4.1.2 APW/ WFIPretreatment and Production system end boundary is atthe inlet valve (inclusive) ofthe PWjWFI storagetank or at the POU if a tank is not installed.
4.1.3 ThePW/WFI storagetank should not be includedin the PW/WFIPretreannent and Production.
PW/WFI 储罐不应包含在 PW/WFI 预处理和生产系统中。
4.1.4 "Industrial" treatment systemsupstreamto the PW/WFI Pretreatment and Production. Including supplyto other plant utilities e.g. steam boilers, potable water usage, feed to cooling towers etc. should not be includedin the PW/ WFI Pretreatment and Production.
4.2.1 A "build clean"concept shall be employed duringthe installation of PW/WFI Pretreatment andProductionsystems: supply of piping/ tubingand equipment in clean condition and installation methodsthat prevent ingress of contaminants.
4.2.2 Incoming feed water shall meet local standards or WHO standards for potable water. Ifthis is notthe case, additional systems shall be installed to improve the water feed parameters before the PW/W FIPretreatment and Production.
4.2.3 The PW/WFI Pretreatment and Production water quality shall show improvement in all qualityparameters as the water advances through the system.
越往PW/WFI 预处理和生产系统的后续阶段，水的所有质量参数应越好。
4.2.4 The following parameters shall be steadily reduced at each stage in the system:在系统每个阶段，应稳步减少以下参数:
microbial total count;
微生物总数
conductivity and;
电导率
TOC
TOC
4.2.5 PW/ WFIquality shallbe according tothe last revisionof the local/national/relevant
Pharmacopoeia. Table 1provides recommendedwater quality.
PW/ WFI 质量应根据当地/国家/相关药典的最新修订版本进行。表1提供了建议的水质。
Table 1- Recommended water quality
表1——建议的水质
＃
Parameter
参数
RO feed
RO进水
After RO
RO出水
PW
纯化水
WFI
注射用水
1
Hardness (PPM CaCO3)
硬度（PPM CaCO3）
≤feed water
≤原水
<1
<1
<1
2
TOC (ppb)
≤feed water
≤原水
< 500
< 500 (online)
＜500（在线）
< 500 (online)
＜500（在线）
3
Endotoxin (EU/ml)
细菌内毒素（EU/ml）
NA
NA
NA
< 0.25
4
Microbial total count (cfu/ml)
微生物总数（cfu/ml）
< 500
< 200
< 100
< 10 cfu/100ml
5
Free Chlorine (ppm)
余氯（ppm）
< 0.05
< 0.05
< 0.05
< 0.05
6
Pseuldomonas(cfu/100 ml)
假单胞菌(cfu/100 ml)
< 1
< 1
< 1
< 1
7
E. coli(cfu/100 ml)
大肠埃希菌(cfu/100 ml)
< 1
< 1
< 1
< 1
8
Total coliforms, Fungus, (cfu/100ml)
总大肠菌群，真菌(cfu/100ml)
< 1
< 1
< 1
< 1
9
Conductivity (μS/cm)
电导率(μS/cm)
Like feed water
与原水相同
<10
< 1.3 (online)
＜1.3（在线）
< 1,3 (online)
＜1.3（在线）
Conductivity shall be measured uncompensated at 25 °C according to USP.
电导率应根据 USP进行无补偿的测量。
4.2.6 A samplingprogramme with acceptance criteriashall be in placeto gather; analyse anddocument this water quality improvement.
应制定取样方案并有接受标准；分析和记录水质的改善。
4.2.7 Duringproduction, thePW/WFI Pretreatmentand Production shallcontrol the maximumwater temperaturein the system. Duringproduction, themaximum temperature of the warmestpoint in the system shall be nomore than 25 °C (guidance value).
4.2.8 Allparts of the PW/WFIPretreatment and Production shall behot water sanitized,from the feed water inletvalve to the PW/WFIfill valve. During sanitization,the PW/WFIPretreatment and Productionshall control thewater temperature in the system.During sanitization,the all the points of the systemshould be at a minimum of 80°C (guidancevalue).
4.2.9 ThePW/WFI Pretreatmentand Production system shall be designed,controlled, regulated, operated and maintainedto ensure that thefinal water quality reliably meetsfinal water quality standardset in 4.2.5.This performance shall be stable underall conditions includingcommon worstcase scenarios,changing seasonsor other fluctuating environmental conditions.
