Working document QAS/20.842
工作文件QAS/20.842
May 2020
二零二零年五月DRAFT WORKING DOCUMENT FOR COMMENTS:
征求意见草案:
Good manufacturing practices:
优良制造规范（GMP）:
water for pharmaceutical use
制药用水
Background
背景
The control of water quality, including microbiological and chemical quality, throughout production, storage and distribution processes is a major concern. Unlike other product and process ingredients, water is usually drawn from an on-demand system and is not subject to testing and batch or lot release prior to use. The assurance of water quality to meet the on-demand expectation is, therefore, essential.
水的制备、存贮和分配过程中对水质的控制，包括微生物和化学质量，是一个重要关注点。与其它产品和工艺成分不同，水通常是来自一个按需运行的系统，在使用之前不会进行检测，也不会进行批放行，因此确保水质符合所需要求就至关重要了。
In recent years, following extensive consultation with stakeholders, several pharmacopoeias have adopted revised monographs on water for injection (WFI) that allow for production by non-distillation technologies, such as reverse osmosis (RO). In 2017, the World Health Organization (WHO) Expert Committee on Specifications for Pharmaceutical Preparations (ECSPP) recommended that the WHO Secretariat collect feedback on whether or not they should revise the WHO specifications and good m
anufacturing practices (GMP) on WFI, and how to do so. Following discussions during several consultations, the ECSPP agreed that the monograph in The International Pharmacopoeia (Water for injections) and the guideline WHO Good manufacturing practices: water for pharmaceutical use (1) should both be revised to allow for technologies other than distillation for the production of WFI. In early 2019, the WHO Secretariat commissioned the preparation of a draft guidance text for the production of WFI by means other than distillation. Following several public consultations, the text was presented to the Fifty-fourth ECSPP. The Expert Committee adopted the Production of water for injection by means other than distillation guideline and recommended that it should also be integrated into WHO’s existing guideline on Good manufacturing practices: water for pharmaceutical use.
近年来，由于干系人提出非常多的建议，几部药典均对注射用水（WFI）进行了修订，允许采用非蒸馏技术如反渗透（RO）制备 WFI。 2017 年， WHO 制剂标准专家委员会（ECSPP）建议 WHO 秘书处收集各方对于是否认为应修订 WHO 标准和 WFI GMP 以及如何修订的反馈。在几次征求意见期间经过讨论之后， ECSPP 同意对国际药典各论（注射用水）和 WHO 指南“GMP：制药用水” 进行修订，允许使用非蒸馏技术制备WFI。2019 年早期，WHO 秘书处协调起草了非蒸馏方法制备WFI 的指南草案。经过几次公开征求意见之后，该文件被提交给第 54 次 ECSPP。专家委员会采纳了“非蒸馏方法制备注射水”的指南，并将建议整合至 WHO 现有指南“GMP：制药用水”中。
This current document is a revision of WHO Good manufacturing practices: water for pharmaceutical use, previously published in the WHO Technical Report Series, No. 970, Annex 2, 2011.
本文件是之前发布为 WHO TRS 970 附录 2， 2011 的“WH O GMP：制药用水”修订本。
1. Introduction
介绍
2. Background to water requirements and uses
水的要求和用途背景
3. General principles for pharmaceutical water systems
制药用水系统的一般原则
4. Water quality specifications
水的质量标准
4.1.  Pharmacopoeial specifications
药典标准
4.2.  Drinking-water
饮用水
4.3.  Bulk purified water
纯化水
4.4.  Bulk highly purified water
高纯水
4.5.  Bulk water for injections
注射用水
4.6.  Other grades of water
其他级别的水
5. General considerations for water purification systems 水净化系统的一般考虑点
6. Water storage and distribution systems
储存和分配系统
7. Good practices for water systems
水系统良好规范
8. System sanitization and bioburden control
系统消毒与生物污染控制
9. Storage vessels
储罐
10. Water distribution
分配系统
11. Biocontamination control techniques
生物污染控制技术
12. Operational considerations
运行的考虑点
12.5 Phase 1
第一阶段
12.6 Phase 2
第二阶段
react to中文12.7 Phase 3
第三阶段
13. Continuous system monitoring
持续系统监测
14. Maintenance of water systems
水系统的维护
15. System reviews
系统回顾
16. Inspection of water systems
水系统的检查
17. References
参考资料
18. Further reading
延伸阅读
1 Introduction and scope
介绍及范围
1.1 This document concerns water for pharmaceutical use (WPU) produced, stored and distributed in bulk form. It intends to provide information about different specifications for WPU; guidance on GMP regarding the quality management of water systems; water treatment (production) systems; water storage and distribution systems; qualification and validation; and sampling, testing and the routine monitoring of water.
本文件包括制药用水（WPU）的生产、储存和分配。本文件提供不同制药用水标准、水系统质量管理的GMP指南、水处理(生产)系统、制药用水储存和分配系统、确认和验证、以及取样、测试和水的日常监测相关的信息。
1.2 Although drinking-water is addressed, the focus of this document is on the treatment, storage and distribution of treated water used in pharmaceutical applications.
虽然提到了饮用水，但本文件的重点是经处理的制药用水的处理、储存和分配。
1.3 This document does not cover water for administration to patients in the formulated state or the us
e of small quantities of water in pharmacies to compound individually prescribed medicines.
