今年5 月，世卫组织（WHO） 修订了自 2012 年起生效的制药用水指南，发布征求意见草案。根据反馈意见，7 月 30 日，WHO发布了该指南草案的修订稿，用于二次征求意见。

基于第二次征求意见收到的反馈，将形成最终版本，并计划于今年10 月举行的第55届药物制剂专家委员会（ECSPP）会议上对此进行讨论，以通过本指南的定稿。

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该版本在初稿的基础上做了较大的修订，主要变化的中英对照总结如下：

第2章：水要求和用途背景

主要变化：强调了水的等级应与产品性质、用途、阶段相匹配。

修订内容：描述水的质量标准时，引用了药典

2.4 Different grades of water quality exist. The appropriate water quality, meeting its defined specification (such as described in a pharmacopoeia), should be used for the intended application.
存在有不同级别的水质。应根据目标用途使用符合指定质量标准的水，如参考药典的要求。
新增内容

2.5 The application of specific types of water to processes and dosage forms should be considered.
2.5应考虑将特定类型的水应用于工艺和剂型。
2.6 Pharmaceutical manufacturers should use the appropriate grade of WPU during, for example, the manufacture of APIs and different dosage forms, for different stages in washing and cleaning, and in the synthesis of materials and products.
2.6制药商应在 生产API和不同剂型，清洗和清洁的不同阶段、以及材料和产品的合成过程中，使用适当级别的WPU（制药用水）。
2.7 The grade of water used should take into account the nature and intended use of the intermediate or FPP and the stage in the manufacturing process at which the water is used.
2.7用水等级应考虑中间体或FPP的性质和预期用途、以及 生产过程中使用该水的阶段。
2.8 Bulk water for injections (BWFI) should be used, for example, in the manufacture of injectable products, such as dissolving or diluting substances or preparations during the manufacturing of parenteral products, and for the manufacture of water for preparation of injections. BWFI should also be used for the final rinse after the cleaning of equipment and components that come into contact with injectable products, as well as for the final rinse in a washing process in which no subsequent thermal or chemical depyrogenization process is applied.
2.8散装注射用水（BWFI）应用于生产注射产品，例如注射产品生产过程中溶解或稀释物质或制剂，以及用于生产注射用水。BWFI还应用于清洁与可注射产品接触的设备和组件之后的最终冲洗，以及用于清洗过程中的最终冲洗（不进行后续热或化学去热原工艺）。

第4章：水的质量标准

新增内容：第 4.2 节“饮用水“增加备注

4.2 Drinking-water饮用水
Note: The requirements for the design, construction and commissioning of drinking water systems are usually controlled through local regulations. Drinking water systems are not usually qualified or validated.
注意：饮用水系统的设计、建造和调试要求通常由当地法规控制。饮用水系统通常未经确认或验证。
删除原第 4.4 节“散装高纯水“的内容
4.4 Bulk highly purified water

第 7 章：水系统的良好实践

主要变化
修订7.2小节-设计和施工方法（design and construction practices）：该部分进行了分类细化，分别从“饮用水贮存、供应和分配系统”以及“纯化水和散装注射用水系统”，阐述了水系统的良好实践。
饮用水-修订

For drinking water storage, supply and distribution systems on-site
Materials of construction should be selected based on the following requirements:
• ability to operate at the temperatures/pressures required;
• lack of impact to the final water quality;
• resistant to any sanitizing chemicals that may be used;
• threaded and flanged joints are permitted; and
• sample valves should preferably be of sanitary design.
Note that the system may have a design life at the end of which it should be replaced/adequately maintained.
用于现场的饮用水存储、供应和分配系统
结构材料应根据以下要求进行选择：
在所需温度/压力下运行的能力；
对最终水质没有影响；
抵抗可能使用的任何消毒化学品；
允许使用螺纹和法兰连接。
进样阀最好采用卫生设计。
请注意，系统可能具有设计寿命，应在使用寿命结束时对其进行更换/充分维护。

