USP30_1231-WATER FOR PHARMACEUTICAL PURPOSES翻译(节选).doc

USP30 WATER FOR PHARMACEUTICAL PURPOSES USP30 制药用水 节选饮用水部分 制药用水 节选饮用水部分 SOURCE OR FEED WATER CONSIDERATIONS 水源或供水系统 To ensure adherence to certain minimal chemical and microbiological quality standards water used in the production of drug substances or as source or feed water for the preparation of the various types of purified waters must meet the requirements of the National Primary Drinking Water Regulations NPDWR 40 CFR 141 issued by the U S Environmental Protection Agency EPA or the drinking water regulations of the European Union or Japan or the WHO drinking water guidelines 为了保证能达到某些化学和微生物的最低质量标准 用于药品生产的水或 者是用于制备各种纯化水的水源必须要符合美国环境保护局 EPA 发布的国 家基本饮用水规定 NPDWR 40 CFR 141 欧盟 日本或 WHO 的有关饮 用水规定也可适用 Limits on the types and quantities of certain organic and inorganic contaminants ensure that the water will contain only small safe quantities of potentially objectionable chemical species Therefore water pretreatment systems will only be challenged to remove small quantities of these potentially difficult to remove chemicals Also control of objectionable chemical contaminants at the source water stage eliminates the need to specifically test for some of them e g trihalomethanes and heavy metals after the water has been further purified 对某些有机和无机污染物的种类和数量进行限定可以保证水中只含有微小 的 可靠数量的潜在的化学物质 因此水的预处理系统只需除掉这些少量的 难以去除的化学物质 而且 从水源开始对这些令人讨厌的化学污染物进行控 制就可以免去在后续纯化过程中对这些化学物质 如 三卤代甲烷和重金属 的检验 Microbiological requirements of drinking water ensure the absence of coliforms which if determined to be of fecal origin may indicate the potential presence of other potentially pathogenic microorganisms and viruses of fecal origin 饮用水规定中的微生物标准保证了水中不存在大肠菌群 如经确定该菌来 自粪便 则预示可能有来自粪便的其他病原微生物和病毒 Meeting these microbiological requirements does not rule out the presence of other microorganisms which could be considered undesirable if found in a drug substance or formulated product 符合国家饮用水的微生物标准并不排除有其他微生物的存在 同时人们也 不希望这些微生物出现在基质药物和配方产品中 To accomplish microbial control Municipal Water Authorities add disinfectants to drinking water Chlorine containing and other oxidizing substances have been used for many decades for this purpose and have generally been considered to be relatively innocuous to humans 为控制微生物 地方水务局在饮用水中加入消毒剂 公认的对人体无害的含氯 消毒剂和其它氧化性消毒剂被用了数十年 However these oxidants can interact with naturally occurring organic matter to produce disinfection by products DBPs such as trihalomethanes THMs including chloroform bromodichloromethane and dibromochloromethane and haloacetic acids HAAs including dichloroacetic acid and trichloroacetic acid The levels of DBPs produced vary with the level and type of disinfectant used and the levels and types of organic materials found in the water which can vary seasonally 但是 这些氧化剂能跟自然存在的有机物反应 产生消毒副产品 DBPs 如 三卤代甲烷 THMs 包括氯仿 溴代二氯甲烷和二溴代一氯甲烷 卤 乙酸 HAAs 包括二氯乙酸和三氯乙酸 随着所用消毒剂种类 用量的变化 和水中有机物的种类的季节性变化 DBPs 的量也有所不同 Because high levels of DBPs are considered a health hazard in drinking water Drinking Water Regulations mandate their control to generally accepted nonhazardous levels However depending on the unit operations used for further water purification a small fraction of the DBPs in the starting water may carry over to the finished water Therefore the importance of having minimal levels of DBPs in the starting water while achieving effective disinfection is important 由于饮用水中高含量的 DBPs 被认为有害健康 饮用水规定中要求把 