PW/WFI 预处理和生产系统应进行设计、控制、规范、操作和维护,以确保最终水质可靠地满足 4.2.5 中设定的最终水质标准。此性能在所有情况下应保持稳定,包括常见的最坏情况、季节变化或其他环境条件波动。
4.3 User Requirements Specifications (URS) scope
用户需求规范(URS) 的范围
The scope of the UserRequirements Specifications sha ll include the following：
用户需求规范的范围包括以下内容：
selection ofwater compendial standard based on products supplied;
根据所供应的产品选择水标准;
specification of thefinal water standard parameters;
最终水标准参数的规范;
safety and Good Manufacturing Practicerequirements for the system;
系统的安全和GMP要求;
list of main components;
主要组件列表;
preliminary sizing of productionflowrate;
生产流速的初步估算;
number of production units;
生产单元的数量;
functional requirements;
功能需求
materials of construction;
材质要求
equipment surface finish;
设备表面抛光
biological control concept;
生物控制要求
high level control: interlocks. alarmsand warnings;
高级控制：互锁、警报和报警;
documentation required (see Clause14);
所需的文件(见第14条);
validation as required by respective authorities and;
The scope of the User Requirements Specifications shall include analysis of incoming waterover allyearly seasons,both chemical and microbiological.
用户需求规范的范围应包括全年不同季节的原水分析，包括化学和微生物。
4.4 Detailed system capacity calculation
详细的系统能力计算
4.4.1 Data and/or estimates of current and futurePW/WFI use shall be used to size the flow rateof thePW/WFI Pretreatment and Production System.
当前和未来PW/WFI使用的数据和/或估算应用于调整 PW/WFI 预处理和生产系统的流速。
4,4.2 The flow rateshall he analysed in conjunctionwith the worst-case consumption scenario. Takinginto account PW/WFIstorage tank size.
应结合最差条件下的用水情况分析流速。考虑 PW/WFI 储罐大小。
4.4.3 A full tabulation of all users, presentand future, shall be compiled, listing the quantity ofPW/WFIrequired, per day, per hour over a week period. Thedraw off flow shall be calculated,from the StorageandDistribution (S&D), perhour of the day and plot the storage tank levels for a full week. In some caseslisting of requiredPW/WFI and take off flowcalculations for a period that exceeds one week may benecessary. In such cases the evaluation period shallbe extended accordingly.
5.1.5 Chlorine dioxide(CD) - generationand dosage of chlorinedioxide to a rangeof 0,1ppm - 0.4 ppm(withsuitable contact time)for control of incoming and system bacterialevels.
5.1.6 Softeners- for replacementof magnesium-calcium,barium and strontiumwith sodium toreducescale precipitationon the RO membraneswith a recommendeddownstream 10 micron-20micron resin trap.
5.1.7 Antiscalant(AS) - addition of chemicalsto RO feedwater to defer hardness precipitationon theRO membranes.
抗垢剂 (AS)—— 在 RO 进水中添加化学品，以减少 RO 膜上的硬沉淀。
5.1.8 Electric scale control(ESC)- resinfree electrolytic precipitation ofscale to stop hardness precipitationon the RO membranes.Also used for heavymetal oxidationand removal. Non sacrificialanode andcathode.
5.1.15 Double PassReverse Osmosis (DPRO) - membranebased process for reduction of: ions,TOC, bacteria and endotoxin. The firstpass permeate is the feed to the second pass. Alwaysoperated with a reject stream.
5.1.16 Continuous Electro De-Ionization(CDI/EDI/CEDI) - for reduction of water ionlevels downstream of RO usingelectrically regenerated resin.
连续电除盐(CDI/EDI/CEDI) - 使用电再生树脂降低 RO 下游的水电水平。
5.1.17 Polishing Ultra filtration -is a membrane basedprocess using molecular weight cut off 6 000or smaller forreduction of endotoxin, TOC andbacteria or post CDI/EDI/CEDI.
5.2 Advantages and disadvantages ofsystem components/treatment stages
系统组件/处理阶段的优缺点
5.3 Materials ofconstruction – General
构造材料——一般要求
5.3.1 All componentsin the PW/WFIPretreatment and Productionsystem shall be manufactured from StainlessSteel (55) 316/316L. All PW/WFI contactparts to befabricated from SS 316L. including:piping/tubing, tanks,pumps, heat exchangers,valves, instruments and otheraccessories.
