2024年3月16日发(作者：)
ISPE Pharmaceutical Engineering Guides For New And Renovated Facilities
必要，也不适用。
MP and EP/passivation processes affect the microscopic amplitude and chemical composition,
respectively，of the stainless surface. These processes are not considered necessary to control microbial
growth due to the relatively high operating temperatures. MP is advocated for final finishing of mechanical
welds and EP/passivation for all stainless steel surfaces to optimize the formation of the corrosion resistant
chromium oxide barrier. 机械抛光和电解抛光/钝化分别影响不锈钢表面的微观振幅和化学组成，一般
提倡用机械抛光MP作为机械焊接的最后抛光，而提倡对所有的不锈钢表面进行电解抛光/钝化以获
取抗腐蚀氧化铬屏障的最佳组成。
The impact of progressive mechanical polishing on the capital cost of stills and other equipment is
considerable, and often can account for 25% to 30% of a ME or VC still cost. MP processes, except when
used to smooth out a mechanical weld or misalignment etc., may be removed from the applicable
specification without fear of compromising the water quality.先进的机械抛光对不锈钢以及其他设备的
固定成本影响是非常大的，通常达到多效蒸发器或压汽蒸发器成本的25% -30%。除非用于抛光机械
焊缝或未对准的地方，在其他不担心水质量受污染的情况下，在适用的详细规程中可以不做机械抛
光处理。
6.5.6.2 Instrumentation and Controls使用仪器及管理
For WFI applications, the level of instrumentation should be sufficient to monitor parameters
considered critical because they relate to ensuring proper hydraulic/thermodynamic functionality
and the production of the appropriate quality of WFI. Instrumentation for critical operating
parameters should be calibratable using National Institute of Standards and Technology (NIST)
traceable equipment. 对于WFI应用来说，检测仪器应达到足以监控关键参数的检测水平，因为
这些关键参数涉及到确保正常的水压/热功能，以及确保合格的WFI的生产。用于监控关键运
行参数的仪器应当使用美国国家标准局(NIST)可追踪的仪器。
5.6.3 Advantages and Disadvantages优点和缺点
table 6-3 Process and Steam Comparison加工和蒸汽比较
Configuration
组件
• Evaporator 蒸发器
• Condenser 冷凝器
Single-Effect单效
YES
YES
Multi-Effect 多效 Vapor Compression 压
汽
YES
YES
YES
NO
YES
YES
NO
YES
• Feed/Blowdown heat NO/optional 无/可选择YES
exchangers给水/爆裂热交换
• Compressor 压缩机
•ASME Coded 是否符合
ASME
• Distillate pump 蒸馏泵
NO
Normally NO
Normally NO
NO
YES
Optional
10
ISPE Pharmaceutical Engineering Guides For New And Renovated Facilities
• Slowdown pump 减速泵
• Feed booster pump
Makeup heat 给水调节泵
• Steam pressure 蒸汽压
Cooling water 冷凝水
Plant Steam Pressure, psig 工
业蒸汽压力
Feed Water Pressure, psig 给
水压力
Condenser Cooling Water
Pressure, psig 冷凝器冷却水
压力
NO
NO Steam or electric
NO
YES Steam
YES
NO Ambient WFI:
-Steam or electric HOT
WFI:-Steam
LOW
NO
30-40
30-50
Not required
LOW
YES
30-60
30-50
30-50
HIGH
YES
100-120
75-90
30-50
MAY BE USED TO YES (not common
GENERATE CLEAN STEAM practice)
是否用于产生清洁蒸汽 能（但通常不用）
YES NO
6.6 REVERSE OSMOSIS (RO)反渗透
RO employs a semi-permeable membrane and a relatively high pressure differential to force water through
the membrane to achieve chemical, microbial, and endotoxin reduction, critical in USP WFI
applications,the feed water is converted into two streams, permeate and reject. The permeate water flows
through the membrane and is produced cold and as such does not have the temperature protection for
microbial growth afforded by the alternate distillation processes. The reject stream discharges
comparatively smaller volume than the permeate, and contains virtually all of the feed water contaminants.
反渗透运用半透膜以及相对高的压差，迫使水通过半透膜，从而降低化学物、微生物以及内毒素。
给水被分为两股，透过水和废水，透过水流通过半透膜，在低温下生成，这样就不会像交替的蒸馏
过程那样，为微生物生长提供温度保护。废水流的体积小于透过水，而且里边几乎含有给水中所有
的污染。
6.6.1 Application应用
RO systems are used as USP WFI pretreatment for distillation processes, or as final treatment for USP
Purified water systems. RO is also an accepted means of producing WFI, and may provide a low capital
and operational cost alternative to distillation. 反渗透系统用于USP注射用水蒸馏之前的预处理，或者
用于USP纯化水系统的终处理，反渗透同样可用于生产注射用水，相比蒸馏来说，反渗透的资产成
本和运行成本都很低。
Membranes that are hot water sanitizable at 80°C are now available for pretreatment and final treatment,
thus eliminating the need for chemical sanitization and simplifying the validation process. These
membranes still require periodic chemical cleaning.在80°C用热水对膜进行消毒，适用于预处理和终处
理。这样就不需要进行化学消毒，从而简化了认证过程。这些膜依然需要定期进行化学清洁。
Membranes, which may allow for continuous operation at 80°C, are under development. This may have a
significant impact on the use of RO as a means of producing USP WFI, since operation of the system at
80°C may nearly eliminate biological concerns. Failure of a membrane or seal will result in permeate
11
ISPE Pharmaceutical Engineering Guides For New And Renovated Facilities
contamination. These problems may be controlled by:可在80°C条件下持续工作的膜依然在开发当中，这
可能对RO作为生产USP注射用水产生显著的影响，虽然在80°C生产几乎可以消除厂家对微生物污染
的担心，但膜和密封的破坏将导致污染，可用以下方法对这些问题进行控制：
• Pretreatment of the feed water给水的预处理
• Appropriate membrane material selection适合的膜材料的选择
• Latest technology membrane design最新技术的膜设计
• Integrity challenges完整性挑战
• Periodic sanitization定期消毒
• Monitoring of microbial levels, conductivity, total organic carbon and differential pressures对微生物水
平，传导率，总有机碳以及压差进行监控。
6.6.2 Description描述
Semi-permeable RO membranes are produced commercially for water purification in spiral wound and
hollow fiber configurations. RO membranes are permeable to some substances such as water and dissolves
gases, while impermeable to other substances such as salts, high molecular weight organics, acids,
bases,colloids, bacteria, and endotoxins. Membranes are available in four basic materials; cellulose acetate,
polyamide, thin film composite, and polysulfone. (Polyamide membranes are virtually identical in
performance to thin film composite membranes.) All three membrane types have advantages and
disadvantages. (See Chapte 5 for more details.)商业上生产的用于水的纯化处理的反渗透半透膜有螺旋
卷式和中空纤维式两种，一些物质比如水和溶解的气体可以通过反渗透膜，而另一些则不能通过，
如盐类、高分子有机物、酸、碱、胶体、细菌以及内毒素。可用四种基本的材料来制作半透膜：醋
酸纤维素，聚酰胺，合成薄膜以及聚乙烯。（聚酰胺膜和合成薄膜的性能几乎一致）这三种膜各有
利弊（详见第5章）
Bacteria and endotoxin removal, required for WFI applications, can be performed at ambient temperatures.
This significantly reduces utility costs compared to alternative elevated temperature processes
(distillation)By operating at ambient temperatures, distribution piping may not require insulation and may
not need to be constructed of stainless steel.注射用水需要去除内毒素，RO可以在环境温度下完成此过
程，和可选择的高温处理过程（蒸馏）相比，其显著降低了使用费用。由于在室温下进行操作，分
配管可能不需要绝缘，也不需要用不锈钢来制造。
For WFI applications, opportunities exist for enhanced control of the single pass unit, by utilizing
multi-pass-product-staged or other combination designs. These configurations improve reliability and
efficiency, while improving water quality and quality assurance over the single pass design.对于注射用水
的生产，可通过使用使水通过多个反渗透装置或其他联合设计，加强对单个反渗透装置的控制。对
比一级反渗透设计，这些联合设计构造提高了可靠性和效率，同时提高了水的质量和数量。
6.6.3 Pretreatment Requirements预处理要求
RO, as the final processing step, may require pretreatment using ion exchange, deionization, RO, and/or
ultrafiltration to improve operability and quality attributes.作为终处理的反渗透系统，需要用离子交换、
12
ISPE Pharmaceutical Engineering Guides For New And Renovated Facilities
消电离作用、反渗透和/或紫外进行预处理，以提高工作性能以及水的品质。
Pretreatment requirements normally include gross particle filtration, scale prevention, and chlorine
dioxide and ammonia gas, are not removed by the RO process, and may be removed by
degasification, caustic addition, ion exchange, or electrodeionization, prior to the final RO process step.
(See Chapter 5 for more details.)预处理要求通常包括总粒子过滤、结垢预防、氯离子清除。反渗透处
理不能去除二氧化碳以及氨气，因此应当在最终反渗透处理步骤之前，用脱汽、碱性添加剂、离子
交换或电法去离子将二氧化碳以及氨气清除。
Due to the stringent microbial and endotoxin control required for parenteral and other critical applications,
the pretreatment prior to the RO should incorporate additional provisions for control and monitoring of
microorganisms.非肠道给药以及其他有更高要求的应用需要严格控制微生物和内毒素，因此在反渗透
之前进行的预处理应当结合附加的预防措施以控制和检测微生物。
Disinfectants, such as chlorine or chloramine, should be maintained, when tolerable, at appropriate levels
throughout the pretreatment chain. Stagnant water resulting from surge tanks or dead legs should be
avoided by design, or by the inclusion of recirculation systems, which should include In-Line microbial
control devices,such as UV sterilizers.在容许范围内，整个预处理链都应保持适宜浓度水平的消毒剂，
比如：氯气和氯胺。应当通过设计来避免缓冲罐或死管中形成停滞水。或者通过再循环系统中的装
置，包括在线微生物控制装置，比如紫外杀菌器。
Regular and appropriate sanitization and cleaning of all unit operations subsequent to and associated with,
the disinfectant (chlorine or chloramine etc.) removal should be scheduled, to maintain and complete the
micro-organism control of the pretreatment system. (See Chapter 4 for further details.)
在定期或适当的对所有操作单元进行消毒和清洁后或同时，要安排去除消毒剂（氯或氯胺等）的计
划，以保证预处理系统的微生物控制及其完整性。（进一步细节见第4章）
6.6.4 Economics经济
Opportunities are available to reduce capital costs associated with the selection of construction
materials,surface finishes, and instrumentation used in the construction of RO units without compromising
the water quality. Operating costs of RO systems are associated mainly with replacement membranes,
water concentrate discharge, electrical power, cleaning and sanitizing chemicals, replacement filters, and
pretreatment cost.在不影响水品质的情况下，对反渗透设备中所用的制造材料、表面抛光、以及检测
仪器进行选择，可以降低设备固定成本。反渗透系统的运行成本主要和膜更换、水浓缩释放、电能、
清洁和消毒化学剂、过滤器更换、预处理费用相关。
6.6.5 Construction Materials制造材料
Construction material selection for RO systems are driven by:供RO系统选择的制造材料由下列条件决
定：
• Structural integrity, based on high operating pressure结构完整：基于高运行压力
• Structural integrity, based on low pressure sections ahead and after the membranes结构完整：基于在膜
前后的低压力部分。
• Chemical compatibility with the contact fluid and its constituents对于接触液体和其成分有化学稳定
13
ISPE Pharmaceutical Engineering Guides For New And Renovated Facilities
性。
• Need to control microorganism growth控制微生物生长的需要。
The low operating temperature of the RO system allows the use of non-metallic construction materials.
Sanitary piping and valves are generally optional features for RO systems, based on the specific
manufacturer and location of the RO in the treatment chain.由于反渗透系统的低运行温度，可以使用非
金属制造材料，反渗透系统的污水管和阀门通常是可选择的项，是否选择取决于特定的制造商以及
反渗透在整个处理系统中的位置。
For the final purification step, it may be very cost effective to utilize mill finish 304 stainless steel
for the feed and concentrate waste piping for the system, maintaining 316L stainless steel or PVDF
and sanitary design for the product piping only.作为最后的纯化步骤，使用经粉碎抛光处理的304
不锈钢作为给水管和浓缩废水管是非常节约成本的。只有生产管道才用不锈钢或PVDF以及消
毒设计。
6.6.6 Surface Finish表面抛光
MP and EP processes are not applicable to non-metallic systems.机械抛光和电去离子不适用于非金属系
统。
6.6.7 Instrumentation and Controls 检测仪器和控制
RO control systems usually use local control and indication, and do not typically require
programmable logic controllers (PLC) as a standard feature. The type and level of instrumentation is
similar among manufacturers. The level of instrumentation should be sufficient to monitor
parameters considered critical because they relate to ensuring proper hydraulic functionality and the
consistent production of quality WFI. Instrumentation for critical operating parameters should be
calibratable using NIST traceable equipment. (See Chapter 9 for more details.)RO控制系统通常使
用内部控制和指示，通常不要求将PLC作为一项标准，在各个生产厂家中，检测仪器的种类
和级别都类似，检测工具的水平应当足以对关键参数进行监控。由于这些关键参数涉及到确
保正常的水压/热，以及确保合格的WFI的生产。用于监控关键运行参数的仪器应当使用美国
国家标准局(NIST)可追踪的仪器。
The typically monitored operating parameters for an RO system are feed pH, feed conductivity, and
product quality (TOC and conductivity). These three parameters should be measured using calibratable
NIST traceable instruments. Recording data may be accomplished manually or electronically using analog
instruments and paper/paperless recording systems.对RO系统来讲，代表性的运行监控参数有给水PH
值、给水电导率、出水质量（TOC及电导率）这三个参数应当用NIST校准过的可追踪的仪器进行测
量。用模拟测量仪器及纸/无纸记录系统将数据手工或电动记录下来。
6.6.8 Advantages and Disadvantages优缺点
Multi-pass can, in most cases, produce water quality consistent with the minimum requirements of USP
WFI. In cases where the feed water quality is such that this is not possible, the use of some type of
14
ISPE Pharmaceutical Engineering Guides For New And Renovated Facilities
, additional RO, UF, ion exchange, or electrodeionization) as a pretreatment may be
required. This is to allow the final point of purification to remain RO and the system to generate consistent
and reliable water within the USP WFI specifications.在多数情况下，多级反渗透生产的水质量可以符合
USP注射用水的最低标准，但当给水质量不好的情况下，成品水质量可能不达标，这时需要使用一
些去离子预处理（比如附加的反渗透、超滤、离子交换或电法去离子）这可使纯化的最后程序依然
使用反渗透，并使系统连续不断地生产出质量可靠的、符合USP注射用水标准的水。
Advantages associated with the design and operation of RO units used as the final treatment step for the
production of WFI are: RO设备作为WFI生产的最后处理步骤，其设计和运行的优点如下：
1) Depending on cost and complexity of pretreatment, RO systems designed for production of USP WFI
may provide for significantly reduced capital costs when compared with distillation processes, while
maintaining the appropriate USP WFI quality.
根据预处理的花费和复杂性，对比蒸馏系统来说，设计用于生产USP注射用水的反渗透系统可显著
降低成本，同时保持了注射用水的质量。
2) The utility requirements are significantly lower for RO systems (electricity for pump horsepower) than
for distillation, resulting in lower operating costs, which may be a very significant factor over the lifetime
of the system.反渗透系统对设施的要求要比蒸馏低的多（只需要使泵运转的电力），这样就降低了运
行成本，这可能是系统寿命的一个非常显著的影响因素。
Disadvantages associated with the design and operation of RO units used as the final treatment step for the
production of WFI are:RO设备作为WFI生产的最后处理步骤，其设计和运行的缺点如下：
1) Membrane fouling and integrity膜污染及完整性
• Bacteria grow-through细菌透膜生长
• Seal leakage or by-passing密封器渗漏或旁流
• Seal failure or damage caused by chemical attack etc.由于化学破坏或其他原因引起的密封器失效或
损坏
• Membrane damage during installation etc.安装过程中的膜损坏
• Membrane damage due to chemical or high temperature attack由于化学或高温破坏而导致的膜损坏
2) Membrane material sensitivity to bacteria and sanitizing agents.膜材料对细菌及消毒剂敏感。
3)Inherent sanitization limitations内部消毒规定
• Periodic chemical or hot water sanitization may be required需要定期化学剂或热水消毒
• Periodic chemical cleaning may be required需要定期的化学剂清洗
4) Pretreatment cost may be high预处理成本高
RO systems provide a method for consistently producing ambient water in accordance with the USP
15
ISPE Pharmaceutical Engineering Guides For New And Renovated Facilities
WFI requirements. This not only reduces utility requirements, but also may reduce installation costs,
since thermal insulation may not be required for storage and 系统可以连续生产符
合USP注射用水标准的水，这不仅降低了对设施要求，同时也降低了安装成本，因为储存和分
配不需要热绝缘。
6.7 USP - WATER FOR INJECTION SYSTEMS COMPARISON USP 注射用水系统
比较
Table 6-4 WFI Systems Comparison注射用水系统比较
UNIT OPERATION (1,2)
运行设备
Capital Cost 资产成本
Chemical Consumption
化学消耗
Energy Consumption
能源消耗
Water Consumption
水消耗
Outside Service Costs
外部服务费用
RO 反渗透 DISTILLATION 蒸馏
2 pass RO 二级反SE 单效蒸馏 ME 多效蒸馏 VC 压汽蒸馏
渗透
M
L
M
M(3)
L
M
N/A
H
H
L
L
H
N/A
H
M
L
L
H
N/A
H
M
L
L Operational Maintenance 运L
行保养
Ratings级别: L = Low低 M = Medium中 H = High高
Notes注意:
1) All Indicators are relative to each other within the specific category在一个特定的种类里所有的指标都
相互联系。
2) Optimum design and operating conditions are assumed以上的数据都来自于：假设设备都处于理想的
设计和操作环境。
3) Total water consumption is dependent on pretreatment selected水的总消耗量决定于预处理的选择。
4) RO may not meet USP TOC levels if feed water TOC is high (>3 ppm)如果给水TOC高于3 ppm，反
渗透处理可能不能达到USP的TOC标准。
16
PHARMACEUTICAL
STEAM
制药用蒸气
7. PHARMACEUTICAL STEAM
7. 制药用蒸气
7.1 INTRODUCTION
7.1 序论
This chapter aims to simplify and standardize the process of selection, programming, and design
of pharmaceutical steam systems. Guidelines, information, and options are provided, along with
advantages and disadvantages, based on the best and most cost effective of current and proven
practices and technologies.
本章旨在简化以及标准化制药用蒸气系统的选择、规划和设计。并以现行和已被证明的最好
的和成本效应最高的实践和工艺为根据，给出一些指导方针、信息资料和选项，以及优缺点。
The absence of regulations governing the use of steam in pharmaceutical processes has resulted in
the proliferation of differing practices and interpretations. Most interpretations are made on the
side of conservatism. Unfortunately, in addition to increasing cost without an associated increase
in benefits, excessive conservatism can result in system complexity, and possibly reduced
reliability. One example is the use of clean steam (non-utility boiler produced steam) where a form
of utility steam (utility boiler produced steam) would be adequate to maintain product quality. The
installation of a clean steam generator when a simple steam reducing station would suffice results
in added equipment and the associated impact on cost, complexity, and reliability.
在制药工艺中指导蒸气使用的法规缺乏导致衍生出不同实践和理解。大多数理解是保守的。
不幸的是，这除了增加成本外没有相应的增加利益，过度的保守能够导致系统复杂并且可能
减少其可靠性。举个例子，在一种公用蒸气（公用锅炉产生的蒸气）就足以维持产品质量的
地方使用清洁蒸气（非公用锅炉产生的蒸气），在一个普通蒸气简化装置就能满足需要时安
装一个清洁蒸气发生器，这导致设备增加并在成本，复杂性以及可靠性方面造成相关影响。
In some instances, interpretations are based on inaccurate assumptions of what is important or
critical. An example is the over specifying of pretreatment or using WFI as feed to solve the
perceived problem.
在某些情况中，理解是建立在不准确假设“什么是重要或关键的”基础上的。举个例子，比
如过度规定预处理或使用注射用水作为给水来解决那些已察觉的问题。
The chapter establishes standard definitions for terms commonly associated with pharmaceutical
steam and provides information that facilitates making correct and cost effective decisions.
本章为制药用蒸气相关的术语制定了标准定义，并为促使作出正确和成本有效的决定提供了
信息。
7.2 cGMP ISSUES
7.2 cGMP出版物
The user has the ultimate responsibility for system design and performance, and for ensuring that
the proper type of steam is used for a given process.
用户对系统的设计和性能拥有最终职责并要确保适当类型的蒸气用于给定的工艺。
There is no FDA or USP minimum standard for clean steam. However, cGMPs for large volume
parenterals (LVPs) issued in 1976 indicated that feed water for boilers supplying steam that
contact components, drug products, and drug product contact surfaces shall not contain volatile
additives such as amines or hydrazines.
对于清洁蒸气，FDA或USP没有最低标准。然而，1976年发行的cGMP关于大容量注射液部
分表明供应蒸气的锅炉的给水、接触组件、药品和药品接触面不能包含挥发性添加剂比如胺
或联胺。
Few regulations govern the design and construction of clean steam generators. There are also no
regulations governing materials of construction, type or level of instrumentation, surface finishes,
or operating temperatures.
很少法规管理清洁蒸气发生器的设计和构造，也没有法规管理构造材料、使用仪器的类型和
等级、表面抛光或操作温度。
Among US Government publications, the FDA's Code of Federal Regulations (CFR) provides
culinary steam recommendations and stipulations related to heat exchanger and tank air vents
design and construction. The Culinary steam recommendations apply to food applications
only.
在美国政府出版物中，FDA的联邦管理法规(CFR)提供厨房用蒸气的优点和关于热交换器及
水罐排气口设计、构造的规定。建议厨房用蒸气只用于食品应用。
US Public Health Service/Dairy Industry Committee, 3A Sanitary Standards, Number 609-02,
adds additional limitations to Culinary steam feed water additives for food applications. It should
be noted that boiler feed water additives permitted in food for human consumption may not be
acceptable in drinking water or orally ingested drug products.
美国公共卫生部门/乳制品工业委员会，3A卫生标准，编号609-02，为食品应用而对厨房用
蒸气给水添加剂增加附加限制。应该注意人用食品中的锅炉给水添加剂不能用于饮用水或口
服药品。
7.2.1 Steam Attributes
7.2.1 蒸气特质
7.2.1.1 Quality
7.2.1.1
质量
The term "Quality" when referring to steam indicates the level of steam saturation. There are no
FDA or USP regulations relating to minimum "steam quality" or the level of non-condensable
gasses present in pharmaceutical steam. (See Section 7.4.)
当涉及蒸气时，“质量”术语表示蒸气饱和标准。没有关于最低“蒸气质量”或在制药用蒸
气中不可压缩气体标准的FDA或USP法规。（参看7.4部分）
European regulators have defined specific criteria for pharmaceutical steam used for equipment
sterilization. (European Standard EN 285 - Steam Sterilizers - reference section 13.3) These cover
acceptable levels of saturation or dryness, the level of superheat, and the volume of
non-condensable gases present.
