2.3 Responsibility for Production Activities 2.3生产作业的职责
The responsibility for production activities should be described in writing and should include, but not necessarily be limited to:
1. Preparing, reviewing, approving, and distributing the instructions for the production of intermediates or APIs according to written procedures
2. Producing APIs and, when appropriate, intermediates according to pre-approved instructions 3. Reviewing all production batch records and ensuring that these are completed and signed 4. Making sure that all production deviations are reported and evaluated and that critical deviations are investigated and the conclusions are recorded
5. Making sure that production facilities are clean and, when appropriate, disinfected 6. Making sure that the necessary calibrations are performed and records kept 7. Making sure that the premises and equipment are maintained and records kept 8. Making sure that validation protocols and reports are reviewed and approved 9. Evaluating proposed changes in product, process or equipment
10. Making sure that new and, when appropriate, modified facilities and equipment are qualified 生产作业的职责应当以文字形式加以说明，并应当包括，但不限于以下内容： 1. 按书面程序起草、审核、批准和分发中间体或原料药的生产指令； 2. 按照已批准的指令生产原料药或者中间体； 3. 审核所有的批生产记录确保其完整并有签名；
4. 确保所有的生产偏差都已报告、评价，对关键的偏差已做了调查，并记录结论； 5. 确保生产设施的清洁，必要时要消毒； 6. 确保进行必要的校验，并有记录；
7. 确保对厂房和设备进行保养，并有记录； 8. 确保验证方案和报告的审核与批准；
9. 对产品、工艺或设备拟作的变更进行评估；
10. 确保新的或已改进的生产设施和设备经过了确认。
2.4 Internal Audits (Self Inspection) 2.4内部审计（自检）
2.40 To verify compliance with the principles of GMP for APIs, regular internal audits should be performed in accordance with an approved schedule.
2.40 为确实符合原料药GMP原则，应当按照批准的计划进行定期的内部审计。
2.41 Audit findings and corrective actions should be documented and brought to the attention of responsible management of the firm. Agreed corrective actions should be completed in a timely and effective manner.
2.41 审计结果及整改措施应当形成文件，并引起公司责任管理人员的重视。获准的整改措施应当及时、有效地完成。
2.5 Product Quality Review 2.5产品质量审核
2.50 Regular quality-reviews of APIs should be conducted with the objective of verifying the consistency of the process. Such reviews should normally be conducted and documented annually and should include at least:
A review of critical in-process control and critical API test results
A review of all batches that failed to meet established specification(s)
A review of all critical deviations or nonconformances and related investigations A review of any changes carried out to the processes or analytical methods A review of results of the stability monitoring program
A review of all quality-related returns, complaints and recalls A review of adequacy of corrective actions
2.50 原料药的定期质量审核应当以证实工艺的一致性为目的来进行。此种审核通常应当每年进行一次，并记录，内容至少应当包括：
关键工艺控制以及原料药关键测试结果的审核； 所有不符合既定质量标准的产品批号的审核； 所有关键的偏差或违规行为及有关调查的审核； 任何工艺或分析方法变动的审核； 稳定性监测的审核；
所有与质量有关的退货、投诉和召回的审核； 整改措施的适当性的审核。
2.51 The results of this review should be evaluated and an assessment made of whether corrective action or any revalidation should be undertaken. Reasons for such corrective action should be documented. Agreed corrective actions should be completed in a timely and effective manner.
应当对质量审核结果进行评估，并做出是否需要整改或做任何再验证的评价。此类整改措施的理由应当文件化。获准的整改措施应当及时、有效地完成。
3. PERSONNEL 3. 人员
3.1 Personnel Qualifications 3.1员工的资质
3.10 There should be an adequate number of personnel qualified by appropriate education, training, and/or experience to perform and supervise the manufacture of intermediates and APIs.
3.10 应当有足够数量的员工具备从事和监管原料药和中间体生产的教育、培训和/或经历等资格。
3.11 The responsibilities of all personnel engaged in the manufacture of intermediates and APIs should be specified in writing.
3.11 参与原料药和中间体生产的所有人员的职责应当书面规定。
3.12 Training should be regularly conducted by qualified individuals and should cover, at a minimum, the particular operations that the employee performs and GMP as it relates to the employee’s functions. Records of training should be maintained. Training should be periodically assessed.
