程、原料药生产中影响成品质量的关键工序。
Chapter 2: Organization and PersonnelArticle 3: A pharmaceutical enterprise shall establish production and quality control departments. The responsibilities of departments at all levels and personnel shall be clarified, and each department shall be staffed by an appropriate number of management and technical personnel with expert knowledge, manufacturing experience and organization ability. 第三条药品生产企业应建立生产和质量管理机构。
FDA现场检查条款(中文)
原料药质检目录A总论B质量管理C组织和人员D厂房和设施E设备F文件和目录G材料管理H生产控制和过程控制I原料药和中间体的包装以及起到鉴别作用的标签J贮藏和销售K化验室控制L验证M变化控制N材料的拒收和重新使用O投诉和回收P合同厂家和合同实验室Q代理人和经纪人、贸易商、经销商、分装商和重新贴签商R用细胞培养和发酵的方法制造的原料药S临床试验中所用的原料药项目通过未通过说明A绪论1.自上次FDA检查后，FDA检查报告已经评审，所有不符合规定的区域已经指明。
2.已经评审了来自于地方、国家及其他执法机构所做的检查报告，所有不符合规定的区域已经指明。
3.提供在工厂内所生产的原料药及中间体产品目录。
B质量管理1.质量单位和生产单位互相独立，质量部同时应承担QA和QC的责任。
2.所有与质量有关的活动在操作时是否已经记录？3.在生产、包装和检验时所产生的一切偏差（包括不合格结果）是否已适当调查并采取了纠正行动和做了记录。
a有一个描写失败调查的程序。
b程序描写了可接受的决策标准，其中包括不合格的结果和重试的常规。
c所有的调查研究必须记录并在规定时间进行评审。
d调查研究应包括其结果对有关系统的影响的评价。
e一旦原因查出，应建立一个整改和随访的计划。
4.质量单位是否在成批使用原材料以前已批准了所有原料。
项目通过未通过评价a是否对隔离的物料有适当的释放体系？5是否有程序及时地对执法检查，严重GMP偏差，产品缺陷、回收和投诉进行通知性管理？6是否所有的记录已评审其完整性、准确性和资料的适当记录并字迹清楚？是否在需要时能提供与有关文件的交叉文件。
7质量单位的责任a是否规定了专人释放或拒收中间体和原料药？b是否已建立释放或拒收原料药、中间体、包装材料和标签材料的体系？c质量单位是否全部审查了批生产记录和实验室控制记录以后才释放原料进行销售？d质量单位是否审查和批准了规格、要求和主生产指令？e质量单位是否审查和批准了影响原料药和中间体质量的程序？f质量单位是否进行了内部质量审计？g质量部是否已审计了原材料、中间体和原料药的合同制造商？1）应具有每种成分的可接受的供应商名录。
国外GMP检查详细条款[1]
![国外GMP检查详细条款[1]](https://img.taocdn.com/s3/m/44b667956bec0975f465e2f0.png)
A 工厂总体印象1厂房与设施、设备1.1 规划/设计：将差错、混淆、交叉污染，灰尘、泥土的累积情况减少到最低限度。
1.2 有效的清洁和维护，且经批准1.3 有控制啮齿动物、昆虫和害虫的SOP，确保建筑物内无昆虫、动物（尤其是龋齿动物），鸟类的存在。
1.4 厂房等建筑物维护良好1.5 检查垃圾箱、标签、产品，废弃物料不断被清除（没有积压）。
1.6 关于卫生的SOP：要有做卫生的时间表、方法、工具。
做卫生的设备要方便易拿有秩序进行的清洁、消毒（包括更衣室?change room，洁具间，盥洗室，食堂）1.7 要有足够的光线，通风系统，过滤系统，测量仪器灰尘控制，适当的湿度、压力和温度。
（外面的空气过滤，回风，达到最低的要求。
）1.8 环境定期监控并记录1.9 生产区：合理的人流物流，足够的空间。
1.10 高致敏性药品的生产要在单独的设施中进行（如青霉素、生物制品、某些抗生素、激素和细胞霉素的生产要在专门的设施中进行。
）1.11 工业用毒药（杀虫剂和除草剂）不应出现在生产药品的厂房中。
1.12 有足够的生产空间和中间站面积1.13 在产尘的地方有捕尘和集尘装置1.14 所有的排水都能收集在排水管里1.15 管道，装置的连接处和其他设施不应有难清洁的地方。
1.16 管道上应贴标签，标出物料和流向。
1.17 地板，墙壁，天花板采用容易清洁的材料。
1.18 贮藏区：确保好的储藏条件（干净、干燥、温度）1.19 设立专署贮藏区：比如易燃的物品、阴凉库、低湿度间。
要有监控报警装置在非正常情况下报警2休息室、盥洗室2.1 休息室、吸烟区和点心间应该和其他区域分开。
2.2 盥洗室的设置对于使用人员应容易上盥洗室且便利。
2.3 盥洗室不能直接和生产区或储藏区相连，要保持干净，通风。
2.4 有肥皂、毛巾、卫生纸，必要时有淋浴设施。
2.5没有外来物料。
（标签、药品）3接收区域3.1 接收和发放区域要能保护原料或产品不受天气影响。
FDA无菌原料药检查指南-中英文版
GUIDE TO INSPECTIONS OF STERILE DRUG SUBSTANCE MANUFACTURERSFDA无菌原料药检查指南Note: This document is reference material for investigators and other FDA personnel. The document does not bind FDA, and does no confer any rights, privileges, benefits, or immunities for or on any person(s).注：本文件是FDA现场检查官和其他FDA人员的参考资料。
本文件并不束缚FDA，也不赋予任何人任何权利、特权、好处以便获得赦免。
One of the more difficult processes to inspect and one which has presented considerable problems over the years is that of the manufacture of sterile bulk drug substances. Within the past several years, there have been a number of batches of sterile bulk drug substances from different manufacturers which exhibited microbiological contamination. One manufacturer had approximately 100 batches contaminated in a 6 month time period. Another had approximately 25 batches contaminated in a similar period. Other manufacturers have had recalls due to the lack of assurance of sterility. Although the Inspection Guide for Bulk Drug Substances provides some direction for the inspection of the sterile bulk drug substance, it does not provide the detailed direction needed.在过去多年中，现场检查最难的，也是出现问题最多的领域就是无菌原料药的制造。