欧洲法规对用于设备灭菌的制药用蒸气规定了具体标准。(欧洲标准EN 285-蒸气灭菌器-参
考13.3部分)。这些包含饱和或干燥标准、过热标准和不可压缩气体体积。
7.2.7.2 Purity
7.2.7.2
纯度
Purity requirements for steam used in pharmaceutical manufacturing and product development are
driven by the product characteristics, manufacturing process, and the intended use of the product.
The product manufacturer is responsible for ensuring that steam used to process the product is
appropriate.
用于制药生产和产品研制的蒸气纯度要求由产品特性、生产工艺和产品预期用途决定。药品
生产商有责任确保将合适的蒸气用于药品生产。
Though steam purity requirements are product specific, it may be impractical to reliably produce
special steam for each situation. Manufacturing operations typically generate and distribute only
one or two steam purity grades, commonly grouped.
虽然蒸气纯度要求是因产品特性而不同，但为每个情况可靠地生产特殊蒸气是不实用的。生
产操作典型地产生和分配一般分组为一种或两种的蒸气纯度等级。
7.3 TYPES OF STEAM
7.3 蒸气类型
Pharmaceutical steam is classified into two (2) types based on their respective sources. These are:
1) Utility-Boiler produced steam, hereafter called Utility Steam.
2) Non-Utility Boiler produced steam, hereafter called Clean Steam.
根据它们各自的来源，制药用蒸气分为两种类型。它们是：
1)公用锅炉产生的蒸气，此后叫做公用蒸气。
2)非公用锅炉产生的蒸气，此后叫做清洁蒸气。
7.3.1 Utility Steam
7.3.1 公用蒸气
Utility steam is characterized with usually having:
• Chemical additives to control scale and corrosion
• Relatively high pressure with the potential of generating superheat during expansion
• Relatively high pH
公用蒸气通常具有以下特征：
• 用于控制水垢和腐蚀产物的化学添加剂
• 伴随在膨胀时产生过热潜在性的相对高压
• 相对的高pH值
Chemical additives: Utility steam is produced, in most cases, using conventional fire-tube steam
boilers, normally of steel construction. Such boilers are almost always provided with systems that
inject additives in the feed water to protect the boiler and steam distribution piping from scale and
corrosion. Some of these scale and corrosion inhibitors may, and often do, include amines and
other substances that may not be acceptable in steam being used in pharmaceutical processes. The
user must determine what additives are used, and verify if they are acceptable in the particular
application, i.e., do not add any impurities or create a reaction in the drug product.
化学添加剂：在多数实例中，使用常规钢结构火管蒸气锅炉产生公用蒸气。这种锅炉几乎总
是规定在给水中注入添加剂来保护锅炉和蒸气分配管道以免产生水垢和腐蚀。一部分这些水
垢和腐蚀抑制剂可能并且经常使用，包括胺和不适用于制药工艺所用蒸气的其他物质。用户
必须决定使用哪种添加剂并且验证它们是否可适用于特定应用，比如，不能在药品中添加任
何杂质或产生反应。
Utility steam can be filtered to remove particulate matter, but filtration does not remove dissolved
substances and volatiles such as amines.
可以过滤公用蒸气除去颗粒物，但是滤器无法去除已溶解物质和挥发物比如胺。
Superheat: Superheated steam is produced in water tube boilers by reheating the steam or by
generating the steam at a higher pressure in a fire tube boiler and then reducing the pressure
through a regulating valve. When the pressure is reduced, the energy in the higher temperature
steam is dissipated to generate steam at the lower pressure and produce superheated steam above
the corresponding saturation temperature. Superheat is dissipated downstream of the regulating
valve due to heat loss in the line.
过热：在水管锅炉中通过再加热蒸气产生过热蒸气或者在火管锅炉中通过在更高的压力下产
生蒸气然后使用调节阀减低压力来产生过热蒸气。当压力减低时，较高温度蒸气中的能量消
散会产生较低压力下的蒸气并同时产生超过相应饱和温度的过热蒸气。由于管线的热损失，
过热在调节阀的下游消散。
pH control: In order to protect carbon steel from corrosion by the steam, it is necessary to use
additives to raise the pH to between 9.5 -10.5.
pH控制：为保护碳钢制品不被蒸气腐蚀，有必要使用添加剂将pH值升高到9.5-10.5之间。
7.3.2 Clean Steam (CS)
7.3.2 清洁蒸气(CS)
Pharmaceutical clean steam is generated from treated water free of volatile additives, such as
amines or hydrazines, and is used for thermal disinfection or sterilization processes. It is
considered especially important to preclude such contamination from injectable drug products:
制药用清洁蒸气是从不含有挥发性添加剂（例如胺或联胺）的净水中产生，并用于热灭菌或
灭菌过程。从注射用药品中清除这类污染是尤其重要的：
Clean steam is characterized as having:
• No additives
• No generated superheat except when the generated pressure is significantly higher than the
use pressure of the steam. (See Section 7.3.1 - Superheat.)
• Relatively low pH
清洁蒸气具有下列特征：
• 没有添加剂
• 不产生过热，除非产生的压力显著高于蒸气使用压力（参看7.3.1部分-过热）
• 相对低pH值
There are many terms used in the pharmaceutical industry to describe Clean Steam. These
include Clean Steam, Pure Steam, Pyrogen Free Steam, WFI Steam, and USP Purified Water
steam. There is no standard or accepted definition for any of these terms. However, the most
commonly used terms are "Pure Steam" and" Clean Steam". In this Guide, the term "Clean
Steam" is used in lieu of all others.
The condensate of Clean Steam has no buffer, and may have a relatively low pH compared to that
of utility steam.
在制药工业中有很多术语用于描述清洁蒸气。这些包括清洁蒸气、纯蒸气、无热原蒸气、
注射用水蒸气和USP纯化水蒸气。对任何这些蒸气都没有标准或公认定义。然而，大多数
通常使用的术语是“纯蒸气”和“清洁蒸气”。在本指南中，使用“清洁蒸气”术语替代
其他所有术语。
清洁蒸气的冷凝液没有缓冲系统，并且与公用蒸气相比它具有相对低pH值。
7.4 BACKGROUND AND INDUSTRY PRACTICES
7.4 背景和工业实践
7.4.1 Purity of sterilizing steam
7.4.1 灭菌蒸气纯度
When steam or the resulting condensed water comes in direct or indirect contact with the drug
product, the purity should be equivalent to the water purity acceptable for final rinsing of the drug
contact surfaces.
当蒸气或其产生的冷凝水与药品有直接或间接接触时，其纯度应该与最终冲洗药品接触面合
格的水纯度相同。
Note: A continuous supply of Dry Saturated Steam at the point of use is considered necessary for
efficient steam sterilization. Water carried by the steam in suspension may cause damp loads and
superheated steam is considerably less effective than saturated steam when used for sterilization.
Non-condensable gases if contained in the steam may prevent the attainment of sterilization
conditions in parts of the sterilizer load.
注意：为了有效蒸气灭菌，有必要考虑在用点连续供应干燥饱和蒸气。蒸气带来的悬浮的水
可能引起潮湿，当用于灭菌时，过热蒸气比饱和蒸气的效果低的多。如果蒸气中含有不可压
缩气体，则可能会防碍灭菌器中的一些部位达到灭菌条件。
7.4.2 Steam used for humidification
7.4.2 用于增湿作用的蒸气
When steam is used for indirect humidification, such as injection into HVAC air streams prior to
final air filtration, the steam does not need to be purer than the air that it is being mixed with.
However, when humidifying process areas, the potential level of impurities, including amines and
hydrazines should be evaluated in order to ascertain the impact on the final drug product. This is
particularly important in areas where open processing takes place, such as aseptic filling suites and
formulation areas. If the diluted water vapor is found to contribute significantly to the
contamination of the drug, a purer grade of steam should be selected.
当蒸气用于间接增湿作用时（如：在最终过滤之前注入HVAC的空气气流），蒸气没有必要
比将要混入的空气更纯净。然而，当给加工区增湿时，为了确定对药品终产品的影响，应该
评价包括胺和联胺的杂质潜在水平。这对开放的加工区非常重要，例如无菌填充室和合成区
域。如果发现稀释的水汽显著地增加药品污染时，应该选择更加纯净级别的蒸气。
7.4.3 Common practices
7.4.3 普通实践
It is common practice to generate pharmaceutical steam from compendial waters and test the
steam condense for equivalency to the compendial standard. This practice ignores the ability of
the pharmaceutical steam generator to remove impurities. This overprocessing is wasteful and
unnecessary. An exception is when the steam quantity is small and the cost and maintenance of a
dedicated feed water pretreatment system exceeds the cost of using compendial water.
Pharmaceutical Clean Steam is commonly used in applications where utility steam would suffice;
such as non-critical room humidification and high purity water heat exchangers.
常见的行为是用药典规定的水来生成制药用蒸气，并以等同的药典标准来检测蒸气的冷凝
水。该行为忽略了制药用蒸气发生器去除杂质的能力。过度处理是浪费和不必要的。但当蒸
气需求量很少，并且对专用的给水预处理系统的维护成本超过了使用药典规定的水的成本
时，这就是个例外。制药用清洁蒸气通常用于公用蒸气可以满足的应用区域，例如非关键房
间增湿作用和高纯化水热交换器。
Table lists the commonly accepted industry standards and highlights the trend in the
pharmaceutical industry to provide "purer than necessary" steam and over-specified feed water.
列表中列出通常公认的工业标准和制药工业趋势的要点从而提供“比所需更加纯净的”蒸气
和过度具体说明的给水。
7.4.4 Industry and Baseline Practices in the Production of steam
7.4.4 蒸气产生企业和基线实践
Table 7-1 Practices in the Production of Steam
表7-1 蒸气产生实践
Intended Use of Steam
蒸气预期用途
Method of generation
产生方法
Parenteral and Non-Parenteral Dosage form
The use of a sanitary clean steam generator with
applications where steam is in direct contact entrainment for the control of endotoxins & liquid
with the drug. carry-over (SCSG) is both baseline and common
蒸气直接接触药品的无菌和非无菌制剂应用industry practice.
灭菌清洁蒸气发生器的用途伴随带走内毒素&液
体携带污染(SCSG)控制是基线和普通工业实践
Critical step in the manufacture of API where
The use of an SCSG is both baseline and common
steam is in direct contact with the Active
industry practice.
Pharmaceutical Ingredient (API).
SCSG的用途是基线和普通工业实践
蒸气直接影响API的API生产的关键步骤
Non-Critical step in the manufacture of an API
where added impurities may be removed in a
subsequent step.
加入的杂质可以在后续步骤中去除的API生
产的非关键步骤
SCSGs are commonly used; however, utility steam
is the acceptable baseline application.
通常使用SCSG，然而公用蒸气也是合适的基线应
用。
WHILE THE USE OF A SCSG IS COMMON
PRACTICE, AN ALTERNATIVE APPROACH IS TO
Sterilization of USP water systems.
USP水系统的灭菌
USE UTILITY STEAM PLUS HOT USP WATER,
FLUSHING & WASTE TESTING.
当SCSG的用途是普通实践时，可选方法是使用公
用蒸气加上热USP用水，冲洗&废物测试
Process humidification for dosage form
application where steam is in direct contact
with the drug, where open processing takes
place and where the potential level of amines,
SCSGs are commonly used and are the Baseline
hydrazine's etc. in the condensate has been
application.
determined to have a detrimental effect on the
通常使用SCSG并且SCSG是基线和普通工业实践。
drug product.
蒸气直接接触药品，进行开放工艺和已确定
冷凝液中胺、联胺等的潜在水平对药品有不
利影响的制剂增湿过程应用
Humidification of non-critical HVAC systems
such as rooms and areas where the drug is not SCSGs are commonly used but utility steam may be
directly exposed to the room atmosphere. totally acceptable.
非关键HVAC系统的增湿，例如药品不直接通常使用SCSG，但公用蒸气也能够完全合格
暴露在房间大气中的房间和区域
Where open processing takes place and where the
potential level of amines, hydrazine's etc. in the
condensate has been determined to have a
detrimental effect on the drug product the baseline
HUMIDIFICATION OF PROCESS &
and common practice is the use of a SCSG. However,
if it has been determined that the impurities have an
CRITICAL CLEANROOMS.
insignificant effect on the drug product, a utility
工艺 & 关键洁净室的增湿
steam source would qualify as the baseline approach.
在进行开放工艺和已确定冷凝液中胺、联胺等的潜
在水平对药品有不利影响的地方，基线和普通实践
是使用SCSG。然而，如果已确定杂质对药品具有
无关紧要的影响，公用蒸气来源将作为基线方法确
认。
It is common practice to use a SCSG as the
energy source. The baseline approach would be to
Energy source for non-critical & cGMP heat
use a utility steam source coupled with a cGMP heat
exchangers.
exchanger design.
非关键& cGMP热交换器的能源
使用SCSG作为能源是普通实践。基线方法是将使
用与cGMP热交换器设计配对的公用蒸气能源
Sterilization of fermentation vessels.
发酵容器的灭菌
It is common practice as well as the
baseline approach to use utility steam.
这是与使用公用蒸气基线方法一样好的普通实践。
Figure 7-1 Pharmaceutical Steam System Planning
Pharmaceutical Steam System
Planning
STEAM
API critical
API non-critical
REQUIREMENTS
RE-EVALUATE SYSTEM
DESIGN BOUNDARIES AND
Sanitary or simple
SYSTEM
CONSTRAINTS
CS generation
DESIGN
Delivery flow rate
USE POINT
CRITERIA
Auto/Manual
control
DISTRIBUTION
SYSTEM
Pipe sizing & insulation
制药用蒸汽系统
计划
系统
API 关键步骤
要求
API 非关键步骤
系统
灭菌或普通CS产生
再评价系统设计
成本/安全性要求
设计
边界和约束
使用点
输送流速
自动/手动
控制
分配
管道类型 & 绝缘体
标准
系统
7.5 SYSTEM PLANNING
7.5 系统设计
Pharmaceutical Steam System Planning, shown in the Figure 7-1 is a graphic representation of the
system boundaries, limitations, and restrictions. Initial system planning reveals primary
boundaries that establish the cornerstone for design criteria. These system boundaries are steam
Requirements, System Design, Use Point Criteria, and Distribution System requirements.
在图表7-1中显示的制药用蒸气系统计划是系统边界、界限和限制的图解表示。最初的系统
计划显示为设计标准确立基础的主要边界。这些系统边界是蒸气要求、系统设计、使用点标
准和分配系统要求。
The arrows encircling each boundary represent limitations that establish more specific operating
strategies and ranges. To allow more flexibility in final planning and detailed design the designer
should always indicate ranges of acceptability, rather than a specific value or position.
围绕在每个边界的箭头代表确立更多详细操作对策和范围的界限。为了允许更多适应性在最
终计划和详细设计，设计者应该始终标明可接受范围，而不是具体数值或状态。
7.5.1 Steam Requirements
7.5.1 蒸气要求
The planning process starts with the listing of all steam requirements and applications that include:
• Company standards including QA/QC requirements and published Sop's
• The categorization of use-point by:
• Type of application (Humidification, critical or non-critical, API, and Dosage for
applications)
• Purity selection (this is based primarily on the application and the endotoxin and
chemical purity criteria set for the product for which the steam, or its condensate, will be
in contact with. The selection must consider underlying factors which have impacts on
purity control, installed and operating cost, maintenance, and practicality)
• Steam quality (dryness, non-condensable limits, and maximum superheat)
设计过程是从把所有蒸气要求和应用列表开始，蒸气要求和应用包括：
• 公司标准，包括QA/QC要求和发行的Sop
• 使用点如下分类
• 应用类型（增湿作用，关键或非关键，API，和应用剂量）
• 纯度选择（这首先建立在将使用哪种蒸气或其冷凝液产品的应用、内毒素和化学纯
度标准设置的基础上。选择必须考虑潜在影响纯度控制的因素、安装和操作成本、
维护以及实用性。）
• 蒸气质量（干燥、非凝界限和最高过热）
7.5.2 System Design
7.5.2 系统设计
Pharmaceutical steam is generated using different methods. The most appropriate method for each
application must be selected. (See the Pharmaceutical Steam Purity Decision Tree, Section 7.6.)
The process continues with an evaluation of the steam system requirements (generation) that
includes: the selection of the type of generation system that would satisfy each category, which
would include:
• The types of generation systems available. (If both pyrogen free clean steam and clean steam
without endotoxin limits is required, the practicality and economy of producing only the
higher grade should be raised.)
• The source of utility steam or electrical power (The plant steam requirement for clean steam
as well as utility steam and the option of electric powered steam generators should be
considered.)
• The type and number of systems required based on feedback from the "Distribution System"
evaluation.
• The condensate sampling needs.
• Safety considerations
使用不同的方法产生制药用蒸气。对每个应用必须选择大多数适当方法。（参看制药用蒸气
纯度决策树，7.6部分。）用蒸气系统要求（产生）的评估来继续过程，该系统要求包括：
产生系统类型的选择将要满足如下每个种类：
• 可用产生系统类型（如果无热原清洁蒸气和无内毒素限制的清洁蒸气都需要，那么应该
提高只产生较高级别蒸气的实用性和经济性）
• 公用蒸气的电源或电力动力（与公用蒸气一样的清洁蒸气的车间蒸气要求和电力蒸气发
生器的选项都应该一起考虑。）
• 系统的类型和数量要求以“分配系统”评估的反馈为根据
• 冷凝液抽样需要
• 安全性考虑
7.5.3 Use Point Criteria
7.5.3 用点标准
The third step defines the specific delivery requirement ranges for clean steam at the point of use
including:
• Utilization, which is determined from each overall system peak demand(s), average demand,
and the relationships between peak demand time periods and their flow rates.
• Pressures and flow levels
• Use periods and histogram analysis, if available
• Quality
• Purity
第三步为在使用点的清洁蒸气规定详细交付要求范围包括：
• 使用是由每个完整系统的高峰需求、平均需求和高峰需求时间周期与其流速关系决定
• 压力和流量水平
• 使用周期和柱状图分析，如果可得到
• 质量
• 纯度
7.5.4 Distribution System
7.5.4 分配系统
The fourth step includes the distribution system evaluation, which includes;
• Condensate, non-condensable and moisture removal
• Pipe size and Insulation requirements including:
• Materials of construction, sanitary design requirements and surface finish
• Physical location of each use point
• Heat and temperature losses
• Natural drainage
第四步包括如下分配系统评价：
• 冷凝液，非凝液和湿度去除
• 管道型号和绝缘体要求，包括：
• 构造材料，清洁设计要求和表面抛光度
• 每个使用点的物理位置
• 热量和温度损失
• 自然排水
Note: Since the steam quality will decline, due to heat losses, with time, the efficiency of the
insulation and the length of the distribution system, the quality at the use point will not be
expected to reflect the generation quality level.
注意：由于热损失，随着时间、绝缘体效能和分配系统的长度，蒸气质量将下降，因此在使
用点的蒸气质量将不能反映产生质量水平。
7.5.5 Re-evaluation of system boundaries and constraints
7.5.5 系统边界和限制的再评价
These sequential steps are repeated and re-evaluated as information in the design process iterates,
and further criteria about the overall system boundaries are identified. (See Figure 7-3.)
In operations with a requirement for only one grade of steam, the steam system is designed to
meet the most stringent requirements of the most demanding product or process. With more than
one purity grade of steam, products and processes are often categorized and fed by the most
appropriate system. The number of types of steam generated is most often a function of the
volume of steam consumed and variation of purity required.
重复和再评价这些连续步骤作为信息设计过程的重复并且确认关于整个系统边界进一步的
标准（参看图表7-3）。一种设备的操作中只有一种蒸气等级，蒸气系统的设计要符合大多
数高要求产品或工艺的大多数严格要求。伴随超过一种蒸气纯度等级，常常把产品和工艺分
类并且提供大多数适合的系统。产生蒸气类型的数量大多数经常是消耗蒸气体积和所需纯度
变化的作用。
7.6 PHARMACEUTICAL STEAM PURITY DECISION TREE
7.6 制药用蒸气纯度决策树
Figure 7-2 Pharmaceutical Steam Purity Decision Tree
图表 7-2 制药用蒸气纯度决策树
START
Steam for
Humidification
Is Product
Exposed to Air?
Steam for Process
or Sterilization
Steam for Energy
Transfer
YES
YES
Does Steam
Contact the
Product?
NO
NO
CLEAN STEAM
Could Corrosion
Inhibitors or Pyrogens
Compromise Product?
NO
Utility Steam
Appropriately Filtered
Utility Steam
YES
The figure above provides "Baseline" requirements for most pharmaceutical steam
applications. Purity requirements for steam used in pharmaceutical manufacturing and
product development are driven by the product characteristics, manufacturing process
and the intended use of the product. Specific product and process characteristics may
dictate that more or less stringent criteria is appropriate.
起始
增湿
蒸汽
工艺或灭菌
蒸汽
能量转换
蒸汽
产品是否暴露
在空气中？
是
是
蒸汽是否
接触产品？
否
否
否
是否腐蚀抑制剂或
热原危及产品？
适当滤过的
蒸汽
公用蒸汽
是
清洁蒸汽
上面的图表为大多数制药用蒸汽应用提供“基线” 要求。用于制药生产和产品
研发的蒸汽纯度要求由产品的特性、生产工艺和预期用途决定。特殊产品和工艺
特性可能要求更多或更少的严格标准是适合的。
7.7 PROCESS AND SYSTEM DESCRIPTION
7.7 工艺和系统描述
7.7.1 Utility Steam
7.7.1 公用蒸气
Utility Steam is produced in conventional plant utility boilers whose typical design and construction
are well known and will not be covered in this chapter.
公用蒸气是用常规车间公用锅炉产生，该锅炉的典型设计和构造是大家都知道的，本章将不
再提及。
7.7.2 Clean Steam (CS)
7.7.2 清洁蒸气(CS)
Clean Steam is produced in specially designed non-fired generators or from the first effect of
multi-effect WFI stills, which do not use scale or corrosion inhibitor additives. The generator is
fed with water pretreated for the purpose of removing elements that contribute to scaling or
corrosion, and the materials of construction are resistant to corrosion by steam that has no
corrosion inhibitors.
清洁蒸气是在特别设计的非加热发生器或者在不使用水垢或腐蚀抑制添加剂的多效WFI蒸
馏器第一效中产生。发生器使用的给水是经过去除可促成水垢或腐蚀的元素的预处理，而且
发生器的构造材料对没有腐蚀抑制剂的蒸气腐蚀具有抵抗力。
The dedicated CS generator is very similar in design and construction to the first effect of a
multi-effect still. For information on multi-effect (ME) stills, see Chapter 6.
专用CS发生器在设计和构造上与多效WFI蒸馏器的第一效非常类似。关于多效蒸馏器的资
料，参看第六章。
7.7.2.1 CS obtained from a ME still
7.7.2.1
从多效蒸馏器获得的清洁蒸气
When Clean Steam is obtained from the ME still, the first effect is usually fitted with two valves;
one to isolate the remaining effects and the other to isolate the Clean Steam use points. Depending
on the manufacturer, the still may or may not produce steam when the still is producing WFI.
当清洁蒸气从ME蒸馏器获得时，通常安装两个阀门，一个用于隔离其余效，另一个用于隔
离清洁蒸气使用点。当蒸馏器生产WFI时，能不能生产蒸气取决于制造商。
Advantages: 优点
• Does not require a separate generator with the associated cost, space, installation, operation,
and maintenance
• 不需要单独的发生器以及相关成本、空间、安装、操作和维护。
Disadvantages: 缺点
• Output is limited to the capability of the first effect of the ME still
• May not produce steam when the still is producing WFI. In an ME, the steam generated in the
first effect becomes the motive (power) steam for the second effect, which in turn produces
motive steam for the third effect, etc. Therefore, the impact of the diverted steam is
multiplied by the number of effects, and WFI production is significantly reduced.
