Good manufacturing practices: water for pharmaceutical use
優良生產規範（GMP）：製藥用水
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.
水的製備、存貯和分配過程中對水質的控制，包括微生物和化學質量，是一個重要關注點。與其它產品和工藝成分不同，水通常是來自一個按需運行的系統，在使用之前不會進行檢測，也不會進行批放行，因此確保水質符合所需要求就至關重要了。
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 In early 2019, the WHO Secretariat commissioned the preparation of a draft guidance text for the production of WFI by means other than distillation.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.
近年來，由於干係人提出非常多的建議，幾部藥典均對注射用水（WFI）進行了修訂，允許採用非蒸餾技術如反滲透（RO）製備WFI。2017年，WHO製劑標準專家委員會（ECSPP）建議WHO秘書處收集各方對於是否認為應修訂WHO標準和WFI GMP以及如何修訂的反饋。在幾次徵求意見期間經過討論之後，ECSPP同意對國際藥典各論（注射用水）和WHO指南「GMP：製藥用水」進行修訂，允許使用非蒸餾技術製備WFI。2019年早期，WHO秘書處協調起草了非蒸餾方法製備WFI的指南草案。經過幾次公開徵求意見之後，該文件被提交給第54次ECSPP。專家委員會採納了「非蒸餾方法製備注射水」的指南，並將建議整合至WHO現有指南「GMP：製藥用水」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.
本文件是之前發布為WHO TRS 970附錄2，2011的「WHO GMP：製藥用水」修訂本。
1. Introduction 概述
2. Background to water requirements and uses 水的需求和使用背景
3. General principles for pharmaceutical water systems 製藥用水系統的一般原則
4. Water quality specifications 水的質量標準
4.1.Pharmacopoeial specifications 藥典標準
4.2.Drinking-water 飲用水
4.3.Bulk purified water 散裝純化水
4.4.Bulk highly purified water 散裝高純水
4.5.Bulk water for injections 散裝注射用水
4.6.Other grades of water 其它級別的水
5. General considerations for water purification systems 水純化系統的一般考量
6. Water storage and distribution systems 水的存貯和分配系統
7. Good practices for water systems 水系統優良規範
8. System sanitization and bioburden control 系統消毒和生物負載控制
9. Storage vessels 貯罐
10. Water distribution 水分配
11. Biocontamination control techniques 生物汙染控制技術
12. Operational considerations 運行考量
12.5 Phase 1 第一階段
12.6 Phase 2 第二階段
12.7 Phase 3 第三階段
13. Continuous system monitoring 系統連續監控
14. Maintenance of water systems 水系統的維護
15. System reviews 系統回顧審核
16. Inspection of water systems 水系統的檢查
References參考文獻
Further reading 延伸閱讀
1. Introduction and scope 概述與範圍
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.
本文涉及的是以散裝形式存貯和分配的製藥用水（WPU）。其目的是提供關於WPU的不同標準信息、水系統質量管理方面的GMP指南、水處理（製備）系統、水存貯和分配系統、確認和驗證，以及水的取樣、檢測和常規監測。
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.
雖然也提到了飲用水，但本文件的關注點在於水的處理以及準備用於製藥用途的處理後的水的存貯和分配。
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.
本文不包括已配製好供患者攝入的水，和藥房配製個人處方藥時所用的少量的水。
1.4 The document can be used in whole or in part, as appropriate, to the section and application under consideration.
本文可整體使用，亦可根據考量部分使用和應用（適當時）。
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，本文結尾「延伸閱讀」部分還包括有一些相關出版物，可作為WPU供水系統規劃、安裝和使用的額外背景資料使用。
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「原料藥GMP」和WHO「藥品GMP：主則」的補充。
2. Background to water requirements and uses 水的需求與使用背景
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.
水是製藥行業中被廣泛使用的一種物質。它在活性藥用成分（API）、中間體和製劑（FPP）生產、加工和配方中被廣泛用作原料或起始物料，還被用於製備溶劑和試劑，以及用於清潔。水因其極性和氫鍵的原因，具有獨特的化學特性，它可以溶解、吸收、吸附或懸浮不同物質。這其中就包括本身可能有害的汙染物，或是可與目標產品物質發生反應的物質，從而導致對健康的危害。因此水需要符合所需的質量標準，從而降低這些風險。
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.
在水的製備、存貯和分配過程中，應對水的微生物和化學質量進行控制。水在使用之前通常不會進行檢測，不會進行批放行。它通常是來自按需製備系統。檢測結果通常只有在水已經被使用之後才能取得，因為微生物測試可能會需要一段時間來培養。因此保證水的質量符合所需要求是至關重要的。
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:
為降低水的製備、存貯和分配有關的風險，同時考慮水的特性用途，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;
• 確保預處理（飲用水製備）、處理（WPU如純化水（PW）和WFI的製備），和存貯與分配系統有恰當的設計、安裝、運行和維護
• to perform periodic sanitization;
• 定期消毒
• to take the appropriate measures in order to prevent chemical and microbial contamination; and
• 採取恰當措施防止化學和微生物汙染
• 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.
存在有不同級別的水質。應根據目標用途使用符合指定質量標準的水。
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