fda厂房建设标准
fda厂房建设标准FDA factory construction standardsfda厂房建设标准In order to ensure the safety and quality of pharmaceutical products, the FDA has stringent standards for the construction of pharmaceutical factories.为了确保药品的安全和质量，FDA对制药厂房的建设标准非常严格。
From a structural standpoint, the FDA requires that pharmaceutical factory buildings meet specific load-bearing requirements to ensure safety in the event of natural disasters such as earthquakes or high winds.从结构的角度来看，FDA要求制药厂房建筑物满足特定的承重要求，以确保在自然灾害如地震或强风发生时的安全性。
Moreover, the FDA also mandates that pharmaceutical factory buildings be designed to facilitate efficient and thorough cleaning to maintain a sterile environment.此外，FDA还要求制药厂房建筑物的设计要便于进行高效和彻底的清洁，以保持无菌环境。
In terms of materials used, the FDA requires that pharmaceutical factory buildings be constructed using non-porous, durable materials that can withstand frequent sanitization processes.在使用的材料方面，FDA要求制药厂房建筑物采用非多孔、耐用的材料，能够经受频繁的消毒过程。
FDA-GMP中英文对照标准版
DIRECTION OF GMP (GOOD MANUFACTURING PRACTICE )OF RAW MATERIALS BY FDATable of Contents 目录1. INTRODUCTION1.1 Objective 目的1.2 Regulatory Applicability法规的适用性1.3 Scope 范围2. QUALITY MANAGEMENT .质量管理2.1 Principles 总则2.2 Responsibilities of the Quality Unit(s) 质量部门的责任2.3 Responsibility for Production Activities 生产作业的职责2.4 Internal Audits (Self Inspection) 内部审计（自检）2.5 Product Quality Review 产品质量审核3. PERSONNEL 人员3.1 Personnel Qualifications 人员的资质3.2 Personnel Hygiene 人员卫生3.3 Consultants 顾问4. BUILDINGS AND FACILITIES 建筑和设施4.1 Design and Construction 设计和结构4.2 Utilities 公用设施4.3 Water 水4.4 Containment 限制4.5 Lighting 照明4.6 Sewage and Refuse 排污和垃圾4.7 Sanitation and Maintenance 卫生和保养5. PROCESS EQUIPMENT 工艺设备5.1 Design and Construction 设计和结构5.2 Equipment Maintenance and Cleaning 设备保养和清洁5.3 Calibration. 校验5.4 Computerized Systems 计算机控制系统6. DOCUMENTATION AND RECORDS 文件和记录6.1 Documentation System and Specifications 文件系统和质量标准6.2 Equipment cleaning and Use Record 设备的清洁和使用记录6.3 Records of Raw Materials, Intermediates, API Labeling and Packaging Materials原料、中间体、原料药的标签和包装材料的记录6.4 Master Production Instructions (Master Production and Control Records)生产工艺规程（主生产和控制记录）6.5 Batch Production Records (Batch Production and Control Records)批生产记录（批生产和控制记录）6.6 Laboratory Control Records 实验室控制记录6.7 Batch Production Record Review 批生产记录审核7. MATERIALS MANAGEMENT 物料管理7.1 General Controls 控制通则7.2 Receipt and Quarantine 接收和待验7.3 Sampling and Testing of Incoming Production Materials 进厂物料的取样与测试7.4 Storage 储存7.5 Re-evaluation 复验8. PRODUCTION AND IN-PROCESS CONTROLS 生产和过程控制8.1 Production Operations 生产操作8.2 Time Limits 时限8.3 In-process Sampling and Controls 工序取样和控制8.4 Blending Batches of Intermediates or APIs 中间体或原料药的混批8.5 Contamination Control 污染控制9. PACKAGING AND IDENTIFICATION LABELING OF APIs AND INTERMEDIATES原料药和中间体的包装和贴签9.1 General 总则9.2 Packaging Materials 包装材料9.3 Label Issuance and Control 标签发放与控制9.4 Packaging and Labeling Operations 包装和贴签操作10. STORAGE AND DISTRIBUTION.