• 输出量受多效蒸馏器的第一效的容量限制
• 当蒸馏器产生WFI时不能产生蒸气。在一个多效蒸馏器中，蒸气发生器第一效成为第二
效起动（动力）蒸气，依次产生起动蒸气为第三效，等等。然而，输送蒸气的影响受数
量的，并且WFI产量显著减少。
The still manufacturer should be consulted in advance, if simultaneous production of WFI and
Clean Steam is desired.
如果希望同时得到WFI和CS产品，应该预先咨询蒸馏器生产商。
7.7.2.2 CS Produced from a Sanitary Clean Steam Generator
7.7.2.2
从灭菌的清洁蒸气发生器产生的清洁蒸气
CONFIGURATION OF A TYPICAL SANITARY CS GENERATOR
典型清洁CS发生器的配置
There are various designs of CS generators. All are evaporators.
They can be of the vertical or the horizontal type, depending on the manufacturer and the
overhead space available.
The disengagement space and the separator may be housed in the same vessel as the evaporator or
in a separate vessel.
CS发生器有几种不同的设计。所有的都是蒸发器。
取决于生产商和顶部可用空间，它们可以是垂直或水平类型。
脱离空间和分离器可以在同一容器作为蒸发器或在分离器中。
Sanitary construction includes Tungsten inert Gas (TIG) welding (see section on fabrication
button systems) wherever possible or mechanical welding with the inner surface ground smooth
after welding. All removable connections use In-Line "sanitary" fittings. Flanges and threaded
connections are not considered "sanitary".
卫生结构包括：可用钨惰性气体(TIG)焊接（见装配钮系统部分）处或焊接后内表面光滑的
机械焊接。所有可移动的连接处都使用在线“卫生”连接件。通常认为法兰和螺纹连接件是
不“卫生”的。
Heat Exchangers, using Utility Steam as the heat source, including the evaporator should be of the
double tube sheet, tubular design to prevent the contamination of the Clean Steam by the heating
medium.
使用公用蒸气作为热源的热交换器（包括蒸发器）应是双管板的，管道设计应能防止清洁蒸
气被加热介质污染。
Most CS generators, except those with very small output, are fitted with feed water heaters. In
addition, a blowdown cooler is used to avoid discharge of very hot and flashing water.
多数CS生成器（极小产量的除外）都是适合给水加热器的。此外，采用一个吹风冷却器，
抑避免排出非常热的水。
A feed pump may be required if the feed water supply pressure is inadequate. Depending on
system design and the manufacturer, a feed pressure of approximately 8-10 psig above the
maximum expected Clean Steam pressure is required. This allows for pressure drop in piping and
valves.
当给水压力不够时，则需要一个泵。根据系统设计和制造商，要求给水压力要比预期的清洁
蒸气压力最大值大约大8-10 psig。这样就允许压力在管线中和阀门处降低了。
A sample cooler fitted with conductivity meter and alarms is often used to monitor Clean Steam
condensate purity. This is an optional feature whose use should be decided based on need.
Conductivity of the condensate will provide information regarding the suitability and applicability
of the distributed steam for its final use.
经常用装配有电导率计量表和警报器的样品冷凝器来监测清洁蒸气冷凝液的纯度。这是可选
择的，可根据需要来决定是否使用。冷凝水的电导率可提供分配的蒸气对器最终使用的适应
性和适用性的相关信息。
PROCESS AND OPERATING PRINCIPLE OF A TYPICAL SANITARY CS GENERATOR:
典型清洁CS发生器的工艺和操作原理
Clean Steam is normally generated in a shell-and-tube heat exchanger evaporator. Feed water is
introduced on one side of the tubes, while the heating medium is introduced on the other side.
Heating of the feed water to above the boiling temperature causes the water to evaporate,
producing steam. The heating medium does not come in direct contact with the feed water or with
the clean steam, and is normally utility steam. However, CS generators may be designed to utilize
other heating mediums. The main differences in the designs are the evaporator and separator.
通常在管壳式热交换蒸发器中产生清洁蒸气。当在另一侧引入传热介质时，在一侧的管中引
入给水。超过煮沸温度的给水加热引起水的蒸发产生蒸气。传热介质不能直接接触给水或清
洁蒸气，传热介质通常是公用蒸气。然而，可以设计CS发生器利用其他传热介质。设计的
主要不同是蒸发器和分离器。
a) Operation 操作
Clean Steam pressure is maintained by a feedback control loop, which modulates the supply steam
control valve. The evaporator feed water is independently controlled using a level sensor and feed
water pump.
通过调整供应蒸气控制阀的反馈控制回路维护清洁蒸气压力。使用液面监测器和给水泵独立
控制蒸发器给水。
b) Steam Supply 蒸气供应
The utility steam supplied to the generator at typically 100 psig to 120 psig (7.0 to 8.5 Ks/cm
2
gauge or 7.9 to 9.25 bars) must be at a higher pressure than the required clean steam pressure. In
general, for a given size generator, the greater the differential between the utility steam pressure
and the clean steam pressure the higher the clean steam production rate. Utility steam pressure
should be at least 30-40 psig (2.25 Ks/cm
2
or 2.0 bars) higher than the clean steam pressure, to
optimize the production rate. Utility steam consumption will be approximately 10% to 20%
greater than the quantity of clean steam produced.
在典型的100磅/平方英寸到120磅/平方英寸 (7.0到8.5 Ks/cm
2
标准规格或者7.9到9.25巴)压力
下供应给发生器的公用蒸气压力必须比所需清洁蒸气压力更高。一般而言，对于一个给定尺
寸的发生器，在公用蒸气压力和清洁蒸气压力之间更大的差别是更高的清洁蒸气产生率。为
优化产生率，公用蒸气压力应该比清洁蒸气压力最少高30-40 psig (2.25 Ks/cm
2
或2.0 bars)。
公用蒸气消耗将比清洁蒸气产生量大约高10%到20%。
c) Clean Steam Pressure 清洁蒸气压力
Clean Steam pressure is selected by the user. Typical units are designed for pharmaceutical
applications at 40 - 60 psig (3.75 - 5.1 bars).
用户选择清洁蒸气压力。为制药应用把典型设备设计为 40 - 60 磅/平方英寸（3.75 - 5.1巴）。
d) Separator 分离器
Entrainment separators are normally designed to function over an optimum range of steam
velocity. If the volume of steam increases substantially, carryover of endotoxins can occur. This
condition can exist if the steam pressure differential significantly exceeds design conditions.
Under these conditions, the velocity of the steam through the separator may be excessive. The
manufacturer should be consulted regarding the output of the generator at the highest possible
pressure difference. An alarm and equipment shutdown is recommended and can be incorporated
into the controls to protect against such conditions.
输送分离器通常设计的大于蒸气速度的最适范围。如果蒸气体积大量增加，则会出现携带内
毒素。如果蒸气压力显著的超过了设计条件，则会出现这种情况。在这些情况下，蒸气流过
分离器的速度就可能过高。应咨询制造商关于在可能的最高的压差下生成器的产量。推荐使
用警报并关闭设备，并且将此整合到控制元件中以避免这类情况的出现。
e) Feed Water Level 给水水位
The Feed water level is controlled to protect against flooding of the evaporator and carryover of
endotoxins by a high level alarm and subsequent shutdown. Evaporator level condition does not
affect clean steam purity, but is an indication of insufficient feed water or excessive blow down.
控制给水水位来防止蒸发器溢出和高水位警报及后继停止的内毒素携带污染。虽然蒸发器水
位状态不影响清洁蒸气纯度，但是它是不充足给水或过度排放的指示。
7.8 SIZING THE CLEAN STEAM SYSTEM
7.8 清洁蒸气系统的尺寸
Figure 7-3 Sizing the Clean Steam System
图7-3 清洁蒸气系统的尺寸
Define Generator location and
identify users and their locations
Identify steam and
condensate attributes
Is
compendial
Is >90% dryness
purity required for
NO
required?
condensate?
YES
Is
Compendial
purity required for
condensate?
YES
YES
Is
pyrogen free
Condensate test for
NO
steam required?
pyrogens not required
NO
YES
Install steam separators
Identify Develop a time/flow
at all “dry”, and traps at
pressure relationship for
all use points. Insulate
requirements each use point
all lines and fittings.
Is
there adequate
Consider electric
Consider filtered
NO
plant steam
energy or a utility
utility steam
capacity?
boiler upgrade
Condensate test at use point
YES
required and calorimeter test
for steam quality (dryness)
may be required
NO
Consider filtered
utility steam
Calculate maximum
pressure/flow rate and
steam consumption
Size the CS
Generator(s)
Proceed
确定生成器的位置并标明使用者
以及它们的位置
鉴定蒸汽和冷凝水的性质
冷凝水是
是否要求干
否要达到药典规定
否
燥>90%
的纯度？
是
否
冷凝水
是否要达到药典
考虑用过滤过的公
规定的纯度？
共蒸汽
是
是
蒸汽是否要
不需检测冷凝液的热
否
求无热源
源
否
是
在所有的干燥区安装
鉴定压力要给各个用点制定时间/计算最大的压力/流
蒸汽分离器，在所有用
流量关系 率和蒸汽消耗量
求
点安装疏水器。隔离所
有的线和配件。
是
否有充分的
考虑用电能或改
考虑用过滤过的
确定CS生成
车间蒸汽容量
良的公共锅炉
NO
器的尺寸
公共蒸汽
要考虑要求的用点的检测以
是
及可能会要求用热量计测量
可着手进行
蒸汽的质量（干燥）
7.8.1.1 CS Produced from a Simple Clean Steam Generator
7.8.1.1 从普通清洁蒸气发生器中产生的CS
There are applications where pyrogen free steam and sanitary construction features are not
required, and at the same time, Utility Steam cannot be used. In such cases, it may be most
economical to utilize a simple Clean Steam generator of the most economical design. Savings may
be worthwhile when the elimination of the steam separator is combined with non-sanitary features
such as :
• Non-Sanitary pipe and fittings
• Non-sanitary instruments and valves
• No polishing
• Minimum controls
也存在很多应用即不需要无热原蒸气和清洁结构特点并且同时不能使用公用蒸气。在这些实
例中，能够最大经济地利用大多数经济设计的普通清洁蒸气发生器。当蒸气分离器去除兼有
如下非清洁特征时，节约是有价值的：
• 非清洁管和配件
• 非清洁仪器和门阀
• 不抛光
• 最小量控制
The elimination of the separator alone does not provide significant cost savings. It is important to
remember that the separator's function is more than removal of endotoxins. It removes
entrainment, which includes all types of contaminants present in the feed water, except volatiles.
Without an entrainment separator, impurities from the feed water may well be entrained in the
steam and the moisture content of the steam as it leaves the generator, can be much higher than in
the standard entrained generator. Thus the feed water purity becomes a critical factor in
controlling the steam purity if entrainment is not incorporated in the design.
分离器的去除独自不提供重要成本节约。是重要的记住分离器的功能比去除内毒素。去除雾
沫，包括在给水中存在的污染物除挥发物之外所有类型，。没有一个雾沫分离器，杂质给水
中的在蒸气中产生蒸气湿度它离开发生器时，可能更高比在发生器中产生的标准。因此，如
果在设计中不包含雾沫夹带，给水纯度对控制蒸气纯度而言变成一个关键因素。
Independent sanitary entrainment devices are available for installation at, or close to the point of
use, and may be used with typical "Simple CS generators" as well as to control additional
moisture build up due to heat losses in the distribution system of Sanitary CS Generators.
在用点或用点附近安装独立的清洁输送装置，这是典型的“普通CS生成器”使用的，同时
由于清洁的CS生成器的分配系统中存在热流失，它还用于控制产生的额外水分。
7.8.2 Steam Condensate Sampling
7.8.2 蒸气冷凝液的取样
7.8.2.1 Purity Sampling
7.8.2.1
纯度取样
When required by the process, the steam purity shall be monitored through acceptable sampling
techniques. A slipstream of the steam may be passed through a sample condenser/cooler, fitted
with a sampling valve. (See Section 7.2.1 for information on Steam Attributes.)
当程序要求时，应用适当的取样技术检测蒸气的纯度。蒸气的切向流可能会穿过配有取样阀
的样品收集器/冷凝器。（关于蒸气属性资料见7.2.1部分）
To ensure that the steam does not contribute to drug product contamination, sampling should be
included during commissioning, as a good engineering practice, and/or prior to each time the
steam is used.
作为一个好的工程实践，为了确保蒸气不污染产品，取样应在中进行并且/或在蒸气每次使
用前。
If the sampling requirement is for endotoxin or pyrogen testing, the sample cooler, tubing and
valve should be of sanitary construction.
如果为了检测内毒素或热源进行的取样，则样品冷凝器、管道和阀门都应是经消毒的。
Sample coolers can be fitted to the CS generator, or located in the distribution line, or at the use
point (recommended location), or a combination thereof. It is common practice to fit sample
coolers with conductivity monitors and alarms.
样品冷凝器可以装配在CS生成器上，或位于分配线上，或位于用点（推荐的位点），或是
它们的联合。通常会给样品冷凝器安装上电导率检测器和警报器。
Endotoxin removal: The condensate sample from a Clean Steam generator with separator is
expected to show 3-4 log
10
level reduction in pyrogens compared to the level in the feed water.
内毒素的去除：用分离器从清洁蒸气生成器中收集的冷凝样品，其热源水平预期是比给水少
3-4 log
10
。
7.8.2.2 Steam "Quality" Sampling
7.8.2.2
蒸气“质量”取样
Steam "Quality" sampling may be employed to determine the level of saturation and
non-condensable gasses. This can be determined by applying a steam calorimeter and measuring
the dryness or saturation level. A steam calorimeter measures the percentage by weight of steam in
a mixture of steam and entrained water.
蒸气“质量”取样可用于确定饱和的和不可压缩气体的水平。这可通过使用一个蒸气热量计
以及测量干燥或饱和水平来确定。蒸气热量计是通过称量蒸气和生成的水的混合物中蒸气的
重量来测量百分含量的。
7.8.3 Materials of Construction
7.8.3 构建的材料
7.8.3.1 Materials of Construction for Sanitary and Simple CS Generators
7.8.3.1
卫生的普通
CS
生成器的构建材料
Structural integrity and chemical compatibility with the contact fluid and its constituents are two
of the more practical issues that drive construction material selection for CS systems.
CS系统的构建材料的选择有两个实际的问题：结构的完整性以及材料与同它接触的液体及
液体成分的化学配伍性。
The inherent corrosion potential forces CS manufacturers to consider relatively inert metal
including stainless steel or titanium etc. Sanitary piping and valves, considered unnecessary for
utility and simple CS generators, are often standard features for CS systems based on the specific
manufacturer and model. The materials chosen should not contribute to contamination of the drug
product. Typical materials of construction for Sanitary and Simple CS Generators are:
固有的腐蚀可能性促使CS生产商考虑使用相对不活泼的材料，包括：不锈钢或钛等。考虑
到对于公共设施和普通CS生成器来说是非必须的，在特定的生产商和型号的基础上，清洁
的管线和阀门通常是CS系统的标准特征。所选择的材料应不会助长对产品的污染。清洁的
和普通CS生成器的构建材料通常是：
Evaporator and separator:
蒸发器和分离器：
Shell, tubesheets, and internals:
外壳，管板和内部结构：
Evaporator tubes:
蒸发器管道：
Heat exchangers热交换器
(FEED HEATER, BLOW DOWN &SAMPLE
COOLER):（加热器、放气和样品冷凝器）
300 series S.S
300系列不锈钢
300 series or titanium, or other suitable alloy
300系列或钛，或其他适用的合金
300 SERIES
300系列
300 series for water and Clean Steam, and carbon
Piping:管线
steel for utility steam contact
300系列用于水和清洁蒸气，碳钢用于公共蒸气
Valves:阀门
300 series and elastomers/diaphragms for water
Skid and structural:滑轨和结构材料： Carbon steel碳钢
7.8.3.2 Materials of Construction for Utility Steam Generation
7.8.3.2
公共蒸气生成器的结构材料
Chemical compatibility with the Utility boiler generated steam and the carried over feed water
chemicals are required for all materials used to condition the contaminated steam.
对用于condition污染的蒸气的所有材料都要求其与公共锅炉产生的蒸气以及给水中携带的
化学试剂的化学配伍性。
Based on the particulate levels in the steam and the required steam purity, more than one filtration
stage may be utilized.
基于特定的蒸气水平以及要求的蒸气纯度，可能需要使用多级过滤。
Distribution of Utility Steam following filtration follows similar practices as CS to control
condensate build up, non-condensable gases and saturation levels as required for the application.
Acceptable materials must be relatively inert and may include SS or tin-coated copper.
合适的材料必须是相对不活泼的并且可能包括不锈钢或镀锡铜。
7.8.4 Surface Finish
7.8.4 表面抛光
Mechanical polishing (MP), electropolishing (EP), and passivation processes are implemented in
some stainless CS systems. Chlorine and/or chlorides will damage the generator regardless of the
finish.
某些不锈CS系统需完成机械抛光（MP）、电抛光（EP）以及钝化过程。如果不抛光的话，
氯和/或氯化物会损伤生成器。
The operating temperatures of these systems are more than sufficient for inhibiting
microbiological growth. Therefore, MP is advocated for final finishing of mechanical welds, with
mill finishes and final passivation to optimize the formation of the corrosion resistant chromium
oxide barrier. Electropolishing will also optimize the chromium oxide barrier, and should be
considered if passivation is not an option.
这些系统的操作温度足以抑制微生物的生长。因此，为了形成最佳的抗腐蚀的氧化铬阻挡层，
在机械焊接的最终抛光、打磨抛光以及最终钝化是最好使用机械抛光。电抛光也能形成最佳
的氧化铬阻挡层，当不能选择钝化作用时，可考虑它。
7.8.5 Pretreatment for CS (Sanitary and Simple) Generators
7.8.5 CS（清洁的和普通的）生成器的预处理
The feed water pretreatment for a CS generator is born from three separate and distinct
considerations:
CS生成器的给水预处理应从三个不同的和独特的方面考虑：
1) Scale formation. 水垢形成
2) Corrosion.腐蚀
3) Volatiles which carryover with the steam and may affect steam purity. 蒸气中可能会携带挥
发物，并且这些挥发物可能影响蒸气纯度
7.8.5.1 Scale
7.8.5.1
水垢
Scale formation is a function of generator feed water chemistry, concentration (depends on blow
down rate), and temperature. It is independent of design and make, and is outside the control of
the generator manufacturer or the operator.
生成器的给水的化学性质、浓度（取决于放水率）以及温度挥导致水垢形成。它和设计和制
造无关，并且也不是受生成器的制造商或操作者控制的。
Because scale inhibitors are not used, and because of the relatively high operating temperatures of
the CS generator, the total dissolved solids (TDS) of the feed water should be very low. Silica is of
particular concern. Most manufacturers stipulate a level of less than 1 ppm (parts per million);
some go as high as 5 ppm. In addition to having low TDS (Total Dissolved Solids), the feed water
should have no measurable hardness. It is therefore common to use Dl or reverse osmosis as
pretreatment to the CS generator. All CS generators will invariably experience some form of scale
build-up and therefore must include routine visual inspections, plus cleaning of the generator
during shutdown periods when appropriate.
由于没有使用污垢抑制剂，并且CS生成器的操作温度较高，给水的总溶解固体(TDS)会很低。
最值得关注的是硅。一些制造商规定给水的硅含量要小于1 ppm；有些是5 ppm。除了要求
TDS (总溶解固体)低之外，给水中还应不含有可测到的硬度。因此通常使用离子交换装置或
反渗透对CS生成器的给水进行预处理。所有的CS生成器都不可避免的会形成水垢，因此必
须对其进行定期目检，此外还要在停工期间对其进行清洁处理。
Using compendial water as feed is wasteful, unless the steam quantity is small and the cost and
maintenance of a dedicated feed water pretreatment system exceeds the cost of using compendial
water.
用药典规定的水作为给水是浪费的，除非所需蒸气数量很小以及专用的给水预处理系统的成
本和维护费用超过了使用药典规定的水的费用。
Some manufacturers offer generators to operate on softened water. Usually, the rate of blow down
is increased in order to maintain low concentration.
一些制造商提供的生成器可用于软化的水。通常未来维持低浓度需要增加放水率。
Note: If the TDS of the soft water is relatively high, soft scale (such as sodium scale and sludge)
can form.
注：如果软化水的TDS较高，就会形成软水垢（如钠水垢和淤泥）。
7.8.5.2 Corrosion
7.8.5.2
腐蚀
The most common cause of corrosion is free chlorine, not chlorides.
腐蚀通常都是由游离氯而不是氯化物引起的。
Chlorine and chlorides, at any detectable level, are very detrimental to stainless steel. The higher
the temperature and chlorine level, the more severe is the attack. Chlorine is known to migrate and
concentrate in localized cells where the level can reach tens, or hundreds of ppm, while the
concentration in the main stream is a fraction of a ppm.
任何可检测浓度的氯和氯化物对不锈钢是非常有害的。温度和氯的含量越高，危害越大。众
所周知，氯是可以移动的并且可以在某小空间里聚集，此时它的浓度可达到10或100 ppm，
虽然在主液流中的浓度还不到1 ppm。
Chlorine can be removed from the feed water by chemical injection of a reducing agent such as
sodium bisulfate, or by passing the chlorinated water through carbon filters.
可向给水中添加还原剂（如：亚硫酸钠）或者将经氯处理的水经过碳过滤器来将氯去除。
7.8.5.3 Volatiles
7.8.5.3
挥发物
Dissolved gasses and substances that are volatile at the operating temperature of the CS generator
will carryover with the steam. If such substances are objectionable or may potentially compromise
product quality, they must be removed at the pretreatment stage. Ammonia and CO
2
(carbon
dioxide) are examples of volatile gases that will have an effect on the conductivity, such that a
condensate sample may not meet USP requirements for Purified or WFI Water.
在CS生成器的操作温度下可挥发的不溶气体和物质会带走蒸气。如果这些物质是不利的或
可能对产品质量有潜在危害的，那么在预处理阶段必须将它们去除。氨水和CO
2
(二氧化碳)
就是挥发气体的例子，它们会对电导率有影响，这样冷凝水样就可能满足不了USP对纯化水
或注射用水的要求。
For more details on pretreatment and the advantages and disadvantages of the different processes,
refer to Chapters 4 and 5 of this Guide.
预处理和不同的处理的优缺点的详细内容，参见该手册的第4章和第5章。
7.8.6 Treatment of Utility steam
7.8.6 公共蒸气的处理
When utility steam is considered, it may be necessary to filter/condition the steam. In certain
applications, may also be necessary to change the steam boiler treatment and substitute additives
that do not contain amines or hydrazine.
当考虑使用公共蒸气时，可能需要过滤/处理它们。当应用于特定情况时，可能还需要改变
蒸气锅炉的处理以及替换不含胺或肼的添加剂。
Since the type and degree of conditioning are dependent on the application, as well as on the
quality of the utility steam and additives present, this Guide cannot address all possible scenarios.
因为提供的条件的类型和程度取决于蒸气的应用以及公共蒸气的性质和使用的添加剂，所以
该手册不可能描述所有的可能情况。
Prior to the elimination of amines and hydrazines, by the substitution for standard boiler
pretreatment additives the Utility Steam boiler manufacturer should be consulted regarding the
impact on equipment warranty performance and expected life. Some of the substitute additives are
not as effective as the standard.
