WHO制药用水GMP指南2020（中英文版）

Good manufacturing practices: water for pharmaceutical use

优良生产规范（GMP）：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。
Inrecent 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 manufacturing 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  In early 2019, the WHO Secretariat commissioned the preparation of a draft guidance text for the production of WFI by means other than distillation.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 Committeeadopted 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“WHO GMP：制药用水”修订本。

Introduction 概述

Background to water requirements and uses 水的需求和使用背景
General principles for pharmaceutical water systems 制药用水系统的一般原则
Water quality specifications 水的质量标准
Pharmacopoeial specifications 药典标准
Drinking-water 饮用水
Bulk purified water 散装纯化水
Bulk highly purified water 散装高纯水
Bulk water for injections 散装注射用水
Other grades of water 其它级别的水
General considerations for water purification systems 水纯化系统的一般考量
Water storage and distribution systems 水的存贮和分配系统
Good practices for water systems 水系统优良规范
System sanitization and bioburden control 系统消毒和生物负载控制
Storage vessels 贮罐
Water distribution 水分配
Biocontamination control techniques 生物污染控制技术
Operational considerations 运行考量
Phase 1 第一阶段
Phase 2 第二阶段
Phase 3 第三阶段
Continuous system monitoring 系统连续监控
Maintenance of water systems 水系统的维护
System reviews 系统回顾审核
Inspection of water systems  水系统的检查
References 参考文献
Further reading 延伸阅读

1.    Introduction and scope 概述与范围
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; guidanceon 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.
本文涉及的是以散装形式存贮和分配的制药用水（WPU）。其目的是提供关于WPU的不同标准信息、水系统质量管理方面的GMP指南、水处理（制备）系统、水存贮和分配系统、确认和验证，以及水的取样、检测和常规监测。
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.
虽然也提到了饮用水，但本文件的关注点在于水的处理以及准备用于制药用途的处理后的水的存贮和分配。
1.3  This document does not cover water for administration to patients in the formulated state or the use of smallquantities of water in pharmacies to compound individually prescribed medicines.
本文不包括已配制好供患者摄入的水，和药房配制个人处方药时所用的少量的水。
1.4  The document can be used in whole or in part, as appropriate, to the section and application under consideration.
本文可整体使用，亦可根据考量部分使用和应用（适当时）。
1.5  In addition to this document, the “Further reading” section at the end of this document includes some relevant publications that can serve as additional background material when planning, installing and using systems intended to provide WPU.
除本文外，本文结尾“延伸阅读”部分还包括有一些相关出版物，可作为WPU供水系统规划、安装和使用的额外背景资料使用。
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WHO“原料药GMP”和WHO“药品GMP：主则”的补充。

2.    Background to water requirements and uses 水的需求与使用背景
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.
水是制药行业中被广泛使用的一种物质。它在活性药用成分（API）、中间体和制剂（FPP）生产、加工和配方中被广泛用作原料或起始物料，还被用于制备溶剂和试剂，以及用于清洁。水因其极性和氢键的原因，具有独特的化学特性，它可以溶解、吸收、吸附或悬浮不同物质。这其中就包括本身可能有害的污染物，或是可与目标产品物质发生反应的物质，从而导致对健康的危害。因此水需要符合所需的质量标准，从而降低这些风险。
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.
在水的制备、存贮和分配过程中，应对水的微生物和化学质量进行控制。水在使用之前通常不会进行检测，不会进行批放行。它通常是来自按需制备系统。检测结果通常只有在水已经被使用之后才能取得，因为微生物测试可能会需要一段时间来培养。因此保证水的质量符合所需要求是至关重要的。
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:
为降低水的制备、存贮和分配有关的风险，同时考虑水的特性用途，以下方面非常重要：
•      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（饮用水制备）、处理（WPU如纯化水（PW）和WFI的制备），和存贮与分配系统有恰当的设计、安装、运行和维护
•      to perform periodic sanitization;
•      定期消毒
•      to take the appropriate measures in order to prevent chemical and microbial contamination; and
•      采取恰当措施防止化学和微生物污染
•      to prevent microbial proliferation.
•      防止微生物激增
2.4  Different grades of water quality exist. The appropriate water quality, meeting its defined specification, should be usedfor 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。

       文章来源：允咨GMP制药技术

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