ISPE 8.储存和分配系统

PHARMACEUTICAL STORAGE and DISTRIBUTION SYSTEMS 贮存和分配系统 8. STORAGE AND DISTRIBUTION SYSTEMS 8. 贮存和分配系统 8.1 INTRODUCTION 8.1 序论 This chapter provides an overview of eight common distribution configurations and a decision tree to help decide which system best suits the operating requirements. A comparison of tank versus tankless systems is addressed, as well as alternative materials of construction available, and ancillary equipment related to overall distribution systems. Common industry practices are listed as examples, to help clarify regulatory requirements. 本章提供一个八种普通分配配置的概述以及一个决策树来帮助决定什么系统最适合操作设备。连同有效结构的可选材料，以及和整个分配系统有关的辅助设备一起，对有水罐和无水罐系统进行比较。以列表上记载的普通工业实践作为实例来帮助阐明法规要求。 8.2 SYSTEM DESIGN 8.2 系统设计 8.2.1 General Considerations 8.2.1 一般须考虑之事项 A storage system is used to accommodate peak flow requirements against usage rates. The storage system must maintain the feed water quality to ensure the appropriate quality of the end use of product. Storage allows a smaller, less costly pretreatment system to meet peak demand. A smaller treatment system operates closer to the ideal of continuous, dynamic flow. Large manufacturing sites, or systems serving different buildings, may use storage tanks to separate one section of the loop, and others to minimize cross contamination. 贮存系统根据使用率来调节高峰水流的需要量，它必须维持给水质量来确保产品最终使用时的质量。贮存允许较低、较少的成本预处理系统来满足高峰要求。一个小型预处理系统的操作是接近于连续的动态流量的。大的生产场所或为不同建筑服务的系统可以用贮水罐将回路的一部分和其他部分分开以将相互污染减少到最低。 The main disadvantage of a storage tank is its capital cost, and the cost of associated pumps, vent filters, and instrumentation. However, this is usually less than the increased cost of pretreatment equipment sized to handle the peak use rate in the facility. 贮存罐的主要缺点是它的资产成本和相关泵、气滤器和仪器操作的成本。然而，这通常小于按照工厂中处理高峰使用率类型制造的预处理设备增加的成本。 Another disadvantage of storage is that it introduces a region of slow moving water, which can promote bacterial growth. 贮存罐的另外一个缺点是它采用了一个水流缓慢的区域，该区域可能促进细菌生长。 8.2.2 Capacity 8.2.2 容积 Criteria affecting storage capacity include the user's demand profile or the amount of use, duration, timing, and diversity, (in the case of more than one user), balance between the supply of pre- and final- treated waters, and whether the system is recirculating or non-recirculating. Careful consideration of these criteria will affect cost and water quality. 影响贮存容量的包括用户需求或使用量，持续时间，周期和多样性（对于多个用户），预处理水供给和终处理水供给之间的平衡，以及系统是再循环还是非再循环。对这些标准的仔细考虑将影响成本和水质。 The storage tank must provide reserve to minimize cycling of the treatment equipment and to reduce pump cavitation. It should provide sufficient reserve to enable routine maintenance and orderly system shutdown in the event of an emergency, which can vary from few to many hours, depending on the size and configuration of the system and maintenance procedures. 贮存罐必须有储备水来使处理设备循环降到最低并减少泵空泡形成。它还应该紧急事件时，能提供足够的储备水来进行日常维护和系统轮班的停工。紧急事件可能会从几小时到许多小时，这取决于系统的容量和配置以及维护程序。 8.2.3 Storage Tank Location 8.2.3 贮存罐位置 It may not be cost-effective to locate storage tanks as close as possible to the point of use, within high-cost, GMP-finished areas. It may be more advantageous to locate them close to the generation equipment, for ease of maintenance. Utility areas are acceptable for this purpose, if access is provided (and the area is kept clean). 在高成本、GMP区域内，尽可能靠近使用点安置贮水罐并不会节约成本。将它们安置在生成设备附近是较有利的，因为维护方便。如果能提供通道（并且保持公共区域清洁），为了维护方便也可以把储罐安置在公共区。 