准，应当指定合适的物理/化学特性、微生物总数、控制菌和/或内毒素的规格标准。
4.33 Where water used in the process is treated by the manufacturer to achieve a defined quality, the treatment process should be validated and monitored with appropriate action limits. 4.33 在工艺用水为达到规定质量由制造商进行处理时，处理工艺应当经过验证，并用合适的处置限度来监测。
4.34 Where the manufacturer of a nonsterile API either intends or claims that it is suitable for use in further processing to produce a sterile drug (medicinal) product, water used in the final isolation and purification steps should be monitored and controlled for total microbial counts, objectionable organisms, and endotoxins.
4.34 当非无菌原料药的制造商打算或者声称该原料药适用于进一步加工生产无菌药品（医疗用品）时，最终分离和精制阶段的用水应当进行微生物总数、致病菌和内毒素方面的监测和控制。
4.4 Containment 4.4 限制
4.40 Dedicated production areas, which can include facilities, air handling equipment and/or process equipment, should be employed in the production of highly sensitizing materials, such as penicillins or cephalosprins.
4.40 在高致敏性物质，如青霉素或头孢菌素类的生产中，应当使用专用的生产区，包括设施、空气处理设备和/或工艺设备。
4.41 The use of dedicated production areas should also be considered when material of an infectious nature or high pharmacological activity or toxicity is involved (e.g., certain steroids or cytotoxic anti-cancer agents) unless validated inactivation and/or cleaning procedures are established and maintained.
4.41 当涉及具有感染性、高药理活性或毒性的物料时（如，激素类或抗肿瘤类），也应当考虑专用的生产区，除非已建立并维持一套经验证的灭活和/或清洗程序。
4.42 Appropriate measures should be established and implemented to prevent cross-contamination from personnel and materials moving from one dedicated area to another. 4.42 应当建立并实施相应的措施，防止由于在各专用区域间流动的人员和物料而造成的交叉污染。
4.43 Any production activities (including weighing, milling, or packaging) of highly toxic nonpharmaceutical materials, such as herbicides and pesticides, should not be conducted using the buildings and/or equipment being used for the production of APIs. Handling and storage of these highly toxic nonpharmaceutical materials should be separate from APIs.
4.43 剧毒的非药用物质，如除草剂、杀虫剂的任何生产活动（包括称重、研磨或包装）都不应当使用生产原料药所使用的厂房和/或设备。这类剧毒非药用物质的处理和储存都应当与原料药分开。
4.5 Lighting 4.5 照明
4.50 Adequate lighting should be provided in all areas to facilitate cleaning, maintenance, and
proper operations.
4.50 所有区域都应当提供充足的照明，以便于清洗、保养或其它操作。
4.6 Sewage and Refuse 4.6 排污和垃圾
4.60 Sewage, refuse, and other waste (e.g., solids, liquids, or gaseous by-products from manufacturing) in and from buildings and the immediate surrounding area should be disposed of in a safe, timely, and sanitary manner. Containers and/or pipes for waste material should be clearly identified.
4.60 进入和流出厂房及邻近区域的污水、垃圾和其它废物（如生产中的固态、液态或气态的副产物），应当安全、及时、卫生的处理。废物的容器和/或管道应当显著地标明。
4.7 Sanitation and Maintenance 4.7 卫生和保养
4.70 Buildings used in the manufacture of intermediates and APIs should be properly maintained and repaired and kept in a clean condition.
4.70 生产中间体和原料药的厂房应当适当地保养、维修并保持清洁。
4.71 Written procedures should be established assigning responsibility for sanitation and describing the cleaning schedules, methods, equipment, and materials to be used in cleaning buildings and facilities.
4.71 应当制定书面程序来分配卫生工作的职责，并描述用于清洁厂房和设施的清洁的计划、方法、设备和材料。
4.72 When necessary, written procedures should be established for the use of suitable rodenticides, insecticides, fungicides, fumigating agents, and cleaning and sanitizing agents to prevent the contamination of equipment, raw materials, packaging/labeling materials, intermediates, and APIs.
