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should be maintained. Training should be periodically assessed.
3.2 Personnel Hygiene
3.20 Personnel should practice good sanitation and health habits.
3.21 Personnel should wear clean clothing suitable for the manufacturing activity with which they are involved and this clothing should be changed, when appropriate. Additional protective apparel, such as head, face, hand, and arm coverings, should be worn, when necessary, to protect intermediates and APIs from contamination.
3.22 Personnel should avoid direct contact with intermediates and APIs.
3.23 Smoking, eating, drinking, chewing and the storage of food should be restricted to certain designated areas separate from the manufacturing areas.
3.24 Personnel suffering from an infectious disease or having open lesions on the exposed surface of the body should not engage in activities that could result in compromising the quality of APIs. Any person shown at any time (either by medical examination or supervisory observation) to have an apparent illness or open lesions should be excluded from activities where the condition could adversely affect the quality of the APIs until the condition is corrected or qualified medical personnel determine that the person’s inclusion would not jeopardize the safety or quality of the APIs.
3.3 Consultants
3.30 Consultants advising on the manufacture and control of intermediates or APIs should have sufficient education, training, and experience, or any combination thereof, to advise on the subject for which they are
3.2 员工的卫生
3.20 员工应当养成良好的卫生和健康习惯。
3.21 员工应当穿着适合其所从事生产操作的干净服装，必要时应当更换。其它保护性用品如头、脸、手和臂等遮护用品必要时也应当佩带，以免原料药和中间体受到污染。
3.22 员工应当避免与中间体或原料药的直接接触。
3.23 吸烟、吃、喝、咀嚼及存放食品仅限于与生产区隔开的指定区域。
3.24 患传染性疾病或身体表面有开放性创伤的员工不应当从事危及原料药质量的生产活动。在任何时候（经医学检验或监控检查）任何患有危及到原料药质量的疾病或创伤的人员都不应当参与作业，直到健康状况已恢复，或者有资格的医学人员确认该员工不会危及到原料药的安全性和质量。
3.3 顾问
3.30 中间体或原料药生产和控制的顾问应当有足够的学历，受训和经验，能胜任所承担的工作。
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retained.
3.31 Records should be maintained stating the name, address, qualifications, and type of service provided by these consultants.
4. BUILDINGS AND FACILITIES 4.1 Design and Construction
4.10 Buildings and facilities used in the manufacture of intermediates and APIs should be located, designed, and constructed to facilitate cleaning, maintenance, and operations as appropriate to the type and stage of manufacture. Facilities should also be designed to minimize potential contamination. Where microbiological specifications have been established for the intermediate or API, facilities should also be designed to limit exposure to objectionable microbiological contaminants, as appropriate.
4.11 Buildings and facilities should have adequate space for the orderly placement of equipment and materials to prevent mix-ups and contamination.
4.12 Where the equipment itself (e.g., closed or contained system) provides adequate protection of the material, such equipment can be located outdoors.
4.13 The flow of materials and personnel through the building or facilities should be designed to prevent mix-ups and contamination.
4.14 There should be defined areas or other control systems for the following activities:
3.31 顾问的姓名、地址、资格和提供服务的类型都应当有文字记录。
4. 建筑和设施 4.1 设计和结构
4.10 用于中间体和原料药生产的厂房和设施的选址、设计和建造应当便于清洁，维护和适应一定类型和阶段的生产操作。设施的设计应尽量减少潜在的污染。如果中间体或原料药的生产有微生物限度要求，那么设施设计应相应的限制有害微生物的污染。
4.11 厂房和设施应有足够空间，以便有秩序地放置设备和物料，防止混淆和污染。
4.12 自身能对物料提供足够保护的设备（如关闭的或封闭的系统），可以在户外放置。
4.13 通过厂房和设施的物流和人流的设计应当能防止混杂和污染。
4.14 以下活动应当有指定区域或其它控制系统：
● Receipt, identification, sampling, and ● 来料的接收、鉴别、取样和待验，等待放
quarantine of incoming materials, pending 行或拒收； release or rejection ● 中间体和原料药放行或拒收前的待验； ● Quarantine before release or rejection of ● 中间体和原料药的取样
intermediates and APIs ● 不合格物料处理（如退货、返工或销毁）
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前的贮存； ● Sampling of intermediates and APIs
● Holding rejected materials before further ● 已放行物料的贮存；
disposition (e.g., return, reprocessing or ● 生产操作； destruction) ● 包装及贴标签操作；
● 实验室操作。 ● Storage of released materials
● Production operations
● Packaging and labeling operations ● Laboratory operations
4.15 Adequate and clean washing and toilet 4.15 应当为员工提供足够和清洁的盥洗设facilities should be provided for personnel. 施。这些盥洗设施应当装有冷热水（视情况These facilities should be equipped with hot 而定）、肥皂或洗涤剂，干手机和一次性毛巾。and cold water, as appropriate, soap or 盥洗室应当与生产区隔离，但要便于达到。detergent, air dryers, or single service towels. 应当根据情况提供足够的淋浴和/或更衣设The washing and toilet facilities should be 施。 separate from, but easily accessible to, manufacturing areas. Adequate facilities for showering and/or changing clothes should be provided, when appropriate.