8.2.4 Types of Storage Tanks 8.2.4 贮存罐类型 Vertical storage tanks are common but horizontal tanks may be necessary if overhead space is limited. For recirculating systems, tank design should include an internal spray ball to ensure that all interior surfaces are wetted for microbial control. Jacketing is usually provided in hot systems, to maintain water temperature over long periods without makeup; or to temper high influent temperatures, to preclude excessive rouging and pump cavitation. To avoid the absorption of carbon dioxide and its effect on conductivity, inert blanketing of the tank headspace should be considered. Storage tanks must be fitted with a sub-micron hydrophobic vent filter to reduce bio-burden and particles. 通常会用垂直储罐，但当上空空间有限时，则需要采用水平储罐。对于再循环系统，设计储罐时，应将内部喷洗球包括在内，以确保所有的内表面湿润以控制微生物。热系统通常会采用夹套结构，以能够长时间的维持水温；或者调节过高的流入液体温度；以排除过度生锈以及泵空化。为了避免吸收二氧化碳影响电导率，应考虑在储罐顶空采用惰性封层。储罐上必须安装一个疏水亚微粒气滤器，以减少生物负荷和微粒。 The maximum size of a single storage vessel is often limited by the space available in the facility. It may be necessary to resort to multiple tanks to obtain the desired capacity. In this case, interconnecting piping must be carefully designed to assure adequate flow through all supply and return branches. 单个储罐的最大尺寸通常受车间的可用空间限制。可能会要用多个储罐来达到预想的容量。在这种情况下，必须仔细设计互相连接管线，以确保所有供应和返回分支管道能达到足够的流量。 8.3 SYSTEM DISTRIBUTION DESIGN 8.3 系统分配设计 8.3.1 General Considerations 8.3.1 一般须考虑事项 Proper design of both the water storage and distribution systems is critical to the success of a pharmaceutical water system. 制药水系统的成功关键在于：正确的设计水的储存和分配系统。 The optimal design of any water storage and distribution system must accomplish three things: 1. Maintain the quality of the water within acceptable limits. 2. Deliver the water to the use points at the required flow rate and temperature. 3. Minimize capital and operating expenses. 任何水储存和分配系统的最适设计都必须完成以下三件事： 1. 保持水质在合格的限度内。 2. 输送到用点的水的流速和温度是符合要求的。 3. 将资产成本和操作费用降到最低。 Although items 2 and 3 are well understood, item 1 is often misinterpreted. It is not necessary to protect the water from every form of degradation, only to maintain the quality within acceptable limits. For instance, water stored in the presence of air absorbs CO2 increasing the conductivity. This degradation can be avoided by blanketing the storage vessel with nitrogen. However, for many systems this would be a wasteful expenditure if the increased conductivity were still within the required specification. 尽管第2条和第3条都很好理解，但是第1条总是被曲解。不必要防止水的任何形式的降格，只要能将水质维持在合格标准内就可以了。例如，如果水存储的场所存在空气，水就会吸收二氧化碳从而升高电导率。可在储罐的上层加上氮封就可以避免这种降格。但是，如果升高后的电导率仍在要求的规格内，对于多数系统来说，进行氮封就是一种浪费。 As technology has improved over the years, many design features such as storage at elevated temperature, constant circulation, use of sanitary connections, polished tubing, orbital welding, frequent sanitization, and the use of diaphragm valves have become common place. To incorporate all of these features into each new design typically leads to ever escalating costs with little if any reduction in risk of contamination. Although each of these items provides a level of security, it is a mistake to assume that all of them need to be in every system. Many systems operate successfully with one or more of these design features omitted. In such cases, the cumulative effect of the other design features is adequate to prevent degradation of the water. 