储存和分发10.1 Warehousing Procedures 入库程序10.2 Distribution Procedures 分发程序11. LABORATORY CONTROLS 实验室控制11.1 General Controls 控制通则11.2 Testing of Intermediates and APIs 中间体和原料药的测试11.3 Validation of Analytical Procedures 分析方法的验证11.4 Certificates of Analysis分析报告单11.5 Stability Monitoring of APIs 原料药的稳定性监测11.6 Expiry and Retest Dating 有效期和复验期11.7 Reserve/Retention Samples 留样12. VALIDATION .验证12.1 Validation Policy 验证方针12.2 Validation Documentation 验证文件12.3 Qualification 确认12.4 Approaches to Process Validation 工艺验证的方法12.5 Process Validation Program 工艺验证的程序12.6 Periodic Review of Validated Systems 验证系统的定期审核12.7 Cleaning Validation 清洗验证12.8 Validation of Analytical Methods 分析方法的验证13. CHANGE CONTROL 变更的控制14. REJECTION AND RE-USE OF MATERIALS.拒收和物料的再利用14.1 Rejection 拒收14.2 Reprocessing 返工14.3 Reworking 重新加工14.4 Recovery of Materials and Solvents 物料与溶剂的回收14.5 Returns 退货15. COMPLAINTS AND RECALLS 投诉与召回16. CONTRACT MANUFACTURERS (INCLUDING LABORATORIES)协议生产商（包括实验室）17. AGENTS, BROKERS, TRADERS, DISTRIBUTORS, REPACKERS, AND RELABELLERS 代理商、经纪人、贸易商、经销商、重新包装者和重新贴签者17.1 Applicability 适用性17.2 Traceability of Distributed APIs and Intermediates已分发的原料药和中间体的可追溯性17.3 Quality Management 质量管理17.4 Repackaging, Relabeling, and Holding of APIs and Intermediates原料药和中间体的重新包装、重新贴签和待检17.5 Stability 稳定性17.6 Transfer of Information 信息的传达17.7 Handling of Complaints and Recalls 投诉和召回的处理17.8 Handling of Returns 退货的处理18. Specific Guidance for APIs Manufactured by Cell Culture/Fermentation用细胞繁殖/发酵生产的原料药的特殊指南18.1 General 总则18.2 Cell Bank Maintenance and Record Keeping 细胞库的维护和记录的保存18.3 Cell Culture/Fermentation 细胞繁殖/发酵18.4 Harvesting, Isolation and Purification 收取、分离和精制18.5 Viral Removal/Inactivation steps 病毒的去除/灭活步骤19. APIs for Use in Clinical Trials 用于临床研究的原料药19.1 General 总则19.2 Quality 质量19.3 Equipment and Facilities设备和设施19.4 Control of Raw Materials 原料的控制19.5 Production 生产19.6 Validation 验证19.7 Changes 变更19.8 Laboratory Controls 实验室控制19.9 Documentation 文件20. Glossary 术语1. INTRODUCTION 1. 简介1.1 Objective 1.1目的This document is intended to provide guidance regarding good manufacturing practice (GMP) for the manufacturing of active pharmaceutical ingredients (APIs) under an appropriate system for managing quality. It is also intended to help ensure that APIs meet the quality and purity characteristics that they purport, or are represented, to possess.本文件旨在为在合适的质量管理体系下制造活性药用成分（以下称原料药）提供有关优良药品生产管理规范（GMP）提供指南。
FDA工业指南 非青霉素β内酰胺类药品防止交叉污染的指导原则2013.4
工业指南非青霉素β-内酰胺类药品防止交叉污染的指导原则目录I.简介II.背景III.建议You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of this guidance.本指南代表当前FDA对本议题的看法。
本指南并不授予任何人任何特权，也不对FDA或公众起任何约束作用。
如果有替代的方法能满足法律法规的要求，则可以使用该替代方法。
如果想要讨论替代方法，请与FDA负责实施该指南的工作人员联系。
如果不能与指定的合适FDA工作人员联系，请拨打该指南标题页列出的电话号码。
