WHO961文件-附件6无菌药品良好生产规范(中英文)

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_中英文_附录2 WHO药品GMP指南

These two parts were subsequently supplemented by further guidelines which are integral parts of these GMP for pharmaceutical products. All these texts are available on the Medicines web page (http.www.who.int/medicines/organization/qsm/activities/qualityassurance/gmp/gmpc over.html). 这两部分随后通过药品GMP指南不可缺少的一部分内容进一步补充，这些内容可在药品网站上查到： (http.www.who.int/medicines/organization/qsm/activities/qualityassurance/gmp/gmpc
9. Personnel 人员 General 概述 Key personnel 关键人员 10. Training 培训 11. Personal hygiene 人员卫生 12. Premises 厂房 General 概述 Ancillary areas 辅助区域 Storage areas 仓储区域 Weighing areas 称量区域 Production areas 生产区域 Quality control areas QC区域 13. Equipment 设备 14. Materials 物料 General 概述 Starting materials 起始物料 Packaging materials 包装材料 Intermediate and bulk products 中间体和成品 Finished products 制剂 Rejected, recovered, reprocessed and reworked materials 不合格、回收、返工和重加工物料 Recalled products 召回产品 Returned goods 退货 Reagents and culture media 试剂和培养基 Reference standards 标准品 Waste materials 废弃物料 Miscellaneous 其他 15. Documentation 文件 General 概述 Documents required 需要的文件 16. Good practices in production 生产良好规范 General 概述 Prevention of cross-contamination and bacterial contamination during production生产过程中交叉污染和额细菌污染的预防

ISPE指南列表中英对照（更新至2015.5月）-17.02.21张开宇

ISPE指南列表中英对照（更新至2015.5月）-17.02.21张开宇GAMP?Good Practice GuidesGAMP 5: A Risk-Based Approach to Compliant GxP Computerized SystemsGAMP 5: 保证GXP计算机系统符合性的基于风险的方法A Risk-Based Approach to Calibration Management (Second Edition)基于风险的校正管理方法（第二版）A Risk-Based Approach to Electronic Records and Signatures基于风险的电子记录和签名方法A Risk-Based Approach to GxP Compliant Laboratory Computerized Systems (Second Edition)基于风险的GXP符合性实验室计算机化系统方法（第二版）A Risk-Based Approach to GxP Process Control Systems (Second Edition)基于风险的GXP工艺控制体系方法（第二版）A Risk-Based Approach to Operation of GxP Computerized Systems - A Companion Volume to GAMP 5基于风险的GXP计算机系统操作方法---GAMP 5姊妹篇A Risk-Based Approach to Regulated Mobile Applications基于风险的移动APP管理方法A Risk-Based Approach to Testing of GxP Systems (Second Edition)基于风险的GXP系统检测方法（第二版）Electronic Data Archiving电子数据归档Global Information Systems Control and Compliance全球信息系统控制和符合性IT Infrastructure Control and ComplianceIT基础设施控制和符合性Legacy Systems遗留系统Manufacturing Execution Systems – A Strategic and Program Management Approach生产执行系统—策略和编程管理方法GAMP Good Practice Guides Under Development制订中的GAMP GPGISPE Baseline? Pharmaceutical Engineering Guides for New and Renovated FacilitiesISPE基准：新设施和创新型设施药品工程指南Volume 1: Active Pharmaceutical Ingredients (Second Edition) - Revision to Bulk Pharmaceutical Chemicals卷1：活性药物成分（第二版）---对散装药用化学品的修订Volume 2: Oral Solid Dosage Forms (Second Edition)卷2：口服固体制剂（第二版）Volume 3: Sterile Product Manufacturing Facilities (Second Edition)卷3：无菌药品生产设施（第二版）Volume 4: Water and Steam Systems (Second Edition)卷4：水和蒸汽系统（第二版）Volume 5: Commissioning and Qualification卷5：调试和确认Volume 6: Biopharmaceutical Manufacturing Facilities (Second Edition)卷6：生物药品生产设施（第二版）Volume 7: Risk-Based Manufacture of Pharmaceutical Products (Risk-MaPP)卷7：基于风险的药品生产（风险MAPP）Baseline Guides Under Development制订中的基准指南ISPE GuidesISPE Guide: Science and Risk-Based Approach for the Delivery of Facilities, Systems, and EquipmentISPE指南：基于风险的设施、系统和设备传送科学方法ISPE Guide: Biopharmaceutical Process Development and ManufacturingISPE指南：生物药品工艺开发和生产（新出版）ISPE Guides Under Development在制订中的ISPE指南ISPE Good Practice Guides 优良规范指南ISPE Good Practice Guide: Applied Risk Management for Commissioning and QualificationISPE GPG：在调试和确认中应用风险管理ISPE Good Practice Guide: Approaches to Commissioning and Qualification of Pharmaceutical Water and Steam Systems (Second Edition)ISPE GPG：药用水和蒸汽系统调试和确认方法（第二版）（新出）ISPE Good Practice Guide: Assessing the Particulate ContainmentPerformance of Pharmaceutical Equipment (Second Edition) ISPE GPG：制药设备颗粒密闭性能的评估（第二版）ISPE Good Practice Guide: Booklet LabelsISPE GPG：书册标签ISPE Good Practice Guide: Clinical Supply SystemsISPE GPG：临床补给系统（新出）ISPE Good Practice Guide: Cold Chain ManagementISPE GPG：冷链管理ISPE Good Practice Guide: Comparator ManagementISPE GPG：对照组管理ISPE Good Practice Guide: Development of Investigational Therapeutic Biological ProductsISPE GPG：临床前治疗用生物产品开发ISPE Good Practice Guide: Good Engineering PracticeISPE GPG：优良工程规范ISPE Good Practice Guide: Harmonizing the Definition and Use ofNon-Investigational Medicinal Products (NIMPs)ISPE GPG：协调非临床前药品的定义和使用ISPE Good Practice Guide: Heating, Ventilation, and Air Conditioning (HVAC)ISPE GPG：HVACISPE Good Practice Guide: Interactive Response Technology ISPE GPG：互动反馈技术ISPE Good Practice Guide: MaintenanceISPE GPG：维护ISPE Good Practice Guide: Ozone Sanitization of Pharmaceutical Water SystemISPE GPG：制药用水系统的臭氧消毒ISPE Good Practice Guide: Packaging, Labeling, and Warehousing FacilitiesISPE GPG：包装、贴标和仓储设计ISPE Good Practice Guide: Process GasesISPE GPG：工艺用气ISPE Good Practice Guide: Project Management for the Pharmaceutical IndustryISPE GPG：制药行业的项目管理ISPE Good Practice Guide: Quality Laboratory FacilitiesISPE GPG：质量化验室设施ISPE Good Practice Guide: Technology Transfer (Second Edition)ISPE GPG：技术转移（第二版）（新出）ISPE Good Practice Guides Under Development制订中的ISPE GPGPQLI? Guides 药品质量生命周期实施指南PQLI Overview Good Practice GuidePQLI概览GPGProduct Quality Lifecycle Implementation (PQLI) from Concept to Continual ImprovementPart 1: Product Realization using QbD, Concepts and Principles从概念到持续改进的药品质量生命周期实施（PQLI）第一部分：利用质量源于设计（QbD）实现实现，概念和原则Product Quality Lifecycle Implementation (PQLI) from Concept to Continual ImprovementPart 2: Product Realization using QbD, Illustrative Example 从概念到持续改进的药品质量生命周期实施（PQLI）第二部分：利用质量源于设计（QbD）实现实现，实例解说Product Quality Lifecycle Implementation (PQLI) from Concept to Continual ImprovementPart 3: Change Management System as a Key Element of a PharmaceuticalQuality System从概念到持续改进的药品质量生命周期实施（PQLI）第三部分：药品质量体系关键要素变更管理Product Quality Lifecycle Implementation (PQLI) from Concept to Continual ImprovementPart 4: Process Performance and Product Quality Monitoring System(PP&PQMS)从概念到持续改进的药品质量生命周期实施（PQLI）第四部分：工艺性能和药品质量监测体系（PP&PQMS）ISPE PQLI Guides Under Development制订中的ISPE PQLI指南。

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。

WHO第961号技术报告_附件7_药物生产技术转移指南(中英文)