在替换标准锅炉预处理添加剂以消除胺和肼前，应向公共蒸气锅炉制造商咨询关于对设备保
证的性能和预期的寿命的影响。一些替代的添加剂还没有标准的有效。
7.9 COST IMPLICATIONS
7.9 相关成本
Determining the economics of pharmaceutical steam production is complex. Costs are quite
predictable, but vary greatly depending on scale of operation, system design, actual usage, etc.
The total operating cost to produce pharmaceutical steams is obtained by adding the cost of feed
water to the costs of pretreatment and final treatment (primary ion removal and polishing). The
type of pharmaceutical steam system design option selected is typically based on feed water TDS,
silica and hardness levels, organic and colloidal content, as well as anticipated steam system utility
costs (acid, caustic, salt, power, and source water). Consideration should also be given to
maintenance requirements and available resources.
确定制药用蒸气生产的经济学是很复杂的。费用是可预知的，但会随着操作规模、系统设计、
实际使用等的变化而变化。生产制药用蒸气的总操作成本是将给水的成本加上预处理和终处
理(主要是去离子和抛光)的成本。设计选择的制药用蒸气系统类型通常基于给水的TDS、硅
和硬度水平、有机物和胶体含量以及蒸气系统的预期的公共用品成本（酸、碱、盐、粉末和
原水）。要考虑到维护要求和可用资源。
7.10 STEAM “QUALITY”
7.10 蒸气“质量”
Steam quality is defined as the saturation percentage of steam to water or more explicitly, the ratio
of the vapor mass to the mass of the steam mixture.
蒸气质量的定义是蒸气对水的饱和百分比，或者更确切的说就是水汽和蒸气混合物的比率。
Dry Saturated Steam with minimum superheat is necessary for efficient steam sterilization.
最小化过热的饱和干蒸气是进行有效蒸气灭菌的必要。
Water can be generated and carried by steam within distribution systems in two ways:
在分配系统中生成水或蒸气携带水的方式有两种：
1) In suspension as moisture when the steam is not 100% saturated
当蒸气不是100％饱和时，在悬液中以湿气的方式
2) As condensate separated from the steam
以从蒸气中分离的冷凝液的方式
Water vapor carried in suspension may be reduced by: adding more heat or raising the temperature,
reducing the pressure, or adding a steam entrainment separator. Water moisture and condensate
may be reduced by steam traps.
以悬液方式带入的水汽可通过以下方式减少：加热或提高温度、降低压力或添加一个蒸气雾
漠分离器。湿气和冷凝液可通过疏水器来减少。
7.11 DISTRIBUTION
7.11 分配
Distribution systems for clean steam follow the same good engineering practices commonly used
for utility steam with the exception that contact materials must be inert to the aggressive nature of
clean steam. Corrosion-resistant 304,316,or 316L grade stainless steel "tubing" or solid-drawn
"pipe" are commonly used. Surface finish is not critical due to the self-sanitizing nature of the
clean steam. Mill finish or 180-grit mechanically polished pipe or tubing is sufficient. TIG Orbital
welding and post-installation passivation is considered appropriate for this application. Piping
must be designed to allow for thermal expansion and to drain condensate.
清洁蒸气分配系统应遵循同样的良好的工程规范，该规范通常用于公共蒸气，但“接触材料
必须是惰性的，可耐受清洁蒸气的破坏”除外。通常使用抗腐蚀的304、316或316L级的不
锈钢管，或整体拉制的管。由于清洁蒸气具有自消毒性，所以表面抛光不是关键因素。打磨
抛光或180-砂纸机械抛光的管道就足够了。可考虑使用TIG 轨焊以及安装后钝化。设计的管
道必须允许热膨胀以及排放冷凝液。
Note: Drains should have air breaks.
注意：排水会有空气阻断。
Sanitary clamps or pipe flanges are most commonly used where the piping must be broken, but
welded connections are used as much as possible to eliminate maintenance costs and potential for
leaks. Threaded connections may be suitable for instrumentation if positioned to drain condensate
and remain hot. Ball valves are commonly used for isolation because elastomeric diaphragms do
not hold up well in this service. Where diaphragm valves are used, Teflon-encapsulated EPDM
diaphragms give the best long-term performance.
当管道破裂时，最常用的是清洁磁夹或管道法兰，但应尽可能用焊接以消除维护成本和泄漏
的可能性。当用于排放冷凝液并保持热度时，装配螺纹连接件可能是合适的。隔离时常用球
阀，因为人造橡胶隔膜在该设备中不能起到很好的控制作用。当需要使用隔膜阀的时，特富
龙-被囊的EPDM隔膜长期操作性能最好。
Steam quality sampling may be determined during "commissioning" and consistency ensured
based on the proper location and subsequent maintenance of traps, entrainment separators, and
vents. (The subject of maintenance cannot be over emphasized when these devises are involved
due to the small orifices required in the separation of gas and liquid.)
取样的蒸气质量可determined during "commissioning" and consistency ensured 基于正确的定
位以及对疏水器、传送隔离器和呼吸器后续的维护。(当涉及到这些仪器时，由于在气液分
离时要求的小通气口，不要过分强调维护。)
7.11.1 Line Sizing
7.11.1 管线尺寸
The steam distribution header should be sized for a maximum velocity of 7,200 feet per minute
(120 ft/sec or 37 m/sec) to limit erosion and extend the life expectancy of the piping. Condensate
line sizing should follow good engineering practices for utility condensate.
蒸气分配扬程的尺寸应适合7200英尺每分钟（120 ft/s或37 m/s）的最大速率，以限制腐蚀并
延长管线的预期寿命。冷凝管线的尺寸应遵循关于公共冷凝液的良好工程规范。
7.11.2 Water Moisture Removal
7.11.2 水分去除
Water vapor forms in steam systems due to heat loss, causing a change in the liquid/vapor ratio or
steam "quality”.
由于热损失，蒸气系统中会形成水汽，从而导致液/汽比发生变化或蒸气“质量”发生变化。
Steam may be dried of moisture by reducing the generated pressure just prior to the point of use to
coincide with the steam temperature of saturation at the reduced pressure.
就在用点之前将压力降低，并保持饱和蒸气的温度和降低的压力一致，来除去蒸气中的水分。
Moisture entrained in the steam can also be removed by installing an In-Line separator at the point
of use, just prior to, or just after, the regulator. If the separator is located upstream of the regulator,
the regulator should be protected from water damage (wire drawing) and impingement damage on
the regulator diaphragms.
也可以在用点（就在调节器前面或后面）安装一个在线分离器来去除蒸气中产生的湿气。如
果分离器位于调节器的上游，应防止调节器受水损伤（电线图）并且避免调节器的隔膜受到
冲击。
In-line separators are available in sizes from 1/2" to 6" (approx. 1 cm to 15 cm) and remove
moisture with a series of baffles on which the suspended water droplets impinge and fall out by
gravity to the drain, which must be piped to a trap. Separators have a separation efficiency of
better than 99% in the removal of all liquid and solid entrainment exceeding 10 microns.
可用的在线隔离器的尺寸可从1/2"到6" (大约1 cm-15 cm)，隔离器是用一系列档板来去除水
分，悬浮的水在档板上形成水滴，然后因重力作用落到排放装置中，该排放装置必须接上一
个疏水器。分离器在去除所有的液体以及带走大于10微米的固体上的分离效果大于99％。
7.11.3 Condensate Removal
7.11.3 冷凝水的去除
Condensate is the water that has separated from the liquid vapor mixture and forms in steam
systems due to heat losses and natural separation effects. Lines should be designed to prevent the
buildup of condensate to avoid dangerous water hammer and to eliminate potential cold spots
where bacteria can grow. Any untrapped vertical length of pipe will quickly fill with condensate.
If this condensate is allowed to stand for sufficient time, it can cool and become a breeding ground
for bacteria. This bacteria could possibly be entrained back into the main distribution header and
contaminate use points downstream. Worst case condensate removal locations should be sampled
monthly for presence of bacteria. The following practices are commonly employed to minimize
these concerns:
冷凝水是从液体水汽混合物中分离出来的水，它是由于热流失而在蒸气系统中形成的，是一
个自发的分离作用。设计的管线应可防止冷凝水的形成，以避免危险的水锤并消除细菌生长
的冷点的可能性。任何未安装疏水器的管道的垂直段都会填上冷凝水。如果该冷凝水能在此
待足够长的时间，它就会冷却并称为细菌的孵育地。这些细菌就可能进入主分配扬程中并污
染下游的用点。冷凝水最难去除的位点应每月检测一次是否有细菌生长。通常采用下列行为
来减少这些忧虑：
• Each line is adequately supported to avoid sagging and subsequent condensate accumulation.
每条管线都应充分的支撑，以避免沉降以及后续的冷凝水的沉积。
• Steam traps are installed at all points where condensate can collect (e.g., at least every 100
feet (30 meters) of line, upstream of control valves, at the bottom of vertical risers, etc.).
Steam traps used for clean steam service should be sanitary design and self-draining.
在所有可收集冷凝水的位点都安装疏水器（如：至少每100英尺（30米）管线安装一个、
控制阀的上游、垂直上升管的底端等）。用于清洁蒸气的疏水器应是清洁的并且可自排
水的。
• If the main distribution header is above the use points, the branches to the users should be
routed from the top of the header to avoid excessive condensate loads at the branch. Each
branch should be trapped to avoid condensate buildup.
如果主要的分配扬程都高于用点，通向使用者的分支管道都应从扬程的顶端出来，以避
免分支管道上存有过多的冷凝水。每个分支管道都应安装疏水器以避免形成冷凝水。
• An alternative is to run the main distribution header below the use points. Then the branches
can drain back to the main distribution header; avoiding the need for additional traps.
可选择使用在低于用点的位置运行主分配扬程。这样分支管线就可以回流到主分配扬
程，这就避免了对额外的疏水器的需求。
• The requirement to trap each branch can be waived for short drops from main headers to
vessels or other equipment that are in frequent use where the sterilization and water hammer
is not impacted by the collected condensate. An example is a drop from a main distribution
header to a media storage tank, which is sterilized daily. The condensate built up in the
vertical drop line has only a limited time to cool and is quickly eliminated by the trap at the
bottom of the vessel when the block valve is opened. The vertical drop is sterilized daily with
the vessel, so there is little chance for bacteria to grow.
各个分支管线安装疏水器的要求是可免除的，当灭菌和水锤不受收集的冷凝水影响时，
只要将主扬程和容器或其他常用的设备间的落差减少。比如主分配扬程到一个每天都要
灭菌的介质储罐间的落差。在垂直下落线中生成的冷凝水的冷却时间很短，并在打开截
止阀时，很快的被容器底端的疏水器排出。垂直下落线以及容器是每天灭菌的，因此细
菌的生长机会很小。
7.11.4 Non-Condensable Gas Removal
7.11.4 不可压缩气体的去除
Air and other non-condensable gases should be minimized from pharmaceutical steam systems.
Since air
acts as an insulator, incomplete sterilization can occur in the process. Air in a system
offers a very effective barrier to the heat transfer which will lead to a reduced temperature at the
surface of a tube, system component or process equipment.
应将制药蒸气系统中的空气和其他不可压缩气体降到最少。因为空气就象是一个绝缘体，在
处理过程中就会出现灭菌不完全。系统中的空气对热传输来说是一个有效的屏障，这就会导
致管、系统元件或处理设备的表面温度降低。
Air can be discharged using steam traps, however excessive levels may slow down the discharge
of condensate. The subcooled condensate can then lead to insufficient sterilization temperatures
due to the excess water.
可使用疏水器来排出空气，但是，空气含量过高就会降低冷凝是排出速度。然后，由于水过
多，低温冷却的冷凝水就会导致达不到灭菌温度。
The removal of air can be achieved by placing thermostatic pharmaceutical steam traps with the
inlet in the upward position. These should be placed in positions where air is prone to collect such
as the terminal points of the main and large branches of the steam header, high points in the tanks,
reactors and sterilizers, etc. In the case of air and condensate discharge at the bottom of large
vessels, the air and condensate should be separated by correct piping practices.
可用放置恒温的制药用疏水器并使其进气口朝上来除去空气。应将它们放置在空气易于收集
的地方，如：蒸气扬程的主要的以及大分支管道的终点、槽、反应器和消毒起的高点等。当
在大容器底端排出空气和冷凝水时，应分别对它们采用独立的管道。
7.11.5 Superheat
7.11.5 过热
While higher-pressure steam can be used to compensate for superheat, the latent heat, or killing
power of the potentially superheated steam is reduced at higher pressures; leading to increased
sterilization cycles.
当使用较高压力的蒸气来补偿过热时，潜在的热量或潜在的过热蒸气的杀伤力会在较高压力
下降低；从而导致增加灭菌循环。
7.12 FOUR EXAMPLES OF CORRECT PIPING PRACTICE
7.12 四个正确布线的例子
Figure 7-4 Vessel Sterilization
图7-4 容器灭菌
ISPE 8
STORAGE and DISTRIBUTION SYSTEMS
贮存和分配系统
目录
8. STORAGE AND DISTRIBUTION SYSTEMS
8.1 INTRODUCTION
8.2 SYSTEM DESIGN
8.3 SYSTEM DISTRIBUTION DESIGN
8.4 MATERIALS OF CONSTRUCTION
8.5 SYSTEM COMPONENTS
8.6
COMPARISON OF WFI SYSTEMS WITH STORAGE TANK AND WITHOUT STORAGE "TANK
8.7 MICROBIAL CONTROL DESIGN CONSIDERATIONS
8.8 CONTINUOUS MICROBIAL CONTROL
8.9 PERIODIC STERILIZATION/SANITIZATION
8.10 SYSTEM DESIGN FOR STERILIZATION/SANITIZATION
8. 储藏和分配系统
8.1 序论
8.2 系统设计
8.3 分配系统设计
8.4 结构材料
8.5 系统组件
8.6 有储罐和无储罐的注射用水系统间的比较
8.7 微生物控制设计考虑因素
8.8 连续微生物控制
8.9 定期灭菌/消毒
8.10 灭菌/消毒的系统设计
1 / 53
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
2 / 53
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.
影响贮存容量的标准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
3 / 53
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 CO
2
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
4 / 53
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.
较合理的方法是：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° 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
5 / 53
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
6 / 53
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
7 / 53
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
8 / 53
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。
9 / 53
Figure 8-1 Distribution Decision Tree
图表 8-1 分配决策树
Distribution Decision Tree
QA Release Req'd
Batched
YES
Before Use?
system (1)
NO
Continuous Branched /One
YES
Recirculation? Way system(1)
YES
Hydraulics limiting?
YES
Parallel Loops
Single Tank(3)
NO
Hot Storage, Hot
Hot Users
YES
Distribution(4)
Only?
NO
Hot
Low Temp
YES YES
Storage Desired?
Users Only?
NO
NO
Ambient Storage/ Ambient
Distribution(5)
Parallel Loops
More Than A Few Low
YES
Single Tank(3)
Temp Users
NO
Point Of Use Heat
Exchangers(8)
10 / 53
Energy
Consumption Critical?
NO
Hot Storage, Cool
and Reheat(6)
YES
Hot Tank, Self Contained
Distribution (7)
Energy
Consumption Critical?
NO
Hot Storage, Cool
and Reheat(6)
YES
Hot Tank, Self Contained
Distribution (7)
分配决策树
使用前 批次系统
是
需要QA放行？ (1)
否
多分支/单通道
连续
是
再循环？
系统(1)
是
平行回路，
液压限
是
单个水罐(3)
？
否
只有 热贮存，
是
热分配(4)
热使用者？
否
只有 要求 能源消耗是否 热水罐，
是是是
低温使用者？ 热贮存？ 是关键？ 独立分配(7)
否
否
否
环境温度存储,
热贮存，冷却
环境温度分配(5)
和再加热(6)
不仅仅是 平行回路， 能源消耗是否 热水罐，
是 是
低温使用者 单个水罐(3)是关键？ 独立性分配(7)
否
否
热交换器
热贮存，冷却
使用点(8)
和再加热(6)
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
11 / 53
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
12 / 53
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).
13 / 53
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 require hot (greater than 65℃) water.
Temperature is maintained in the storage tank by steam supplied to the tank jacket or alternatively
by a heat exchanger on the circulating loop. Water is generally returned to the top of the tank
through a spray ball to ensure that the entire top surface is wetted. This system provides excellent
microbial control and is simple to operate. In addition, tank and loop sanitization is required less
frequently, or not at all, if a temperature of 80℃ is maintained. This type of system is universally
accepted by regulatory agencies.
当所有的用点都需要热水（高于65℃）时，才选择该构型。通过储罐夹套中的蒸气来维持储
罐的温度或者在回路上安装一个热交换器。水通常是通过喷洗球到达储罐的顶部，以确保整
个顶部表面湿润。该系统能很好的控制微生物并且操作简单。此外，当温度能维持在80℃时，
该系统对储罐和回路的消毒频率要求低，或者就不需要。这类系统通常是被法规机构接受的。
14 / 53
Areas of concern include protecting workers from scalding, cavitation in the circulation pump,
moisture condensation on the vent filter, and the formation of rouge. Scalding is minimized by
operating at lower temperature (65℃) or by proper training and personal protective gear. Cavitation
is avoided by accounting for the high vapor pressure of hot water in the net positive suction head
(NPSH) calculations. Condensation is prevented by positioning the hydrophobic vent filter for good
drainage and by heating the filter with either a low pressure steam jacket or electric tracing. Avoid
overheating as this can melt the filter cartridge. Rouge formation is controlled by passivation and by
operating at a lower temperature. It can be eliminated by using non-metallic or lined components.
需要考虑的问题包括：防止工人烫伤，防止循环泵中形成空泡，防止湿气在气滤器上聚集以
及水锈的形成。通过在较低温度(65℃)下操作或者对工人适当的培训以及配有适当的防护工具
来将烫伤可能降低到最小。可通过计算气蚀余量来计算热水的高水汽压力以避免空泡形成。
给疏水气滤器配有很好的排水工具并且用低压蒸气夹套加热或电子描计法就可以避免湿气聚
集。但是要避免过热，因为这会熔化过滤芯。钝化或在低温下操作就可控制水锈的形成。采
用非金属的或有线纹的组件就可消除水锈的形成。
Figure 8-5 Hot Storage, Hot Distribution
图表8-5 热贮存，热分配
Figure 8-6 and Figure 8-7 Ambient Storage, Ambient Distribution
图表8-6和图表8-7 环境温度存储,环境温度分配
15 / 53
This system is most advantageous when the water is generated at ambient temperature, will be used
only at ambient temperature, and there is adequate time for sanitization.
当水在环境温度产生同时只在环境温度使用，并且有足够的时间灭菌时，该系统是极其有利
的。
Since the water is stored at ambient temperature with no disinfectant, microbial control is not as
good as hot storage system configurations. However, good microbial control is possible provided
sanitization is conducted on a frequent basis. Frequent sanitization is usually accomplished by
allowing the water level in the storage tank to drop through use, then heating the remaining contents,
and circulating through the loop for set amount of time. Reducing the water level limits the energy
and time required to sanitize. Heat is provide by steam supplied to the tank jacket, or alternatively,
by a heat exchanger on the circulating loop. Cooling may be required to prevent temperature
increases due to heat buildup from the pump, and for cool down after sanitization. Water
consumption is low if the level in the storage tank is allowed to drop through use prior to
sanitization and moderate if it is drained.
由于在环境温度下贮存的水没有经过灭菌，因而其微生物控制不如热贮存系统配置的那样好。
然而，只要消毒达到一定的频率，良好微生物控制是可能实现的。经常消毒通常是这样来实
现的：在使用时让储罐中的水位下降，然后加热剩余的水，再用这个加热的水在系统中循环
一定的时间。降低水位就限制了消毒所需的能量和时间。可用供应给储罐夹套的蒸气来加热
或者用循环回路上的热交换器加热。因泵会产热以及消毒后需降温，因此可能需要冷却。如
果储罐中的水位在消毒前是允许下降的并且当水被排出后水位还是适度的，那么水的消耗就
很低。
The capital and operating costs of this system are minimal. Another advantage is that it can provide
high flow rates of ambient pharmaceutical water, without need for complex points of use heat
exchangers. Its major disadvantage is the time required to sanitize, which is longer than the
previously described systems, due to the need to heat and cool the contents of the storage tank.
该系统的资产成本和运行成本都很低。另一个优点是它能提供环境温度下高流速的制药用水，
而无需复杂的使用热交换器的位点。它的主要缺点是：由于要加热并冷却储罐中的内含物，
因此，它的消毒时间要比上述的几个系统长。
16 / 53
Figure 8-6 Ambient Storage and Ambient Distribution
图表8-6 环境温度存储,环境温度分配
Many pharmaceutical water users have found that storing and distributing water at ambient
temperatures with periodic sanitization, (utilizing either clean steam or heating to 80℃ for
microbial control) to be safe and cost effective. The ambient system can also be effectively operated
with an ozonated storage and a periodically ozonated loop, in lieu of hot water sanitization (see
Figure 8-7). Levels of 0.02ppm to 0.2ppm of ozone protect the water from microbial
recontamination. Ozone needs to be completely removed from process water prior to usage, using
UV radiation. Consideration therefore must be given to verifying/assuring that ozone has been
eliminated, such as the use of In-Line monitors.
许多使用制药用水的用户已经发现在环境温度下存储和分配水并进行定期消毒（用干净的蒸
汽或加热到80℃进行微生物防治）是安全且成本有效的。用一个臭氧存储器及一个定期生成
臭氧的回路也能代替热水消毒（见图8-7），有效地操作环境温度系统。0.02ppm到0.2ppm
的臭氧水平即能防止水受到微生物的再污染。使用前，应当使用UV辐射将臭氧从过程用水
中完全去除。因此必须考虑验证/确保臭氧已经去除，比如使用在线监测。
One advantage of ozonation or chemical sanitization, is that these methods allow the use of plastics
as a material of construction (popular in Europe for purified water systems).
臭氧或化学消毒的一个好处是可以将塑料用作一种构建材料（在欧洲普遍用于纯化水系统）。
Figure8-7 Ozonated Storage and Distribution
17 / 53
图8-7 臭氧的储存和分布
Figure 8-8 Hot Storage, Cool and Reheat
图8-8 热储存、冷却和再加热
This system is most advantageous when the water is generated hot, tight microbial control is
required, and there is little time for sanitization. It provides excellent microbial control and is easily
sanitized. It requires less capital than point of use exchangers, if there are multiple low temperature
use points. Hot water from the storage tank is cooled through the first heat exchanger, circulated to
the use points, and then reheated in a second exchanger before returning to the storage tank.
Sanitation of the loop is accomplished by turning off the cooling medium on a periodic basis. Water
consumption is minimized since no flushing is required. The major disadvantage of this
configuration is it's high energy consumption, since it cools and reheats the circulating water
regardless of whether it is drawn out of the loop.
