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WHO工作文件 QAS/19.786 征求意见稿 英文官网原文点击阅读原文 工作计划
PRODUCTION OF WATER FOR INJECTION BY MEANS OTHER THAN DISTILLATION 采用非蒸馏方法制备注射用水 1. INTRODUCTION 前言 1.1. Water is widely used in the pharmaceutical industry. It is often used as a raw material, an ingredient in formulations, to prepare reagents, in cleaning and in the manufacture of active pharmaceutical ingredients (APIs), intermediates and finished pharmaceutical products (FPP). 水在制药行业被广泛使用。通常用作原料、制剂辅料、制备试剂、用于API清、中间体和制剂（FPP）洁和生产。 1.2. Water for pharmaceutical use must meet quality requirements and specifications as published in standards and Pharmacopoeia. Water of required quality for its intended use should be produced by appropriate methods. 制药用水必须符合标准和药典中发布的质量要求和标准。用于既定用途所需质量的水应采用适当方法制备。 2. SCOPE 范围 2.1. This document provides guidance for the production of Water for Injection (WFI) by means other than distillation. The principles may be applied to other qualities of water produced, meeting other specifications. 本文件提供非蒸馏方式注射用水制备指南。这些原则可适用于符合其它质量标准，所制备水的其它质量。 2.2. The document is not exhaustive, but aims to provide guidance on the main principles to be considered. Other guidelines and literature should also be consulted. 该文件并非穷尽清单，但其目标是提供要考虑的主要原则。同时亦应参考其它指南和文献。 3. MONOGRAPHS 各论 3.1. Manufacturers should have a specification for WFI. 生产商应具备WFI的质量标准。 3.2. Monographs for WFI are published in various national Pharmacopoeia, as well as in The International Pharmacopoeia, and provide for the minimum requirements for the quality of WFI. 不同国家药典以及《国际药典》里发布的WFI各论，并提出了WFI最低质量要求。 3.3. WFI should meet the specification as published in current monographs of the Pharmacopoeia, recognized by the Medicines Regulatory Authority. WFI应符合由药监机构认可的药典中的现行各论里的质量标准。 4. LIFECYCLE APPROACH 生命周期方式 4.1. Good practices during each stage of the lifecycle in the production and control of WFI should be considered. 在WFI制备和控制的生命周期各阶段均应考虑优良规范。 4.2. Stages in the life cycle in production include, but are not limited to, the collection and treatment of source water, treatment of potable water used in production of WFI, production of WFI, storage, distribution and use of WFI. 制备的生命周期各阶段包括但不仅限于采集和处理源水、处理WFI制备所用自来水、WFI制备、WFI存贮、分配和使用。 4.3. Principles of risk management and data governance should be implemented in each relevant stage of the life cycle. 在生命周期各相关阶段应实施风险管理和数据管理原则。 5. RISK ASSESSMENT 风险评估 5.1. An appropriate method for the production of WFI should be used. 应使用适当的方法制备WFI。 5.2. Risks and controls should be identified for each stage of the life cycle of the production, storage, distribution, use and control of WFI. 应识别WFI制备、存贮、分配、使用和控制整个生命周期的各阶段的风险和控制。 5.3. Risks should be identified and assessed to determination of the scope and extent of validation and qualification of the system, including the computerized system used for the control of production and monitoring of WFI. 应识别并评估风险，以确定系统验证和确认的范围和深度，包括WFI制备和监测控制所用计算机化系统。 5.4. Where production methods other than distillation are used, specific attention should be taken to ensure: 如果使用了非蒸馏制备方法，需要特别注意确保： - that there is no risk of contamination of water; - 水没有污染风险 - the appropriateness of user requirement specifications (URS); - 用户需求标准（URS）的适当性 - feed-water quality; - 源水质量 - sequence of purification stages required; - 所需纯化步骤的顺序 - the extent of pre-treatment required; - 所需预处理的程度 - appropriately designed and located sampling points; - 取样点设计和定位恰当 - controls are in place to prevent deadlegs and contamination; and - 有控制防止死管和污染 - in-line monitoring. - 在线监控 6. CONTROLSTRATEGY控制策略 6.1. There should be no risk of contamination of WFI produced, stored or circulated. 所制备、存贮或循环的WFI不应有污染风险。 6.2. An appropriate control strategy should bedefined to ensure that all risks identified are eliminated, or reduced to an acceptable level. 应定义适当的控制策略以确保消除或降低识别的所有风险于可接受水平。 6.3. Special attention should be given to, for example, the selection of components, their material of construction, preventive maintenance, life cycle and sanitization. 