如果有文件化的证据证明接收单位可以正常地再次生产出所转移的产品、工艺或方法，使用其符合与转出单位协商同意的一系列既定的规格，则可以认为技术转移已经成功。
1.8 In?the event that the RU identifies particular problems with the process during the transfer, the RU should communicate them back to the SU to ensure continuing knowledge management.
?如有需要，应对转出单位和接收单位进行综合技术差异分析，包括技术风险评估和潜在法规差异
?????????adequately trained staff should be available or should be trained at the RU:
接收单位应具有经过充分培训地员工ቤተ መጻሕፍቲ ባይዱ或培训其员工
为使转移成功，应符合以下一般原则和要求
?????????the project plan should encompass the quality aspects of the project and be based upon the principles of quality risk management;
—???????接收单位和转出单位的所在国法规要求，以及任何该产品将要销售的国家的法规要求，均应进行考虑，并在整个转移程序项目期间有一致的解释
—???????there should be effective process and product knowledge transfer.
—???????工艺和产品知识转移应有效果

FDA无菌加工生产的无菌药品指南中英文对照版

监控程序
VI. COMPONENTS AND CONTAINER/CLOSURES .................................................... 27
药品成分和容器 /密封 A. Components..................................................................................................................................27
法规架构 B. Technical Framework .......................................................................................................iologics Evaluation and Research Food and Drug Administration
1401 Rockville Pike, Rockville, MD 20852-1448 /cber/guidelines.htm.
辅助洁净区域 C. Clean Area Separation ................................................................................................................ 11
净化区的隔离 D. Air Filtration ................................................................................................................................ 12

无菌药品和无菌工艺行业指南翻译

无菌药品和无菌工艺行业指南——无菌药品生产质量管理规范（cGMP指南）药物评价研究中心与生物制品评价研究中心共同成立的协调办公室和法规事务办公室一同对改指南做出修订。

引言该指南描述了美国食品药品监督管理局现行的一些设想，这些设想在上述题目中有所体现，该规范没有臆造任何权利，或将之授予任何组织或个人，其执行并不使FDA或公众社会承担义务。

如果有一种途径能够很好的满足当前所采用的法令和规章制度的要求，那就可以应用该途径。

假如你对所采用的途径有任何问题，都可以和负责该指南实施的FDA人员联系，如果不能确定相应的FDA人员，也可以电话联系，其联系电话已经在该指南扉页中列出。

Ⅰ简介：本指南旨在协助厂商满足FDA的cGMP规章的要求，特别是针对无菌药品和生物制品的无菌生产过程，该指南可以代替1987年制定的无菌药物生产企业无菌生产指南（无菌生产工艺指南），该修订版是1987年指南的修订和进一步说明。

为了使无菌药物建立一种简便的药物申请和生物制品许可申请，该指南文件应该与无菌药品提交指南互作补充（标题为：人用和兽用药物的无菌生产工艺验证文件申请的提交指南）。

在药物申请中的一些信息和数据类型在提交指南中有所描述，这主要是为了说明制造商的无菌工艺的有效性。

该指南通过对程序和法规的解释来帮助确保无菌生产厂商的设施满足相关CGMP要求，例如满足厂房设计、设备适用性、工艺验证和质量控制的要求。

包括该指南的FDA指南文件并非要求强制执行。

另外，指南是FDA现在一些构想的体现，它应当被视作一种建议性的文字，除非在个例中提到特殊的法律法规要求时，可以另当别论。

代理机构指南中所用语言都只是给我们的一种建议或者忠告，而非是要求。

在该指南出现的文字内容中包括了CFR（Code of Federal Regulation：美国联邦法规）的210和211章节中的部分内容，在药品cGMP中有所体现。

