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4.5 Lighting
4.50 Adequate lighting should be provided in all areas to facilitate cleaning, maintenance, and proper operations.
4.6 Sewage and Refuse
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.
4.7 Sanitation and Maintenance
4.70 Buildings used in the manufacture of intermediates and APIs should be properly maintained and repaired and kept in a clean condition.
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.
4.72 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.
5. PROCESS EQUIPMENT 5.1 Design and Construction
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.
4.5 照明
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 排污和垃圾
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 卫生和保养
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 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 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. 工艺设备 5.1 设计和结构
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。
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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.
5.12 Production equipment should only be used within its qualified operating range.
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.
5.14 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.
5.15 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.
5.16 A set of current drawings should be maintained for equipment and critical installations (e.g., instrumentation and utility systems).
5.2 Equipment Maintenance and Cleaning 5.20 Schedules and procedures (including assignment of responsibility) should be established for the preventative maintenance of equipment.
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 生产设备应该只在其确认的操作范围内运行。
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 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 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 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 设备保养和清洁
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）。
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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: ● Assignment of responsibility for cleaning
of equipment ● Cleaning schedules, including, where
appropriate, sanitizing schedules ● A complete description of the methods and
materials, including dilution of cleaning agents used to clean equipment ● When appropriate, instructions for
disassembling and reassembling each article of equipment to ensure proper cleaning ● Instructions for the removal or obliteration
of previous batch identification ● Instructions for the protection of clean
equipment from contamination prior to use ● Inspection of equipment for cleanliness
immediately before use, if practical ● Establishing the maximum time that may
elapse between the completion of processing and equipment cleaning, when appropriate
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.
5.23 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).
5.21 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：
● 设备清洗职责分配；
● 清洗计划，必要时包括消毒计划；
● 方法和材料的详尽描述，包括用于清洗设
备的清洗剂的稀释方法；
● 为确保正确的清洗，根据具体情况还应当
包括包装设备拆卸和安装的方法；
● 拿走或抹掉上一批的标识；
● 使用前防止已清洁的设备被污染；
● 如果可行，使用前对设备进行检查；
● 根据情况，规定生产结束和清洗之间允许
的最大时间间隔。
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 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。
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5.24 Nondedicated equipment should be cleaned between production of different materials to prevent cross-contamination.
5.25 Acceptance criteria for residues and the choice of cleaning procedures and cleaning agents should be defined and justified.
5.26 Equipment should be identified as to its contents and its cleanliness status by appropriate means.
5.3 Calibration
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.
5.31 Equipment calibrations should be performed using standards traceable to certified standards, if they exist.
5.32 Records of these calibrations should be maintained.
5.33 The current calibration status of critical equipment should be known and verifiable.
5.34 Instruments that do not meet calibration criteria should not be used.
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.
5.4 Computerized Systems
5.40 GMP-related computerized systems should be validated. The depth and scope of validation depends on the diversity, complexity, and
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 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 设备内容物及其清洁状况应当用合适的方法标明。
5.3 校验
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 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 校验记录应当加以保存。
5.33 应当知道并可证实关键设备的当前校验状态。
5.34 不应当使用不符合校验标准的仪器。
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 计算机控制系统
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。
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criticality of the computerized application.
5.41 Appropriate installation and operational qualifications should demonstrate the suitability of computer hardware and software to perform assigned tasks.
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.
5.43 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.
5.44 Written procedures should be available for the operation and maintenance of computerized system.
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.
5.46 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.
5.47 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 critical component of the system.
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 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 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 应当有计算机化系统操作和维护的书面程序。
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 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 对计算机化系统所作的变更应当按照变更程序进行，并应当经过正式批准、记录成文并作测试。所有变更记录都应当保存，包括对系统的硬件、软件和任何其它关键组件的修改和升级。这些记录应当证明该系统维持在验证过的状态。
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