PW/WFI 预处理和生产系统中的所有部件均应由不锈钢(SS) 316/316L 制造。所有 PW/WFI 接触部件均由 SS 316L 制造，包括:管道/管道、储罐、泵、热交换器、阀门、仪器和其他附件。
5,3.2 Additionalmaterials thatshall be used are as following:
应使用的其他材料如下:
EPDM:
三元乙丙橡胶PTFE-Polytetrafluoroethylene(PTFE);
聚四氟乙烯fluoroelastomers (FKM PEEK);
含氟弹性体(FKMPEEK)
PFA;
PFA塑料highgrade(low impurity) fusedquartz and;
高级(低杂质)熔融石英othernon-corroding. hot water sanitization(HW5) resistant. non-particlesheddingand nonleaching materials.
其他非腐蚀、耐热水消毒 (HW5)、非颗粒脱落和非脱脂材料。
5.3.3 For materials of construction,exposure to hotwater sanitizationat 80℃- 90℃shallbe taken intoaccount.
对于构筑材料，应考虑能在80°C- 90°C下暴露于热水消毒。
5.3.4 Elastomersand plasticsshall be compatible with national regulations.
弹性体和塑料应符合国家规定。
5.4 Stainless steel (55) piping– General
不锈钢管道——一般要求
5.4.1 SS piping/tubingin contactwith free chlorine and/orlow conductivitywater shall be SS 316/316L
与无余氯和/或低电导率的水接触的 SS 管道应为 SS 316/316 L
5.4.2 SS tubing shallhave dimensions as pernational standards.
SS 管的尺寸应达到国家标准。
5.4.3 Tubingmay be seamlessor welded withseam.
管道可以是一体的，也可以用接缝焊接。
5.4.4 Materialused for piping and fittings shall meetthe pressure requirements for the systemand specifically forthe high pressureRO feed andconcentrate.
用于管道和配件的材料应满足系统的压力要求，特别是高压RO 进水和浓水。
5.4.5 Welding shallbe performedwith TIG/GTAW99,97 %or better,argonshieldgasshall be used.
焊接应使用TIG/GTAW99.97 %或更高的氩气保护。
5.4.6 Thedimensions of the physicalair break shallbe at least 50 mmfrom the bottom of piping/tubing to the highestpoint on the drain.Piping/tubingshall have identification labelswithin line of sight ofaccess areas. Thecontent of the pipingand direction of nowshall be clearly indicated.
combinations of inert, Hot Water Sanitization (HWS)resistant, non-particle shedding and nonleaching elastomers.
惰性、耐热水消毒 (HWS)、非颗粒脱落和非脱脂的弹性体组合。
5.4.8 Dead legs:
死角
Dead Legs shall bemeasured by theterm L/D, where L is the legextension from theinside diameterwall normal to the flowpatternor directionand D is theinside diameter of the extensionor leg of a tubing fittingor the nominaldimension of a valve or instrumentand;
Dead legs should beavoided whereeve r possible. otherwise L/Dratio should be3:1 or less
应尽可能避免死角。如不可避免，L/D应为 3:1 或更少。
5.5 Non-final product water piping/ tubing in the PW/ WFIpretreatment and production
PW/WFI 预处理和生产系统中的非最终水管道
5.5.1 Only butt welding for piping/tubing weldingshall be used.
管道焊接只可使用对焊。
5.5.2 Butt-welding may be manual or by orbital we lding machine.Inspection with borescope and passivation is not required.
对焊可以是手动的，也可以是轨道焊接机焊接。无需使用内窥镜进行检测和钝化。
5.5.3 Piping/tubing standards shall be 3A/food grade with flangeor Tri Clamp (TC) connections.
管道标准应为3A/食品级，带法兰或卡箍(TC) 连接。
5.5.4 Piping/tubing internal finish may be polished or standardmill surface finish .
管道内部表面处理可抛光或标准轧机表面抛光
5.5.5 Valves installed may be of the fo llowing types: ba ll,angle, diaphragm, need le and butterfly.
安装的阀门可为：球阀、角阀、隔膜阀、针阀和蝶阀。
5.5.6 Threaded connections shall not be used.
不得使用螺纹连接。
5.6 Piping/ tubing in contact with PW/ WFI product
与最终PW/WFI接触的管道
5.6.1 Minimum acceptable ID polish shall be Ra≤0,6 micron.
最低可接受ID 抛光应为Ra≤0.6微米。
5.6.2 Butt-welding shall be by orbital welding machine whereever possible, a minim um of 70 % of automatic welds shall be inspected and 100% of manual welds with borescope shall be inspected.