引用的文字内容主要是想通过本指南提供的一部分条款来帮助读者加深理解，这些在表格中的例子只是摘引，并不详尽，读者可以参阅CFR的全文，以便彻底了解相关章节的条款。

EU GMP 附录1：无菌药品的生产-英文

PrincipleThe manufacture of sterile products is subject to special requirements in order to minimize risks of microbiological contamination, and of particulateand pyrogen contamination. Much depends on the skill, training and attitudes ofthe personnel involved. Quality Assurance is particularly important, and this type of manufacture must strictly follow carefully established and validated methods of preparation and procedure. Sole reliance for sterility or other quality aspects must not be placed on any terminal process or finished product test.Note: This guidance does not lay down detailed methods for determining the microbiological and particulate cleanliness of air, surfaces etc. Reference should be made to other documents such as the EN/ISO Standards.General1. The manufacture of sterile products should be carried out in clean areas entry to which should be through airlocks for personnel and/or for equipment and materials. Clean areas should be maintained to an appropriate cleanliness standard and supplied with air which has passed through filters of an appropriate efficiency.2. The various operations of component preparation,product preparation and filling should be carried out in separate areas within the clean area. Manufacturing operations are divided into two categories; firstly those where the product is terminally sterilised, and secondly those which are conducted aseptically at some or all stages.3. Clean areas for the manufacture of sterile products are classified according to the required characteristics of the environment. Each manufacturing operation requires an appropriate environmental cleanliness level in the operational state in order to minimise the risks of particulate or microbial contamination of the product or materials being handled.In order to meet “in operation” conditions these areas should be designed to reach certain specified air-cleanliness levels in the “at rest” occupancy state. The “at-rest” state is the condition where the installation is installed and operating, complete withproduction equipment but with no operating personnel present. The “in operation” state is the condition where the installation is functioning in the defined operating mode with the specified number of personnel working.The “in operation” and “at rest” states should be defined for each clean room or suite of clean rooms.For the manufacture of sterile medicinal products 4 grades can be distinguished.Grade A: The local zone for high risk operations, e.g. filling zone, stopper bowls, open ampoules and vials, making aseptic connections. Normally such conditions are provided by a laminar air flow work station. Laminar air flow systems should provide a homogeneous air speed in a range of 0.36 – 0.54 m/s (guidance value) at the workingposition in open clean room applications. The maintenance of laminarity should be demonstrated and validated.A uni-directional air flow and lower velocities may be used in closed isolators and glove boxes.Grade B: For aseptic preparation and filling, this is the background environment for the grade A zone.Grade C and D: Clean areas for carrying out less critical stages in the manufactureof sterile products.Clean room and clean air device classification4. Clean rooms and clean air devices should be classified in accordance with EN ISO 14644-1. Classification should be clearly differentiated from operationalprocess environmental monitoring. The maximum permitted airborne particle concentration for each grade is given in the following table.5. For classification purposes in Grade A zones, a minimum sample volume of 1m should be taken per sample location. For Grade A the airborne particle classification is ISO 4.8 dictated by the limit for particles ≥5.0 µm. For Grade B (at rest) the airborne particle classification is ISO 5 for both considered particle sizes. . For Grade C (at rest & in operation) the airborne particle classification is ISO 7 and ISO 8 respectively. For Grade D (at rest) the airborne particle classification is ISO 8. For classification purposesEN/ISO 14644-1 methodology defines both the minimum number of sample locations and the sample size based on the class limit of the largest considered particle size and the method of evaluation of the data collected.6. Portable particle counters with a short length of sample tubing should be used for classification purposes because of the relatively higher rate of precipitation of particles ≥5.0µm in remote sampling systems with long lengths of tubing. Isokinetic sample heads shall be used in unidirectional airflow systems.7. “In operation” classification may be demonstrated during normal operations, simulated operations or during media fills as worst-case simulation is required for this. EN ISO14644-2 provides information on testing to demonstrate continued compliance with the assigned cleanliness classifications.Clean room and clean air device monitoring8. Clean rooms and clean air devices should be routinely monitored in operation and the monitoring locations based on a formal risk analysis study and the results obtained during the classification of rooms and/or clean air devices.9. For Grade A zones, particle monitoring should be undertaken for the full duration of critical processing, including equipmentassembly, except where justifiedby contaminants in the process that would damage the particle counter or present a hazard, e.g. live organisms and radiological hazards. In such cases monitoring during routine equipment set up operations should be undertaken prior to exposure to the risk. Monitoring during simulated operations should also be performed. The Grade A zone should be monitored at such a frequency and with suitable sample size that all interventions, transient events and any system deterioration would be captured and alarms triggered if alert limits are exceeded. It is accepted that it may not always be possible to demonstrate low levels of ≥5.0 µm particles at the point of fill when filling is in progress, due to the generation of particles or droplets from the product itself.10. It is recommended that a similar system be used for Grade B zones although the sample frequency may be decreased. The importance of the particle monitoring system should be determined by the effectiveness of the segregation between the adjacent Grade A and B zones. The Grade B zone should be monitored at such a frequency and with suitable sample size that changes in levels of contamination and any system deterioration would be captured and alarms triggered if alert limits are exceeded.11. Airborne particle monitoring systems may consist of independent particle counters; a network of sequentially accessed sampling points connected by manifold to a single particle counter; or a combination of the two. The system selected must be appropriate for the particle size considered. Where remote sampling systems are used, the length of tubing and the radii of any bends in the tubing must be considered in the context of particle losses in the tubing. The selection of the monitoring system should take account of any risk presented by the materials used in the manufacturing operation, for example those involving live organisms or radiopharmaceuticals.12. The sample sizes taken for monitoring purposes using automated systems will usually be a function of the sampling rate of the system used. It is not necessary for the sample volume to be the same as that used for formal classification of clean rooms and clean air devices.13. In Grade A and B zones, the monitoring of the ≥5.0 µm particle concentration count takes on a particular significance as it is an important diagnostic tool for early detection of failure. The occasional indication of ≥5.0 µm particle counts may be false counts due to electronic noise, stray light, coincidence, etc. However consecutive or regular counting of low levels is an indicator of a possible contamination event and should be investigated.Such events may indicate early failure of the HVAC system, filling equipment failure or may also be diagnostic of poor practices during machine set-up and routine operation.14. The particle limits given in the table for the “at rest” state should be achieved after a short “clean up” period of 15-20 minutes (guidance value) in an unmanned state after completion of operations.15. The monitoring of Grade C and D areas in operation should be performed in accordance with the principles of quality risk management. The requirementsand alert/action limits will depend on the nature of the operations carried out, but the recommended “clean up period” sh ould be attained.16. Other characteristics such as temperature and relative humidity depend on the product and nature of the operations carried out. These parameters should not interfere with the defined cleanliness standard.17. Examples of operations to be carried out in the various grades are given in the table below (see also paragraphs 28 to 35):18. Where aseptic operations are performed monitoring should be frequent using methods such as settle plates, volumetric air and surface sampling (e.g. swabs and contact plates). Sampling methods used in operation should not interfere with zone protection. Results from monitoring should be considered when reviewing batch documentation for finished product release. Surfaces and personnel should be monitored after critical operations. Additional microbiological monitoring is also required outside production operations, e.g. after validation of systems, cleaning and sanitisation.19. Recommended limits for microbiological monitoring of clean areas during operation:Notes (a) These are average values. (b) Individual settle plates may be exposed for less than 4 hours.20. Appropriate alert and action limits should be set for the results of particulate and microbiological monitoring. If these limits are exceeded operating procedures should prescribe corrective action.Isolator technology21. The utilisation of isolator technology to minimize human interventions in processing areas may result in a significant decrease in the risk of microbiological contamination of aseptically manufactured products from the environment. There are many possible designs of isolators and transfer devices. The isolator and the background environment should be designed so that the required air quality for the respective zones can be realised. Isolators are constructed of various materials more or less prone to puncture and leakage. Transfer devices may vary from a single door to double door designs to fully sealed systems incorporating sterilisation mechanisms.22. The transfer of materials into and out of the unit is one of the greatest potential sources of contamination. In general the area inside the isolator is the local zone for high risk manipulations, although it is recognised that laminar air flow may not exist in the working zone of all such devices.23. The air classification required for the background environment depends on the design of the isolator and its application. It should be controlled and for aseptic processing it should be at least grade D.24. Isolators should be introduced only after appropriate validation. Validation should take into account all critical factors of isolator technology, for example the quality of the air inside and outside (background) the isolator, sanitisation of the isolator, the transfer process and isolator integrity.25. Monitoring should be carried out routinely and should include frequent leak testing of the isolator and glove/sleeve system.Blow/fill/seal technology26. Blow/fill/seal units are purpose built machines in which, in one continuous operation, containers are formed from a thermoplastic granulate, filled and then sealed,all by the one automatic machine. Blow/fill/seal equipment used for aseptic production which is fitted with an effective grade A air shower may be installed in at least a grade C environment, provided that grade A/B clothing is used. The environment should comply with the viable and non viable limits at rest and the viable limit only when in operation.Blow/fill/seal equipment used for the production of products which are terminally sterilised should be installed in at least a grade D environment.27. Because of this special technology particular attention should be paid to, at least the following:•equipment design and qualification•validation and reproducibility of cleaning-in-place and sterilisation-in-place •background clean room environment in which the equipment is located •operator training and clothing•interventions in the critical zone of the equipment including any aseptic assembly prior to the commencement of filling.Terminally sterilised products28. Preparation of components and most products should be done in at least a grade D environment in order to give low risk of microbial and particulate contamination, suitable for filtration and sterilisation. Where the product is at a high or unusual risk of microbial contamination, (for example, because the product actively supports microbial growth or must be held for a long period before sterilisation or is necessarily processed not mainly in closed vessels), then preparation should be carried out in a grade C environment.29. Filling of products for terminal sterilisation should be carried out in at least a grade C environment.30. Where the product is at unusual risk of contamination from the environment, for example because the filling operation is slow or the containers are wide-necked or are necessarily exposed for more than a few seconds before sealing, the filling should be done in a grade A zone with at least a grade C background. Preparation and filling of ointments, creams, suspensions and emulsions should generally be carried out in a grade C environment before terminal sterilisation.Aseptic preparation31. Components after washing should be handled in at least a grade D environment. Handling of sterile starting materials and components, unless subjectedto sterilisation or filtration through a micro-organism-retaining filter later in the process, should