由于这些年技术的发展，许多设计特征，如：在高温下存储、连续恒定循环、清洁连接件的使用、抛光的管、轨焊、频繁消毒以及隔膜阀的使用等都已经变得很普通了。如果在每个新设计中将这些特征都考虑进去的话，通常会导致费用过大，但在降低污染风险（如果有的话）上成效很小。尽管这些条目都可以提供一定水平的清洁，但如果认为在每个系统中都要用到这些条目则是错误的。在这种情况下，其他的设计特征的累积作用就足以避免水质的降格。 A more reasonable approach is to utilize design features that provide the greatest reduction in contamination risk at the most reasonable cost, and add the more expensive features in the design phase, only if they are required to maintain quality within acceptable limits. The systems should be designed to be robust, so features do not have to be added later, affecting cost and schedule. The idea of selecting design features based on "return" on investment where "return" is defined as reduction in contamination risk, can be very helpful in controlling system cost and in evaluating different alternatives. Ultimately, the effectiveness of each system design is determined by the quality of the water delivered to the users. The challenge for the design engineer is to know what features to include, to achieve the required degree of protection with the lowest lifecycle cost. 较合理的是：采用在最合理的费用上能最大的降低污染风险的设计特征；或者是，只有在必须用到那些最昂贵的设计特征才能维持水质在合格限度内时，才采用它们。应将系统设计的很健全和坚固，这样就不需要后来再添加一些设计特征，影响费用和计划。设计特征是根据在投资上的“回返”来选择的（此处“回返”的定义是：降低污染风险），这非常利于系统成本控制以及评估不同的选项。最终，通过输送给用户的水质来确定各个系统设计的效果。设计工程师的挑战是：要知道应该包括哪些设计特征，才能在最低的寿命循环成本下达到要求的防护程度。 EXAMPLE 实例 A USP compendial water system is designed with a 316L SS storage and distribution system and operates normally at 80°C.The tubing is all sanitary, orbital welded, with minimal clamps and zero dead leg diaphragm valves at the use points. Water is kept circulating through the tubing at a minimum return velocity of 3ft/sec. In this case, use of high mechanical polish tubing (<20 Ra) with electropolishing may not be required. The risk of contamination for such a system is already low, and the impact of this upgraded surface finish is questionable. The benefits that will be achieved by further improving the quality of finish may not be justified. 美国药典规定的水系统设计的是用316L SS存储和分配系统并且通常在80°C下操作。所有管道都是清洁的、用轨焊的，在用点使用最少的夹具和无死角的隔膜阀。水是循环流过管道的，并且要保证它们在回路中的流速不低于3ft/sec。在这种情况下，是不需要使用电抛光的高机械抛光管道(<20 Ra)。这样的系统的污染风险已经很低了，而且，这些升级的表面抛光的影响是还未确定。现在还没能证明提高抛光质量带来的益处。 However, if the same system were open to the atmosphere, consideration would be given to installing a 0.2micron vent filter on the storage vessel, as the reduction in contamination risk is quite large for a relatively small investment. Similarly, if the zero dead leg valves, were replaced with less expensive valves with larger dead legs, you might consider increasing the minimal circulation velocity to help compensate. 然而，如果这样的系统是暴露在空气中的，应考虑在储罐上安装一个0.2微米的气滤器，因为这样的投资相对小，但是可以较大的降低污染风险。同样的，如果用一个有着较大死角的较便宜的阀替换无死角的阀，则需要考虑用增加最低循环速度来补偿。 The purpose of the following chapter sections is to provide information to help the user evaluate the advantages, disadvantages and cost effectiveness of many of the design features commonly used to protect water from degradation. A method of selecting/optimizing system storage and distribution design is also presented. 以下章节部分给用户提供了一些信息，以帮助用户去评价许多设计特征的优点、缺点和费用，这些设计参数通常用于防止水降格的。此外，以下章节还提供了选择/优化系统存储和分配的设计方法。 As a general rule, a water system is optimized as a result of the following: 按常规，水系统是按照以下几条来优化的： 1) Minimizing the time the water is held at conditions which favor growth 2) Minimizing changes to water temperature 3) Contacting all areas during sanitization 1）在有利于微生物生长的条件下，减少水的停留时间。 