DBPs 控制在可接受的无危害水平 但是从水的后续纯化中使用的单元操作来 看 源水中很少量的 DBPs 都能被带到纯化的最终阶段 因此 在达到消毒效 果的同时 保证饮用水中含有最小程度的 DBPs 是很重要的 DBP levels in drinking water can be minimized by using disinfectants such as ozone chloramines or chlorine dioxide Like chlorine their oxidative properties are sufficient to damage some pretreatment unit operations and must be removed early in the pretreatment process The complete removal of some of these disinfectants can be problematic For example chloramines may degrade during the disinfection process or during pretreatment removal thereby releasing ammonia which in turn can carry over to the finished water 可以用臭氧 氯胺或者二氧化氯这些消毒剂来减少水中的 DBPs 含量 比 如氯 它们的氧化能力足以破坏一些预处理单元操作 必须在预处理程序中尽 早除去 要完全除去其中一些消毒剂会有些困难 例如 氯胺在消毒过程或预 处理过程中会发生降解 释放出氨 而这些氨又能被带入成品水中 Pretreatment unit operations must be designed and operated to adequately remove the disinfectant drinking water DBPs and objectionable disinfectant degradants A serious problem can occur if unit operations designed to remove chlorine were without warning challenged with chloramine containing drinking water from a municipality that had been mandated to cease use of chlorine disinfection to comply with ever tightening EPA Drinking Water THM specifications 预处理单元操作必须经过合理的设计和运行 以便充分地去除消毒剂 饮 用水 DBPs 和令人讨厌的消毒剂降解物 为遵守更严格的 EPA 饮用水 THM 规 定 市局会被要求停止使用含氯消毒剂而改用氯胺消毒剂 如果设计为用来除 氯的单元操作毫无预兆地被用于这些含氯胺的城市饮用水 就会出现一系列的 问题 The dechlorination process might incompletely remove the chloramine which could irreparably damage downstream unit operations but also the release of ammonia during this process might carry through pretreatment and prevent the finished water from passing compendial conductivity specifications The purification process must be reassessed if the drinking water disinfectant is changed emphasizing the need for a good working relationship between the pharmaceutical water manufacturer and the drinking water provider 这个除氯过程可能会不完全地除去一些氯胺 从而不可逆地破坏下游单元 操作 在此过程中释放的氨会被带入预处理程序 使得成品水的电导率无法达 标 如果饮用水的消毒剂发生变化 则必须对纯化过程进行再评价 这一过程 强调了制药用水厂商和饮用水供应者之间良好协作的必要性 Drinking Water This type of water can be referred to as Potable Water meaning drinkable or fit to drink National Primary Drinking Water Primary Drinking Water or National Drinking Water Except where a singular drinking water specification is stated such as the NPDWR U S Environmental Protection Agency s National Primary Drinking Water Regulations as cited in 40 CFR Part 141 this water must comply with the quality attributes of either the NPDWR or the drinking water regulations of the European Union or Japan or the WHO Drinking Water Guidelines 饮用水 此类水也可称为可以饮用或适合饮用的水 国家基本饮用水 基 本饮用水 或国家饮用水 除了对某种饮用水标准做了说明 如 NPDWR 美国环境保护局发布的国家基本饮用水规定 40 CFR 141 此类水必须符合 NPDWR 欧盟 日本或 WHO 的有关饮用水规定中的质量指标 It may be derived from a variety of sources including a public water utility a private water supply e g a well or a combination of these sources Drinking Water may be used in the early stages of cleaning pharmaceutical manufacturing equipment and product contact components 饮用水可能来自公用水系统 私人供水系统 井 或包含上述两种渠道的综 合水系统 饮用水可能被用于制药设备和与产品接触的部件的前期清洗 Drinking Water is also the minimum quality of water that should be used for the preparation of official substances and other bulk pharmaceutical ingredients Where compatible with the processes the allowed contaminant levels in Drinking Water are generally considered safe for use for official substances and other drug substances 饮用水也是用于制备正式产品和其他药物成分的水的最低质量标准 