be done in a grade A environment with grade B background.32. Preparation of solutions which are to be sterile filtered during the process should be done in a grade C environment; if not filtered, the preparation of materials and products should be done in a grade A environment with a grade B background.33. Handling and filling of aseptically prepared products should be done in a grade A environment with a grade B background.34. Prior to the completion of stoppering, transfer of partially closed containers, as used in freeze drying should be done either in a grade A environment with grade B background or in sealed transfer trays in a grade B environment.35. Preparation and filling of sterile ointments, creams, suspensions and emulsions should be done in a grade A environment, with a grade B background, when the product is exposed and is not subsequently filtered.Personnel36. Only the minimum number of personnel required should be present in clean areas; this is particularly important during aseptic processing. Inspections and controls should be conducted outside the clean areas as far as possible.37. All personnel (including those concerned with cleaning and maintenance) employed in such areas should receive regular trainingin disciplines relevant to the correct manufacture of sterile products. This training should include reference to hygiene and to the basic elements of microbiology. When outside staff who have not received such training (e.g. building or maintenance contractors) need to be brought in, particular care should be taken over their instruction and supervision.38. Staff who have been engaged in the processing of animal tissue materials or of cultures of micro-organisms other than those used in the current manufacturing process should not enter sterile-product areas unless rigorous and clearly defined entry procedures have been followed.39. High standards of personal hygiene and cleanliness are essential. Personnel involved in the manufacture of sterile preparations should be instructed to report any condition which may cause the shedding of abnormal numbers or types of contaminants; periodic health checks for such conditions are desirable. Actions to be taken about personnel who could be introducing undue microbiological hazard should be decided by a designated competent person.40. Wristwatches, make-up and jewellery should not be worn in clean areas.41. Changing and washing should follow a written procedure designed to minimize contamination of clean area clothing or carry-through of contaminants to the clean areas.42. The clothing and its quality should be appropriate for the process and the grade of the working area. It should be worn in such a way as to protect the product from contamination.43. The description of clothing required for each grade is given below:•Grade D: Hair and, where relevant, beard should be covered. A general protective suit and appropriate shoes or overshoes should be worn. Appropriate measures should be taken to avoid any contamination coming from outside the clean area.•Grade C: Hair and where relevant beard and moustache should be covered. A single or two-piece trouser suit, gathered at the wrists and with high neck and appropriate shoes or overshoes should be worn. They should shed virtually no fibres or particulate matter.•Grade A/B: Headgear should totally enclose hair and, where relevant, beard and moustache; it should be tucked into the neck of the suit; a face mask should be wornto prevent the shedding of droplets. Appropriate sterilised, non-powdered rubber or plastic gloves and sterilised or disinfected footwear should be worn. Trouser-legs should be tucked inside the footwear and garment sleeves into the gloves. The protective clothing should shed virtually no fibres or particulate matter and retain particles shed by the body.44. Outdoor clothing should not be brought into changing rooms leading to grade B andC rooms. For every worker in a grade A/B area, clean sterile (sterilised or adequately sanitised) protective garments should be provided at each work session. Gloves should be regularly disinfected during operations. Masks and gloves should be changed at least for every working session.45. Clean area clothing should be cleaned and handled in such a way that it does not gather additional contaminants which can later be shed. These operations shouldfollow written procedures. Separate laundry facilities for such clothing are desirable. Inappropriate treatment of clothing will damage fibres and may increase the risk of shedding of particles.Premises46. In clean areas, all exposed surfaces should be smooth, impervious and unbroken in order to minimize the shedding or accumulation of particles or micro-organisms and to permit the repeated application of cleaning agents, and disinfectants where used.47. To reduce accumulation of dust and to facilitate cleaning there should be no uncleanable recesses and a minimum of projecting ledges, shelves, cupboardsand equipment. Doors should be designed to avoid those uncleanable recesses; sliding doors may be undesirable for this reason.48. False ceilings should be sealed to prevent contamination from the space above them.49. Pipes and ducts and other utilities should be installed so that they do not create recesses, unsealed openings and surfaces which are difficult to clean.50. Sinks and drains should be prohibited in grade A/B areas used for aseptic manufacture. In other areas air breaks should be fitted between the machine or sink and the drains. Floor drains in lower grade clean rooms should be fitted with traps or water seals to prevent back- flow.51. Changing rooms should be designed as airlocks and used to provide physical separation of the different stages of changing and so minimize microbial and particulate contamination of protective clothing. They should be flushed effectively with filtered air. The final stage of the changing room should, in the at-rest state, be the same grade as the area into which it leads. The use of separate changing rooms for entering and leaving clean areas is sometimes desirable. In general hand washing facilities should be provided only in the first stage of the changing rooms.52. Both airlock doors should not be opened simultaneously. An interlocking system or a visual and/or audible warning system should be operated to prevent the opening of more than one door at a time.53. A filtered air supply should maintain a positive pressure and an air flow relative to surrounding areas of a lower grade under all operational conditions and should flush the area effectively. Adjacent rooms of different grades should have a pressure differential of 10 - 15 pascals (guidance values). Particular attention should be paid to the protection of the zone of greatest risk, that is, the immediate environment to which a product and cleaned components which contact the product are exposed. The various recommendations regarding air supplies and pressure differentials may need to be modified where it becomes necessary to contain some materials, e.g. pathogenic, highly toxic, radioactive or live viral or bacterial materials or products. Decontamination of facilities and treatment of air leaving a clean area may be necessary for some operations.54. It should be demonstrated that air-flow patterns do not present a contamination risk,e.g. care should be taken to ensure that air flows do not distribute particles from a particle- generating person, operation or machine to a zone of higher product risk.55. A warning system should be provided to indicate failure in the air supply. Indicators of pressure differences should be fitted between areas where these differences are important. These pressure differences should be recorded regularly or otherwise documented.Equipment56. A conveyor belt should not pass through a partition between a grade A or B area anda processing area of lower air cleanliness, unless the belt itself is continually sterilised (e.g. in a sterilising tunnel).57. As far as practicable equipment, fittings and services should be designed and installed so that operations, maintenance and repairs can be carried out outside the clean area. If sterilisation is required, it should be carried out, wherever possible, after complete reassembly.58. When equipment maintenance has been carried out within the clean area, the area should be cleaned, disinfected and/or sterilised where appropriate, before processing recommences if the required standards of cleanliness and/or asepsis have not been maintained during the work.59. Water treatment plants and distribution systems should be designed, constructed and maintained so as to ensure a reliable source of water of an appropriate quality. They should not be operated beyond their designed capacity. Water for injections should be produced, stored and distributed in a manner which prevents microbial growth, for example by constant circulation at a temperature above 70°C.60. All equipment such as sterilisers, air handling and filtration systems, air vent and gas filters, water treatment, generation, storage and distribution systems should be subjectto validation and planned maintenance; their return to use should be approved. Sanitation61. The sanitation of clean areas is particularly important. They should be cleaned thoroughly in accordance with a written programme. Where disinfectants are used, more than one type should be employed. Monitoring should be undertaken regularly in order to detect the development of resistant strains.62. Disinfectants and detergents should be monitored for microbial contamination; dilutions should be kept in previously cleaned containers and should only be stored for defined periods unless sterilised. Disinfectants and detergents used in Grades A and B areas should be sterile prior to use.63. Fumigation of clean areas may be useful for reducing microbiological contamination in inaccessible places.Processing64. Precautions to minimize contamination should be taken during all processing stages including the stages before sterilisation.65. Preparations of microbiological origin should not be made or filled in areas used for the processing of other medicinal products; however, vaccines of dead organisms or of bacterial extracts may be filled, after inactivation, in the same premises asother sterilemedicinal products.66. Validation of aseptic processing should include a process simulation test using a nutrient medium (media fill).Selection of the nutrient medium should be made based on dosage form of the product and selectivity, clarity, concentration and suitability for sterilisation of the nutrient medium.67. The process simulation test should imitate as closely as possible the routine aseptic manufacturing process and include all the critical subsequent manufacturing steps. It should also take into account various interventions known to occur during normal production as well as worst-case situations.68. Process simulation tests should be performed as initial validation with three consecutive satisfactory simulation tests per shift and repeated at defined intervals and after any significant modification to the HVAC-system, equipment, process and number of shifts. Normally process simulation tests should be repeated twice a year per shift and process.69. The number of containers used for media fills should be sufficient to enable a valid evaluation. For small batches, the number of containers for media fills should at least equal the size of the product batch. The target should be zero growth and the following should apply:•When filling fewer than 5000 units, no contaminated units should be detected.•When filling 5,000 to 10,000 units:a) One (1) contaminated unit should result in an investigation, includingconsideration of a repeat media fill;b) Two (2) contaminated units are considered cause for revalidation, followinginvestigation.•When filling more than 10,000 units:a) One (1) contaminated unit should result in an investigation;b) Two (2) contaminated units are considered cause for revalidation, followinginvestigation.70. For any run size, intermittent incidents of microbial contamination may be indicative of low-level contamination that should be investigated. Investigation of gross failures should include the potential impact on the sterility assurance of batches manufactured since the last successful media fill.71. Care should be taken that any validation does not compromise the processes.72. Water sources, water treatment equipment and treated water should be monitored regularly for chemical and biological contamination and, as appropriate,for endotoxins. Records should be maintained of the results of the monitoring and of any action taken.73. Activities in clean areas and especially when aseptic operations are in progress should be kept to a minimum and movement of personnel should be controlled and methodical, to avoid excessive shedding of particles and organisms due to over-vigorous activity. The ambient temperature and humidity should not be uncomfortably high because of the nature of the garments worn.74. Microbiological contamination of starting materials should beminimal. Specifications should include requirements for microbiological quality when the need for this has been indicated by monitoring.75. Containers and materials liable to generate fibres should be minimised in clean areas.76. Where appropriate, measures should be taken to minimize the particulate contamination of the end product.77. Components, containers and equipment should be handled after the final cleaning process in such a way that they are not recontaminated.78. The interval between the washing and drying and the sterilisation of components, containers and equipment as well as between their sterilisation and use should be minimised and subject to a time-limit appropriate to the storage conditions.79. The time between the start of the preparation of a solution and its sterilisation or filtration through a micro-organism-retaining filter should be minimised. There should be a set maximum permissible time for each product that takes into account its composition and the prescribed method of storage.。