当水加热，需要严密的微生物防治，且只有一点时间用来消毒的话，用这个系统是最方便的。
它提供了很好的微生物防治且十分便于消毒。如果存在多种低温使用点的话，相对于使用交
换器的点而言它只需要很少的资金投入。储存罐出来的热水经过第一个热交换器冷却，流至
使用点，并在回到储存罐前在第二个交换器内再度加热。定期关闭冷却介质即可对回路进行
消毒。因为无须冲洗衣，所以耗水量也减少了。此种配置最主要的缺点是它的高能耗，这是
因为不管是否从回路中取水，循环水都会冷却并需要再加热。
Figure 8-8 Hot Storage, Cool and Reheat
图8-8 热储存、冷却和再加热
18 / 53
Figure 8-9 Hot Storage, Self-Contained Distribution
图8-9 热存储、自主分配
This configuration is most advantageous when water is generated hot, there are many low
temperature water users, and energy consumption is critical. It provides the benefits of the cool and
reheat loop without the large energy requirement. Hot water from the storage tank is cooled through
the heat exchanger, circulated to the use points, and the returned to the pump suction bypassing the
storage tank. The loop is sanitized on a periodic basis by turning off the cooling medium and
opening up the return to the storage tank, allowing hot water to flow through the loop. An
alternative is to flush the lower temperature water to drain until the loop becomes hot and then
return the flow to the storage tank. The water in the storage tank is kept hot through a steam jacket
or heat exchanger on an external pump around loop.
当水加热，有许多低温水使用者且能耗是关键时，用此种配置是最有利的。它的最大好处是
无须大量能耗即可冷却并再回热回路。储存罐出来的热水经热交换器冷却，流至各使用点，
并不经储存罐回到抽水泵中。此回路通过定期关闭制冷介质并打开通往储存罐的回路，使热
水流经回路来进行消毒。另一种选择是用低温水冲洗并将其排出直至回路变热，然后将水流
引起储存罐内。储存罐内的水通过一个蒸汽套或回路附近的一个外部泵上的热交换器来保温。
When water is drawn out of a point of use valve, hot water from the storage tank flows into the loop
and is cooled by the heat exchanger. The hot water flushes the short section of line between the
storage tank and the circulation pump preventing a deadleg. In most pharmaceutical installations,
this happens many times per day so the line stays relatively hot. If the usage rate is low, a small
19 / 53
amount of water can be returned to the storage tank on a continuous or timed basis, keeping this line
flushed. A third alternative is to return the circulating water to just downstream of the storage tank
outlet valve, so the deadleg is negligible.
当水从一个使用阀点取出时，热水从储存罐出来流入回路并通过热交换器冷却。热水冲洗了
储存罐和循环泵之间的短线部分，避免了盲管。在大多数制药装置中，这种情况每天都发生
很多次，因此这个短线保持着相对较热的温度。如果使用率很低的话，少量水可以连续或同
时返回储存罐，而保持这条线被冲洗。第三种选择是将循环水仅返回至储存罐排水阀的下游，
因此支路也可以忽略。
Figure 8-9 Hot Storage, Self-Contained Distribution
图8-9 热存储、自主分配
Figure 8-10, Fiqure 8-11, and Figure 8-12 Hot Storage, Hot Distribution, Point of Use Heat
Exchanger
图8-10，图8-11，及图8-12热存储、热分配，热交换器使用点
This configuration is identical to Figure 8-5 except that use points requiring water at lower
temperature are equipped with point of use heat exchangers. Figure 8-10, Figure 8-11, and Figure
8-12 show three different designs for these exchangers. All three allow flushing water to drain to
lower microbial counts and adjusting temperature before opening up the point of use valve. All three
also allow for sanitizing the exchanger and downstream piping when water is not called for at the
20 / 53
drop. The schemes differ in capital cost, sanitation method, and in the amount of water used for
flushing. Sanitization is accomplished using low pyrogen steam in Figure 8-10. In Figure 8-11
sanitization is accomplished by circulating hot water from the loop, through the point of use
exchanger, back to the main loop. The operation in Figure 8-11 can be facilitated by installing a
block valve at the return of the main loop. The valve would be closed immediately prior to starting
the sub loop, to
prevent back flow from the main loop. The initial draw of point of use water would
be diverted to drain. Figure 8-12 is sanitized by flushing hot water from the main loop once through
to drain. Tube-in-tube or serpentine type coolers could be used, as well as double tube sheet
exchangers, which are depicted.
除了需要低温水的使用点装备有热交换器使用点外，这种配置和图8-5是一样的。图8-10，
图8-11以及图8-12展示了这些热交换器的三种不同的设计。这三种设计都支持冲水引流来降
低微生物数，并在打开使用点阀门前调节温度。这三种设计也都允许在不需要水流下时对交
换器和下游管道进行消毒。这几种设计在成本投入、消毒方式以及冲洗用水量上都有所不同。
图8-10中是用低热原的蒸汽进行消毒。图8-11中，热水通过使用点的交换器返回到主回路，
通过回路中热水的循环来完成消毒。在图8-11中可以通过在主回路的返回途中安装一个截止
阀来完成操作。在启动支路时应立即关闭此阀门，来防止主回路中的水回流。用水点的最初
抽出的水将排出。图8-12则是冲洗热水，使之一次通过主回路然后引流的方式进行消毒。除
了描述的那种双管片式交换器外，还可以使用套管式或蛇管式冷却器。
Point of use exchangers are most advantageous when there are both hot and lower temperature
water use points off the same loop, and the number of low temperature users is small. Since they
maintain the water hot until it is drawn from the loop, they provide excellent microbial control,
provided they are frequently flushed or sanitized when not in use. As the number of low temperature
users increases, the capital costs and space requirements become prohibitive, and one of the other
configurations should be considered. Water consumption is high due to flushing, although this is
minimized by the scheme shown in Figure 8-11. Energy consumption is moderate because only
water drawn out of the loop is cooled but additional energy must be spent to make up water flushed
to drain. Maintenance requirements are high due to the added exchangers and valves. Complexity is
high as each exchanger must be properly flushed and sanitized. Each drop is limited in capacity by
the sizing of the exchanger. The scheme shown in Figure 8-11 results in added pressure drop in the
main loop, which leads to a larger circulation pump.
当同一个回路外即有热水也有低温水使用点时且低湿使用者数量较少时，使用点交换器是最
好的。因为它能一直维护水是热的直至它从回路中流出，只要在不用时经常冲冼或消毒它就
能提供很好的微生物防治效果。随着低温使用者的数量上升，成本投资和空间要求都会增加，
此时应当考虑其它配置中的一种了。虽然图8-11中展示的设计能降低一些，但耗水量还是因
为冲洗的原因而很大。因为只是有水从回种中取出时才被冷却因此耗是适度的，但是还必须
花费额外的能耗在维护冲水排流上。因为添加了交换台器和阀门，因此维护要求也很高。每
个交换器都必须适当冲洗并消毒，因此也很复杂。能力的每次下降也受到交换器尺寸的限制。
图书8-11中所展示的设计导致了主回路中额外的压差，这就需要一个更大的循环泵。
21 / 53
Figure 8-10 Single Point of Use, Steamed
图8-10 单一使用点，蒸汽处理
22 / 53
Figure 8-11 Point of Use Installed in Sub-loop
图8-11 安装在分回路上的使用点
23 / 53
Figure 8-12 Point of Use Heat Exchanger with Multiple Branch Users
图8-12 带多支路使用者的热交换器使用点
8.3.5 Storage and Distribution Comparison Table
8.3.5 存储和分配对照表
Table 8-1 compares several storage and distribution options currently used in the pharmaceutical
industry. Comparisons are made based upon capital, energy, operating costs, maintenance,
validatability, and other factors. Each category is rated low (L), medium (M), or high (H) for each
system relative to the other systems presented. The particular storage and distribution choice for a
given scenario will depend upon the specific situation being addressed, and the priority the end user
gives to each of the categories, with quality being the foremost priority.
表8-1中将现今制药行业所用的几种存储和分配方案做了比较。对照依据投资、能量、操作
成本、维护、可验证性及其它因素。每个系统相对于提出的其它系统，用低（L）、中（M）
或高做了分类规定。所给方案的特殊存储分配选择将取决于写明的具体情况，并且以及给每
个种类的最终用户优先权。
Table 8-1 Comparison of Storage and Distribution Options
表8-1 储存和分配方案的比较
Category
1.
Batched
2.
Branched
3. Parallel 4.
Loops, Single Hot
5.
Ambient
24 / 53
6.
Hot
7. 8. 9.
Tankless Hot Tank, Point of
分类
System
分批系统
/One Way
分支/单向
Tank
并行回路，单
罐
Storage,
Hot
Distributio
n
热存储，热
分配
Storage,
Ambient
Distributio
n
环境温度
存储，环境
温度分配
Storage,
Reheat
热存储，冷
却及再加
热
Self.
Distributio
n
热罐，自主
分配
Use Heat Ambient
Exchanger
使用点热
交换器
Loop
无罐式环
境温度环
路
contained
Cool and
Capital Cost
投资成本
Water
Consumption
耗水
Energy
Consumption
耗能
H
H
L
H
M
M
L
L
L-M
L-M
M
L
M
M
H
H
L
M
L L Depends on L
loops
取决于回路
L H M M L
Validatabllity Simple
可验证性
Operabllity
可操作性
简单
Complex
复杂
Complex
复杂
Complex
复杂
Complex
复杂
Simple
简单
Average
一般
Average
一般
Simple
简单
Average
一般
Average
一般
Average
一般
Average
一般
Average-
Complex
一般-复杂
H
Average
一般
Average
一般
Depends on Simple
loops
取决于回路
简单
Maintenance M
Requirements
维护要求
Tank
Turnover
水罐循环
Non-Critica
l
不重要
L Depends on M
loops
取决于回路
L M M M
Limited
受限
Average for
Non-Critica
ambient tank,
l
non-critical
for hot tank
对环境温度
水罐来说一
般，对热水罐
来说不重要
不重要
Average
一般
Average
一般
Limited
受限
Non-Critica
l
不重要
Not
Applicable
不适用
Line Flushing Critical
Requirements
线冲要求
重要
Critical
重要
Depends on Non-Critica
loops
取决于回路
l
不重要
Average
一般
Non-Critica
l
不重要
Average
一般
Average
一般
Critical
重要
Average
一般
Limited by Excellent
Ability to
QA hold
Respond to
Large Peak
受QA掌握
Demands
高峰要求的
响应能力
Loop
Control
Requirements
Average Simple
简单
限制
优秀
Average to Excellent
Excellent
一般-优秀
优秀
Excellent
(Cold
Surge
Volume)
优秀（冷冲
击体积）
Average-
Excellent
一般-优秀
Limited by
Average
exchanger
sizing
受交换器
尺寸限制
一般
Critical
关键
Simple
简单
Average
一般
Average
一般
Average
一般
Critical
重要
Average
一般
Balancing and
一般
25 / 53
回路平衡及
控制要求
Microbial/
Endotoxin
Growth
Potential
微生物/内毒
素生长的可
能性
Most
Advantageous
When:
何种情况下
最有利
Method of
Tight
Generation
Reliable.
required
before
Small
required.
生成方法
不可靠。用
水前需要
QA放行。
必须要求
小系统。
Capital,
Use,
Continuous
is Not
QA release
Frequent
Sanitizatio
资本紧，连
繁冲洗或
消毒。
Multiple
Temperatures
Hydraulic
Limitation
度或液压限
制。
Hot Water
High Peak
Tight
is
Demands
for
Cold
Microbial
Control,
Space
High Peak
Both hot
Demands
for
and warm
Constraints
temperature
or Tank
Turnover a
concern,
L-M H(3) Hot=L L M(1) L-M(2) L-M(2) M Hot=L
Amb=M Amb=M
Required.
Required or
Generated
Microbial
Critical
需要热水，
水产生热
或微生物
防治很关
键
Ambient or
Limited
Water is
Water,
Hot, or
Control is
Generated
Temp
环境温度
水或冷水
的高峰要
求，制成的
水是环境
温度的。
Sanitization
Ambient to
water
Cold Water
required
Time for
Flushing or
需要多种温
and number
Limited
and Unit
Capital
of low
空间限制
或水罐循
环是一个
考虑因素，
有限的投
资。
users is low
Energy
, Energy
Water is
at Ambient
concern,
temperature
users
严格的微
生物控制，
有限的消
毒时间。能
量成本不
考虑，有很
多低温使
用者。
concern,
water use.
n.
system is
续使用，频
temperature
cost not a
Costs a
many low
many low
需要热水
temperature
或温水，并
users
环境温度
可冷水的
高峰要求，
并且单元
能量成本
考虑，有很
多低温使
用者。
且低温使
用者是少
数
Least
Advantageous
When:
何种情况下
最不利
Capital and
Sporadic
operating
concern
投资和操
作成本是
一个老婆
因素
Demand
cost is a
Use
operating
concern
偶尔要求
使用，或操
作成本是
一个考虑
因素
Hydraulic
difficult
困难
Initial
Energy
is Tight
最初可用
的投资或
能量很紧
Space.
Per Unit
Sanitization
Per Unit
Energy
Initial
into
schedule
消毒不适
合操作计
划
High
demands
Ambient
or Cold
Water
对环境或
冷水要求
很高
balancing is
Capital or
will not fit
Energy
Availability
operating
High
每个单元
能量成本
很高
Capital or
for
Cost s
Cost is
Energy
High. or
tank
a concern
每个单元
能量成本
很高，或者
水罐循环
是一个老
婆因素
Availability
空间、可用
的最初投
资或能量
很紧
turnover is
is Tight
Profile, or
液压平衡很
cost a
Legend: L = Low M = Medium H = High Amb = Cold or Ambient Conditions
图例：L=低 M=中 H=高 Amb=冷却或环境条件
26 / 53
Notes:
注意：
1) Lower with hot water sanitization once every 24 hours.
每24小时用热水低层消毒一次。
2) Storage tank is always hot, loop is cold or ambient, and hot water sanitized once every 24
hours. Loop return is heated prior to reentering storage tank.
储存罐一直是热的，回路是冷的或环境温度，每24小时进行一次热水消毒。在返回储存
罐前对回路进行加热。
Frequent hot water flushing or steaming can effectively control bioburden. High turnover of the
water in each branch due to use (at least once daily) can significantly reduce bioburden.
热水的频繁冲洗或蒸汽蒸煮能有效的控制生物负荷。因为使用（每天至少一次）而使水在每
个支路里高度循环能显著减少生物负荷。
MATERIALS OF CONSTRUCTION
构建材料
Pharmaceutical equipment and piping systems rely extensively, on stainless steels to provide the
non-reactive, corrosion-resistant construction needed in manufacturing and heat sterilization.
However, thermoplastics are available that may offer improved qualities, or lower cost. Less
expensive plastics such as polypropylene(PP) and polyvinyl chloride(PVC) may be acceptable for
non-compendial systems. Others, such as polyvinylidene fluoride(PVDF) offering greater heat
resistance, may be suitable for compendial waters, although they require continuous support in hot
applications. The cost of a PVDF system may be approximately 10-15 percent lower than the cost of
a stainless steel system once factors such as passivation, boroscope radiographic inspection, etc., are
included. New methods of joining PVDF tubing leave a weld much smoother than possible with
stainless steel. At higher temperatures, however, thermal expansion of the plastic becomes a major
concern.
制药设备和管道系统非常广泛的采用不锈钢，以提供制造和消毒过程中所需要的不反应、耐
腐蚀的构造。但是，也可以采用热塑性塑料，它能够提高质量或降低成本。对于非药典规定
的系统，也可以使用较便宜的塑料如聚丙烯（PP）和聚氯乙烯（PVC）。其它的，像有更高
抗热性的聚偏氟乙烯（PVDF），也适用于药典规定水，虽然它们在热点应用中需要连续支持。
如果包括钝化、光学孔径仪放射性检查等因素的话，PVDF系统的成本可能比不锈钢系统的
成本低10-15个百分点。接入PVDF管道的新方法留下的焊接处比不锈钢可能留下的更平滑。
但是，在更高的温度下，塑料的热膨胀就成为一个主要的考虑因素
While certain changes to higher grade materials (higher alloys such as AL6N and Hastelloy) and
methods of fabrication to assure compliance can yield minor improvements, others may only
provide minor gain despite considerable additional expense.
当发生某些变化，改用高级材料（像AL6N和哈氏合金之类的高等合金）及确保适宜的构建
方法时能产生较少的改善时，其它的仅能提供较少的收益，尽管额外花费相当可观。
Material selection should be consistent (all 316L or all 304L etc.) throughout the distribution,
storage, and processing systems, if regular passivation is planned.
27 / 53
如果设计了规则钝化，那么在整个分配、储存和处理系统中，材料的选择应当一致（都是316L
或都是304L等）。
For compendial water, the use of 316L stainless steel is preferred.
对于药典规定用水，使用316L不锈钢是首选。
Insulation for stainless piping should be free of chlorides, and hangers provided with isolators to
preclude galvanic corrosion.
不锈钢管道的隔离应当是无氯化物的，并且用带有绝缘器的吊架预先排除电流腐蚀。
304L and 316L stainless steel has been the industry preference in tanks for the storage of
compendial waters. Jacket material in contact with the shell should be compatible, to avoid
chromium depletion in the weld-affected zones. Non-compendial water storage may not require the
same level of corrosion resistance or the use of low carbon nickel chromium alloys and special
finishes, depending on the owner's water specifications.
304L和316L不锈钢已经成为工业上用于存储药典规定用水水罐的首选。和外壳接触的夹套
材料应当匹配，以避免焊接区域脱铬。非药典规定用水的存储可能不需要同等级别的抗腐蚀
能力，或使用低碳的镍铬合金并作特殊抛光，这取决于使用者的水质。
High purity water distribution systems, using the material and finishes specified by the design,
should be joined using acceptable welding or other sanitary techniques. The distribution and storage
systems should be installed in accordance with cGMPs and fabricated, manufactured, procured, and
installed in strict accordance with explicit operating procedures.
根据设计使用材料和特定抛光的高纯度水的分配系统，应当用可接受的焊接或其它消毒卫生
技术进行连接。分配和存储系统的安装应当符合cGMPs，而装配、制造、获得及安装应严格
遵循外部操作规程。
Orbital welding has become the preferred method for joining high purity metallic water piping
systems, due to the greater control over critical weld parameters and the smooth weld bead
characteristics of the process. However, hand welding is still employed and may be required in
certain situations.
连接高纯度金属水管道系统，首选轨道焊接，因为它能很好的控制严格的焊接参数以及工艺
的光滑焊缝特性。但是，手焊仍旧保留，它可能在特定情况下需要。
304 and 316 stainless steel have been preferred grades for use in metallic piping systems due to their
high chromium and nickel content and ease of automatic welding. Low carbon and low sulfur
grades of stainless steel are preferred for compendial systems, and control and inspection of the
welding process is necessary to limit corrosion and crevices in the system. A maximum sulfur
content of 0.04% would be ideal for welding but any mismatch in the sulfur content of the mating
parts will easily cause the weld to weaken, outweighing the advantages lower sulfur levels.
304L和316L不锈钢因为其较高的镍铬含量及便于自动熔接，已经成为金属管道系统使用的
首选。低碳和低硫级的不锈钢是药典规定用水的首选，并且控制并检查焊接工艺十分有必要，
这样可以防止系统出现腐蚀和裂缝。最大0.04%的含硫量对于焊接来说是最理想的，但是连
接部件中含硫量出现任何差错都很容易引起焊接弱化，这比较低的硫水平更重要。
28 / 53
Where possible, all fittings, valves, tubing, and weldable pieces of the same nominal size (diameter)
should be purchased and manufactured from steel with the same specification and Heat Number in
order to standadize the weld quality for each tubing size.
在可能的地方，购买的同一标称尺寸的所有配件、阀门、管道和可焊接部分都应当由相同规
格和加热号（熔炉编号）的钢材制造，从而使每个管道尺寸的焊接质量标准化。
8.4.1 Comparision of Materials of Construction for Tanks and Distribution Systems
8.4.1 水罐和分配系统的构建材料比较
Table 8-2 Comparison of the relative values of key factors in the design and installations of
water systems
表8-2 设计和安装水系统时的关键因素的相对值比较
Installed Cost
安装成本
PVDF ABS POLYPRO PVC
316LSS
TUBING
304LSS
TUBING
316LSS
PIPING
304LSS
PIPING
M M L L M M M M
Ease of
Installation (1) H M M
安装容易度
Steam
Sanitizable
蒸汽消毒
Y N N
H M M H H
N Y Y Y Y
Hot Water
Sanitizable Y N N
热水消毒
Ozone
Sanitizable
臭氧消毒
Chemical
Sanitizable
化学消毒
Y N N
N Y Y V Y
N Y Y Y Y
Y Y Y Y Y Y Y Y
Rouging
Susceptibility
N N N
过氧化铁易感
度
Corrosion
Resistance
抗腐蚀性
Availability
有效率
Extractables
可萃取物
H H H
N Y Y Y Y
H H M H M
M L M
L M L
H H M H H
H L L L L
Degree of H H H N/A L L L L
29 / 53
Thermal
EXPANSION
热膨胀度
Joining Method
连接方法
-TRICLAMP
三向夹扣
-Solvent
溶解
-THERMAL
FUSION
热熔
-WELD
焊接
External
Support
外部支持
Y N Y N Y Y Y Y
N Y N Y N N N N
Y N Y N N N N N
N N N N Y Y Y Y
H H H M L L L L
Legend: Y=Yes N=No H = High M = Medium L = Low
图例： Y=是 N=否 H=高 M=中 L=低
Notes:
注意：
1) Based on skilled labor requirements, ease of welding, ease of visual inspection, shop
fabrication requirements, etc.
取决于熟练工人要求、焊接容易性、目检容易性，运输组装要求等。
2) The steam pressure and steam temperature control is critical to keep both below the
manufacturer's ratings.
对蒸汽压力和蒸汽温度的控制十分关键，必须保持在制造商定值之下。
8.4.2 Workmanship
8.4.2 技巧
Fabrication should be performed by certified welders in a controlled environment to preclude
contamination of equipment and material surfaces. Facilities dedicated to the fabrication of stainless
steel (or higher grade alloys) are preferred, to avoid contamination by carbon steel. Fabrication must
follow an approved quality assurance plan. There needs to be adequate documentation in the design
and construction of the system, including up to date P&IDs, system isometrics, weld test reports,
etc.
应当由合乎标准的焊接工人在受控环境内进行装配，以排除设备和物料表面的污染。优先选
用不锈钢（或更高级别的合金）装配专用设备，以避免被含碳钢污染。装配必须遵循经批准
的质量保证计划。设计和建造系统时需要完备的文件，包括最新的P&IDs，系统管图，焊接
测试报告等等。
Tubing and piping welds, whether orbital or manual, must have a smooth internal diameter contour
without excessive concavity or convexity, bead wandering, misalignment, porosity, or discoloration.
30 / 53
One hundred percent photographic or radiographic analysis, while utilized to an increasing extent, is
neither cost effective nor infallible. Appropriate sampling is strongly recommended.
无论是轨道还是手动，管子件和管道的焊接都必须保证内径表面平滑，没有明显的凹凸面，
游移珠、对不准、多孔或脱色现象。当所使用到越来越大的程度时，百分之一百的摄影或放
射照像分析也不一定成本有效或准确无误。强烈推荐进行适当采样。
8.5 SYSTEM COMPONENTS
8.5 系统组件
Heat Exchangers热交换器
Shell and tube, tube-in-tube, and plate and frame heat exchangers are employed. Although plate and
frame units may offer a cost advantage, they are used less often in the distribution portion of the
system in compendial service because of the perceived greater risk of contamination. However, they
are common in the pretreatment side prior to final purification. In a shell and tube exchanger treated
water flows through the tube bundle; the risk of contamination from cooling or heating media can be
significantly reduced by means of a double tube sheet. Complete drainability of the u-tube bundle is
achieved by weep holes located at the low point of each chamber in the exchanger channel.
Ensuring a positive pressure differential on the "clean" side can further reduce contamination risk.