3.12 应当由有资格的人员定期进行培训，内容至少应当包括员工所从事的特定操作和与其职能有关的GMP。培训记录应当保存，并应当定期对培训进行评估。
3.2 Personnel Hygiene 3.2 员工的卫生
3.20 Personnel should practice good sanitation and health habits.
3.20 员工应当养成良好的卫生和健康习惯。
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.
3.21 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 Personnel should avoid direct contact with intermediates and APIs.
3.22 员工应当避免与中间体或原料药的直接接触。
3.23 Smoking, eating, drinking, chewing and the storage of food should be restricted to certain designated areas separate from the manufacturing areas.
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 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.
3.24 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 Consultants 3.3 顾问
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 retained.
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。
3.31 Records should be maintained stating the name, address, qualifications, and type of service provided by these consultants.
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. BUILDINGS AND FACILITIES 4. 建筑和设施 4.1 Design and Construction 4.1 设计和结构
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.
4.10 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 Buildings and facilities should have adequate space for the orderly placement of equipment and materials to prevent mix-ups and contamination.
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 Where the equipment itself (e.g., closed or contained system) provides adequate protection of the material, such equipment can be located outdoors.
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 The flow of materials and personnel through the building or facilities should be designed to prevent mix-ups and contamination.
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 There should be defined areas or other control systems for the following activities: 以下活动应当有指定区域或其它控制系统：
4.15 Adequate and clean washing and toilet facilities should be provided for personnel. These facilities should be equipped with hot and cold water, as appropriate, soap or detergent, air dryers, or single service towels. The washing and toilet facilities should be separate from, but easily accessible to, manufacturing areas. Adequate facilities for showering and/or changing clothes should be provided, when appropriate. 4.15 应当为员工提供足够和清洁的盥洗设施。这些盥洗设施应当装有冷热水（视情况而定）、肥皂或洗涤剂，干手机和一次性毛巾。盥洗室应当与生产区隔离，但要便于达到。应当根据情况提供足够的淋浴和/或更衣设施。
4.16 Laboratory areas/operations should normally be separated from production areas. Some laboratory areas, in particular those used for in-process controls, can be located in production areas, provided the operations of the production process do not adversely affect the accuracy of the laboratory measurements, and the laboratory and its operations do not adversely affect the production process, intermediate, or API.
4.16 实验室区域/操作通常应当与生产区隔离。有些实验室区域，特别是用于中间控制的，可以位于生产区内，只要生产工艺操作对实验室测量的准确性没有负面影响，而且，实验室及其操作对生产过程，或中间体，或原料药也没有负面影响。
4.2 Utilities 4.2 公用设施
4.20 All utilities that could affect product quality (e.g., steam, gas, compressed air, heating, ventilation, and air conditioning) should be qualified and appropriately monitored and action
should be taken when limits are exceeded. Drawings for these utility systems should be available.4.20 对产品质量会有影响的所有公用设施（如蒸汽，气体，压缩空气和加热，通风及空调）都应当确认合格，并进行适当监控，在超出限度时应当采取相应措施。应当有这些公用设施的系统图。
4.21 Adequate ventilation, air filtration and exhaust systems should be provided, where appropriate. These systems should be designed and constructed to minimize risks of 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.
4.21 应当根据情况，提供足够的通风、空气过滤和排气系统。这些系统应当根据相应的生产阶段，设计和建造成将污染和交叉污染降至最低限度，并包括控制气压、微生物（如果适用）、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 If air is recirculated to production areas, appropriate measures should be taken to control risks of contamination and cross-contamination.
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 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.
4.23 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 Drains should be of adequate size and should be provided with an air break or a suitable device to prevent back-siphonage, when appropriate.
4.24 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 Water 4.3 水
4.30 Water used in the manufacture of APIs should be demonstrated to be suitable for its intended use.
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 Unless otherwise justified, process water should, at a minimum, meet World Health Organization (WHO) guidelines for drinking (portable) water quality.
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 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.
4.32 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
美国FDA原料药生产质量管理规范（ 中英文）
