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工厂主文件SMF（site m-aster file）或PMF（plant m-aster file），对从事原料药出口的制药企业来说并不陌生，主要是介绍整个工厂的一些基本情况，以供国际注册时官方机构或客户审核与了解。在网上可以搜索到很多英文的官方版本，属于指南性的文件，网上也有相应的中文译本。本文（英文内容）是以指南为基础编写的一份原料药SMF范本，现翻译后放上来与大家共享，希望对从事此项工作的同仁会有所帮助。另外，有什么不同意见或翻译及解释不对的地方还请讨论与指正。
1.General Information 一般信息 Trade name, as registered by legal authority：Shanghai XX Co. Ltd 公司名称：略 [注：直译为经过法定机构注册的商业名称，我理解为递交SMF的公司名称] Legal entity / Judicial: Joint Venture Company 公司性质： 合资公司 [注：直译为法律实体，我理解为公司的性质，比方说合资公司(Joint Venture Company)或股份有限公司(Limited Liability Company)等] Address, phone and fax of the head office: XX 地址，总部办公室电话和传真：略。 1.1 Introduction 介绍 英文略。 【注：在这一部分可以介绍公司总的情况，包括公司什么时候建立，总资产，年销售量，有几个生产车间，生产哪些品种，除了原料药之外的其它剂型等（也就是介绍自己的优势）。最好附上该原料药生产厂区在整个公司的地理图以及该产品的厂区外形图] Within the Division there are other supporting functions, which include: Technical Support and Quality Control, Materials Management (i.e. Procurement, Planning, Warehousing and Dispatch), Engineering, Registration of product (Regulatory Affairs) and Quality Assurance. 在该生产区内有其它的一些支持功能，包括：技术支持以及质量控制，原料管理（如原料的采购，采购计划，仓库和发货），工程，注册（法规事务）和质量保证。 [注：这里列出的是与该原料药生产有关的所有部门，按实际情况列出即可] The company has been registered with AAA as a manufacturer and the Department of Health has issued a manufacturing license. 该公司已作为原料药A的生产商进行了注册，并且食品药品监督管理局已颁发了生产许可证。 [注：Department of Health直译为健康部门，在这里应该是指食品药品监督管理局] Name and address of manufacturing site: XX 生产厂地名称和地址：略。 Contact person: XX 联系人：略。 Name of company: XX 公司名称：略。 Telephone number: XX 电话号码：略。 Contact person (24 hrs) : XX 联系人（24小时）：略。 Fax number of contact person: XX 联系人的传真号：略。 Street address: XX 街道地址：略。 Postal address: XX 邮政地址：略。 1.2 Senior Management
高级管理 Senior management Name Function Telephones/fax 高级管理 姓名 岗位 电话/传真 Site Manager or most responsible person 略 厂地经理或负责人 Production Head 略 生产部领导 QA Head QA领导 QC Head QC领导 Engineering Head 工程领导 1.3 General Information on the site 关于该生产厂地的一般信息 [注：以上信息为整个公司的一般信息，如果一个公司有几个生产厂地，则针对该原料药A生产厂地的一般信息需要在此单独列出] a. Name of Site 生产厂地的名称 b. Telephone (24/24) and fax numbers. 电话号码 （24/24）及传真号 c. Postal address including code and street address 邮政地址，包括邮政编码以及街道地址 d. Manufacturing Authorization 药品生产许可证 【注：直译为生产授权，指食品药品监督管理局颁发的药品生产许可证，以附件的形式附上扫描件】 1.4 Quality System The CCC Quality System is based on the requirements of the EU Guidelines, the Code of Federal Regulations Q7A and local GMP requirements. 公司的质量系统是按照欧盟指导方针，Q7A联邦法规要求以及当地GMP要求建立的。 The Quality System involves the integration of all functions on the site to achieve the legal, standard and company requirements. 质量系统包括了本生产厂地所有功能的要素，以达到合法的、标准的以及公司的要求。 A fully documented quality system is established and maintained which ensures that products and / or services that are bought, produced, released and sold meet the specified requirements of the relevant specifications and / or contract and ultimately the requirements of the manufacturing license. 建立并保持了完整的质量系统文件，以确保所购买、生产、放行及销售的产品或服务符合相关标准所指定的要求，从而最终满足生产许可的要求。 The Quality Unit performs regular internal quality audits. The results of every audit are documented and reviewed. 质量部门执行定期的内部质量审计。每一次审计结果都记录并且经过审核。 A system for corrective and preventive actions (CAPA) is in place to ensure continuous improvement of all quality related operations and systems. 有纠正预防措施系统，以确保所有与质量相关的操作及系统得到连续地改进。 Annual Management Reviews are held, deviations are discussed and action taken accordingly. 保持了年度回顾，对偏差进行讨论并采取了相应的行动。 The Quality Unit is also responsible for handling product quality complaints and product recalls. 质量部门也负责处理产品质量投诉及产品的召回。 【注：这一节主要是概述整个公司的质量方针，质量系统的管理、职责、程序、记录等】 2. Personnel