Similarly, a plate and frame unit should be operated with the cleaner water side at higher pressure
than the heating or cooling medium. Conductivity meters may be used for monitoring leakage. Unit
design should permit full drainage and ready access for inspection and cleaning.
壳管式、管套式以及板框式热交换器都可以选用。虽然板框式装置有成本优势，但是它却很
少应用于药典使用系统的分配部分，这是因为已经认识到其在污染方面存在很大的隐患。但
是，它却广泛应用于终纯化前的预处理过程。在壳管式交换器中，处理水流经管束，来自于
冷却和加热介质的污染能够明显减少，这是由于它的双管层。U型管束的完全引流是通过位
于交换器罐内各舱室下端的渗漏孔实现的。确保干净侧的正压差能够进一步减少浸染风险。
同样，板框式装置内，干净水侧的压力也应当高于加热或制冷介质侧。可以用电导率仪测泄
漏。装置设计应当允许完本排净以准备接受检查和清洁。
Vent Filters通气过滤器
Used on storage tanks in compendial water service to reduce contamination during drawdown. Units
are constructed of hydrophobic PTFE or PVDF to prevent wetting and generally rated at 0.1 to 0.2
microns. Filters should be capable of withstanding sterilization temperatures and sized for
maximum fill or drawdown rates to effectively relieve the negative pressure created by high
temperature sanitization cycles. Filters in hot systems are usually jacketed to minimize condensate
formation that could result in blinding vessel exhaust hydrophobic filters. Storage tanks should be
rated for full vacuum, (or have vacuum protection), if steam is used for sterilization. Installation
should also allow for drainage of condensate caused by high operating or sanitizing temperatures,
and ease of replacement. The filter cartridges need to be appropriate for the filter housing. Vent
filters should be integrity tested for compendial water storage tanks, but may not need to be
validated as sterile filters.
31 / 53
将其用于药典规定水服务中的储存罐上以减少下游污染。此装置由疏水性的PTFE或PVDF
构成防止浸湿，一般标称在0.1到0.2微米。过滤器应当能够耐受灭菌温度，并且尺寸制造为
最大填充或下落率，从面有效降低由高温灭菌循环带来的负压。热系统中的过滤器通常有夹
套保护以减少冷凝水的形成，它会导致盲态容器消耗疏水过滤器。如果用蒸汽消毒的话，储
存罐的等级应当是完全真空（或有真空保护）。安装也应当允许将由高的操作和消毒温度引
起的冷凝水排净，且易于更换。过滤筒应当与过滤外罩匹配。通气过滤器应当针对药典规定
储水罐做完整测试，但是无须像无菌过滤器一样进行验证。
Pumps and Mechanical Seals泵和机械密封
Centrifugal pumps are commonly employed in distribution systems. Performance curves and suction
head requirements should be reviewed to preclude cavitation, which might lead to particulate
contamination. The generation of pump heat over extended periods of low or no draw off should
also be considered, since significant temperature rise in cold systems, or cavitation due to vapor
pressure in hot systems could occur. Casing drains allow for full system drainage, where the pumps
are at the low point of the distribution. Although with double mechanical seals, with WFI or other
compatible seal, water flushing may minimize the possibility of contamination; single mechanical
seals flushed to the outside have also been used. In extremely critical applications, polished rotating
elements may be warranted. The installation of dual pumps, for standby purposes, should ensure
flow throughout the system.
离心泵广泛用于分配系统。应当检查其工作特性曲线及吸头要求，以预防空穴，这会导致粒
子污染。因为冷系统中的温度明显上升，也或者由热系统中的蒸气压力会形成空泡，所以应
当考虑泵产生的热量超出下面的扩展期，或没有从中排去的情况。排水套管允许系统完全排
净，此处泵在分配的低点。虽然有双机械密封，带WFI或其它药典规定密封的，用水冲洗可
以减少污染的可能性；但是也已经使用单机械密封来冲洗外侧。在极端严格的应用中，能够
保证抛光旋转元件。作为备用的双重泵安装，应当确保流经全部系统。
8.5.4 Piping System Components
8.5.4 管道系统组件
a) Piping and Tubing: Extruded seamless and/or longitudinally welded tubing is commonly used
in systems two inches in diameter and smaller. Recently, welded steel tubing (ASTM A-270),
similar to seamless in appearance, has become available at significantly lower cost. PVDF has also
been shown to be a viable alternative.
管道和管件：挤压无缝管和/或纵向焊接管普遍用于直径2英尺或更少的系统。近来，焊
接钢管（SATM A-270），外观与无缝管类似，已经有效地降低了成本。PVDF也已经成为另
一种选择。
b) Fittings: Single fittings may be manufactured from as few as one, to as many as five pieces.
This can materially affect the suitability of the end product, in terms of weld content, documentation,
and cost.
配件：单独配件的制造少则一个，多则5份。在焊接容量、文件及成本角度看，这对终
产品的适应性能造成重大影响。
Valves: The trend in the industry has been to use diaphragm valves in high purity systems,
32 / 53
particularly in isolation applications. For steam service, sanitary ball valves may be acceptable and
require less maintenance.
阀门：工业趋已经开始在高纯度系统中使用隔膜阀，特别是在隔离应用中。对于蒸汽使
用，也可以接受卫生的球阀，它只需很少的维护。
The following is a summary water system components, listing the common industry practice, and
listing a advantages and disadvantages:
下面是水系统组件的汇总，列出了普遍的工业应用，以及优缺点。
System Components Comparison Table
系统组件对照表
Table 8-3 System Components Comparison
表8-3 系统组件对照
Item
项目
Valves
阀门
industry Practice
工业应用
Diaphragm
隔膜
Advantages
优点
Drainable*
可排水
Sanitizable
可消毒
Cleanable
可清洁
No steam seal
无蒸汽密封
No body pockets
无机体袋
Low cost
成本低
Tight shutoff
关闭严密
Low maintenance
维护率低
Disadvantages
缺点
Higher initial cost and maintenance
初期成本及维护较高
Wears out quicker
磨损很快
Not absolute shutoff for high pressure
systems
高压系统下不能完全关闭
Plug/Ball
栓/球
Need stem seal
需要蒸汽密封
Have body pockets where bacteria
may linger, making sanitization
difficult
有机体袋，可能会留下细菌，使得
消毒变得困难
Need stem seal
需要蒸汽密封
Have body pockets
有机体袋
Butterfly
蝶形
Low cost
成本低
Tight shutoff
关闭严密
Low maintenance
维护率低
33 / 53
Gaskets
垫圈
Elastomers,
including Viton
合成橡胶，包括氟
胶
Silicone
硅胶
Temperature resistant
耐温
Less expensive
价格低
Temperature resistant
耐温
Less expensive
价格低
Temperature resistant
耐温
Less expensive
价格低
Best temperature
resistance Inert
最好的耐温惰性
Chemical resistant
耐化学品
Chemical resistant
耐化学品
EPDM
Steaming not recommend
不建议蒸煮
Teflon
聚四氟乙烯
Cold flow in service
冷流在役
More expensive
费用高昂
Expensive
价格高
Sensitive to pinching
不耐挤压
Teflon encapsulated
有外包的聚四氟乙
烯
Vent Filters
通气过滤器
Good temperature resistance
良好的耐温性
Good chemical resistance
良好的耐化学品性
Bioburden and particulate Possible plugging due to wetting
0.2 Micron
reduction 可能由于浸湿造成堵塞
Hydrophobic
生物负荷和粒子减少 Cost
Membrane
成本
0.2微米的疏水膜
Steam jacketed or
electric traced
housing
蒸汽套或电伴热外
罩
More expensive
Double tube sheet Sanitary design
费用高昂
(Shell and tube) 卫生设计
双管层（壳和管） Protection against plant to clean
side leaks
防止车间对洁净侧泄漏
Heat
Exchangers
热交换器
34 / 53
Single tube sheet Less expensive than double tube Need to maintain a higher Delta P on
(Shell and tube) sheet clean side is operationally difficult
单管层（壳和管） 费用相对双管层较低 在洁净侧需要维持一个较高的δP，
操作困难
Concentric pipe
同心环纹管
Low leak potential
泄漏可能性低
Low heat transfer coefficient,
requiring a large surface area
导热系数低，需要很大的表面积
Greatest leak potential
泄漏可能性最大
Needs double gasketing
需要双垫圈
Less expensive
费用低
Lower maintenance
维护率较低
Plate and Frame
板框式
Least Expensive
费用最低
Pumps
泵
Centrifugal
离心式
Commonly available
普遍可用
Positive
Displacement
正位移式
More expensive
Commonly available
费用高昂
普遍可用
Higher Maintenance
More efficient when higher
维护率较高
discharge pressure is required
需要较高的排放压时最有效
Constantly being flushed
经常冲洗
Higher on-stream reliability
运转可靠性较高
Less expensive
价格低
Minimal crevicing
裂缝最小
Ease of inspection
便于检查
Ease of Disassembly
便于拆分
More expensive, both installation and
operation
安装和操作的费用高昂
Mechanical
Seals
机械密封
Double
双
Single
单
For non-shrouded impeller type,
cleanability an issue
对于无屏蔽涡轮型，可清洁性是一
个问题
Pressure limitations
压力限制
Size limitations
尺寸限制
Connection
Types
连接类型
Sanitary clamper
清洁的夹持器
35 / 53
Flanged
法兰
Easier in piped systems
管道连接系统中很简便
Good in high pressure applications
高压应用良好
Recommended for >4" OD
建议>4" OD
Good thermal efficiency
良好的热效率
High cost
成本高
Gasket protrusion
垫圈突出
Greater chance for crevicing
裂缝机会很大
Significant welding required
需要明显焊接
Tanks
水罐
Jacketed (1/2 pipe)
夹套式(1/2管)
Jacketed (full jacket)
夹套式(全夹套)
Less welding leading to lower
Less thermal efficient
热效率低
probability of weld failure
焊接处少使得焊接失败的可低性
很低
Allows for complete external Requires an external heat exchanger
inspection of the tank 需要一个外部热交换器
允许对水罐进行完全的外部检查
Safety relief device prevents tank
rupture should vent filter become
blocked
在通气过滤器阻塞时，安装卸放
装置能防止水罐破裂
Tank to be designed as an
atmospheric tank rather than a
pressure vessel
水罐将被设计成一个大气压罐而
不是高压罐
Non-Jacketed
无夹套式
Rupture
Discs
爆破片
* lf canted at the correct angle, and installed in pitched lines
如果在正确的角度倾斜，并安装在斜线上
8.6 COMPARISON OF WFI SYSTEMS WITH STORAGE TANK AND WITHOUT
STORAGE TANK
8.6 有储存罐和没有储存罐的WFI系统比较
Figure 8-13 Tankless Ambient Distribution
图8-13 无水罐式环境温度分配
36 / 53
It is possible to feed sub-loops off a single main loop without the use of an intermediate storage tank
(Figure 8-13). This configuration is most advantageous when space or capital constraints are tight.
The sub-loop is generally a circulating loop. Water drawn out of the main loop when a point of use
valve is opened cannot return to the main since the sub-loop is at a lower pressure. This provides a
degree of isolation between the sub-loop and the main, or other, sub-loops. The major disadvantage
is that there is no storage capacity. Usually this capacity is provided by a storage tank on the main
loop.
由一个单独的没有使用中间存储罐的主回路向支回路供水是有可能的（图8-13）。当空间或
投资受到严格约束时，这咱配置是最有利的。支回路一般是循环回路。当使用点的阀门打开
时从主回路流出的水不能再返回主回路，这是因为支回路的压力较低。这就在支回路和主回
路或其它支回路之间提供了一定程序的隔离。它的主要缺点是没有储存能力。通常此能力是
由主回路上的储存罐提供的。
Table 8-4 Comparison of WFI Systems: with Storage Tank and without Storage Tank
表8-4 WFI系统比较：带储存罐式和不带储存罐式
STORAGE TANK SYSTEM
储存罐系统
Advantages
优点
Disadvantages
缺点
Provides air break to minimize back contamination
Added capital expense of tank, filter, etc.
of hot WFI supply.
水罐、过滤器等的额外费用支出
用空气断路器来减少供应热WFI时的后污染。
Minimize WFI cooler capacity by averaging hot
WFI feed flow into tank.
使平均的热WFI进水流入水罐，从而减少了WFI
的制冷容量。
Sanitization/steamout may be more involved than
for a tankless system.
相对于无罐系统，更可能涉及到消毒卫生处理/
蒸汽取出问题。
Provide cooled WFI "surge" volume ready on If the system is drained daily, potential loss of
37 / 53
demand to facilitate production schedules.
随时准备为提供所需的冷却WFI“波动”，以促
进生产计划的完成。
WFI may be greater than tankless loop.
如果系统每天排净的话，潜在的WFI损失可能
会比无储存罐系统要高。
Positive point to relieve system pressure due to
normal venting or hot water sanitization.
积极面是通过正常的排水或热水消毒减轻了系统
压力。
Once operational, conditions easier to maintain than
tankless system. Potential problems easier to isolate.
一旦运转起来，条件比无水罐系统更容易维持。
潜在问题更易解决。
Eliminate back pressure control valve cavitation by
dividing pressure drop between valve and spray
balls.
借助分开阀门和喷淋球之间的压差，从而排除了
反压控制阀里的空穴。
TANKLESS SYSTEM
无罐系统
Advantages
优点
Decreased capital expense (no tank, filter, etc.)
成本支出缩减（无水罐、过滤器等）
Increased perception of improved system sterility
due to "totally welded tubing”
由于“全部焊接管件”使得对改善系统无菌性的
认知加深。
Disadvantages
缺点
WFI tank may be required to satisfy peak demands
of ambient system.
可能需要WFI罐来满足周围系统的高峰需求。
Thermal expansion of WFI during hot water
sanitization has nowhere to relieve, except flush to
drain.
在热水消毒期间WFI的热膨胀何处都不会减
轻，除非冲洗排净。
If system is drained daily, potential WFI lost may be
More difficult to isolate than storage tank system.
less than storage tank system.
相比储存罐系统，隔离更加困难。
如果系统每天排净的话，潜在的WFI损失可能会
比储存罐系统要低。
System hydraulics more difficult to
manage/control than storage tank system.
相比储存罐系统，维护/控制系统的疏水性更加
困难。
8.7 MICROBIAL CONTROL DESIGN CONSIDERATIONS
8.7 微生物防治设计考虑因素
In any given water storage and distribution system, there are certain fundamental conditions that can
always be expected to aggravate a microbial problem. Likewise, several basic measures will always
tend to counteract such problems. Fundamental conditions that typically could aggravate the
38 / 53
problem include:
在给出的任何水存储和分配系统中，必然存在一个根本条件，它可能一直会加重微生物问题。
同样，也将采取几个基本措施来防止这类问题。典型的将加重微生物问题的根本条件包括：
• Stagnant conditions and areas of low flow rates
停滞条件以及低流速区域
• Temperatures that promote microbial growth (15-55°C)
促进微生物生长的温度(15-55°C)
• Poor quality supply water
供给水质量差
Some basic measures that have been shown to alleviate such problems are:
已经表明可以减轻此类问题的基本措施是：
• Maintaining ozone levels of 0.02ppm to 0.2ppm
将自氧水平维护在0.02ppm 到 0.2ppm
• Continuous, turbulent flow
连续涡流
• Elevated temperatures
提高温度
• Proper slope
适当倾斜
• Smooth, clean surfaces that minimize nutrient accumulation
平滑干净的表面，减少营养物质的蓄积
• Frequent draining, flushing, or sanitizing
频繁的排水、冲洗或消毒
• Air breaks in drain piping
排水管中的空气断路器
• Ensuring no leaks in the system
确保系统没有泄漏
• Maintaining positive system pressure
维持系统正压
All pharmaceutical water must meet the EPA standard for microbiological quality of potable water;
which means it must basically be free of specific indicator organisms. Beyond that, microbiological
quality for non-compendial water should be based upon its intended use and the types of products
that will be formulated with it.
所有制药用水都必须达到饮用水微生物水平的EPA标准，这意味着它必须不含特定的指示剂
有机体。此外，非药典规定用水的微生物质量应当依据基使用意图及以其为配方的产品类型。
It is important to note though that although the required microbial population acceptance level for
USP compendial purified water is 100 CFU/ml, reliance on such a single parameter can be
misleading. The 100 CFU/ml limit may generally be applied to the manufacture of solid oral dosage
forms. Many times, however, aqueous or topical formulations require tighter controls to maintain
product quality. The USP points out that these types of products have been the subject of recalls
when found to be contaminated with gram negative organisms, and the typical microbiological flora
of water are gram negative organisms.
39 / 53
值得注意的是，虽然USP药典规定纯化水所需的菌体接受水平是100CFU/ml，但是只依赖这
个单一标准很可能产生误解。100CFU/ml的限制通常用于制造固态内服制剂。但是在很多时
候，水剂或局部制剂成本需要更严格的控制以维持产品质量。USP指出那些已经发现被革兰
氏阴性菌污染的的产品种类已经被召回，而水的典型微生物菌丛就是革兰氏阴性菌。
A common appropriate approach to dealing with this key issue involves the use of trend analysis.
Using such an approach, alert and action levels are related to the system norm. In this context,
strategies for responding to the alert and action levels can, and should, be developed. Even with the
most conscientious design, there may be places in which biofilm can form. Good Engineering
Practices, such as eliminating deadlegs, ensuring adequate flow velocities through out the system,
and periodic sanitization help control microbial activity.
处理此关键问题普遍适宜的方法是使用趋向分析。用此方法，警报和行动级别都和系统统正
常有关。在此文中，能够而且应当发展对警报和行动级别的回应策略。即使用了最负责的设
计，所在地还是有可能形成生物膜。良好的工程实践，比如去除盲管，确保以适当流速通过
系统，以及定期消毒可以帮助防治微生物效能。
It is common practice, therefore, to store and distribute water in a circulating system under any of
the following scenarios:
因此，下述任何一种情况下，在循环系统中存储和分配水的只是一般操作：
. At coupons which are self-sanitizing such as above 65℃ or under ozone.
在取样管处于65℃以上或臭氧中的自消毒条件下
. At conditions that limit microbial growth such as below 10°C with periodic sanitization.
在类例10℃以下且进行定期消毒的微生物生长受限的条件下
. At ambient temperatures where sanitization is determined by the validated methods that
control microbial growth
在已用控制微生物生长的验证方法确定了消毒处理地方的环境温度下
Regulatory Clarification to Common Industry Practices
一般工业实践的法规说明
The following are industry practices that are all Good Engineering Practices (GEPs), and have been
perceived in the past to reduce the chance of microbial growth.
下面是良好工程规范（GEPs）的工业操作，在过去就已经认识到通过它可以减少微物的生长
机能。
If you collectively ignore all of these items, you increase the likelihood of having a bioburden
problem. These items include finishes, storage tank orientation, storage tank isolation, storage tank
turnover, piping slope and drainability, deadlegs and velocity.
如果你忽略了所有这些问题，那么你就会增大造成生物负荷问题的可能性。这些问题包括抛
光、储存罐的定向、储存罐的隔离、储存罐的循环、管道倾斜和可排水性、盲管以及速度。
Finishes
抛光
Common industry practices typically range from milled pipe to 320 grit (0.38 microns Ra)
mechanical polish with electropolish. Electropolishing is a reverse plating process, which improves
the surface finish of mechanically polished stainless steel piping and equipment. It reduces surface
40 / 53
area and removes surface intrusions caused by mechanical polishing, which may cause subsequent
rouging, and/or discoloration. After mechanically polishing or electropolishing the system, the
polishing compounds should be confirmed to have been completely removed from the pipe, so as
not to accelerate corrosion.
一般典型的工业规范范围从打磨管到用电解法抛光的320粒度（0.38微米Ra）的机械抛光管。
电解光抛光与电镀工艺相反，它能改善机械抛光处理的不锈钢管及设备的表面精制程度。它
减少了表面积，并除去了由机械抛光引起的表面突入，这些突入随后可能引起铁氧化，和/或
脱色。将系统进行机械抛光或电解抛光处理后，应当确证抛光组件已经从管道中完全移出，
从而避免锈蚀加速。
The benefits for electropolish or finishes smoother than 0.76 microns Ra (approx. 180 grit or 30
micro inch) are questionable.
电解抛光或磨光平滑器相较 0.76微米 Ra（约180粒度或30微寸）的益处并不可靠。
Systems operating at ambient temperature or with infrequent sanitization may require a smoother
surface finish. The interior surfaces of stainless piping systems, in compendial water service, are
typically ground and/or electropolished, at considerable cost, to achieve a smooth surface of
minimal porosity (0.4 to 1.0 microns Ra), in order to reduce bacterial adhesion and enhance
cleanability. A viable alternative is extruded PVDF piping, which can produce a smoother surface
than most metallic systems, without recourse to polishing, although PVDF has other disadvantages.
(See Section 8.4.)
在环境温度下操作系统或只是偶尔消毒可能需要更光滑的表面磨光处理。服务于药典规定用
水的不锈钢管系统的内表面，通常是磨平和/或电解抛光处理的，花费较高但得到了最低孔度
（0.4到1.0微米Ra）的光滑表面，从而减少了细菌的粘附并提高了清洁能力。另一种选择是
挤压式PVDF管道，虽然PVDF有其它缺点（见8.4节），但是无须抛光它的表面就比大多
数金属系统更平滑。
Storage Tank Orientation
储存罐定向
Vertical orientation is the most common because of the following advantages:
垂直定向是最普遍的，它具有以下优点：
• Lower fabrication cost
建造成本更低
• Less dead volume
死体积更少
• Simpler spray ball design
喷淋球设计更简单
• Less floor space required
占地面积更小
• Horizontal vessels are used where height is a constraint
水平容舱用于高度有限处
Storage Tank Isolation
储存罐的隔离
41 / 53
Common practice for compendial and non-compendial waters where microbial contamination is a
concern is to use a 0.2 micron hydrophobic vent filter.
在担心微生物污染的地方，药典规定及非药典规定用水的一般操作是用一个0.2微米的疏水通
气过滤器。
For hot storage vessels, the vent filter must be heated to minimize moisture condensation. An
alternate practice is to blanket the tank with 0.2 micron filtered air or nitrogen. Nitrogen blanketing
can be used if CO
2
absorption is a concern, or if final product oxidation is a problem.
对于热储存罐而言，通气过滤器必须加热以减少水份凝集。另一种方案是用经0.2微米过滤后
的空气或氮气封罐。如果担心吸入CO
2
，或者终产品氧是一个问题时，可以采用氮封。
Storage Tank Turnover
储存罐循环
Common practice is 1-5 tank turnovers per hour.
一般规范是每小时循环1-5罐。
The turnover rate may be important for systems using external sanitization or polishing equipment.
对于使用外部消毒或抛光设备的系统来说，循环率可能很重要。
The turnover rate is less important when storage is under sanitizing conditions, including hot storage
or ozone. It may be less important under conditions that limit microbial growth, such as cold storage
(4-10℃), but this must be demonstrated by documentation.
当在消毒条件下储存时，包括热储存或臭氧，循环率不是很重要。在微生物生长受限的条件
下，如冷储存（4-10℃），它也不重要，但是这些必须用文件证实。
Some storage tank turnover is required to avoid dead areas.
需要一定的储存罐循环来消除死体积。
System Drainability
系统的可排水性
Systems that will be steam sterilized must be fully drainable to assure complete condensate removal.
将用蒸汽消毒灭菌的系统必须能将水完全排净，从而确保可以将冷凝水全部移出。
Systems that will never be steam sterilized do not need to be fully drainable, as long as water is not
allowed to stagnate in the system.