工艺 过程相一致时 饮用水中的可允许污染物水平对用于正式产品和其他药物的水 来说是相对安全的 Where required by the processing of the materials to achieve their required final purity higher qualities of water may be needed for these manufacturing steps perhaps even as pure as Water for Injection or Purified Water Such higher purity waters however might require only selected attributes to be of higher purity than Drinking Water see Figure 2 below Drinking Water is the prescribed source or feed water for the production of bulk monographed pharmaceutical waters 由于原料处理要求达到相应的最终纯度 这些工艺过程需要更高品质的水 纯度可能相当于注射用水或纯化水 但是这种纯度的水可能只在某些限度上要 求高于饮用水 饮用水是生产制药专用水的指定水源 The use of Drinking Water specifications establishes a reasonable set of maximum allowable levels of chemical and microbiological contaminants with which a water purification system will be challenged As seasonal variations in the quality attributes of the Drinking Water supply can occur due consideration to its synthetic and cleaning uses must be given The processing steps in the production of pharmaceutical waters must be designed to accommodate this variability 饮用水规定的使用建立了一套合理的对水纯化系统造成威胁的化学和微生物污 染物的最大允许量 随着季节的改变 饮用水的水质会发生变化 水的应用也 要经过相应的调整 Suggested Methodologies 水的微生物检测的推荐方法 The following general methods were originally derived from Standard Methods for the Examination of Water and Wastewater 17th Edition American Public Health Association Washington DC 20005 Even though this publication has undergone several revisions since its first citation in this chapter the methods are still considered appropriate for establishing trends in the number of colony forming units observed in the routine microbiological monitoring of pharmaceutical waters 以下这些通用的方法均摘录自 水和废水检验的标准方法 第 17 版 美国公众健康协会 华盛顿特区 20005 虽然这本出版物从它第一次被本章 节引用开始已经改版多次 但这些方法仍然适用于制药用水的日常微生物检测 中对菌落生长趋势的观察 It is recognized however that other combinations of media and incubation time and temperature may occasionally or even consistently result in higher numbers of colony forming units being observed and or different species being recovered 虽然大家公认培养基中的化合物 培养时间和培养温度可能会偶尔影响甚 至持续地导致菌落数量的增加和 或者不同种类细菌的出现 The extended incubation periods that are usually required by some of the alternative methods available offer disadvantages that may outweigh the advantages of the higher counts that may be obtained The somewhat higher baseline counts that might be observed using alternate cultural conditions would not necessarily have greater utility in detecting an excursion or a trend 一些可用的替代方法要求延长培养时间 这样做会增加菌落数 其带来的不利 因素可能比其优势更突出 采用替代方法得到的稍微偏高的菌落计数结果在测 定一种偏移和趋势的试验中并没有更大的用途 In addition some alternate cultural conditions using low nutrient media tend to lead to the development of microbial colonies that are much less differentiated in colonial appearance an attribute that microbiologists rely on when selecting representative microbial types for further characterization It is also ironical that the nature of some of the slow growers and the extended incubation times needed for their development into visible colonies may also lead to those colonies being largely nonviable which limits their further characterization and precludes their subculture and identification 另外 一些替代的培养条件用低营养型培养基可以诱导形态差别不大的菌 落生长 生物学家依靠菌落特征来选择具有代表性的微生物种类来做进一步特 征描述 具有讽刺意义的是一些生长缓慢的细菌的特性以及为了使它们生长成 可见菌落所需要延长的培养时间这两种因素可能会导致大量的这些菌落无法生 长 因而限制了对它们进一步的特征描述 并且妨碍了它们的继续培养和鉴定 Methodologies that can be suggested as generally satisfactory for monitoring