I. INTRODUCTIONI. 简介This guidance describes the importance of implementing manufacturing controls to prevent cross-contamination of finished pharmaceuticals and active pharmaceutical ingredients (APIs) with non-penicillin beta-lactam drugs. This guidance also provides information regarding the relative health risk of, and the potential for, cross-reactivity in the classes of sensitizing beta-lactams (including both penicillins and non-penicillin beta-lactams). Finally, this guidance clarifies that manufacturers generally should utilize separate facilities for the manufacture of non-penicillin beta-lactams because those compounds pose health risks associated with cross-reactivity.本指南描述了对非青霉素β-内酰胺类成品和原料药的生产过程进行控制，以防止交叉污染的重要性。
- 1、下载文档前请自行甄别文档内容的完整性，平台不提供额外的编辑、内容补充、找答案等附加服务。
- 2、"仅部分预览"的文档,不可在线预览部分如存在完整性等问题,可反馈申请退款(可完整预览的文档不适用该条件!)。
- 3、如文档侵犯您的权益，请联系客服反馈,我们会尽快为您处理(人工客服工作时间：9:00-18:30)。
3.1 Facility Design and Layout厂房设置及布置This page will address various regulatory issues related to this section of the GMP Institute framework. Click below to view the issues that are relevant to you. Penicillin Issues青霉素问题What do the CGMPs mean by separate facilities? Must the buildings be totally separated, or are the CGMPs satisfied when the floors are physically separated with separate air filtration units installed?CGMP规定独立的厂房是什么意思？厂房必须完全独立吗？在安装有独立的空气过滤系统的情况下，楼层之间采取物理隔离可以吗？Is it acceptable to manufacture penicillin and non-penicillin products in the same facility on a campaign (i.e., the conversion of production facilities to a different product line on a routine basis) basis, with adequate cleaning validation procedures in place?在同一个厂房里生产青霉素和非青霉素产品，在有足够清洁的前提下，可接受吗？Is it acceptable to manufacture penicillin products in the same facility as cephalosporin?在同一个厂房内生产青霉素和头孢产品可以接受吗？Can a facility that produced penicillin dosage forms be decontaminated and renovated for production of non-penicillin solid dosage forms provided there is no further penicillin production in the renovated facility?一个生产制剂的厂房，如果在去除污染和改造的前提下且不会再被用于生产青霉素产品，可否用于生产非青霉素产品，Is there an acceptable level of penicillin residue in non-penicillin drug products?在非青霉素药品中青霉素的残留标准是多少？If a firm's only operation is performing finished packaging operations for bulk tablet and capsule drug products, must it still maintain separate facilities and equipment for packaging penicillin products?如果一个公司的操作仅仅是片剂和胶囊的包装，也必须是独立的厂房及设备吗？What do the CGMPs mean by separate facilities? Must the buildings be totally separated, or are the CGMPs satisfied when the floors are physically separated with separate air filtration units installed?CGMP规定独立的厂房是什么意思？厂房必须完全独立吗？在安装有独立的空气过滤系统的情况下，楼层之间采取物理隔离可以吗？References:21 CFR 211.42(d) Design, and construction features21 CFR 211.46(d) Ventilation, air filtration, air heating and cooling21 CFR 211.176 Penicillin contaminationFederal Register, 9/29/78 (Vol.43, No.190, Book 2) Preamble to the CGMPs at comment 142CGMP regulations [21 CFR 211.42(d) and 211.46(d)] require separation of penicillins from non-penicillins during processing. The discussion of the comments in the preamble to the regulations note that "…isolation