TGAGMP中英对照

TABLE OF CONTENT 目录CHAPTER 1 - QUALITY MANAGEMENT (1)Principle (1)Quality Assurance (1)Good Manufacturing Practice for Medicinal products (GMP) (2)Quality Control (3)Product Quality Review (4)Quality Risk Management (5)CHAPTER 2 - PERSONNEL (7)Principle (7)General (7)Key Personnel (7)Training (9)Personal Hygiene (9)CHAPTER 3 - PREMISES AND EQUIPMENT (11)Principle (11)Premises (11)General (11)Production Area (11)Storage Areas (13)Quality Control Areas (13)Ancillary Areas (14)Equipment (14)CHAPTER 4 - DOCUMENTA TION (15)Principle (15)General (15)Documents required (16)Specifications (16)Specifications for starting and packaging materials (16)Specifications for intermediate and bulk products (17)Specifications for finished products (17)Manufacturing Formula and Processing Instructions (17)Packaging Instructions (18)Batch Processing Records (18)Batch Packaging Records (19)Procedures and records (20)Receipt (20)Sampling (20)Testing (21)Other (21)CHAPTER 5 - PRODUCTION (22)Principle (22)General (22)Prevention of cross-contamination in production (23)V alidation (24)Starting materials (24)Processing operations - Intermediate and bulk products (25)Packaging materials (25)Packaging operations (26)Finished products (27)Rejected, recovered and returned materials (28)CHAPTER 6 - QUALITY CONTROL (29)Principle (29)General (29)Good Quality Control Laboratory Practice (30)Documentation (30)Sampling (30)Testing (31)On-going Stability Programme (32)CHAPTER 7 - CONTRACT MANUFACTURE AND ANALYSIS (35)Principle (35)General (35)The Contract Giver (35)The Contract Acceptor (36)The Contract (36)CHAPTER 8 - COMPLAINTS AND PRODUCT RECALL (38)Principle (38)Complaints (38)Recalls (39)CHAPTER 9 - SELF INSPECTION (40)Principle (40)CHAPTER 1 QUALITY MANAGEMENT质量管理PRINCIPLE 原则The holder of a manufacturing authorisation must manufacture medicinal products so as to ensure that they are fit for their intended use, comply with the requirements of the Marketing Authorisation and do not place patients at risk due to inadequate safety, quality or efficacy. The attainment of this quality objective is the responsibility of senior management and requires the participation and commitment by staff in many different departments and at all levels wi thin the company, by the company’s suppliers and by the distributors. To achieve the quality objective reliably there must be a comprehensively designed and correctly implemented system of Quality Assurance Incorporating Good Manufacturing Practice, and thus Quality Control and Quality Risk Management. It should be fully documented and its effectiveness monitored. All parts of the Quality Assurance systems should be adequately resourced with competent personnel, and suitable and sufficient premises, equipment and facilities. There are additional legal responsibilities for the holder of the manufacturing authorisation and for the authorised person(s).制造商生产的药品必须能满足药品本身的潜在用途，符合市场的要求并且对使用者不存在药品安全、质量和疗效方面的危险。

药品微生物实验室质量管理指导原则

主要变化
1、名称 “药品微生物实验室规范指导原则”（2010年版） “药品微生物实验室质量管理指导原则”（2015年版） 2、增订
由8个修订为13个，增加了以下5个要素。
-试剂 -样品 -检验方法 -污染废弃物的处理 -检测结果的质量保证和检测过程的质量控制
3、修订 -每一个要素均进行了不同程度的修订 -环境（实验室的布局和运行）
培养基或试剂的批量
培养基或试剂完整的可追溯单位，是指满足产品要求（内部控制）和性能测试，产品型号和质量稳定的一定量的半成品或成品。这些产品在特定的生产周期生产，而且编号相同。
培养基及试剂的性能
在特定条件下培养基对测试菌株的反应。
培养基的定义和分类
培养基的分类依据 1 按组成成分分类 2 按状态分类 3 按用途分类 4 按制备方法分类
标准比对
WHO药品微生物实验室良好实施规范（12个要素，5个附录） -人员 -环境 -检验方法验证 -设备 -试剂和培养基 -标准物质和标准菌株 -抽样 -样品处理和确认 -污染废弃物的处理 -检测结果的质量保证和检测过程的质量控制 -实验步骤 -实验报告
附录 1 附录 2 附录３附录 4 附录 5 区域的实例设备维护实例不同实验室设备的校准的检验和周期实例设备资质和监控实例标准培养物的使用
培养基的定义和分类
3.按用途分类
（1）运输培养基：在取样后和实验室处理前保护和维持微生物活性
且不允许明显增殖的培养基。运输培养基中通常不允许包含使微生物增殖的物质，但是培养基应能保护菌株。（例如：缓冲甘油氯化钠溶液）（2）保藏培养基：用于在一定期限内保护和维持微生物活力，防止长期保存对其的不利影响，或使其在长期保存后容易复苏的培养基。（例如：营养琼脂斜面）（3）悬浮培养基：将测试样本的微生物分散到液相中，在整个接触过程中不产生增值或抑制作用磷酸盐缓冲。（例如：磷酸盐缓冲液）（4）复苏培养基：能够使受损或应激的微生物修复，使微生物恢复正常生长能力，但不一定促进微生物繁殖的培养基。

WHO GMP补充指南验证(中英对照)

Annex 4附件4Supplementary guidelines on good manufacturing practices: validation 药品生产质量管理规范补充指南：验证1Introduction简介2Scope范围3Glossary术语4Relationship between validation and qualiﬁcation验证和确认之间的联系5. Validation5.1. Approaches to validation验证方法5.2. Scope of validation验证范围5Qualiﬁcation确认6Calibration and veriﬁcation校准和核实7Validation master plan验证主计划8Qualiﬁcation and validation protocols确认和验证方案9Qualiﬁcation and validation reports确认和验证报告10Qualiﬁcation stages确认程序11Change control变更控制12Personnel人员References参考文献Appendix 1附录1Validation of heating, ventilation and air-conditioning systems采暖、通风和空气净化系统的验证Appendix 2附录2Validation of water systems for pharmaceutical use制药用水系统的验证Appendix 3附录3Cleaning validation清洁验证Appendix 4附录4Analytical method validation分析方法验证Appendix 5附录5Validation of computerized systems计算机系统的验证Appendix 6附录6Qualiﬁcation of systems and equipment系统和设备的确认Appendix 7附录7Non-sterile process validation非灭菌工艺的验证1. Introduction简介Validation is an essential part of good manufacturing practices (GMP). It is, therefore, an element of the quality assurance programme associated with a particular product or process. The basic principles of quality assurance have as their goal the production of products that are ﬁt for their intended use. These principles are as follows:验证是药品生产管理规范（GMP）的一个重要组成部分；也正因如此，所以它同时也是产品或工艺的质量保证计划的一个不可或缺的要素。

《药品生产质量管理规范》(2010年修订)附录[参考]

关于发布《药品出产质量办理规范（2010年修订）》无菌药品等5个附录的布告2011年02月24日发布国家食品药品监督办理局公告2011年第16号关于发布《药品出产质量办理规范（2010年修订）》无菌药品等5个附录的布告有关办理事宜的布告根据卫生部令第79号《药品出产质量办理规范（2010年修订）》第三百一十条规则，现发布无菌药品、质料药、生物制品、血液制品及中药制剂等5个附录，作为《药品出产质量办理规范（2010年修订）》配套文件，自2011年3月1日起实施。

特此布告。

附件：1．无菌药品2．质料药3．生物制品4．血液制品5．中药制剂国家食品药品监督办理局二○一一年二月二十四日附录1：无菌药品第一章规模第一条无菌药品是指法定药品规范中列有无菌查看项意图制剂和质料药，包含无菌制剂和无菌质料药。

第二条本附录适用于无菌制剂出产全进程以及无菌质料药的灭菌和无菌出产进程。

第二章原则第三条无菌药品的出产须满意其质量和预订用处的要求，应当最大极限下降微生物、各种微粒和热原的污染。

出产人员的技能、所承受的训练及其作业态度是到达上述方针的要害要素，无菌药品的出产有必要严厉依照精心规划并经验证的办法及规程进行，产品的无菌或其它质量特性绝不能只依托于任何办法的终究处理或制品查验（包含无菌查看）。

第四条无菌药品按出产工艺可分为两类：选用终究灭菌工艺的为终究灭菌产品；部分或悉数工序选用无菌出产工艺的为非终究灭菌产品。

第五条无菌药品出产的人员、设备和物料应经过气锁间进入洁净区，选用机械接连传输物料的，应当用正压气流保护并监测压差。

第六条物料预备、产品制造和灌装或分装等操作有必要在洁净区内分区域（室）进行。

第七条应当根据产品特性、工艺和设备等要素，承认无菌药品出产用洁净区的等级。

每一步出产操作的环境都应当到达恰当的动态洁净度规范，尽或许下降产品或地址理的物料被微粒或微生物污染的危险。

第三章洁净度等级及监测第八条洁净区的规划有必要契合相应的洁净度要求，包含到达“静态”和“动态”的规范。

国际法规指南对无菌生产的规定

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GoodManufacturingPractice药品生产质量管理规范

GoodManufacturingPractice药品生产质量管理规范GMP英语PIC/S的全称为：Pharmaceutical Inspection Convention/Pharmaceutical Inspection Cooperation Scheme, PIC/S(制药检查草案), 药品检查协会(PIC/S) ,也有人称PIC/S为医药审查会议/合作计划（PIC/S）PIC的权威翻译：药品生产检查相互承认公约API(Active Pharmaceutical Ingrediet) 原料药又称：活性药物组分AirLock 气闸Authorized Person 授权人Batch/Lot 批次Batch Number/Lot-Number 批号；Batch Numbering System 批次编码系统；Batch Records 批记录；Bulk Product 待包装品；Calibration 校正；Clean area洁净区；Consignmecnt（Delivery）托销药品。