pharmaceutical water systems are as follows However it must be noted that these are not referee methods nor are they necessarily optimal for recovering microorganisms from all water systems The users should determine through experimentation with various approaches which methodologies are best for monitoring their water systems for in process control and quality control purposes as well as for recovering any contraindicated species they may have specified 接下来所描述的是公认的适用于制药用水系统检测的方法 但是要注意的 是它们不是仲裁方法 也不是从所有水系统中回收微生物的最佳方法 使用者 需要通过各种方法进行试验来确定哪种方法最适于用来检测他们的水系统 哪 种最适用于水的质量控制 以及哪种最适用于回收他们指定的不得检出的微生 物种类 Drinking Water POUR PLATE METHOD OR MEMBRANE FILTRATION METHOD1 Sample Volume 1 0 mL minimum2 Growth Medium Plate Count Agar3 Incubation Time 48 to 72 hours minimum Incubation Temperature 30 to 35 饮用水倾注平皿法 或 膜过滤法 1 样品用量 最低为 1 0ML 培养基 平皿计数琼脂 TGYA 培养时间 至少 48 72 小时 培养温度 30 35 Purified Water POUR PLATE OR MEMBRANE FILTRATION METHOD1 Sample Volume 1 0 mL minimum2 Growth Medium Plate Count Agar3 Incubation Time 48 to 72 hours minimum Incubation Temperature 30 to 35 纯化水倾注平皿法 或 膜过滤法 1 样品用量 最低为 1 0ML 培养基 平皿计数琼脂 TGYA 培养时间 至少 48 72 小时 培养温度 30 35 Water for Injection MEMBRANE FILTRATION METHOD1 Sample Volume 100 mL minimum2 Growth Medium Plate Count Agar3 Incubation Time 48 to 72 hours minimum Incubation Temperature 30C to 35C 注射用水膜过滤法 1 样品用量 最低为 100ML 培养基 平皿计数琼脂 TGYA 培养时间 至少 48 72 小时 培养温度 30 35 1A membrane filter with a rating of 0 45 m is generally considered preferable even though the cellular width of some of the bacteria in the sample may be narrower than this The efficiency of the filtration process still allows the retention of a very high percentage of these smaller cells and is adequate for this application Filters with smaller ratings may be used if desired but for a variety of reasons the ability of the retained cells to develop into visible colonies may be compromised so count accuracy must be verified by a reference approach 最好使用孔径为 0 45 m 的滤膜 即使样品中一些细菌的直径比 0 45 m 还小 微孔滤膜过滤这一步骤仍然可以截留大部分这些直径小的细菌 仍 然适用于这部分操作 如果愿意的话 可以使用更小孔径的滤膜 但是由于各 种原因 这些截留细胞要长成可见菌落的能力可能会被抵消 因此计数的准确 性要经过参考方法的验证 2When colony counts are low to undetectable using the indicated minimum sample volume it is generally recognized that a larger sample volume should be tested in order to gain better assurance that the resulting colony count is more statistically representative The sample volume to consider testing is dependent on the user s need to know which is related to the established alert and action levels and the water system s microbial control capabilities and the statistical reliability of the resulting colony count In order to test a larger sample volume it may be necessary to change testing techniques e g changing from a pour plate to a membrane filtration approach Nevertheless in a very low to nil count scenario a maximum sample volume of around 250 to 300 mL is usually considered a reasonable balance of sample collecting and processing ease and increased statistical reliability However when sample volumes larger than about 2 mL are needed they can only be processed using the membrane filtration method 如果使用的是最少样品用量 菌落太少无法计数时 通常认为要加大样品用量 以保证得到的菌落数在统计学上具有代表性 样品的用量可以由使用者的判断 用量关系到已确定的微生物限度标准和水系统的微生物含量 和菌落计数结 果的统计学可靠性来定 为了检测更大的样品量 改变检测方法是很有必要的 例如 从倾注平皿法变成膜过滤法 然而 在菌落数量很少甚至为零的情况下 大约 250 到 300 mL 的样品用量不仅有利于样品收集 方便操作 还有利于增 加统计学可信度 但是如果样品用量需要超过 2 mL 则只能使用膜过滤法 3Also known as Standard Methods Ag