.72 必要时，还应当对合适的灭鼠药、杀虫剂、杀真菌剂、烟熏剂和清洁消毒剂的使用制定书面程序，以避免对设备、原料、包装/标签、中间体和原料药的污染。
5. PROCESS EQUIPMENT 5. 工艺设备
5.1 Design and Construction 5.1 设计和结构
5.10 Equipment used in the manufacture of intermediates and APIs should be of appropriate design and adequate size, and suitably located for its intended use, cleaning, sanitation (where appropriate), and maintenance.
5.10 中间体和原料药生产中使用的设备应当有合理的设计和足够的尺寸，并且放置在适宜于其使用、清洁、消毒（根据情况而定）和保养的地方。
5.11 Equipment should be constructed so that surfaces that contact raw materials, intermediates, or APIs do not alter the quality of the intermediates and APIs beyond the official or other established specifications.
5.11 设备的构造中与原料、中间体或原料药接触的表面不会改变中间体和原料药的质量而使其不符合法定的或其他已规定的质量标准。
5.12 Production equipment should only be used within its qualified operating range.
5.12 生产设备应该只在其确认的操作范围内运行。
5.13 Major equipment (e.g., reactors, storage containers) and permanently installed processing lines used during the production of an intermediate or API should be appropriately identified. 5.13 中间体或原料药生产过程中使用的主要设备（如反应釜、贮存容器）和永久性安装的工艺管道，应当作适当的识别标志。
5.14 Any substances associated with the operation of equipment, such as lubricants, heating fluids or coolants, should not contact intermediates or APIs so as to alter the quality of APIs or intermediates beyond the official or other established specifications. Any deviations from this practice should be evaluated to ensure that there are no detrimental effects on the material’s fitness for use. Wherever possible, food grade lubricants and oils should be used.
5.14 设备运转所需的任何物质，如润滑剂、加热液或冷却剂，不应当与中间体或原料药接触，以免影响其质量，导致无法达到法定的或其它已规定的质量标准。任何违背该规定的情况都应当进行评估，以确保对该物质效果的适用性没有有害的影响。可能的话，应当使用食用级的润滑剂和油类。
5.15 Closed or contained equipment should be used whenever appropriate. Where open equipment is used, or equipment is opened, appropriate precautions should be taken to minimize the risk of contamination.
5.15 应当尽量使用关闭的或封闭的设备。若使用开放设备或设备被打开时，应当采取适当的预防措施，将污染的风险降至最小。
5.16 A set of current drawings should be maintained for equipment and critical installations (e.g., instrumentation and utility systems).
5.16 应当保存一套现在的设备和关键装置的图纸（如测试设备和公用系统）。
5.2 Equipment Maintenance and Cleaning 5.2 设备保养和清洁
5.20 Schedules and procedures (including assignment of responsibility) should be established for the preventative maintenance of equipment.
5.20 应当制订设备预防性保养的计划和程序（包括职责的分配）。
5.21 Written procedures should be established for cleaning equipment release for use in the manufacture of intermediates and APIs. Cleaning procedures should contain sufficient details to enable operators to clean each type of equipment in a reproducible and effective manner. These procedures should include:
5.21 应当制订设备清洗及允许用于中间体和原料药生产的书面程序。清洁程序应当尽量详细，使操作者能对各类设备进行可重复的、有效 的清洗。这些程序应当包括：
5.22 Equipment and utensils should be cleaned, stored, and, where appropriate, sanitized or sterilized to prevent contamination or carry-over of a material that would alter the quality of the intermediate or API beyond the official or other established specifications.
5.22 设备和用具应当清洁、存放，必要时还应进行消毒或灭菌，以防止污染或夹带物质影
响中间体或原料药的质量导致其不符合法定的或其它已规定的质量标准。
5.23 Where equipment is assigned to continuous production or campaign production of successive batches of the same intermediate or API, equipment should be cleaned at appropriate intervals to prevent build-up and carry-over of contaminants (e.g., degradants or objectionable levels of microorganisms).