FDA（FOOD AND DRUG ADMINISTRA TION）：（美国）食品药品管理局IND（INVESTIGA TIONAL NEW DRUG）：临床研究申请（指申报阶段,相对于NDA而言）；研究中的新药（指新药开发阶段，相对于新药而言，即临床前研究结束）NDA（NEW DRUG APPLICA TION）：新药申请ANDA（ABBREVIATED NEW DRUG APPLICATION）：简化新药申请TREATMENT IND：研究中的新药用于治疗ABBREVIATED（NEW）DRUG：简化申请的新药DMF（DRUG MASTER FILE）：药物主文件（持有者为谨慎起见而准备的保密资料，可以包括一个或多个人用药物在制备、加工、包装和贮存过程中所涉及的设备、生产过程或物品。

只有在DMF持有者或授权代表以授权书的形式授权给FDA，FDA在审查IND、NDA、ANDA时才能参考其内容）HOLDER：DMF持有者CFR（CODE OF FEDERAL REGULATION）：（美国）联邦法规PANEL：专家小组BA TCH PRODUCTION：批量生产；分批生产BA TCH PRODUCTION RECORDS：生产批号记录POST-OR PRE- MARKET SURVEILLANCE：销售前或销售后监督INFORMED CONSENT：知情同意（患者对治疗或受试者对医疗试验了解后表示同意接受治疗或试验）PRESCRIPTION DRUG：处方药OTC DRUG（OVER—THE—COUNTER DRUG）：非处方药GMP文件常见缩写ABPI Association of the British Pharmaceutical IndustryADR Adverse Drug ReactionAE Adverse EventAIM Active Ingredient ManufacturerANDA Abbreviated New Drug ApplicationANOV A Analysis of VarianceASM: Active Substance ManufacturerATC Anatomical Therapeutic ChemicalATX Animal Test Exemption CertificateBAN British Approved NameBIRA British Institute of Regulatory AffairsBNF British National FormularyBP British PharmacopoeiaC of A Certificate of AnalysisC of S Certificate of SuitabilityCENTRE FOR DRUG EV ALUATION (CDE)Centre for Pharmaceutical Administration (CPA)CMS Concerned Member StateCMS每个成员国COS Certificate of SuitabilityCPMP Committee for Proprietary Medicinal ProductsCRA Clinical Research AssociateCRF Case Report FormCRO Contract Research OrganisationCTA Clinical Trial ApplicationCTC Clinical Trial CertificateCTD Common Technical DocumentCTX Clinical Trials ExemptionDDD Defined Daily DoseDGC Daily Global ComparisonDIA Drug Information AssociationDMF Drug Master FileDrug Registration Branch (DR, Product Evaluation & Registration Division, CPAEDQM (European Directorate for the Quality of Medicines) 欧洲联盟药品质量指导委员会EEA 欧洲经济地区EGMA European Generics Medicine AssociationELA Established Licence ApplicationEMEA European Medicines Evaluation AgencyEMEA （European Agency for the Evaluation of Medicinal Products）欧洲联盟药品评价机构EP European Pharmacopoeia EPAR European Public Assessment ReportsESRA European Society of Regulatory AffairsEuropean Pharmacopoeia Commission 欧洲药典委员会FDA FDA Food and Drug Administrationfinal evaluation report (FER)free sale certificates (FSCs)GCP Good Clinical PracticeGCP药品临床研究管理规范GLP Good Laboratory PracticeGLP 药品临床前安全性研究质量管理规范GMP Good Manufacturing PracticeGMP 药品生产质量管理规范GSP药品销售管理规范Health Sciences Authority (HSA)HSA’s Medicines Advisory Committee (MAC)IB Investigators BrochureICH International Conference for HarmonisationIDMC Independent Data-Monitoring CommitteeIEC Independent Ethics CommitteeIND Investigational New DrugINN International Non-proprietary Name International Conference on Harmonisation (ICH)IPC In Process ControlIRB Institutional Review BoardLICENCE HOLDERMA Marketing AuthorisationMAA Marketing Authorisation ApplicationMAA上市申请MAH Marketing Authorisation HolderMAH 销售许可持有者MCA Medicines Control AgencyMHW Ministry of Health and Welfare (Japan)MR Mutual RecognitionMRA 美国与欧盟的互认协议MRAs (Mutual Recognition Agreements) 互相認證同意MRFG Mutual Recognition Facilitation GroupMRP Mutual Recognition ProcedureNAS New Active SubstanceNCE New Chemical EntityNDA New Drug Applicationnew chemical entities (NCEs)new drug applications (NDAs)NSAID Non Steroidal Anti Inflammatory DrugNTA Notice To ApplicantsOOS Out of SpecificationOTC Over The CounterPAGB Proprietary Association of Great BritainPh Eur European PharmacopoeiaPIL Patient Information LeafletPL Product LicencePOM Prescription Only MedicinePRODUCT OWNERPSU Periodic Safety UpdatesQA Quality AssuranceQC Quality ControlRAJ Regulatory Affairs JournalRMS Reference Member StateRMS相互认可另一成员国RSD Relative Standard DeviationRx Prescription OnlySAE Serious Adverse EventSMF Site Master FileSOP Standard Operating ProcedureSOP （STANDARD OPERATION PROCEDURE）标准运作程序SPC/SmPC Summary of Product Characteristics summary of product characteristics(SPC)Therapeutic Goods Administration (TGA)USP US PharmacopoeiaVMF Veterinary Master FileVPC Veterinary Products CommitteeA．A．A Addition and Amendments 增补和修订AC Air Conditioner 空调器ADR Adverse Drug Reaction 药物不良反应AFDO Association of Food and Drug Officials 食品与药品官员协会（美国）ACC Accept 接受AQL Acceptable Quality Level 合格质量标准ADNA Abbreviated New Drug Application 简化的新药申请BOM Bill of Material 物料清单BPC Bulk pharmaceutical Chemiclls 原料药CBER Center for Biologics Evaluation Research 生物制品评价与研究中心CFU Colony Forming Unet 菌落形成单位DMF Drug Master File 药品管理档案CDER Cemter for Drug Evaluation amd Research 药物评价与研究中心CI Corporate Identity (Image) 企业识别（形象）CIP Cleaning in Place 在线清洗CSI Consumer Safety Insepctor 消费者安全调查员CLP Cleaning Line Procedure 在线清洗程序DAL Defect Action Level 缺陷作用水平DEA Drug Enforcement Adminestration 管制药品管理DS Documentation Systim 文件系统FDA Food and Drug Administration 食品与药品管理局（美国）GA TT General Agreemernt on Tariffs and Trade 关贸总协会GMP Good Manufacturing Practice Gvp 药品生质量管理规范GCP Good Clinical Practice 药品临床实验管理规范GLP Good Laboratory Practice 实验室管理规范GSP Good Supply Practice 药品商业质量规范GRP Gook RaTAIL Practice 药品零业质量管理规范GAP Good Agriculture Practice 药材生产管理规范GVP Gook Validation Prctice 验证管理规范GUP Gook Use Practice 药品重用规范HV AC Heating Ventilation Air Conditioning 空调净化系统ISO Intematonal Organization for Standardization 车际标准化组织MOU Memorandum of Understanding 谅解备忘录PF Porduction File 生产记录用表格OTC Over the Counter (Drug) 非处方药品PLA Product License Application 产品许可申请QA Quality Assurance 质量保证QC Quality Control 质量控制QMP Quality Management Procedure 质量管理程序SDA State Drug Administration 国家药品监督管理局SMP Standard Managmert Procedure 标准管理程序SOP Standard Operating Procedure 标准操作程序TQC Tatal Quality Control 全面质量管理USA Uneted States Pharmacopeia 美国药典。

GMP附件一：无菌产品生产(中文翻译版)

附件1：无菌产品的生产导览1范围无菌产品的生产涵盖范围广，包括多种无菌产品类型（活性物质、无菌赋形剂、初级包装材料和最终制剂成品）、包装大小（单个单位到多个单位）、工艺（从高度自动化的系统到人工操作）和技术（如生物技术，经典小分子生产和密闭系统）。

本附件提供的总体原则应用于基于质量风险管理（QRM）原则的所有无菌产品生产，以确保最终产品免受微生物、微粒和热原污染。

本文档所有内容均适用QRM，而不是某个章节。

当文中规定具体限度或频率时，这些限度或频率应被视为最低要求。

之所以特别规定，是因为在监管历史中曾经发现过这些对病患安全带来影响的问题。

本附件的目的是为无菌产品的生产提供指导。

但是，某些原则和指南，例如污染控制策略、厂房设计、洁净室分类、资格认证、监测和人员更衣等，可用于指导某些非无菌产品的生产，如某些液体、膏剂、软膏剂和低微生物负载的生物制品中间体。