4.16 Laboratory areas/operations should 4.16 实验室区域/操作通常应当与生产区隔normally be separated from production areas. 离。有些实验室区域，特别是用于中间控制Some laboratory areas, in particular those used 的，可以位于生产区内，只要生产工艺操作for in-process controls, can be located in 对实验室测量的准确性没有负面影响，而且，production areas, provided the operations of the 实验室及其操作对生产过程，或中间体，或production process do not adversely affect the 原料药也没有负面影响。 accuracy of the laboratory measurements, and the laboratory and its operations do not adversely affect the production process, intermediate, or API. 4.2 Utilities 4.2 公用设施
4.20 All utilities that could affect product 4.20 对产品质量会有影响的所有公用设施quality (e.g., steam, gas, compressed air, （如蒸汽，气体，压缩空气和加热，通风及heating, ventilation, and air conditioning) 空调）都应当确认合格，并进行适当监控，should be qualified and appropriately 在超出限度时应当采取相应措施。应当有这monitored and action should be taken when 些公用设施的系统图。 limits are exceeded. Drawings for these utility systems should be available.
4.21 Adequate ventilation, air filtration and 4.21 应当根据情况，提供足够的通风、空气exhaust systems should be provided, where 过滤和排气系统。这些系统应当根据相应的appropriate. These systems should be designed 生产阶段，设计和建造成将污染和交叉污染and constructed to minimize risks of 降至最低限度，并包括控制气压、微生物（如
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contamination and cross-contamination and should include equipment for control of air pressure, microorganisms (if appropriate), dust, humidity, and temperature, as appropriate to the stage of manufacture. Particular attention should be giving to areas where APIs are exposed to the environment.
4.22 If air is recirculated to production areas, appropriate measures should be taken to control risks of contamination and cross-contamination.
4.23 Permanently installed pipework should be appropriately identified. This can be accomplished by identifying individual lines, documentation, computer control system, or alternative means. Pipework should be located to avoid risks of contamination of the intermediate or ApI.
4.24 Drains should be of adequate size and should be provided with an air break or a suitable device to prevent back-siphonage, when appropriate.
4.3 Water
4.30 Water used in the manufacture of APIs should be demonstrated to be suitable for its intended use.
4.31 Unless otherwise justified, process water should, at a minimum, meet World Health Organization (WHO) guidelines for drinking (portable) water quality.
4.32 If drinking (portable) water is insufficient to ensure API quality and tighter chemical and/or microbiological water quality specifications are called for, appropriate specifications for physical/chemical attributes, total microbial counts, objectionable organisms, and/or endotoxins should be established.
4.33 Where water used in the process is treated
果适用）、灰尘、湿度和温度的设备。特别值得注意的是原料药暴露的区域。
4.22 如果空气再循环到生产区域，应当采取适当的控制污染和交叉污染的风险。
4.23 永久性安装的管道应当有适宜的标识。这可以通过标识每根管道、提供证明文件、计算机控制系统，或其它替代方法来达到。管道的安装处应当防止污染中间体或原料药。
4.24 排水沟应当有足够的尺寸，而且应当根据情况装有空断器或适当的装置，防止倒虹吸。
4.3 水
4.30 原料药生产中使用的水应当证明适合于其预定的用途。
4.31 除非有其它理由，工艺用水最低限度应当符合世界卫生组织（WHO）的饮用水质量指南。
4.32 如果饮用水不足以确保原料的质量，并要求更为严格的化学和/或微生物水质规格标准，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 在工艺用水为达到规定质量由制造商进
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by the manufacturer to achieve a defined quality, the treatment process should be validated and monitored with appropriate action limits.
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.
4.4 Containment
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.
4.41 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.
4.42 Appropriate measures should be established and implemented to prevent cross-contamination from personnel and materials moving from one dedicated area to another.
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.
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 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 限制
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 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 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 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。
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