2）减少水温的变化 3）在消毒时应接触到所有区域 One system design can be said to be better than another, if it accomplishes these goals to the same degree, but at a reduced lifecycle cost. Examples of storage and distribution concepts commonly used today are presented in subsequent sections of this Guide, to help demonstrate the idea of optimal system design. 如果某系统设计能在同一程度上达到上述这些目标并且寿命循环成本低，那么就可以说该系统是较好的。该指南后面的章节将给出现在常用的存储和分配的概念的例子，以助于对最佳系统设计概念的证明。 8.3.2 Distribution Design Concepts 8.3.2 分配设计概念 The two basic concepts developed for distribution of pharmaceutical waters are referred to as the "batch" and "dynamic/continuous" distribution concepts. 制药用水的分配的两个基本概念是“批次”分配和“动态的/连续的”分配。 The batch concept utilizes at least two storage tanks. While one is being filled, the other is in service providing pharmaceutical waters to the various process users. After one tank has been filled from the water final treatment system, it is isolated and the water inside is tested. Only after testing is that tank put into service. The water is often drained after 24 hours, but can be validated for longer periods of time. At the completion of the draining operation, the vessel and distribution system is usually sanitized before refilling. 批次概念是至少要用两个储罐。当一个正在装填水时，另一个用于为不同加工程序上的用户提供制药用水。当用终处理系统中出来的水将一个储罐填满后，它是隔离的并且它内部的水是经检测的。只有经检测后，那个储罐才能使用。通常是24小时后就将水排出，但是可验证是否能放置更长时间。在排水操作完成后，储罐和分配系统通常是要经消毒后才能再使用的。 The dynamic/continuous concept off-sets the peak instantaneous water demand, put on the overall water system through utilization of a single water storage vessel which simultaneously receives final pretreatment system make-up, stores the water in the vessel, and ultimately supplies it to the various process users while maintaining water quality. 动态/连续概念弥补了同时需水时的需水量峰值，打开整个水系统，只用单个储水罐同时来接收最后的预处理系统制备的水、在储罐中存储水以及最后将水供应到各个加工程序的用户处，同时还要维持水质。 The advantage of the "batch" distribution concept, over the "dynamic/continuous" distribution concept, is that the water is tested before use with tank QA/QC lot release (water used in each product batch lot is traced and is identifiable). The advantages of the "dynamic/continuous" distribution concept include lower lifecycle costs, as well as less complex piping around the storage vessel, and a much more efficient operation. 对于“动态/连续”分配来说，“批次”分配的好处是水在使用前是经检测的，并且储罐上标有QA/QC的放行签（用于每个生产批次的水是可以追溯和识别的）。“动态/连续”分配的优点有：低寿命循环成本以及储罐周围的管线不复杂并且操作起来更有效。 Once a system distribution concept has been selected, the following additional storage and distribution design considerations should be carefully evaluated: 一旦选择了某个系统分配概念，就应该仔细评估下述附加的存储和分配设计考虑因素： • System configuration including whether series or parallel loops are required, distribution loop points of use, cooling requirements (steam-able, sub-loop or multiple branched heat exchanger assemblies), reheat requirements, if any, secondary loop tanks versus tankless system considerations, etc. 系统配制包括：是否要求串联或并联的回路，分配回路上的用点，冷却要求（可用蒸气的、在次级回路或多分支上装配热交换器），再加热要求，考虑使用无储罐的系统或第二个回路储罐，等。 • Hot (65-80°C), cold (4-10°C), or ambient temperature process use point requirements 用点要求的热(65-80°C)、冷(4-10°C)或环境温度 • Sanitization method (steam, hot water, ozone, or chemical) 消毒方法（蒸气、热水、臭氧或化学试剂） 8.3.3 Distribution Decision Tree 8.3.3 分配决策树 The decision tree in Figure 8-1 is presented to aid in the analysis of distribution design. Most of the systems in use today are represented by one of these eight configurations, but other designs may also be acceptable. In evaluating which configuration is optimal for a given situation, the designer needs to consider many factors, including the requirements for Quality Assurance release, the desired specification of wafer (DI, USP WFI, etc.), hydraulic limitations, the required temperature at each drop, the number of use points, and the Cost of energy. 图表8-1中的决策树有助于分配设计的分析。当今大多数使用的系统都是这八种配置中的一种，但是其他设计也是适用的。在评估哪种配置最适合于给定条件时，设计者需要考虑许多因素，包括QA放行要求、水预期需要达到的技术指标（DI、USP WFI等等）、液压限制、每个下降部分所需温度、使用点数量以及能源成本。 Decision tree guide 1) Batched System 2) Branched/One Way 3) Parallel Loops, Single Tank 4) Hot Storage, Hot Distribution 5) Ambient Storage, Ambient Distribution 6) Hot Storage, Cool and Reheat 7) Hot Tank, Self-contained Distribution 8) Point of Use Heat Exchanger 决策树 1) 批次系统 2) 多分支/单通道 3) 平行回路，单个水罐 4) 热贮存，热分配 5) 环境温度存储,环境温度分配 6) 热贮存，冷却和再加热 7) 热水罐，独立分配 8) 热交换器使用点 Each configuration varies in the degree of microbial control provided and in the amount of energy required. Better microbial control is usually achieved by minimizing the amount of time water is exposed to conditions favoring microbial growth. Configurations that store water at sanitizing conditions such as hot, under ozone, or circulation at turbulent velocities, are expected to provide better microbial control than those that do not. Naturally, hot circulating systems are more forgiving than cold systems from a microbiological perspective. However, adequate microbial control may be achieved in other configurations provided they are frequently flushed or sanitized. In any case, system design should prevent stagnation, which promotes formation of biofilm. 根据提供的微生物控制程度和要求的能源量来选择不同的构型。通常减少水在微生物易于生长的条件下的暴露时间能较好的控制微生物。那些能在消毒条件下（如：热、臭氧或高速循环）储水的构型要比没有这些条件的构型能更好的控制微生物。显然，从微生物上来说，热循环系统要比冷系统好。然而，经常冲洗或消毒的构型能达到充分的微生物控制。在任何情况下，在设计系统时候都应考虑防止滞流，因为滞流可促进生物膜的形成。 Energy usage is minimized by limiting the amount of water changing temperature. Configurations storing water hot but supplying it to the use points at lower temperature must cool the water before use. Energy requirements are minimized by cooling only that water drawn from the system. Configurations that constantly cool and reheat water utilize more energy than systems that do not. 通过限制水温变化量来降低能耗。存储的是热水但供应给用点的水是低温的构型则必须在使用前将水冷却。只用来自系统的水来冷却可以降低能耗。需要不断冷却和再加热的水的构型的耗能要高于那些没有这些需求的系统。 The configurations delivering lower temperature water are shown with a single cooling exchanger for clarity. Usually the cooling medium is tower water since this is the least expensive to generate. In most parts of the world, tower water is not cold enough to allow use temperatures much below 25°C. A second cooling exchanger using chilled water or glycol must be added if the required use temperature is below 25°C. It is usually cost prohibitive to cool water from 80°C to less than 25°C using chilled water or glycol alone as the chiller size becomes quite large. 输送低温水的构型可用一个单冷却交换器来清晰的显示。冷却介质通常是塔水，因为制备成本最低。世界上的多数地区，塔水的温度不足以将待使用的水的温度降到低于25°C。如果要求使用温度低于25°C，则需要添加一个用冷冻水或乙二醇的冷凝交换器。通常禁止只使用冷冻水或乙二醇来将80°C的水冷却到25°C以下，否则冷却器的尺寸将特别大。 