纯化水和散装注射用水系统 -修订

For purified water and bulk water for injection systems
Note: Construction standards are generally aligned with potable water standards up to the process stage.
• Materials of construction should be appropriate. It should be non-leaching, non- adsorbing, non-absorbing and resistant to corrosion. Stainless-steel grade 316L or PVDC is generally recommended. The choice of material should take into account the intended sanitization method.
• Stainless steel systems should be orbitally welded, with manual welds where necessary. Inter-weldability between materials should be demonstrated with the maintenance of weld quality through a defined process. Documentation for such a system should be kept and should include, as a minimum, the qualification of the welder, welder set-up, work session test pieces (coupons or weld samples), proof of quality of gas used, welding machine calibration record, weld identification and heat numbers, and logs of all welds. Records, photographs or videos of inspection of a defined proportion of welds (e.g. 100% manual welds, 10% orbital welds).
• Joints should be made using sanitary connections, for example, Tri-clover joints. Threaded joints should not be permitted. Polyvinylidene fluoride or polyvinylidene difluoride (PVDF) systems should be fusion joined and visually inspected.
• Passivation should be considered for stainless steel systems, for example, for non- electropolished surfaces (after initial installation and after significant modification) in accordance with a documented procedure defining the solution to be used, its concentration, the temperature and contact time.
• Internal finish should be smooth.
• Flanges, unions and valves should be of a hygienic or sanitary design. Valves should be diaphragm type forged or machined body, with points of use constructed so that they can drain. Sample valves should be sanitary type with the surface roughness of 1.0 micron for PW and WFI systems and are typically installed between process stages and on the distribution loop return. The appropriate checks should be carried out in order to ensure that the correct seals and diaphragms are used and that they are fitted and tightened correctly.
• The system should be installed to promote drainability with a recommended minimum slope of 1/100.
• Where appropriate, pressure or hydro-tests for leaks, spray-ball functionality test and flow turbulence should be considered.
• Provision should be made for on-line measurement for total organic carbon (TOC), conductivity and temperature.
• Documents should provide evidence of system components and qualification. These include as applicable drawings, original or certified copies of certificates of conformity for materials of construction, records of on-site tests performed, weld/joining records, calibration certificates, system pressure test records and records of passivation.
用于纯化水和散装注射用水系统
注意：在整个过程阶段，施工标准通常与饮用水标准保持一致。
结构材料应适当。它应该是非浸出、非吸附、非吸收和耐腐蚀的。通常建议使用不锈钢等级316L或PVDC。材料的选择应考虑到预期的消毒方法。
不锈钢系统应进行轨道焊接，并在必要时进行手工焊接。材料之间的可焊接性应通过规定的过程证明保持焊接质量。应保留此类系统的文件，并且至少应包括焊工的资格、焊工的设置、工作阶段的试件（焊缝样品）、所用气体的质量证明、焊机校准记录、焊缝识别和加热编号，以及所有焊缝的记录。检查一定比例的焊缝的记录、照片或录像（例如100％手工焊，10％轨道焊）。
接头应使用卫生连接制成，例如三叶接头。不允许使用螺纹接头。聚偏二氟乙烯或聚偏二氟乙烯（PVDF）系统应进行熔接，并进行目视检查。
对于不锈钢系统，例如对于未经电抛光的表面（在初次安装后和进行重大改造后），应考虑钝化，要按照规定使用溶液，其浓度、温度和接触时间按照书面程序进行。
内部光洁度应光滑。
法兰、活接头和阀门应设计卫生。阀门应为膜片式锻造或机械加工阀体，其使用点应构造成可以排放的。样品阀应为卫生型，用于PW和WFI系统的表面粗糙度为1.0微米，通常安装在工艺阶段之间和分配回路的回流口上。应进行适当的检查，以确保使用正确的密封件和隔膜，并正确安装和拧紧它们。
应安装系统以提高排水性，建议的最小斜率为1/100。
在适当的情况下，应考虑对泄漏的压力或水压测试，喷球功能测试和流动湍流。
应提供在线测量总有机碳（TOC）、电导率和温度的措施。
文件应提供系统组成和资格证明。这些包括适用的图纸、建筑材料合格证书的原始或经认证的副本、现场测试记录、焊接/连接记录、校准证书、系统压力测试记录和钝化记录。

第 8 章：系统消毒和生物负荷控制

主要变化：修订8.2小节，增加应考虑的其它控制技术
8.2 Controls may include using chemical and/or thermal sanitization procedures as appropriate (e.g. production, storage and distribution). The procedure and conditions used, such as times and temperatures, as well as the frequency, should be defined and proven to be effective for sanitizing all relevant parts of the system. The techniques employed should be considered during the design stage of the system as the procedure and technique may impact on the components and materials of construction.
8.2控制措施可包括酌情使用化学和/或热消毒程序（例如生产，储存和分配）。应该定义所使用的程序和条件（例如时间和温度以及频率），并证明对消毒系统的所有相关部分均有效。在系统的设计阶段应考虑采用的技术，因为程序和技术可能会影响构造的组件和材料。

第 10 章：水分配

主要变化：删除了热交换器使用的一些具体要求。

删除内容

10.4 Where heat exchangers are employed to heat or cool WPU within a system, precautions should be taken in order to prevent the heating or cooling utility from contaminating the water.
如果使用了热交换器加热或冷却系统中的WPU，则应采取预防措施防止加热或冷却系统对 水产生污染。
10.5 Secure types of heat exchangers, such as double tube plate, double plate and frame, or tube and shell configuration, should be considered. Where these types are not used, an alternative approach whereby the utility is maintained and monitored at a lower pressure than the WPU may be considered. The latter approach is not usually appropriate in BWFI systems.
应考虑使用安全型的热交换器，如双管板、双板和双框，或管壳设计的热交换器。如果不是 使用此类热交换器，则应考虑维持公用系统的压力低于WPU并进行监测。后一种方法通常 不合适用于BWFI系统。

第11章：运行考量，包括一些确认和验证原则

主要变化
删除原第 11 章“生物污染控制技术“（11. Biocontamination control techniques）的内容。原 12 章运行考量（Operational considerations）修改为11章：运行考量，包括一些确认和验证原则（Operational considerations including some qualification and validation principles）
删除内容

12.2 There should be documented evidence of consideration and execution of stages of qualification including, as appropriate, URS, factory acceptance testing (FAT), site acceptance testing (SAT), design qualification (DQ), IQ, OQ and PQ.
应有书面证据证明考虑和执行了不同阶段的确认，包括（适当时）URS、工厂接收测试 （FAT）、现场接收测试（SAT）、设计确认（DQ）、IQ、OQ和 PQ。

第14章（原15章）：系统回顾

主要变化
删除原15.4-15.9的内容，即“工艺和制剂应考虑使用特定类型水”及其相关要求。

第15章（原16章）：水系统检查

主要变化
删除原16.3的内容，即审计或检查中可包括的具体项目。
Ref.: [WHO][2020-07-30]Good manufacturing practices: water for pharmaceutical use