永远不用蒸汽消毒灭菌的系统，只要不允许水郁积在系统中，就不必具有将水全部排净的能
力。
It is good engineering practice to allow for the draining of equipment and associated piping.
考虑设备的排水性及相关的管道是良好的工程规范。
Deadlegs
盲管
Good engineering practice is to minimize or eliminate deadlegs where possible. Common practice is
to limit deadlegs to less than 6 branch pipe diameters or less. This stems from the "6D" rule
contained in the proposed CFR 212 regulations of 1976. Recently, industry experts have suggested
42 / 53
using a guideline of 3D or less. However, this new guideline causes confusion since the proponents
of this standard generally are discussing the length of dead leg from the outer wall of the pipe, while
the original 6D rule describes the distance from the center line of the pipe to the end of the deadleg.
Obviously, if a 1/2" branch is placed on a 3" main, the distance from the center line of the pipe to
the outer wall of the pipe is already 3D. Thus, even a zero deadleg valve might not meet the 3D
requirement.
良好的工程规范会尽可以地减少或剔除盲管。一般规范是限制盲管低于分支管径的6倍或更
少。它源于1976年提议的CFR212法规中所含的“6D”法则。最近，业内专家已经建议采用
3D或更少的指导方针。但是，新指南造成了混淆，这是因为此标准的倡议者一般是从管道外
壁来讨论盲管的长度，而原来的6D法则描述却是从管道的中心线到盲管终端的距离。显而易
见，如果将1/2”的分支安置在3”的主管上，从管道中心线到管道外壁的距离已经是3D了。
因此，即使是零盲管的阀门也有可能不符合3D的要求。
To avoid confusion in the future this Guide suggests that the length of the deadleg be considered
from the outer wall of the pipe. We propose avoiding a hard rule of thumb for maximum allowable
deadlegs. Ultimately, the water must meet the required quality regardless of the length of the
deadleg. Good Engineering Practice requires minimizing the length of deadlegs and there are many
good instrument and valve designs available to do so.
为了避免将来发生混淆，本指南建议从管道的外壁开始考虑盲管长度。我们不打算为盲管允
许的最大值做一个硬性规定。归根结底，不管盲管的长度如何，水都必须符合所需的质量。
良好工程规范要求减少盲管长度，并且许多有效的良好仪器和阀门设计也是这么做的。
It should be recognize that any one-way system can constitute a deadleg if it is not frequently
flushed or sanitized.
应当意识到，如果不经常冲洗或消毒，单向系统很可能构成盲管。
It is important to maintain the system under positive pressure at all times. One common concern is
systems
designed with insufficient return flow, which could draw a vacuum at points of use under periods of
high water usage. This causes an unexpected microbial challenge to the system.
始终维护系统在正压下非常重要。设计的系统返回率不够是一个普遍担心的问题，它会在高
峰用水期将使用点抽成真空。这就会对系统造成意外的微生物麻烦。
Loop Velocity
回路速度
Common practice is to design circulating loops for a minimum return velocity of 3 feet/second or
higher, and for Reynolds numbers in the turbulent region of greater than 2,100.
一般规范中设计循环回路的最小回流速度为3英尺/秒或更高点，并且在湍流区的雷诺数高于
2100。
Return velocities less than 3 feet/second are acceptable for short periods of time, or in systems that
do not favor microbial growth, such as hot, chilled, or ozonated loops.
在短期内，或者系统不利于微生物生长，比如热、冷冻或臭氧回路，回流速度小于3英尺/秒
也可以接受。
43 / 53
A minimum return flow is required to maintain the loop in a flooded condition under positive
pressure.
所需的最小回流速度要能维护回路在正压下处于进水状态。
CONTINUOUS MICROBIAL CONTROL
持续微生物防治
Process water systems generally employ both continuous methods of microbial control, and periodic
sanitizations. This section discusses continuous methods for controlling microbial growth.
水处理系统一般都采用微生物防治连续方式以及定期消毒。此节讨论防治微生物生长的连续
方法。
"Hot" Systems“热”系统
The most effective and reliable means of preventing the growth of bacteria is to operate the system
at temperatures above which bacteria can survive. If the distribution system is maintained in hot
conditions, sanitization on a routine basis can be eliminated.
防治菌体生长最安全有效的方法是在高于菌体存活温度的条件下操作系统。如果分配系统保
持热状态，那么就可以省略常规灭菌。
Systems operating at 80°C have a long history of data showing the prevention of microbial growth.
More recently, companies have been validating water systems at 65°C. The advantages of operating
at lower temperature include energy savings, lower risk of injury, and reducing the amount of
rouging. Systems operating at the higher end of this range have a greater safety margin with regard
to microbial contamination. The effectiveness of temperatures below 80°C must be verified with test
data, on a case by case basis.
在80°C操作系统已经有了悠久的历史数据来表明其对微生物生长的预防。最近，已经有公司
验证了65°C的水系统。在较低温度下运转的优点包括节能、损伤风险低以及减少了过氧化铁
的量。在范围内较高温度下操作，则在微生物污染方面则会更加安全。80°C 以下温度是否有
效必须具体情况具体分析，用试验数据进行验证。
Note that these temperature ranges will not destroy endotoxin. As noted in Chapter 6, where
endotoxin is a concern, the treatment system must be designed to remove it.
注意此温度范围并不能消灭内毒素。正如在第6章中讲明年，在担心内毒素的地方，设计的
处理系统性必须能够去除它。
"Cold" Systems“冷”系统
The use of the term "cold" in this case implies that a system is maintained at a low enough
temperature to inhibit microbial growth. While this has been shown to be effective, the energy costs
associated with it generally make this type system costly to operation. Generally, "Cold" systems
are operated from 4°C to 10°C. Microbial growth rates drop off significantly below 15°C, so the
sanitization frequency of cold systems may be reduced compared to ambient systems. The
44 / 53
effectiveness of a specific temperature, and the associated sanitization frequency in any particular
system, must be determined by statistical analysis, on a case by case basis.
在这里使用“冷”这个词是指维持系统温度足够低以防止微生物生长。虽然已经表明了它的
有效性，但是随之而来的能耗使得这种类型的系统操作费用巨大。一般而言，“冷”系统是
在4°C到10°C操作。微生物生长率在15°C以下明显降低，因此相对环境温度的系统，冷系
统的消毒频率可以减少。任何特定系统中特定温度的效用及相关的消毒频率都必须具体情况
具体分析，用统计分析进行确证。
"Ambient" Systems“环境”系统
Circulation temperatures of any pharmaceutical water system are dictated by either the required
microbial specification or the required temperature for usage. "Ambient" temperature purified water
systems using either ozone and/or hot water sanitizations are common throughout the industry, and
normally result in lower lifecycle costs, as well as reduced energy consumption compared with
either the "hot" or "cold" systems. However, without increased levels of system sanitizations, the
lack of temperature control at the water storage vessel and distribution loop could result in the
formation of a biofilm within the system, which could sporadically and unpredictably produce water
failing microbiological specifications and necessitate non scheduled water system shutdowns.
所有制药水系统的循环温度的规定是根据所需的微生物规定或使用要求温度。用臭氧和/或热
水消毒的“环境”温度纯化水系统，在工业上很普遍，相对“热”或“冷”系统来说，它循
环周期的成本较低，能耗也有所减少。但是，对系统的消毒级别没有提升，储水舱和分配回
路中缺乏温度控制会导致系统内形成生物膜，生物膜会偶尔使水达不到微生物指标，且这种
情况无法预知，这就使计划外的水系统停工成为必然。
Ozone臭氧
Ozone has been shown effective for microbial control. It is a strong oxidant, which chemically
reacts with organisms and destroys them. The destruction of these organisms results in organic
compounds, which may be further degraded by ozone, ultimately to carbon dioxide. Ozone is twice
as powerful an oxidant as chlorine and needs to be dosed continually to maintain concentration.
臭氧对微生物防治的有效性已经表明。它是一种强氧化剂，能和有机体发生化学反应从而消
灭它们。有机体破环后产生有机化合物，它们也会被臭氧进一步降解，最终成为二氧化碳。
臭氧的氧化强度是氯的2倍，需要持续定量以维持浓度。
In any compendial water system and most other applications, water at the use points is expected to
be totally free of ozone. Ozone removal is commonly effected through ultra violet radiation. 254
nanometer UV light converts ozone to oxygen. A common design is to maintain an ozone
concentration between .02 ppm and 0.1 ppm in the storage tank, and use a UV light at the beginning
of the distribution loop for removal. To sanitize the loop itself, the UV light can be turned off during
periods of no use, and the ozone will circulate through the loop. The UV dosage required for ozone
destruction is generally 2 to 3 times that required for microbial control. Testing should be done to
verify absence of ozone at the use points.
在所有药典规定水系统以及其它大多数应用中，都希望使用点的水中不含臭氧。通过紫外照
射一般都能有效去除臭氧。254纳米的U线光能将臭氧转化成氧气。一般设计是将储存罐内
45 / 53
的臭氧浓度维持在.02ppm到0.1ppm之间，并在分配回路的起点处用UV线进行去除。为了对
回路自身进行消毒，不用时可将UV线关掉，臭氧就会在回路内循环流通。清除臭氧所需要
的UV的量一般为防治微生物所需要量的2到3倍。应当进行实验来验证使用点没有臭氧了。
UV Light UV线
Ultraviolet lights have been shown to reduce microbial populations in storage and distribution
systems. UV energy is germicidal in the wavelengths of 200 to 300 nanometers, which falls below
the visible spectrum. UV light de-activates DNA leading to bacteria reduction. A UV light is not a
sterilization device, as it is often referred to. The effectiveness of the light will depend on the quality
of the water in which it is acting, the intensity of the light, flow rate of water, contact time, and the
type of bacteria present.
已经表明紫外线能减少储存和分配系统中的微生物数。UV能在200到300纳米的波长下有杀
菌能力，它属于下述可见光谱。UV线能灭活DNA从而使菌体减少。虽然经常被提及，但
UV线并不是一种灭菌装置。UV线的功效取决于它所在区域的水质、光线强度、水的流速、
接触时间以及存在的菌体类型。
Filtration过滤
Along with other particulate matter, bacteria and endotoxins may be removed via filtration. This
filtration media can be either of the microfiltration (2-0.07 microns) or ultrafiltration (0.1-0.005
micron) scale. The integrity of these filters must be maintained.
连同其它微粒物质一起，菌体和内毒素可以通过过滤一起去除。过滤介质即可以是微滤（2-0.07
微米）级也可以是超滤级（0.1-0.005微米）。必须保证过滤器的完整性。
Microfiltration
微滤
Microfiltration includes the use of depth cartridge filters, pleated filters, and cross flow filtration
membrane elements. These filters can remove particles ranging in size from 100 microns down to
0.1 micron. Depth and pleated filters allow water to flow through a wall of fibers perpendicular to
the water direction (dead ended filters). The particles are then trapped on the outside wall of these
filters, or within the filter walls (for depth filters), due to the pore size of the filter. The filter will fill
up with these particles and then needs to be replaced with a new filter.
微滤包括使用深微过滤器、折叠膜过滤器以及错流过滤膜件。这些过滤器可以去除100微米
到0.1微米范围内的粒子。深度和折叠膜过滤器使水垂直流过一个纤维壁到达水所在方位（盲
端过滤器）。根据过滤器的孔径大小，粒子被截留在过滤器壁之外或之内（对深筒过滤器来
说）。过滤最终将被这些粒子填满，那时就需要更换一个新过滤器。
Ultrafiltration
超滤
Ultrafiltration can be used to remove organics and bacteria, as well as most viruses and pyrogens
from a water source. Filtration is typically from 0.1 micron down to 0.01 micron. Cross flow
ultrafiltration forces the water to flow parallel to the filter media, and the particles which are too
large to pass through the membrane elements are then expelled from the system in a concentrate
stream to drain (typically 5-10% of the feed flow). This allows the filters to be self-cleaning and
46 / 53
eliminates the need to replace these membrane elements frequently. This type of filtration can be
used as a "maintenance " step downstream of the storage tank in certain situations.
超滤可以用来去除有机体和菌体，和从水源去去除大多数病毒及热原一样。过滤一般是从0.1
微米到0.01微米。错流超滤能使水平行流过过滤介质，那些太大粒子经过膜件时就会以浓缩
流的形式被排出系统（一般为进流的5-10%）。它支持过滤器的自清洁，因此无须频繁更换
膜件。某些情况也可以用这种过滤作为储存罐的下游“维持”步骤。
In general for any purified water system, filtration downstream of the storage tank is not
recommended. This comes from concerns of "grow through" where bacteria will colonize on the
upstream side of the filter, and ultimately be found on the downstream side even though the pore
size of the media may theoretically be smaller than the size of the bacteria. An additional concern is
the potential for accumulation of nutrients on the filter media, which may in fact increase the
opportunity for microbial growth. However, filters downstream of a circulation pump are sometimes
used in water systems. System designs should be predicated on obtaining the desired water quality
upstream of the storage tank, using the treatment train. Filters downstream of the storage tank
should not be relied on to purify the water.
一般而言，所有纯化水系统都不建议使用储存罐的下游过滤。这是出于对“生长穿越”的考
虑，在此处细菌将移到过滤器的上游侧，并最终出现在下游侧，尽管介质的孔径尺寸理论上
可能小于菌体大小。另外一个担心是过滤器介质上营养物质蓄积的可能性，事实上它可能会
增加微生物的生长机率。但是，水系统有时可以使用循环泵的下流过滤器。应当基于希望得
到的储存罐下游的水质，用处理措施设计系统。不应当依赖储存罐的下流过滤器纯化水体。
Circulation循环
Most new water systems use a circulating loop for distribution. The primary purpose of circulation
is to reduce the chance of microbial growth, or microbial attachment to the surfaces of the system.
Although the mechanisms are not universally agreed upon, it is thought that the shear forces
associated with turbulent water flow inhibit nutrient concentration and attachment of bacteria to
surfaces. The velocity required to obtain these benefits is generally agreed to be greater than 3 feet
per second, or Reynolds numbers greater than 2,100. Velocity may drop off for short periods of time
during high use times without adversely affecting the system, so long as positive pressure is
maintained in the system. Circulation also serves to maintain proper temperature throughout the
system in hot and cold systems.
大多数的新水系统都采用循环回路进行分配。循环最主要的目的是减小微生物生长或附着在
系统表面的机率。虽然此机制并没有得到普遍认可，但是还是认为水湍流带来的剪切力能阻
止营养物质浓集和菌体在表面的附着。一般认为能制造这些利处的速度要大于3英尺每秒，
或都雷诺数大于2100。高使用率期间，短期的速度下落不会对系统造成不利影响，只要维护
系统正压即可。在热的和冷系统中，循环还可以维持整个系统的适当温度。
Studies have shown that the velocities required to remove biofilm are higher than practical for a
water system (above 15ft/sec). However, a combination of high velocity (5 ft/sec or greater) with an
antimicrobial agent, such as ozone or chlorine, may, over a long enough period of time, effectively
remove biofilm.
研究表明，对于热水系统去除生物膜所需的速度要比实际的高（高于15英尺/秒）。但是，结
47 / 53
合高流速（5英尺/秒或更高一点）和抑菌剂，比如臭氧或氯，就可以在足够长的一段时间内
有效地去除生物膜。
A turbulent condition may be maintained in short dead ended pipe stubs if the length of the stubs is
limited. This limiting length varies with the pipe stub diameter and to a lesser degree with the main
pipe diameter. A rule of thumb for the maximum dead leg is 6 branch pipe diameters. This "rule of
thumb" may be difficult to achieve in large mains with small branches, and may result in
unacceptably long dead legs in large branches. Rather than universally applying "rules of thumb", it
is important to recognize dead legs as an area of concern and take appropriate steps to prevent them
in the original design or implement special provisions to address them if unavoidable. Some of the
factors to consider include operating temperature, velocity in the main, and frequency of use (if the
dead leg is a use point).
如果短管的长度有限的话，那么可以在盲端粗短管中维持湍流状态。限定的长度因粗短管的
直径而异，与主管直径也有关，但程序较轻。经验法则中盲管的最大长度为支路管直径的6
倍。在带有小分支的大型主路中此“经验法则”可能很难实现，而在大分支中又有可能导致
盲管过长无法接受。一般并不应用“经验法则”，意识到盲管是一个关心的问题，并采用适
当步骤来在最初设计时尽可以避免它们，或者在不可避免的时候进行特殊供应来就对它们，
这些更为重要。考虑因素包括操作温度、主管中的流速以及使用频率（如果盲管是使用点的
话）。
PERIODIC STERILIZATION/SANITIZATION定期灭菌/消毒
Periodic sanitization of storage and distribution systems is generally required. Based on monitoring
the microbial quality of the system, a required frequency of sanitization should be formally
established. Sanitization may also be done in response to reaching an "action limit" during routine
testing. Various methods of periodic sanitization are discussed below.
储存和分配系统的定期消毒是普遍要求。根据监测的系统微生物质量，应当正式建立所需的
消毒频率。可以进行消毒来适就常规测试期间到达的“活动极限”。下面讨论定期消毒的几
种不同方法。
Chemical化学品
Various chemicals or combinations of chemicals can be used to periodically sanitize storage and
distribution systems. Chlorine solutions on the order of magnitude of 100 ppm are very effective at
killing organisms, but are not generally used in distribution systems because of corrosion problems
associated with stainless steels. Hydrogen peroxide in concentrations on the order of 5% is a more
practical alternative. Peracetic acid can also be used, generally in concentrations of 1 % or less.
Many different mixtures of these and other chemicals are commercially available for the purpose of
sanitization.
可以用不同的化学品或将不同化学品结合起来对储存和分配系统进行定期消毒。100ppm的氯
溶液能非常有效的杀灭有机体，但是分配系统中一般不用，这是因为会引起不锈钢的腐蚀问
题。浓度为5%的过氧化氢是更为可行的选择。也可以用过氧乙酸，一般尝试为1%或更低一
点。商业上可以用这些化学品的多种不同混合液或其它化学品达到消毒目的。
48 / 53
Verification of the removal of the sanitizing agent is critical. Commercially available indicators (test
strips or sticks) are commonly used to indicate when the amount of rinse water is sufficient. A rinse
water analysis is then required to verify the absence of objectionable chemicals before the system is
placed into service.
验证消毒剂已去除十分关键。当冲水量足够时，商业上一般用指示剂（测试条或测试棒）进
行指征。在笼统投用使用前，需要对冲洗水进行分析，来验证其已经含那些讨厌的化学品。
Ozone臭氧
Sanitation can be done periodically or continuously with ozone: Storage tanks are typically
continuously ozonated, and then the ozone is removed prior to the distribution loop or individual use
points through the use of ultraviolet radiation .The distribution system can be periodically sanitized
by turning off the UV light and, if necessary, increasing the ozone concentration, while allowing it
to circulate through the distribution loop. Concentrations as high as 1 ppm may be needed for
periodic sanitization, particularly if biofilms must be removed.
用臭氧进行消毒可以定期也可以连续：储存槽一般是连续用臭氧处理，然后在分配回路或个
别使用点前用紫外照射进行去除。分配系统可以定期消毒，如果必有的话，关闭UV线并增
加臭氧浓度，使臭氧流经分配回路进行循环。定期消毒可能需要1ppm的浓度，特别是在生物
膜必须去除时。
Heat加热
It has been found that periodic sanitization by heating of the process water system is highly reliable
and effective. The frequency at which sanitization must occur will vary depending on many factors.
已经发现将水处理系统加热来进行定期消毒非常安全有效。消毒的频率将取决于许多因素。
• System design
系统设计
• Size of distribution system
分配系统的大小
• Components of system
系统组件
• Volume of process water in the system
系统中处理水的体积
• Frequency of use of the process water (turnover volume)
处理水的使用频率（循环体积）
• Temperature of the circulating process water
循环处理水的温度
Each distribution system must develop its own microbial profile, and the sanitization cycle and
frequency will have to be developed to fit that system.
每个分配系统必须制定自己的微生物剖面，制定消毒周期和频率时也必须适合系统。
The most straightforward method of sanitization is to heat the circulating process water in the
distribution system to 80°C ± 3°C and hold it at that temperature for a validated period of time. The
use of this heat sanitization has been proven to be very effective and if designed properly can also
be economical. Controls needed to perform this cycle of sanitization can be either manual or
49 / 53
automatic.
消毒最简单的方法是将分配系统中的循环处理水加热到80°C ± 3°C，并将此温度保持一段经
过验证的时间。已经证明加热消毒的方法非常有效，如果设计合理也是很经济的。进行消毒
循环所需的控制可以自动也可以手动。
Because of the types of bacteria found in purified water systems, the use of steam is not required for
effective microbial kill. Steam sterilization of distribution piping may require additional valving for
vents and drains, and may require a higher pressure rating than otherwise needed. Storage tanks are
by their nature more easily steam sterilized and this practice is common, although not required.
因为在纯化水中发现的菌体类型，因此无需使用蒸汽来有效的杀灭微生物。分配管道的蒸汽
消毒可能需要额外的排水排气阀，而且相对其它要求可能会需要更高的压力定额。储存罐本
身就更容易蒸汽消毒，而且这种操作很普遍，即使没有必要。
Hot systems inherently are continuously sanitized. Thus, the need for sanitization should be based
on microbial testing results, or when the system is off line for an extended period of time and the
temperature of the loop drops to below the validated temperature range.
固有加热系统是连续消毒的。因此，消毒要求应当根据微生物检测结果，或者是在系统离线
了很长时间并且回路温度已经降到验证范围以下时。
Depending on the process water specification, a conservative initial sanitization frequency should be
assigned for "cold" systems. After the operating characteristics of the system are determined
through microbial testing, the routine sanitization frequency can be determined.
根据处理水的规定指标，应当为“冷”系统指定一个初期保守消毒频率。通过微生物测定确
定了系统的工作特性之后，就可以制定常规消毒频率了。
Initial Sanitization (Ambient System)
初始消毒（环境温度系统）
Steam sanitization has a successful history, and is probably the most reliable method for sanitization.
However, there is no requirement for steam sanitization in Purified Water or WFI systems. The
following procedure is suggested as one option for hot water sanitization of an ambient system.
蒸汽消毒有一个很辉煌的历史，它有可能是最可靠的消毒方法。但是，对纯化水或WFI系统
中的蒸汽消毒没有要求。建议将下面的过程作为环境温度系统热水消毒的一种可选方案。
Immediately after passivation (for a SS system), the system should be flushed with process water at
a high temperature (80°C±5°C) and all valves opened and points of use flushed. Normally two (2)
times the volume of the system (after conductivity readings), or rinse water tests indicate that no
passivation chemicals are detected, is required. This is the initial sanitization of the system.
钝化后（对于SS系统），应当立即用高温（80°C±5°C）的处理水冲洗系统，并打开所有阀
门冲洗使用点。一般，需要用系统体积的两（2）倍（在电导率读数以后），或者冲洗水检测
表明没有检出钝化化学品。这即是系统的初始消毒。
Once it has been determined that the chemical characteristics for the quality of the process water
have been achieved by USP chemical testing, then microbial samples should be taken after each
component, the points of use, and the storage tank. This initial sampling should show that the
50 / 53
distribution system at any sampling point has no viable bacterial contamination. Once this is
achieved, the system should be brought down to its operating temperature and allowed to stabilize.
一旦用USP化学试验确定处理水水质的化学特性已经达到，那么应当在每个组件、使用点及
储存槽之后采取微生物样本。初步取样应当表明每个取样点所在的分配系统中都没有活菌污
染。这点一经完成，应当立即将系统降到其操作温度并使其稳定。
SYSTEM DESIGN FOR STERILIZATION/SANITIZATION
灭菌/消毒的系统设计
The following sections highlight particular aspects of storage and distribution system design, which
are relevant to sanitization.