人员 2.1 Employees 员工 Activity Number of employees 活动 员工数量 Purchasing 5 采购 Production Site Services 300 生产人员 [注：直译为生产厂地服务，也就是服务于生产的人员，所以应该指直接从事药品生产的人员] Technical Support 10 技术支持 Quality Control 26 质量控制 Quality Assurance 15 质量保证 Storage / Distribution 6 贮存/分发 Others 其它 Total: 略 总人数 2.2 Organization chart and key personnel 组织机构图及关键人员 Name, first name------------Function--------------------Experience in Pharma---------Initial education 姓名------------------------岗位------------------------从事药品生产的经历-----------第一学历 XX--------------------------Head of Production----------10---------------------------Undergraduate XX--------------------------生产领导 XX--------------------------Managing Director-----------XX---------------------------XX XX--------------------------管理主管 XX--------------------------Head of QC------------------XX---------------------------XX XX--------------------------QC领导 XX--------------------------Head of QA------------------XX---------------------------XX XX--------------------------QA领导 XX--------------------------Head of Engineering---------XX---------------------------XX XX--------------------------工程领导 [注：Experience in Pharma是指从事药品生产的工作年限。此处需要附一张组织机构方框图] 2.3 Training 培训 The Human Resources department is responsible for determining the internal and external training needs of all staff. An annual training program is developed from these needs and is approved by the Technical Director and the Head of Quality. 人力资源部负责所有人员内部和外部的培训要求。根据这些要求制订的年度培训计划由技术主管和质量部门的领导批准。 Training is considered as one of the essential features in the management of human resources. Each production unit has the responsibility for identifying the necessary training or retraining required for a given job. As a minimum, training consists of the basic understanding of cGMP requirements and understanding all Standard Operating Procedures (SOPs) applicable to the specific job. 培训是人力资源管理中基本要素之一。每一个生产单位有责任去识别一个岗位所必需的培训或再培训要求。培训至少包括对cGMP基本要求以及适用于指定岗位的所有标准操作规程的理解。 [注：这里是指应该向员工强调cGMP的概念及其基本要求，并且要熟知各自的岗位SOP] To all new employees an initial training is provided, including discussion on the relevant regulations or guidelines and SOPs. The continuous training program is based on the needs of the personnel, while taking into account the requirements determined by the company‘s policy and the management of the department. 对所有的新员工进行进厂培训，包括相关法规或指导方针以及SOPs的讨论。后续的培训是基于人员的需要，同时考虑公司的政策以及部门管理的要求。 [注：initial training直译为最初的培训，对于制药企业而言，应该就是指进厂培训] General cGMP training is provided to all employees. Training typically includes guidelines or procedures concerning cGMPs for production, packaging and testing. Training programs are examinable to assess the training effectiveness. 对所有员工进行总的cGMP培训。培训通常包括cGMP中与生产、包装和测试有关的指导方针或程序。对培训程序进行检查以评估培训的效果。 Records of all training courses attended are compiled and retained. 所有培训课程的记录需要进行汇编并保留。 Type of training: ---------------------------------------------------Employees concerned 培训类型：-----------------------------------------------------------涉及到的员工 Basic training: -----------------------------------------------------All new employees 基础培训: -----------------------------------------------------------所有新员工 Basic GMP training: -------------------------------------------------Those identified 基础GMP培训：--------------------------------------------------------指定人员 GMP refresher training: ---------------------------------------------Those identified GMP进修培训：--------------------------------------------------------指定人员 Continuous training to assigned duties: -----------------------------All employees 指定职责的继续培训：-------------------------------------------------所有员工 2.4 Health and hygiene requirements for personnel 人员的健康与卫生要求 2.4.1 Personnel hygiene requirements including clothing 包括衣服在内的人员卫生要求 The production units provide suitable and sufficient areas for washing and cleaning. All associates involved in the production, packaging or testing are provided with the necessary clothing for the respective function. 生产单位为清洗与清洁提供合适并足够的区域。根据生产、包装或检测各岗位的需求，为所有相关岗位的人员提供必需的服装。 In all Production and Storage areas protective clothing is issued to personnel. Hairnets and overshoes are provided to minimize contamination. 在所有生产及贮存区，给人员提供保护服装。提供发套及套鞋以最大程度地减小污染。 Clothing is changed regularly and use is made of an external laundry service. 