of penicillin production operations…can be achieved by sealing off…the two operations." "…does not necessarily mean…separate buildings." Thus, there can be a "building within a building"- i.e. two buildings are not required. However, there must be total separation of operations, meaning every aspect of the operations must be separate. Adequate separation should include physical barriers and separate air handling systems. Personnel and equipment from the penicillin facility should not enter thenon-penicillin facility. These should operate with well established written procedures and controls. The separation should be audited, procedures validated, and where necessary monitored.CGMP 法规[21 CFR 211.42(d) and 211.46(d)]要求青霉素与非青霉素产品在加工中独立。
相关的讨论观点“青霉素产品操作的隔离可以通过将两个操作完全分开而达到”，“并不需要独立的厂房”。
这样，可以设计成“建筑物中之建筑物”，也就是说，两个建筑是没有必要的。
然而，操作上必须完全隔离，也就是说，每一个方面都应完全隔离。
充足的隔离应当包括：物理上的屏障及通风系统的隔离。
青霉素厂房的人员及设备不应进行非青霉素的厂房。
这些需要建立良好的书面程序并进行控制。
这种隔离应进行审计，程序应经验证，如果需要还应进行监测。
Even with separation, if any possibility of contamination exists, the non-penicillin products must be tested (21 CFR 211.176). An example of possible contamination could be inadequate controls over movement of equipment or personnel. Section 211.176 requires non-penicillin products to be tested for traces of penicillin where the possibility of exposure exists, and not marketed if detectable levels of penicillin are found.即使在隔离状态下，如果存在任何被污染的可能，非青霉素产品应该经过检验。
一个可能污染的例子可能是人员及设备的不充分控制。
Section 211.176要求如果存在青霉素产品暴露的可能，非青霉素产品应经检查，以追踪是否存在青霉素，如果检测到青霉素产品的残留，产品不应销售。
While this section prohibits marketing of products found to be contaminated with penicillin, it does not sanction marketing of non-penicillin products based only on test results that show no detectable levels of such contamination. Other CGMP requirements must still be met. For a discussion on this issue, please review the article "Is it acceptable under section 211.176 to release products to market as long as the products are tested and no penicillin is found?" published in "Human Drug CGMP Notes" (Volume 6, Issue 2, June 1998).当这些禁止上市的产品里发现被青霉素污染时，并不仅仅是根据检测结果证明在污染水平以下而不能流入市场。
同时必须满足其它CGMP要求也。
关于此部分的讨论，请参照"Is it acceptable under section 211.176 to release products to market as long as the products are tested and no penicillin is found?" published in "Human Drug CGMP Notes" (Volume 6, Issue 2, June 1998).Cross contamination issues have been a concern for a number of years, and continue to be problematic. In one penicillin cross-contamination case reviewed it wasdemonstrated how a non-penicillin facility was contaminated by a separate penicillin facility located in the same manufacturing campus. This occurred due to lack of controls regarding movements of personnel, equipment and materials. In another case, CDER concurred with a district recommendation to withhold approval on a sensitizing beta-lactam manufacturing facility that was adjacent to another drug processing building, due to the lack of containment controls which ensured against cross contamination of the other drugs.交叉污染的问题多年来一直是个关注的问题，并且还会继续是个问题。