应特别注意，例如，部件的选择、其结构材质、预防性维护、生命周期和消毒。 6.4. Water-treatment components, storage and distribution systems should be sanitized by appropriate, effective and validated means - at specified intervals. 水处理部件、存贮和分配系统均应采用恰当有效和经验证的方法按规定的时间间隔消毒。 6.5. The materials of construction for components selected for the production, storage and distribution of WFI systems must notbe reactive, additive or absorptive or adversely affect the quality of water produced. Examples of suitable materials include SS 316L, Polyvinylidene Fluoride (PVDF) and Polypropylene (PP). 选择用于WFI制备、存贮和分配系统的部件材质不得发生反应、析出或吸收，或对所制备的水质量有不良影响。适当的材质包括SS316L、PVDF和PP。 6.6. The storage and distribution systems should further be designed to permit a validated, routine sanitisation process. 存贮和分配系统设计应可执行经过验证的常规消毒流程。 6.7. Treatment (also referred to as pre-treatment)of water entering the system should ensure adequate removal of organic particles, matter and microbiological impurities. The treatment should not havea detrimental effect on materials of construction of the water system. 水进入系统的处理（亦称为预处理）应确保足以清除有机颗粒、异物和微生物杂质。处理不应对水系统结构材料有不良影响。 6.8. Techniques such as deionisation, raw water ultrafiltration, electrolytical scale reduction, water softening, descaling,pre filtration and degasification (can be located between the stages of a double pass reverse osmosis (RO) system) should be considered. 应考虑去离子、原水超滤、电解除水垢、水软化、除垢、预过滤和脱气（可放在2次RO之间）等技术。 6.9. All parts of the system, including, for example, RO membranes, storage and distribution systems, should be appropriately designed and constructed to allow for routine sanitisation (thermal or chemical, or a combination thereof). 系统的所有部件，如RO膜、存贮和分配系统，其设计和构造均应合理，保证日常消毒（加热或化学或两者联合方式消毒）。 6.10. Special attention should be given tothe qualification and validation of the WFI system. 应特别注意WFI系统的确认和验证。 6.11. Appropriate sampling techniques should be used to sample water at defined sampling locations in accordance with asampling schedule. 应在指定的取样点根据取样计划使用适当的取样技术取出水样。 7. GOOD PRACTICES IN THE PRODUCTION OF WFI WFI制备优良规范 7.1 WFI should be prepared from drinking-water (usually with further treatment) or purified water as a minimum-quality feed water. WFI制备应采用饮用水（通常要进一步处理）或纯化水作为最低质量源水。 7.2 An appropriate method should be used to produce WFI. The preferred method is distillation. Alternative methods, such as RO, may be considered. 应使用适当的方法制备WFI。优选方法是蒸馏，可考虑替代方法如RO。 7.3 Where RO is used, double-pass RO coupled with other appropriate techniques such as electro-deionisation (EDI), ultrafiltration (UF) or nanofiltration, should be considered. The purification process employed should be proven to be equivalent or better than distillation. 如果使用了RO，则应考虑两级RO配以其它适当的技术如EDI、UF或纳滤。所用纯化工艺应证明等同或优于蒸馏。 7.4 WFI should meet the relevant pharmacopoeia specifications for chemical and microbiological purity (including endotoxin). WFI应符合相关的药典标准中的化学和微生物纯度指标（包括内毒素）。 7.5 Water testing results should be trended. Trend data should be reviewed routinely in order to determine the potential for deterioration in the system. 应对水检测结果进行趋势分析。趋势分析的数据应定期审核以确定系统变差的可能性。 7.6 Appropriate action and alert limits should be specified. Alerts should be reassessed routinely to enable, where possible, a re-evaluation of those control limits. 应规定适当的行动限和警戒限。警戒限应定期重新评估以重新评估这些控制限（可能时）。 7.7 There should be no risk of recontamination of WFI during production, storage and distribution. 在制备、存贮和分配过程中WFI不应有再次污染的风险。 7.8 The system should remain in a validated state throughout its life cycle. 系统在其生命周期内应保持在经过验证的状态。 7.9 The system should be monitored for its ongoing performance within defined parameters, including but not limited to,conductivity, pH, total organic carbon (TOC) and microbial contamination. 应持续监测系统的性能是否在指定参数范围内，包括但不仅限于电导率、pH值、TOC和微生物污染。 7.10 In-line sampling and testing should be supported by off-line testing. 在线取样和检测应有离线检测支持。 7.11 RO membranes should be monitored for any potential integrity breaches. 应监测RO膜可能的完整性问题。 |
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