这些产品虽然不需要做到无菌，但是控制和降低其微生物、微粒和热原污染也很重要。

如果厂商选择将本指南应用于非无菌产品，则应清楚记录所遵循的原则，并说明这些原则的符合情况。

2原则2.1为最大程度降低微生物、微粒和热原污染的风险，无菌产品的生产需满足特定要求。

应考虑以下关键领域：i.应根据GMP的相关内容，对设施、设备和工艺设计进行优化、认证和验证。

应考虑使用合适的技术（如限制进入屏障系统（RABS）、隔离器、机器人系统、快速微生物检测和监测系统），以保护产品免受潜在外部颗粒物和微生物污染源——如人员、物料和周边环境等——的污染，并快速检测环境和产品中的潜在污染物。

ii.人员应具有足够的资格和经验、培训和态度，特别重视生产、包装和流通过程中无菌产品的保护原则。

iii.应由具备合适工艺、工程研发及微生物知识的人员来设计、调试、认证和监测无菌产品的生产工艺和监测系统。

2.2应根据QRM原则，对工艺、设备、设施和生产活动进行管理，采取主动手段，识别、科学评估和控制潜在的质量风险。

药品生产质量管理规范附录

关于发布《药品生产质量管理规（2010年修订）》无菌药品等5个附录的公告2011年02月24日发布国家食品药品监督管理局公告2011年第16号关于发布《药品生产质量管理规（2010年修订）》无菌药品等5个附录的公告有关管理事宜的公告根据卫生部令第79号《药品生产质量管理规（2010年修订）》第三百一十条规定，现发布无菌药品、原料药、生物制品、血液制品及中药制剂等5个附录，作为《药品生产质量管理规（2010年修订）》配套文件，自2011年3月1日起施行。

特此公告。

附件：1．无菌药品2．原料药3．生物制品4．血液制品5．中药制剂国家食品药品监督管理局二○一一年二月二十四日附录1：无菌药品第一章围第一条无菌药品是指法定药品标准中列有无菌检查项目的制剂和原料药，包括无菌制剂和无菌原料药。

第二条本附录适用于无菌制剂生产全过程以及无菌原料药的灭菌和无菌生产过程。

第二章原则第三条无菌药品的生产须满足其质量和预定用途的要求，应当最大限度降低微生物、各种微粒和热原的污染。

生产人员的技能、所接受的培训及其工作态度是达到上述目标的关键因素，无菌药品的生产必须严格按照精心设计并经验证的方法及规程进行，产品的无菌或其它质量特性绝不能只依赖于任何形式的最终处理或成品检验（包括无菌检查）。

第四条无菌药品按生产工艺可分为两类：采用最终灭菌工艺的为最终灭菌产品；部分或全部工序采用无菌生产工艺的为非最终灭菌产品。

第五条无菌药品生产的人员、设备和物料应通过气锁间进入洁净区，采用机械连续传输物料的，应当用正压气流保护并监测压差。

第六条物料准备、产品配制和灌装或分装等操作必须在洁净区分区域（室）进行。

第七条应当根据产品特性、工艺和设备等因素，确定无菌药品生产用洁净区的级别。

每一步生产操作的环境都应当达到适当的动态洁净度标准，尽可能降低产品或所处理的物料被微粒或微生物污染的风险。

第三章洁净度级别及监测第八条洁净区的设计必须符合相应的洁净度要求，包括达到“静态”和“动态”的标准。

Good Manufacturing Practice 药品生产质量管理规范范文

GMP英语PIC/S的全称为：Pharmaceutical Inspection Convention/Pharmaceutical Inspection Cooperation Scheme, PIC/S(制药检查草案), 药品检查协会(PIC/S) ,也有人称PIC/S为医药审查会议/合作计划（PIC/S）PIC的权威翻译：药品生产检查相互承认公约API(Active Pharmaceutical Ingrediet) 原料药又称：活性药物组分AirLock 气闸Authorized Person 授权人Batch/Lot 批次Batch Number/Lot-Number 批号；Batch Numbering System 批次编码系统；Batch Records 批记录；Bulk Product 待包装品；Calibration 校正；Clean area洁净区；Consignmecnt（Delivery）托销药品。

只有在DMF持有者或授权代表以授权书的形式授权给FDA，FDA在审查IND、NDA、ANDA时才能参考其内容）HOLDER：DMF持有者CFR（CODE OF FEDERAL REGULATION）：（美国）联邦法规PANEL：专家小组BA TCH PRODUCTION：批量生产；分批生产BA TCH PRODUCTION RECORDS：生产批号记录POST-OR PRE- MARKET SURVEILLANCE：销售前或销售后监督INFORMED CONSENT：知情同意（患者对治疗或受试者对医疗试验了解后表示同意接受治疗或试验）PRESCRIPTION DRUG：处方药OTC DRUG（OVER—THE—COUNTER DRUG）：非处方药GMP文件常见缩写ABPI Association of the British Pharmaceutical IndustryADR Adverse Drug ReactionAE Adverse EventAIM Active Ingredient ManufacturerANDA Abbreviated New Drug ApplicationANOV A Analysis of VarianceASM: Active Substance ManufacturerATC Anatomical Therapeutic ChemicalATX Animal Test Exemption CertificateBAN British Approved NameBIRA British Institute of Regulatory AffairsBNF British National FormularyBP British PharmacopoeiaC of A Certificate of AnalysisC of S Certificate of SuitabilityCENTRE FOR DRUG EV ALUATION (CDE)Centre for Pharmaceutical Administration (CPA)CMS Concerned Member StateCMS每个成员国COS Certificate of SuitabilityCPMP Committee for Proprietary Medicinal ProductsCRA Clinical Research AssociateCRF Case Report FormCRO Contract Research OrganisationCTA Clinical Trial ApplicationCTC Clinical Trial CertificateCTD Common Technical DocumentCTX Clinical Trials ExemptionDDD Defined Daily DoseDGC Daily Global ComparisonDIA Drug Information AssociationDMF Drug Master FileDrug Registration Branch (DR, Product Evaluation & Registration Division, CPAEDQM (European Directorate for the Quality of Medicines) 欧洲联盟药品质量指导委员会EEA 欧洲经济地区EGMA European Generics Medicine AssociationELA Established Licence ApplicationEMEA European Medicines Evaluation AgencyEMEA （European Agency for the Evaluation of Medicinal Products）欧洲联盟药品评价机构EP European PharmacopoeiaEPAR European Public Assessment ReportsESRA European Society of Regulatory AffairsEuropean Pharmacopoeia Commission 欧洲药典委员会FDAFDA Food and Drug Administrationfinal evaluation report (FER)free sale certificates (FSCs)GCP Good Clinical PracticeGCP药品临床研究管理规范GLP Good Laboratory PracticeGLP 药品临床前安全性研究质量管理规范GMP Good Manufacturing PracticeGMP 药品生产质量管理规范GSP药品销售管理规范Health Sciences Authority (HSA)HSA’s Medicines Advisory Committee (MAC)IB Investigators BrochureICH International Conference for HarmonisationIDMC Independent Data-Monitoring CommitteeIEC Independent Ethics CommitteeIND Investigational New DrugINN International Non-proprietary Name International Conference on Harmonisation (ICH)IPC In Process ControlIRB Institutional Review BoardLICENCE HOLDERMA Marketing AuthorisationMAA Marketing Authorisation ApplicationMAA上市申请MAH Marketing Authorisation HolderMAH 销售许可持有者MCA Medicines Control AgencyMHW Ministry of Health and Welfare (Japan)MR Mutual RecognitionMRA 美国与欧盟的互认协议MRAs (Mutual Recognition Agreements) 互相認證同意MRFG Mutual Recognition Facilitation GroupMRP Mutual Recognition ProcedureNAS New Active SubstanceNCE New Chemical EntityNDA New Drug Applicationnew chemical entities (NCEs)new drug applications (NDAs)NSAID Non Steroidal Anti Inflammatory DrugNTA Notice To ApplicantsOOS Out of SpecificationOTC Over The CounterPAGB Proprietary Association of Great BritainPh Eur European PharmacopoeiaPIL Patient Information LeafletPL Product LicencePOM Prescription Only MedicinePRODUCT OWNERPSU Periodic Safety UpdatesQA Quality AssuranceQC Quality ControlRAJ Regulatory Affairs JournalRMS Reference Member StateRMS相互认可另一成员国RSD Relative Standard DeviationRx Prescription OnlySAE Serious Adverse EventSMF Site Master FileSOP Standard Operating ProcedureSOP （STANDARD OPERATION PROCEDURE）标准运作程序SPC/SmPC Summary of Product Characteristicssummary of product characteristics(SPC)Therapeutic Goods Administration (TGA)USP US PharmacopoeiaVMF Veterinary Master FileVPC Veterinary Products CommitteeA．A．A Addition and Amendments 增补和修订AC Air Conditioner 空调器ADR Adverse Drug Reaction 药物不良反应AFDO Association of Food and Drug Officials 食品与药品官员协会（美国）ACC Accept 接受AQL Acceptable Quality Level 合格质量标准ADNA Abbreviated New Drug Application 简化的新药申请BOM Bill of Material 物料清单BPC Bulk pharmaceutical Chemiclls 原料药CBER Center for Biologics Evaluation Research 生物制品评价与研究中心CFU Colony Forming Unet 菌落形成单位DMF Drug Master File 药品管理档案CDER Cemter for Drug Evaluation amd Research 药物评价与研究中心CI Corporate Identity (Image) 企业识别（形象）CIP Cleaning in Place 在线清洗CSI Consumer Safety Insepctor 消费者安全调查员CLP Cleaning Line Procedure 在线清洗程序DAL Defect Action Level 缺陷作用水平DEA Drug Enforcement Adminestration 管制药品管理DS Documentation Systim 文件系统FDA Food and Drug Administration 食品与药品管理局（美国）GA TT General Agreemernt on Tariffs and Trade 关贸总协会GMP Good Manufacturing Practice Gvp 药品生质量管理规范GCP Good Clinical Practice 药品临床实验管理规范GLP Good Laboratory Practice 实验室管理规范GSP Good Supply Practice 药品商业质量规范GRP Gook RaTAIL Practice 药品零业质量管理规范GAP Good Agriculture Practice 药材生产管理规范GVP Gook Validation Prctice 验证管理规范GUP Gook Use Practice 药品重用规范HV AC Heating Ventilation Air Conditioning 空调净化系统ISO Intematonal Organization for Standardization 车际标准化组织MOU Memorandum of Understanding 谅解备忘录PF Porduction File 生产记录用表格OTC Over the Counter (Drug) 非处方药品PLA Product License Application 产品许可申请QA Quality Assurance 质量保证QC Quality Control 质量控制QMP Quality Management Procedure 质量管理程序SDA State Drug Administration 国家药品监督管理局SMP Standard Managmert Procedure 标准管理程序SOP Standard Operating Procedure 标准操作程序TQC Tatal Quality Control 全面质量管理USA Uneted States Pharmacopeia 美国药典。