定期更换服装并交由外部洗衣店清洗。 [注：各岗位服装的配备、清洗等需根据各公司的实际操作进行描述] 2.4.2 Health requirements for personnel 人员的卫生要求 A basic pre-employment medical examination is undertaken for all employees. 对所有员工进行基本的就业前体检。 Routine basic medical examination on a periodic basis is performed on employees. This is part of the health surveillance program. 员工基本的体检通常定期执行。这是健康监督检查的一部分。 It is the responsibility of the department head to ensure that all employees are working in a healthy environment. The staff is required to report any potential risk or sickness/ disease to the department head immediately. The employee will only return to work when advised to do so by the Health Center Staff. 部门领导有责任确保所有的员工在一个健康的环境中工作。要求全体员工要立即向部门领导汇报任何潜在的风险或疾病。经治愈的员工只有经健康中心许可才能重新上岗。 [注：对于制药企业而言，这里的疾病应该指传染性的疾病。最后一句直译似乎不妥，因此根据实际情况进行了意译] 3. Premises and Equipment 厂房与设备 3.1 Plans 平面图 3.1.1 General Location of the Site 厂地位置 The CCC manufacturing facility is located in an industrial area. The site consists of XXX buildings containing all activities. 公司的生产区位于工业区，厂地由包括了所有生产活动的X个建筑物组成。 3.1.2 Site and Building Plan 厂地与建筑物平面图 The general plan of buildings located on the site is contained in ATTACHMENT. The factory building six years old and was designed according to current Good Manufacturing standards. 厂地建筑物位置平面图见附件。该建筑物有6年的历史且是根据现行良好的生产标准进行设计的。 3.1.3 Detailed Building Plans Detailed building plans are contained in ATTACHMENT. The following key activities are indicated. 建筑物平面图详细说明见附件。指明下面一些关键的活动区： Goods receiving and packaging material storage 货物的接收与包装物料的贮存 Raw material storage 原料的贮存 Milling 粉碎 Weighing 称量 Dispensary 配料 Non sterile API production 非无菌API产品 Primary Packaging 内包装 Secondary Packaging 外包装 QC laboratory QC实验室 Storage areas 贮存区 Dispatch warehouse 仓库分发 Office, staff and administration areas 办公室，人员和管理区 3.1.4 Personnel, Material and Product Flows 人员，原料与产品的流向 Material and personnel flows are contained in ATTACHMENT. 人流与物流图见附件 3.2 Production and Packaging Areas 生产与包装区 The following table lists different operations together with the total surface and room number of the corresponding areas. 下表中列出了不同操作以及相应区域的总表面积与房间数 Type of training --------------------Product XX 类型---------------------------------产品XX Operations concerned-----------------e.g. Reaction and Filtration, Centrifugation and Sieving, Drying, 有关的操作---------------------------Filling and Packaging如反应与过滤,离心与过筛,干燥,填充与包装 Total surface (m²)-------------------500 总表面积 Number of rooms----------------------10 房间数 3.3 Premises mentioned by building references and activities
所提及厂房的建筑特性及其所执行的功能  [注：根据实际厂房情况按此表进行填写，还可包括留样室、QC实验室、称量室、仓库等的具体情况] 3.4 Water Quality Control or Production Personnel who had special education and training will perform the sampling of the water according to the sampling Standard Operation Procedure from predefined sampling points. 水的取样由经过专门教育与培训的质控或生产人员执行，根据取样标准操作规程按预先指定的取样点进行取样。 City Water and Purified Water are used in the process of API A. Purified Water is prepared by a validated water purification system. Purified water is sampled at an interval of 7 days and tested according to Ph.Eur purified water specifications. 在原料药A的生产过程中使用到了城市用水与纯化水。纯化水由一经过验证的水纯化系统制备，每隔7天取样一次，并按欧洲药典纯化水规格进行检测。 City water supplied by local Water Supply Corporation is tested according to the in-house specifications every 15 days. 由当地自来水公司提供的城市用水根据内控规格每15天检测一次。 [注：城市用水的来源必须符合实情，水的检测周期也必须符合公司的SOP要求。此处需以表格的形式列出纯化水及城市用水的质量规格，并明确行动限与警戒限] 3.5 Manufacturing Equipment 生产设备 [注：也就是设备清单，以表格的形式列出生产中所使用主要设备的设备名称、生产者、数量、容量、安装年限等，如离心机、压力过滤器、结晶釜、反应釜、粉碎筛] 3.6 Control Laboratory Equipment 实验室控制设备 All major pieces of quality control laboratory equipment are serviced and calibrated at regular intervals depending on the specific item. Service and calibration is documented in logbooks. The following table references the equipment used for IPC and finished product testing during production: 对QC实验室设备的所有主要部件按规定的项目进行定期维护与校正，维护与校正情况在日志本上进行记录。 [注：列一份QC实验室的设备清单，内容包括设备名称、房间号、数量及安装年限等] 3.7 Maintenance and Calibration 保养与校正 