5.23 若设备指定用于同一中间体或原料药的连续生产，或连续批号的集中生产，应当在适宜是时间间隔对设备进行清洗，以防污染物（如降解物或达到有害程度的微生物）的累积和夹带。
5.24 Nondedicated equipment should be cleaned between production of different materials to prevent cross-contamination.
5.24 非专用设备应当在生产不同物料之间作清洁，以防止交叉污染。
5.25 Acceptance criteria for residues and the choice of cleaning procedures and cleaning agents should be defined and justified.
5.25 对残留物的可接受限量、清洗程序和清洁剂的选择应当规定并说明理由。
5.26 Equipment should be identified as to its contents and its cleanliness status by appropriate means.
5.26 设备内容物及其清洁状况应当用合适的方法标明。
5.3 Calibration 5.3 校验
5.30 Control, weighing, measuring, monitoring, and testing equipment critical for ensuring the quality of intermediates or APIs should be calibrated according to written procedures and an established schedule.
5.30 用于保证中间体或原料药质量的控制、称量、测量、监测和测试设备应当按照书面程序和规定的计划周期进行校验。
5.31 Equipment calibrations should be performed using standards traceable to certified standards, if they exist.
5.31 如果有的话，应当用可追溯到已检定的标准的标准来进行设备校验。
5.32 Records of these calibrations should be maintained. 5.32 校验记录应当加以保存。
5.33 The current calibration status of critical equipment should be known and verifiable. 5.33 应当知道并可证实关键设备的当前校验状态。
5.34 Instruments that do not meet calibration criteria should not be used. 5.34 不应当使用不符合校验标准的仪器。
5.35 Deviations from approved standards of calibration on critical instruments should be investigated to determine if these could have had an effect on the quality of the intermediates(s) or API(s) manufactured using this equipment since the last successful calibration.
5.35 应当调查关键仪器相对于合格校验标准的偏差，以便确定这些偏差对自上次成功校验以来，用该设备生产的中间体或原料药的质量是否有影响。
5.4 Computerized Systems 5.4 计算机控制系统
5.40 GMP-related computerized systems should be validated. The depth and scope of validation depends on the diversity, complexity, and criticality of the computerized application. 5.40 与GMP相关的计算机化系统应当验证。验证的深度和广度取决于计算机应用的差异性、复杂性和关键性。
5.41 Appropriate installation and operational qualifications should demonstrate the suitability of computer hardware and software to perform assigned tasks.
5.41 适当的安装确认和操作确认应当能证明计算机硬件和软件适合于执行指定的任务。
5.42 Commercially available software that has been qualified does not require the same level of testing. If an existing system was not validated at time of installation, a retrospective validation could be conducted if appropriate documentation is available.
5.42 经证明合格的商用软件不需要进行系统水平的检验。如果现行系统在安装时没有进行验证，有合适的文件证明时可进行回顾性验证。
5.43 Computerized system should have sufficient controls to prevent unauthorized access or changes to data. There should be controls to prevent omissions in data (e.g., system turned off and data not captured). There should be a record of any data change made, the previous entry, who made the change, and when the change was made.
5.43 计算机化系统应当有足够的控制，以防止未经许可存取或改动数据。应当有防止数据丢失（如系统关闭而数据未捕获）的控制。任何数据的变更、上一次输入、谁作的变更和什么时候变更都应当有记录。
5.44 Written procedures should be available for the operation and maintenance of computerized system.
5.44 应当有计算机化系统操作和维护的书面程序。
5.45 Where critical data are being entered manually, there should be an additional check on the accuracy of the entry. This can be done by a second operator or by the system itself.
5.45 手工输入关键性数据时，应当另外检查输入的准确性。这可由第二位操作人员或系统本身来进行。
5.46 Incidents related to computerized system that could affect the quality of intermediates or APIs or the reliability of records or test results should be recorded and investigated.
5.46 应当加以记录可能影响中间体或原料药质量、或者记录或测试结果可靠性的与计算机化系统有关的偶发事件，并作调查。
5.47 Changes to computerized system should be made according to a change procedure and should be formally authorized, documented, and tested. Records should be kept of all changes, including modifications and enhancements made to the hardware, software, and any other
美国FDA原料药生产质量管理规范（ 中英文）