本文件不包括处于配方状态的供病人使用的水，或在药房少量使用于配制个别处方药物的水。
1.4 The document can be used in whole or in part, as appropriate, to the section and application under consideration.
本文件可全部或部分(视乎情况而定)用于审议中的部分和申请。
1.5 In addition to this document, the “Further reading” section at the en d of this document includes some relevant publications that can serve as additional background material when planning, installing and using systems intended to provide WPU.
除本文件外，本文件末尾的”延伸阅读”部分还包括一些相关出版物，在计划、安装和使用制药用水系统时可作为补充背景材料。
1.6 This document is supplementary to the World Health Organization (WHO) Good manufacturing practices for active pharmaceutical ingredients (2), and WHO Good manufacturing practices for pharmaceutical products: main principles (3).
本文件是对世界卫生组织(WHO)活物成分GMP(2)和WHO药物成品GMP(3)的补充。2.  Background to water requirements and uses
水的要求和使用背景
2.1 Water is a widely used substance in the pharmaceutical industry. It is extensively used as a raw material or starting material in the production, processing and formulation of active pharmaceutical ingredients (APIs), intermediates and finished pharmaceutical products (FPP), in the preparation of solvents and reagents, and for cleaning (e.g. washing and rinsing). Water has unique chemical properties due to its polarity and hydrogen bonds. It is able to dissolve, absorb, adsorb or suspend different compounds. These would include contaminants that may represent hazards in themselves or that may be able to react with intended product substances, resulting in hazards to health. Water should therefore meet the required quality standards to mitigate these risks.
水是制药工业中广泛使用的物质。它被广泛用作活物成分（API）、中间体和成品（FPP）的生产、加工和配方的原料或起始材料，用于溶剂和试剂的制备，以及用于清洁（如清洗和冲洗）。水由于其极性和氢键，具有独特的化学性质。它能够溶解、吸收、吸附或悬浮不同的化合物。这可能包括本身构成危害或可能与预期产品物质发生反应的污染物，从而对健康造成危害。因此，水应符合必要的质量标准，以减轻这些风险。
2.2 The microbiological and chemical quality of water should be controlled throughout the production, storage and distribution of water. Water is not usually subjected to testing and batch or lot release before use. It is usually drawn from a system on-demand for use.
Results from testing are normally available only after water has already been used as microbiological tests may require periods of incubation. The assurance of quality to meet the on-demand expectation of water is therefore essential.
在水的生产、贮存及分配过程中，应控制水的微生物及化学质量。水在使用之前通常不会经过测试和批放行。它通常来自一个按需使用的系统。由于微生物测试可能需要一段培养期时间，因此一般只有在用水后才可取得测试结果。因此，保证水的质量以满足用水需求是至关重要的。
2.3 To reduce the risks associated with the production, storage and distribution of water and, considering the properties and use of water, it is essential:
为了减少与水的生产、储存和分配有关的风险，并考虑到水的特性和用途，必须:
•to ensure the appropriate design, installation, operation and maintenance of the pre-treatment (production of drinking-water), treatment (production of WPU such as purified water (PW) and WFI), and storage and distribution systems;
•确保预处理(饮用水的生产)、处理(制药用水的制备，如下纯化水(PW)和注射用水(WFI))及贮存和分配系统得到适当的设计、安装、操作和维修;
•to perform periodic sanitization;
•定期进行卫生处理;
•to take the appropriate measures in order to prevent chemical and microbial contamination; and
•采取适当措施，防止化学和微生物污染；以及
•to prevent microbial proliferation.
•防止微生物繁殖。
2.4 Different grades of water quality exist. The appropriate water quality, meeting its defined specification, should be used for the intended application.
水的质量存在不同级别。应使用适当的水质（符合其既定标准）用于其预期目的。
3. General principles for pharmaceutical water systems
制药用水系统的一般原则
3.1 Pharmaceutical water production, storage and distribution systems should be designed, installed, commissioned, qualified, validated, operated and maintained to ensure the consistent and reliable production of water of intended quality.
制药用水的生产、储存和分配系统应该设计、安装、调试、确认、验证、运行和维护，以确保一致和可靠地生产符合预期质量的水。
3.2 The capacity of these systems should be appropriate to meet the average and peak flow demand. The systems should be able to operate continuously for significant periods of time in order to avoid the inefficiencies and equipment stresses that occur when equipment cycles turn on and off too frequently.
系统的能力应适当，以满足平均流量和峰值流量的需求。系统应能够连续长时间运行，以避免因设备频繁开启和关闭而造成的效率低下和设备压力。
3.3 The use of the systems following an initial qualification such as installation qualification (IQ), operational qualification (OQ), performance qualification (PQ) and validation should be approved by the quality unit, e.g. quality assurance (QA).
在初始确认(例如安装确认、运行确认、性能确认和验证)后，系统的使用应由质量部门批准，例如质量保证(QA)。
3.4 Water sources and treated water should be monitored regularly for chemical, microbiological and, as appropriate, endotoxin contamination. The performance of water treatment, storage and distribution systems should also be monitored. Records of the results monitored, trend analysis and any actions taken should be maintained.
应定期监测原水及处理后水的化学、微生物及(如适用)内毒素污染情况。水的处理、储存和分配系统的性能也应监测。应保存监测结果，趋势分析，以及任何所采取行动的记录。

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