4. Production
生产 4.1 Process Flow 工艺流程 Process flow diagrams for A API manufactured on the site, are contained in ATTACHMENT. 原料药A的生产工艺图见附件。 [注：附一张工艺流程图] 4.2 Operations for handling materials and products 原料和产品的操作或处理 Operation or handling------------------------------Responsible Department-----------------------Remarks 操作或处理-----------------------------------------负责部门---------------------------------------备注 Receipt Raterials/Products-------------------------Warehouse-------------------------------------NA 原料/产品的接收------------------------------------仓库 Quarantine Raterials/Products----------------------Warehouse--------------------------------------NA 原料/产品隔离--------------------------------------仓库 Sampling Raterials/Products-------------------------QA 原料/产品取样--------------------------------------质量保证部-------------------------------------NA Manufacturing -------------------------------------Production-------------------------------------NA 生产-----------------------------------------------生产部门 Packaging------------------------------------------Production------------------------------------NA 包装-----------------------------------------------生产部 Quarantine API-------------------------------------Warehouse--------------------------------------NA API隔离--------------------------------------------仓库 Storage/Distribution API---------------------------Warehouse--------------------------------------NA API贮存/分发---------------------------------------仓库 4.3 Rejected materials and products 原料和产品的拒收 Rejected materials are stored isolated in separate containers, which are accordingly labeled as rejected material.. 拒收的原料贮存在单独的容器中，容器上贴有拒收标签。 The material is transferred to a separate area. Quality department decides about reprocessing or waste disposal. 该原料被转移到独立的区域，由质量部门决定是否返工或作为废物处理。 Materials, which fail to meet the specification, are documented in an appropriate document (i.e. analytical report). The document is attached for the finished material to the batch production record. 不符合质量规格的原料以一种适当的文件（如检验报告）进行存档。这份文件附在最终产品的批生产记录中。 4.4 Validated Processes 工艺验证 CCC has validated all of the processes related to the manufacturing and testing of API per the M-aster Validation Plan. See ATTACHMENT 12 for Validated Processes 公司按验证主计划对与原料药的生产和测试有关的所有工艺都进行了验证。 Scope of Validation 验证范围 Process Validation, Analytical Methods, Raw Material Testing, Product testing, Validation of Utilities, Cleaning Validation 工艺验证、分析方法、原料测试、产品测试、设备验证、清洁验证 5. Documentation
文件 5.1 General 总则 All Documentation required by GMP Regulation is issued, managed and controlled by a Document Management System such as batch related documents as M-aster Batch Records - Processing and Packaging Instructions, Raw Data Records, Distribution Records, Standard Operating Procedures, Specifications, Test Methods and non batch related documents such as Qualification and Validation Documents, Complaint and Recalls Records, Environmental Monitoring Records, Utility Monitoring Records, Change Control Documentation, Engineering Drawings, Maintenance and Calibration Records, Equipment Logs, Personnel Training Records, Technical Agreements, Investigation and Reporting Records, Cleaning and Sanitization Records, Entry Records for Controlled Areas, Pest Control Records, Stability Records, Audit Reports, Regulatory Files, etc. 按GMP法规要求制订的所有文件由文件管理系统发行、管理与控制，例如与批生产有关的文件，如批生产记录，生产与包装说明，原始数据记录，分发记录，标准操作程序，规格，检测方法；与批生产无关的文件，如确认与验证文件，投诉与召回记录，环境监测记录，设备监控记录，变更控制记录，工程图纸，保养与校正记录，设备日志，人员培训记录，技术协议，调查研究与报告记录，清洁与卫生记录，控制区人员出入记录，蚊虫控制记录，稳定性记录，审计记录，法规文件等。 Modifications to M-aster Documents are managed through Change Control. 主文件的修订按变更控制程序进行管理。 All incoming raw materials are quarantined until all the tests required by the specification have been performed and found to be satisfactory. 所有进厂的原料被隔离，直到按照指定的规格进行检测并且所有检测结果均符合要求。 A numbered copy of the M-aster batch production record is produced for every batch which serves as an Operating Procedure. 