下面章节着重强调了储存和分配系统设计的特殊面，这与消毒是有关的。
Materials of Construction建造材料
The sanitization methods used must be compatible with the materials in the system. By far the most
widely used material for storage tanks and piping is 300 series stainless steel (generally 316L). This
choice provides the most flexibility with regard to sanitization options. Sanitization with heat, UV,
or ozone can be used in stainless systems practically without restriction. Chemical sanitization must
be carefully managed with regard to concentration, pH, and temperature to avoid corrosive effects
on stainless distribution systems.
采用的消毒方法必须适应系统的材料。储存罐和管道应用广泛应用的材料是300系列的不锈
钢（一般为316L）。此选择使得消毒方案有了最大程度的灵活性。加热、UV或紫外消毒事
实上都可以用于不锈钢系统，没有什么限制。化学消毒则必须小心处理其浓度、pH以及温度，
从而避免对不锈钢分配系统的腐蚀影响。
Other material used for distribution piping is PVDF. PVDF is susceptible to degradation by UV
light. It is common to use stainless piping immediately adjacent to the UV light in a PVDF system
to compensate for this problem. The temperature limitation of PVDF is approximately 140°C, which
is high enough to allow heat sanitization or sterilization.
分配管道所用的另一种材料是PVDF。PVDF很容易受UV线照射发生降解。一般PVDF系统
中都是在马上接近UV线的地方使用不锈钢管来解决这个问题。PVDF的温度极限接受140°C，
这对于加热消毒或灭菌来说足够了。
In stainless systems, the gaskets used must be reviewed for compatibility with the sanitization
method. A widely used gasket material is PTFE or EPDM, both of which have good thermal
memory and excellent resistance to temperature, ozone, and chemical sanitizers. Other gasket
materials must be carefully reviewed for compatibility with the sanitization methods, and to ensure
that they will not leach substances into the water.
在不锈钢系统中，必须检查所用的垫圈是否与消毒方法相容。广泛应用的垫圈材料是PTEF
或EPDF，这二者都有很好的热记忆效应且能耐温度、臭氧和化学消毒剂。其它垫圈材料必须
仔细检查其它与消毒方法的相容性，并确保它们在水中不会析出物质。
The key is to recognize that the materials of construction "shall not be reactive, additive or
absorptive so as to alter the safety, identity, strength, quality, or purity of the drug product beyond
51 / 53
the official or other established requirements" (21 CFR 211.65). The sanitization procedures must
be considered when selecting materials to comply with this requirement.
关键是要认识到建造材料“应当无反应性，无添加或吸收性，这会改变药品的安全性、同一
性、效力、质量或纯度，使之超出了官方或其它已经制定的规定”（21CFR 211. 65）。选择
材料时必须考虑消毒规程要遵从这些要求。
Storage Tank Design储存罐设计
Storage tanks are an area in the system that could be considered at high risk for microbial
contamination because of the large surface area, low velocities, the need for venting, and potential
for "cold spots" in the head space.
可以说储存罐是系统中微生物污染风险最高的区域，这是因为它的表面积大、流速低、需要
排气，而且上部空间有可能存在“冷点”。
Tank size is generally based on economic considerations in combination with the pretreatment train
sizing. From a bacterial standpoint, smaller tanks are preferred because they have higher turnover
rates, which reduce the likelihood of bacterial growth. They also reduce surface areas and make it
easier for ozone to permeate the water, if the tank is ozonated.
罐子的大小一般依据经济考虑以及预处理量。从细菌角度看，罐子越小越好，因为这样循环
率就越高，这就降低了细菌生物的可能性。如果罐用臭氧处理的话，还会缩减表面积，而使
臭氧更容易穿透水。
Spray balls may be used on the return loop to wet the space of storage tanks. The use of a spray ball
serves to keep the top of the tank at the same temperature as the water, in heated systems, and
avoids alternately wet and dry surfaces, which could promote corrosive action with stainless steel
and allow microbial growth. Connections on the top head (relief devices, instrument connections,
etc.) should be kept as close to the head as possible to simplify the spray ball design and get the
benefit of the spray action. An exception is the vent filter, which should be removed far enough
from the storage tank to avoid direct contact from the water spray, which could, blind the filter. If
dip tubes or instruments project down from the head, multiple spray balls may be needed to avoid a
"shadow" being created in the spray pattern.
可以将喷淋球用于返回回路中来对储存罐表面进行加湿。在加热系统中，使用喷淋球可以保
持储罐顶部的温度和水温一致，并避免了表面有干有湿，干湿并存会促进不锈钢腐蚀并造成
微生物生长。上头顶端的连接（卸放装置，仪器连接等等）应当尽可能地靠近上端，从面简
化喷淋球的设计，并获得喷淋的效果。通气过滤器是个例外，它应当尽量远离储存罐以避免
了喷淋水进行直接接触，这将会遮蔽过滤器。如果浸管或仪器从上头伸下来，那么就需要采
取多个喷淋球来避免在喷淋方式上造成“阴影”。
The tanks must be vented to allow filling, and a filter should be used at the vent to avoid airborne
particulate and microbial contamination. To avoid the problem of condensation in the filter and the
resultant potential for colonization and grow through, hydrophobia vent filters are used and/or the
filters are maintained at a temperature above the tank temperature with steam jacketing or electric
tracing.
罐子必须能够排气以进行灌注，应当在排气口使用一个过滤器从而避免空气传播的粒子和微
52 / 53
生物的污染。为了避免凝集及集聚和生长穿越的结合可能性，要使用疏水通气过滤器并且/或
者用蒸汽夹套或电伴热将过滤器的温度维持在罐温以上。
To help avoid microbial growth, and avoid the change in conductivity resulting from absorption of
atmospheric gasses into the water, nitrogen blanketing on the head space may be used. This
eliminates outside air passing into the tank through the vent filter. Note that gasses added to storage
tanks should be appropriately filtered to avoid objectionable contamination.
为了防止微生物生长，并避免由水吸收大气而引起电导变化，可以在上层空间采用氮封。这
样就防止了外面的空气通过过滤器进入储罐。注意充到储存罐中的气体应当适当过滤，从面
避免引起令人讨厌的污染。
Table 8-5 Comparison of Alternate System Designs for Microbial Control in Storage and
Distribution
表8-5 储存和分配中的微生物控制可选的几种系统设计比较
Microbial Control Methodology
微生物控制方法
Installed
Cost
安装成本
Operating Cost
运作成本
Low
低
Low
低
Relative
Effectiveness/Reliability
相关有效性/可靠性
Good
好
Good
好
Ambient system, with ozonated tank, Low
periodic ozone in distribution piping
环境温度系统，带臭氧处理罐，在分配管低
道中定期臭氧消毒
Ambient system with periodic hot water Low
sanitization (note 2)
带定期热水消毒的环境温度系统（注意2）低
Continuous "Cold" system (4-10°C) with Medium
periodic hot water sanitization
带有定期热水消毒的持续“致冷”系统中
（4-10°C）
Continuous "Hot" system (65-80°C) with High
multiple Point of Use Coolers
带有多个致冷器使用点的持续“加热”系高
统（65-80°C）
High, unless cold
Better
water is required
较好
for process
高，除非工艺需
要冷水
Medium
中
Best
最好
Note 1: All systems are circulating
注意1：所有的系统正在循环
Note 2: Operating costs and effectiveness will increase with frequency of sanitization
注意2：操作成本和有效性随着消毒频率增加。
53 / 53
INSTRUMENTATION AND CONTROL
仪器及控制
9. INSTRUMENTATION AND CONTROL
9. 仪器及控制
9.1 INTRODUCTION
9.1 简介
Instrumentation and controls are often used within pharmaceutical water systems to:
通常用制药水系统中的仪器及控制来：
• control the operation of equipment and components
控制设备和组件的运行
• monitor and document the performance of critical equipment
监控并用文件记录关键设备的性能
• monitor and document pharmaceutical water quality
监控并用文件记录制药用水的质量
The concepts and regulatory philosophy of defining critical versus non-critical parameters is discussed as it relates to
instrumentation and controls. This definition could be summarized as:
当它关系到仪器和控制时，就要讨论关键和非关键参数的概念和调控原则了。定义可以总结如下：
"All instruments and control systems should be commissioned following Good Engineering Practices. Critical
instruments and control systems should be commissioned and qualified."
“所有的仪器和控制都应当遵循良好工程规范来进行委认。关键的仪器和控制系统应当进行委认及资格验
证。”
There is no regulatory requirement that requires the use of On-Line instrumentation. A monitoring program may
include a combination of On-Line instrumentation, manual documentation, and laboratory analysis.
没有法规要求命令使用在线仪器。监测程序可能是在线仪器、文件手册及实验室分析的一个结合。
If On-Line instrumentation is used to measure or record a critical parameter, action and alert limits may be established.
The methods of addressing "spikes" are also discussed.
如果用在线仪器来测量或记录关键参数，可以建立行为及警报限。显示“峰形”的方法也要讨论。
Automation can have a significant impact on the cost and performance of a pharmaceutical water system. There is no
single optimum level of instrumentation and control for all systems. The optimum level for a given system balances
the benefits of improved process control, improved documentation, and lower labor costs against the cost of procuring,
installing, validating, and maintaining the instruments and control systems. In many cases, the level of automation for
a pharmaceutical water system should be consistent with that utilized for the manufacturing process it supports.
自动化会对制药水系统的成本及性能产生显著影响。对所有系统而言，仪器和控制并没有一个单一的最佳水
平。给定系统的最佳水平是利益平衡，利益包括改进的工艺控制、改良的文件及相对仪器和控制系统的获得、
安装、验证及维护成本而言降低劳动力成本。很多时候，制药水系统的自动化水平应当与所用制造工艺支持
的水平一致。
9.2 PRINCIPLES
9.2 原则
a)To achieve GMP compliance, the manufacturer must demonstrate, through documented evidence, that the
pharmaceutical water system is in control and consistently produces and delivers water of acceptable quality.
为了顺应GMP，制造商应当用文件证据证明制药用水系统在控制中，并且始终能够生产和输送合格的水。
b) Although many quality attributes can be continuously monitored using On-Line instrumentation, there is no
compendial or regulatory requirement for On-Line monitoring of pharmaceutical water quality. A monitoring program
typically includes a combination of On-Line instrumentation, manual documentation of operational parameters, and
laboratory analysis of water samples.
虽然许多质量特性可以用在线仪器连续监控，但是制药用水水质的在线监控并没有药典规定或法规要求。典
型的监控程序是在线仪器、操作参数的文件手册，以及水样实验室分析结果的结合。
c) Instruments and control systems are critical and must be qualified when they are used to measure, monitor, control,
or record a critical process parameter. A critical parameter is a processing parameter that affects the final water
quality.
仪器和控制系统很关键，当期测量、监测、控制或记录关键过程参数时必须经过资格验证。关键参数是影响
最终水质的过程参数。
For example, the temperature of the final water product may be considered critical for microbial control. In this case,
the temperature controls (e.g., sensors and alarms) would be considered critical. However, it is not necessary to
consider the temperature of the heating media (e.g., steam) as a critical parameter.
例如，最终的产品水的温度对微生物防治来说就是关键的。这时候，就认为温度控制（例如传感器和警报）
是关键。但是，没有必要以为加热介质（例如蒸汽）的温度也是关键参数。
Documentation should clearly indicate which instruments are critical and which are not. It is also advisable to identify
non-critical instruments as such on the field device.
文件应当明确指出哪些仪器是关键，哪些不是。在现场装置上标示出非关键仪器也是明智之举。
d) All instrument and control systems should be designed, installed, calibrated, and maintained appropriately
according to Good Engeering Practice. All critical instruments and controls require qualification.
设计、安装、校准及维修所有仪器和控制系统时都应适当符合良好工程规范。所有关键仪器和控制都需要确
认。
e) Items that should be recorded in the system documentation include maintenance procedures and maintenance work
performed, procedures for sampling and analysis, reporting the results, and trend analysis of the laboratory data. The
monitoring program during start-up typically defines maintenance frequency and alert and action levels for the
process variables.
系统文件中应当记录的项目包括维护规程、进行的维护工作、取样和分析规程、结果报告以及实验室数
据的趋势分析。一般启动期间的监控程序要根据不同工艺对维护频率以及警报和行动级别做一下规定。
9.3 GENERAL INSTRUMENTATION REQUIREMENTS
9.3 一般仪器要求
9.3.1 Instrument Selection and Installation
9.3.1 仪器的选择和安装
a) Instruments should be selected for accuracy and reliability over the entire process range.
应当在整个工艺范围内针对精确性和可靠性选择仪器。
Instruments should be selected and installed in a way that reduces the potential for contamination.
选择和安装仪器应当减少污染的可能性。
• Water contact surfaces should be constructed of materials that are compatible with the water they contact.
Materials of construction and surface finishes (see Chapter 8) are commonly specified for instruments installed in
distribution systems.
接确水的表面应当用与所接触水相容的材料制造。建造材料和表面抛光（见第8章）一般要针对安装在
分配系统内的仪器作详细规定。
• Sensors in direct contact with waters with strict microbial limits should be of sanitary design. Nonsanitary
instrumentation is commonly used in feed water and pretreatment systems.
直接接触有严格微生物限制的水的传感器应当进行无菌设计。非无菌仪器一般用于进水和预处理系统。
• Instruments may be installed directly in the water system or in a side stream that may, or may not, be returned to
the main system.
仪器可以直接安装在水系统中，或安装到能，或不能返回主系统的侧流中。
• Deadlegs should be avoided.
应当避免盲管。
c) When possible, instruments should be installed such that exposure to harsh process conditions, such as pH and
temperature extremes, is avoided. For example, In-Line sensors used to monitor effluent from a deionizer should be
positioned such that exposure to regeneration chemicals is avoided.
如果有可能，安装仪器应当尽量避免暴露于恶劣的加工条件下，比如极端的pH及温度。例如，用来监控去
离子器流出液的在线传感器安装的位置就应当避免暴露于再生化学试剂中。
Instruments that are not compatible with passivation agents, sanitization agents, or sanitization temperatures should be
installed so that they may be easily removed or bypassed. Such devices may need to be sanitized off line.
安装与钝化剂、消毒剂或消毒温度不相容的仪器时应当能够轻松取除或绕过。此类装置可能需要离线消毒。
d) Instruments should be installed in accordance with manufacturers' requirements to ensure proper operation. For
example, flow meters should be installed in the proper orientation and with the correct upstream and downstream
straight run of pipe. The impact of process and ambient conditions on an instrument's accuracy and reliability should
be addressed.
安装仪器应当符合制造商的要求从而确保其正常运转。例如，流量计就应当以正确方位安装，并且有正确
的上游和正游直接流经管道。应当注明工艺及环境条件对仪器精确度和可靠性的影响。
e) Conductivity cells are especially sensitive to the presence of air or steam bubbles, which can be present where there
is turbulence, cavitation, or flashing. Such locations should be avoided.
电导率池对存在的空气或蒸汽气泡特别敏感，那些气泡可能存在于有湍流、空穴或闪蒸的地方。此类位置
应当避免。
f) Accessibility for maintenance should be considered, but improving control response is usually more critical. Poor
response time may be a consequence of the poor placement of a device and, in most cases, can be improved by
installing the device closer to the point of measurement.
应该考虑维修时方便接进，但是通常改善控制响应更为关键。设备安装的位置不好可以导致响应时间弱，
大多情况中，这可以通过将设备安装到离测量点更近的地方即可改善。
9.3.2 Instrument Calibration
9.3.2 仪器校准
a) The calibration of critical instruments should follow a regular program, which provides evidence of consistently
acceptable performance. Non-critical instruments may be calibrated on a frequency deemed appropriate for the
service.
关键仪器的校准应当遵循正规程序，这样可以证明其性能始终可接收。非关键仪器可以以一个对使用来
说恰当的频率来进行校准。
b) Calibration should follow approved procedures and the results should be documented. Each component in a control
loop should be calibrated individually or the loop may be calibrated in its entirety. All calibrations should be traceable
to certified standards (e.g., NIST).
校准应当遵循已经批准的规程，并且应将结果记录成文件。控制回路中的每个组件都应当单独校准，或
者也可以整体校准。所有的校准都应当可溯源至公认标准（比如NIST）。
c) Vendor-supplied calibration certificates should reference the applicable instrument serial numbers. The impact of
shipment and installation on the vendor's calibration should be addressed.
应当参考供应商校准证书中的适用仪器序列号。应当指出运输及安装对供应商校准的影响。
9.3.3 Types of Instrumentation
9.3.3 仪器的种类
9.3.3.1 Conductivity
9.3.3.1
电导率
a) Although non-ion specific, conductivity is a valuable tool for measuring the total ionic quality of water and is a
critical parameter for many high purity water systems. Conductivity limits for Purified Water and WFI are specified in
the USP.
虽然有非离子性，但是电导率依然是测量水中总离子量的有效手段，并且是很多高纯度水系统的关键参
数。纯化水和WFI的电导率极限在USP中有详细规定。
b) On-Line conductivity instrumentation is frequently used to monitor and control the performance of many types of
purification equipment and to continuously monitor the quality of pharmaceutical waters. On-line conductivity
instrumentation may also be used for final quality assurance testing, thus eliminating the need for periodic laboratory
analysis of water samples.
在线电导率仪经常被用来监控多种纯化设备的性能，以及连续监测制药用水的质量。在线电导率仪也可
以用作最终质量保证检测，因此取消了实验室定期分析水样的必要。
c) Temperature has a profound impact upon conductivity measurement. To eliminate this temperature dependence,
most instruments include a temperature sensor in the conductivity probe and one or more algorithms to correct the
actual measurement to a standard temperature. However, due to he inaccuracy inherent in temperature compensation
algorithms, compensated conductivity measurements are not suitable for critical quality assurance testing of USP
purified water and WFI. When In-Line conductivity measurements are used for final quality assurance testing of USP
purified water and WFI, a non-compensated conductivity value and the water temperature must be measured as
required by the USP. Compensated conductivity values used strictly for process control and monitoring are not subject
to USP requirements.
温度对测量电导率有很深的影响。为了消除温度依赖性，大多数仪器都有一个含量温度传感器在内的电
导率控针，及一或两种将实际测量值校准至标准温度的算法。但是，因为温度补偿算法自身不准确，因此补
偿电导率测量就适用于USP纯化水和WFI的关键QA检测。当用在线电导率仪对USP纯化水和WFI进行最
终QA检测时，USP就要求必须测量一个非补偿电导率值和水温。严格用于过程控制和监测的补偿电导率值
并不受USP规定的限制。
d) To operate properly, conductivity sensors must be installed such that there is continuous water flow through the
sensor and air bubbles or solids cannot become trapped inside the electrodes. Air bubbles will result in
lower-than-expected conductivity readings while solids can impact the conductivity in either direction. Clean steam
must be condensed prior to conductivity measurement.
为了正常运转，安装电导率传感器处必须有连续水流经过传感器，而空气气泡固体不能滞留在电极里。
空气气泡将导致电导率读数低于预期值，而固体对电导率的影响则可能向任何一边。清净蒸汽须冷凝后方可
测量其电导率。
e) Conductivity meters may be used throughout a pharmaceutical water system to monitor and control purification
processes or to monitor pharmaceutical water quality. Some examples are:
电导率仪在整个制药用水系统中都可以用来监控纯化工艺或监测制药用水的水质。有一些例子：
• Feed water monitoring can detect seasonal or unanticipated quality changes that could impact pretreatment
equipment operation.
进水监测可以检查出季节性或非预期的质量变化，这些变化能够影响预处理设备的运转。
• RO influent and effluent monitoring allows calculation and trending of percentage rejection. Changes in
percentage rejection may be a sign of membrane failure, scaling or fouling, seal failure, improper pH, inadequate feed
pressure, or too high a recovery rate.
监测RO流入液和流出液可以计算排阻百分率及其发展趁势。排阻百分比的变化可能是膜损坏、结垢或积
垢、密封失败、pH值不当、进压不够或回收率过高的信号。
• Deionizer effluent or in-bed monitoring detects, or predicts, resin exhaustion and allows automatic initiation of
regeneration cycles.
去离子器流出液或床内监测检出或预测出树脂耗竭并允许自动进行再生循环。
• The conductivity of pharmaceutical water may be monitored after the final treatment step to verify acceptable
quality prior to delivery to a storage tank. In addition, conductivity meters are often installed in the return piping of
distribution loops downstream of the final point of use. Many systems include provisions for automatic diversion to
drain or recirculation back through purification equipment when water quality entering the tank is outside the
acceptable range.
可以在终处理步骤之后监控制药用水的电导率从而验证输送到储存罐之前的水质的可接受度。此外，电
导率仪也经常安装在终使用点分配回路下游的返回管道中。当进入储罐的水质超出可接受范围时，很多系统
能将其自动排放或经纯化设备重新循环。
9.3.3.2 Total Organic Carbon (TOC)
9.3.3.2
总有机碳
a) Total Organic Carbon (TOC) is a measure of the carbon dissolved in water in the form of organic compounds. It is
a valuable tool for measuring the aggregate level of organic impurities in pharmaceutical water systems. A TOC test
with a nominal limit of 500 ppd for USP Purifide Water and WFI is a required test in the USP.
总有机碳（TOC）测量的是以有机化合物形式溶解于水中的碳。它是测量制药用水中有机物凝集水平的一
个有效手段。USP规定USP纯化水和WFI要进行TOC测定，标称限是500 ppd。
d) TOC meters are relatively sophisticated analytical instruments. The USP provides guidance on how to qualify an
instrument and how to interpret the instrument results.
TOC仪是一个相对精密的分析仪器。USP中为如何确认仪器及如何解释仪器结果提供了指南。
c) In addition to "continuous" monitoring of equipment performance and pharmaceutical water quality, On-Line TOC
meters may be used for final quality assurance testing, thus eliminating the need for periodic laboratory analysis.
When used for critical assurance testing of USP purified water and WFI, instrument precision, system suitability, test
methodology and calibration procedures must meet USP requirements. Instruments used strictly for process control
and monitoring are not subject to USP requirements.
除了“连续”监测设备性能和制药用水水质外，在线TOC仪也可以用于最终的QA检测，因此就省去了
实验室定期分析的必要。当其用于USP纯化水和WFI的关键保证检测时，仪器精度度、系统适应性、检测方
法以及校准规程都必须符合USP规定。严格用于过程控制和监测的仪器则不受USP规定的限制。
d) TOC is often monitored at several locations in a pharmaceutical water system. Some examples are:
制药用水系统中，有几个位置经常监测TOC。例如：
• Feed water monitoring can detect seasonal or unanticipated quality changes that could impact pretreatment
equipment operation or the potential for resin or membrane fouling.
进水监测可以检查出季节性或非预期能影响预处理设备运转的质量变化，或者树脂或膜结垢的可能性。
• Monitoring TOC downstream of carbon filters, organic scavengers, RO units, and UV lights can verify proper
equipment operation and provide advance warning of bed exhaustion, compromised membranes, or the need for lamp
replacement.
碳过滤器、有机物净化器、RO设备及UV线下游的TOC监测能够确证设备运转正常，并对床耗竭、膜退
化或灯需要更换做出预警。
• TOC levels of pharmaceutical water may be monitored after the final treatment step to verify acceptable quality
发布者：admin，转转请注明出处：http://www.yc00.com/web/1710558740a1777223.html
评论列表（0条）