Figure 8-1 Distribution Decision Tree 图表 8-1 分配决策树 8.3.4 Example System Descriptions 8.3.4 实例系统 The following describes the systems, contained in the accompanying decision tree that can be used successfully to store and distribute high purity water. Figure 8-2 through Figure 8-12 present simplified schematic diagrams (not meant to be P&IDs) of each configuration. 以下描述包含在决策树中的系统，这些系统可以成功用于贮存和分配高纯化水。图表8-2到图表8-12描述了每个配置的简化示意图（不是工艺管道流程图）。 Figure 8-2 Batched Tank Recirculating System 图表8-2 批次水罐再循环系统 This system is used where QA release is required on the water before it goes into the process, One batch tank supplies water to the process, while the other is tilled and tested "for QA release (traditionally -due to unreliable means of Water production). This is a cumbersome system to operate and is usually limited to smaller systems. The disadvantages are the high capital and operating costs. In-line conductivity and TOC measurements can provide nearly the same degree of assurance for less money. 该系统用于在进入加工程序前需QA放行的水。当一个批次储罐向加工程序供水时，另一个储罐的水还在被检测以获得“QA放行”（通常是由于水的制备方法不可靠）。这样的构型运行起来是麻烦的并且这仅限于小系统。它的缺点是资产成本和运行成本高。可采用在线检测电导率和TOC的方法，这可以提供同样的保证程度而费用却很低。 Figure 8-2 Batched Tank Recirculating System 图表 8-2 成批水罐再循环系统 Figure 8-3 Branched/One Way with Limited Points of Use 图表 8-3 带有有限的用点的多分支/单通道构型 This configuration is sometimes used where capital is tight, the system is small, and microbiological quality is of lesser concern. It is also useful where frequent flushing or sanitization of the piping is possible. It is a good application where water use is continuous. It is less advantageous where water use is sporadic/as the line stays stagnant when not in use. Microbial control is more difficult to maintain. A program must be set up to flush (e.g., daily) and sanitize the loop to maintain microbial contamination within acceptable limits. More frequent sanitization may be required; increasing operating costs. It is also more difficult to use On-Line monitoring, as indicative of the quality of the water throughout the system, in a non-recirculating system. 当资金紧张时才采用该构型。该系统很小并且也不太关心微生物特性。当可以经常冲洗和消毒管道时，该构型是很有用的。它的很好的用法是连续使用。对于水是分散的/当不使用时，水流是停滞的情况，它没有优势。由于很难维护微生物的控制，所以必须建立回路的冲洗（如：每天冲洗）以及消毒计划，以将微生物污染控制在合格限度内。还可能会要求更高的消毒频率，这样就会增加运行成本。在非循环系统中也很难使用在线监测来指示整个系统中水的质量。 Figure 8-3 Branched/One Way with Limited Points of Use 图表8-3 带有有限用点的多分支/单通道 Figure 8-4 Parallel Loops, Single Tank 图表8-4 平行回路，单个水罐 This configuration is a combination of any of the loop distribution schemes off one storage tank. Figure8-4 shows a hot storage tank with two separate loops; a hot distribution and a cool and reheat loop. Parallel loops are very common and are most advantageous where multiple temperatures are required, or where the area served is so large that a single loop becomes cost prohibitive or hydraulically impractical. The major concern is to balance the various loops to maintain proper pressure and flow. This is accomplished either by using pressure control valves, or by providing a separate pump for each loop. (Note： A different design is intentionally presented for each loop). 该构型是一个由任何回路分配组合而成的单储罐的组合体。图8-4显示的是有两个单独回路的热储罐；一个热分配和一个冷的以及再加热回路。在需要多个温度，或者场地非常大，用单回路的成本很高或水压不能实现的情况下，用平行的回路是非常普通的也是最有利的。要考虑的最主要的问题是：平衡各种回路以维持适当的压力和流速。这可通过使用压力控制阀，或分别给每个回路安装独立的泵来实现。（注意：不同回路采取不同设计） Figure 8-4 Parallel Loops, Single Tank 图表8-4 平行回路，单个水罐 Figure 8-5 Hot Storage, Hot Distribution 图表8-5 热贮存，热分配 This is the configuration of choice when all use points req