将主批生产记录编号后的副本，按操作程序填写每批的批生产记录。（总是难以翻译顺畅） The guidelines used in the packaging and labeling of APIs are defined in approved packaging assembly specifications. The packaging orders are prepared for specified quantities, and whenever possible, an entire batch is packaged at one time. The packaging is performed in a manner such as to avoid mix-ups and prevent cross contamination. 批准的包装规格中规定了APIs包装与贴签的准则。包装量按规定的数量准备，无论如何，一个完整的批号应在一个时间内包装完成。包装以一种方式进行，以避免混批以及预防交叉污染。 Adequate sampling and controls are set for all the critical process steps for each product to ensure that each operation is satisfactory. 每一批生产中所有关键工艺步骤要设定足够的取样与控制，以保证每一批的操作是令人满意的。 Representative samples of the batch are sampled at various intervals during production and processing to ensure quality of the final product. 在生产与操作过程中，以不同的间隔对生产批的代表性样品进行取样，以确保最终产品的质量。 5.2 SOPs 标准操作程序 A list of all SOPs. 所有SOP的列表 [注：以附录的形式提供一份与生产有关的所有SOP的目录] 6. Quality Control
质量控制 6.1 Release of batches 批放行 Name and function of the person who have responsibility for the release of Packaging materials, Bulk Products, Raw Material: XX, QA manager 负责包装材料、原料药产品、原辅料的人及其岗位 6.2 Brief description of Quality Control System 质量控制系统简述 Quality Control has a well-equipped laboratory for the physical, analytical and microbiological testing of raw materials, intermediates and Finished API. 质量控制部门有一个设备完善的实验室，负责对原料、中间体以及原料药产品进行物理、化学及微生物检测。 A Quality Control sampler takes samples in a sampling booth according to specific sampling plans. 质量控制部门的取样员根据规定的取样计划在取样间进行取样。 The samples are logged into the laboratory and allocated to the relevant section for testing. 所取样品在实验室登记并分发到相关的检测岗位。 Materials and products are tested according to registered testing specifications. Methods have been validated according to the M-aster Validation Program. 原料及产品根据已注册的测试规格进行测试。检测方法已根据验证主计划进行了验证。 Results are reported on a Laboratory Test sheets and supplied to the relevant Supervisor who reviews the results and gives a final disposition on the material or product tested. 检测结果报告在实验室的测试单上，提供给相关的负责结果审核的管理者并对原料或产品的测试结果给出一个最终的处理。 Release of products entails a Batch Record and Quality Control documentation reviewed prior to release. 产品的放行需要一个批记录以及先前被审核放行的质量控制部门的文件。 [注：我理解为需要批记录以及QC的质量检验合格报告单才能放行] 7. Distribution, Complaints and Product Recalls 分发、投诉与产品召回 A procedure is established for the handling of customer complaints and product recalls. The site SOPs describe all necessary steps, starting from the notification recording, investigation and subsequent actions, which must be carried out for any customer complaint received and potential recall. The content of the investigation include Batch Production Record, retest of reserve samples and test of samples provided by customers. All related complaints and recalls must be recorded, including product name, batch number, receiving date, cause of recall, etc. 建立客户投诉与召回的处理程序。厂地SOPs描述了所有必要的步骤，从通知记录，调查以及后来的行动开始，收到的任何客户投诉以及潜在的召回都必须实施。调查内容包括批生产记录、留样样品的复测以及客户提供样品的测试。必须记录所有的投诉与召回，包括产品名称，批号，收到日期，召回的原因等。 8. Self-inspections 自检 In order to monitor the implementation of good manufacturing practice, any necessary corrective measures and regular internal audits are performed in accordance with an approved schedule. A full general GMP inspection is carried out in each year. In addition, inspections for parts of GMP system will be carried out every month. 为了监控GMP的执行情况，应根据批准的时间表执行任何必要的纠正措施以及定期的内部审计。每年执行一次全面的GMP检查，另外，每个月执行一次GMP系统的部分检查。 When the self-inspection has been completed, QA will discuss the deficiencies observed during the inspection with representatives of the departments. Corrective actions will be completed in a timely and effective manner under the supervision of QA. Audit findings and corrective actions will be documented. 自检完成后，QA将与相关的部门讨论审计中所发现的缺陷，在QA的监督下以及时、有效的方式完成纠正行动。审计结果以及纠正行动记录将被存档保存。 . . . . 结束... |
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