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© World Health OrganizationWHO Technical Report Series, No. 961, 2011WHO技术报告丛书961，2011Annex 6WHO good manufacturing practices for sterile pharmaceutical products 附件6无菌药品良好生产规范IntroductionFollowing implementation of these WHO good manufacturing practices (GMP) guidelines (1) within the context of the WHO Prequaliﬁcation of Medicines Programme, clarifying, editorial modiﬁcations have been proposed. These changes were adopted for maintenance purposes. In order to ease reading the full guideline has been reproduced again as an Annex to the current report of the WHO Expert Committee on Speciﬁcations for Pharmaceutical Preparations.引言以下WHO药品质量管理规范（GMP）（1）指南在WHO预审药物设计、阐明、编辑修改中已经被提出。

这些变更的应用以维护的目的。

为了便于阅读，整篇指南已被重新编制并作为WHO药品标准专家委员会报告的一个附件。

LIVZON GROUP FUZHOU FUXING PHARMACEUTICAL CO., LTD.ADD: Jiangyin Industrial Zone, Fuqing, Fujian, 350309, P. R. ChinaTEL:+86-591-85966928; +86-591-85966932; FAX:+86-591-85966925E-MAIL:******************;*****************;**********************WHO good manufacturing practices for sterile pharmaceutical productsWHO无菌药品良好生产规范1. GENERAL CONSIDERATIONS (3)1 总则 (3)2. QUALITY CONTROL (3)2 质量控制 (3)3. SANITATION (5)3卫生 (5)4. MANUFACTURE OF STERILE PREPARATIONS (6)4 无菌产品的生产 (6)5. STERILIZATION (24)5.灭菌 (24)6. TERMINAL STERILIZATION (26)6. 最终灭菌 (26)7. ASEPTIC PROCESSING AND STERILIZATION BY ﬁLTRATION (32)7. 无菌操作和过滤灭菌 (32)8. ISOLATOR TECHNOLOGY (34)8. 隔离技术 (34)9. BLOW/ﬁLL/SEAL TEC HNOLOGY (35)9. 吹/灌/封技术 (35)10. PERSONNEL (36)10. 人员 (36)11. PREMISES (39)11.厂房 (40)12. EQUIPMENT (43)LIVZON GROUP FUZHOU FUXING PHARMACEUTICAL CO., LTD.ADD: Jiangyin Industrial Zone, Fuqing, Fujian, 350309, P. R. ChinaTEL:+86-591-85966928; +86-591-85966932; FAX:+86-591-85966925E-MAIL:******************;*****************;**********************12. 设备 (43)13. FINISHING OF STERILE PRODUCTS (44)13. 无菌产品完成 (44)1. General considerations1 总则1.1 The production of sterile preparations should be carried out in clean areas, entry to which should be through airlocks for personnel and/or for equipment and materials. Clean areas should be maintained to an appropriate standard of cleanliness and supplied with air that has passed through ﬁlters of the required efﬁciency.1.1 无菌产品的生产应在洁净区进行，人员和/或设备和物料进入洁净区应通过气闸室进入。

洁净区应保持适当的洁净度标准并提供经过有效的过滤的空气。

1.2 The various operations of component preparation (such as those involving containers and closures), product preparation, ﬁlling and sterilization should be carried out in separate areas within the clean area. These areas are classiﬁed into four grades (see section 4).1.2 组件的准备（如相关的容器和密闭包装），产品的制备、灌装和灭菌操作应在洁净区内分区域进行。

这些洁净区分为四个等级（见第4节）。

1.3 Manufacturing operations are divided here into two categories:—ﬁrst, those where the product is terminally sterilized; and— second, those which are conducted aseptically at some or all stages.1.3 生产操作在此可以划分为两类：—第一，仅在最后阶段灭菌的产品；—第二，部分或全部工序采用无菌生产工艺的产品。

2. Quality control2 质量控制2.1 The sterility test applied to t he ﬁnished product should only be regarded as the last in a series of LIVZON GROUP FUZHOU FUXING PHARMACEUTICAL CO., LTD.ADD: Jiangyin Industrial Zone, Fuqing, Fujian, 350309, P. R. ChinaTEL:+86-591-85966928; +86-591-85966932; FAX:+86-591-85966925E-MAIL:******************;*****************;**********************control measures by which sterility is assured. The test should be validated for the product(s) concerned.2.1成品的无菌检测仅作为一系列确保无菌度的控制措施的最后一步。

相关产品的无菌度检测应进行验证。

2.2 Samples taken for sterility testing should be representative of the whole of the batch but should, in particular, include samples taken from parts of the batch considered to be most at risk of contamination, for example:•for products that have been ﬁlled aseptically, samples should include containers ﬁlled at the beginning and end of the batch and after any signiﬁcant interruption of work;•for products that have been heat sterilized in their ﬁnal containers, consideration should be given to taking samples from that part of the load that is potentially the coolest.2.2 无菌度检测取样的样品应能代表整个批次，并且应包括最容易受到污染风险的部位的样品。

●无菌灌装的产品，取样应包括灌装前、灌装后和有明显中断的时候。

●仅在在最后步骤进行高温灭菌的产品，应考虑从最凉处取样。

2.3 The sterility of the ﬁ nished product is assured by validation of the sterilization cycle in the case of t erminally sterilized products, and by “media simulation” or “media ﬁ ll” runs for aseptically processed products. Batch-processing records and, in the case of aseptic processing, environmental quality records, should be examined in conjunction with the results of the sterility tests. The sterility test procedure should be validated for a given product. Pharmacopoeial methods should be used for the validation and performance of the sterility test. In those cases where parametric release has been authorized in place of sterility testing special attention should be paid to the validation and the monitoring of the entire manufacturing process.2.3 最终产品的无菌度检测，如果是仅在最后步骤灭菌的产品，应确保整个灭菌周期的验证，如果是无菌工艺生产的产品，应确保进行了“培养基模拟”和“培养基灌装”。