对焊应尽可能由轨道焊接机进行，应对70%的自动焊缝进行检查，并对100%的手动焊缝进行内窥镜检查。
5.6.3 Welding shall be performed with TIG/ GTAW, 99,997 % argonshield gas shall be used.
焊接应使用 TIG/GTAW 99.997 %氩气保护。
5.6.4 Test coupons shall be performed every start of work perday and per piping/tubing diameter.
应对每天开始工作和每段管道进行测试取样
5.6.5 Weld logs shall record all the piping/tubing welds in thesystem.
焊接记录应对系统中的所有管道焊接进行记录。
5.6.6 Weld logs shall contain the following minimum information:
焊接记录应至少包含以下信息:
dateof weld;
焊接日期
weldername;
焊接人名字
supervisor/inspector;
主管/检查员
weldidentification number and description;
焊缝识别号和描述
descriptionof items being welded;
焊接物品描述
itemsdiameter and;
物品直径
heatnumbers of the items being welded.
焊接物品的炉号
5.6.7 Passivation shall be performed during commissioning/startup.
应在调试/启动期间进行钝化。
5.6.8 Only certified welders shall he used.
只能使用经过认证的焊工。
5,6.9 Piping/tubing connections shall he Tri Clamp (TC) or othersanitary style connection.
管道连接应使用卡箍(TC) 或其他卫生方式连接。
5.6.10 Threaded or flangedconnections shall not be used.
不得使用螺纹或法兰连接。
5.6.11 Drainage slopes shall apply to the following:
以下方面应使用排水斜坡：
a 1 % minimum drainage slopes shall be designed where everpossible and;
在可能的情况下，须设计1%最小排水斜坡;
the slope direction shall be towards the piping low point, whichshall be drainable.
斜坡方向应朝向管道排水的低点。
5.6.12 Installed valves shall be one of the following types:diaphragm or other aseptic design with barrier between valve mechanism side andPW/WFI side.
安装的阀门应为以下类型之一：隔膜阀或其他无菌设计,阀门机构侧和 PW/WFI 侧之间有屏障。
6Sampling
取样
6.1 Sampling principles
取样规则
6.1.1 There shall be provision for sampling the water upstreamand downstream of all components that could affect the microbial or chemicalquality of the water.
应规定对上游和下游可能影响水微生物或化学质量的所有组件进行取样。
6.1.2 Zero dead leg sample valves shall be used throughout thesystem, both on non PW/WFI piping/tubing and on product water piping/tubing.
在整个系统中，无论是非最终PW/WFI 管道还是最终水管道，均应使用零死角取样阀。
6.1.3 The sample valves shall be installed on short outlet teesso as not to contaminate samples by bioburden growing in the fitting.
取样阀应安装在短出口三通上，以免因生物负荷生长而污染样品。
6.1.4 Every process relevant component in the water system shallhave a sample valve before and after the component, e.g. heat exchanger,filter, pump etc.
水系统中每个工艺相关部件的前后应有一个取样阀，如换热器、过滤器、泵等。
6.1.5 The sample valves shall be above a tundish drain that willallow full drainage of the sample valve flow before taking thesample.
取样阀应位于漏斗排水管之上，在取样之前，允许将取样阀中的水完全排出。
6.1.6 There shall be sufficient clearance between the samplevalve and the tundish to allow insertion of all the standard sample bottles.
取样阀和漏斗之间应有足够的间隙，以便放入所有标准取样瓶。
6.2 Minimum sampling point and locations
最小采样点和位置
beforeand after MMF;
多介质过滤器前后
atsupplied water tank inlet;
供水管入口
aftercirculation pump;
循环泵之后
afterhardness reduction stage;
硬度降低阶段后;
at thecartridge filters inlet and outlet;
滤芯过滤器进出口;
afterheat exchangers;
换热器之后
afterdechlorination stage;
脱氯后;
aftereach RO housing and at their joint stream and;
在各RO后，并在其并流处;
at ROreject lines and;
RO排出口
CDI/EDI/CEDIfeed, product and reject.
CDI/EDI/CEDI进水、出水和排水。
6.3 Sampling conductivity
电导率取样
If an online conductivity instrument is installed and the onlineconductivity has already met national regulations, there is no need for samplesto be taken for off line cond uctivity testing.
如果安装了在线电导率仪器，且在线电导率已符合国家规定，则无需取样离线测试电导率。
7 Instruments
仪器
7.1 Minimum instrumentation for installation
需要安装的最小仪器
7.1.1Pressure indicators (P I):
压力表
localpressure display shall be installed at inlets and outlets of major components;
应在主要组件的入口和出口处安装局部压力显示;
pressureIndicators (PI) shall be installed at pump outlet, before and after filtrationelements and;
应在泵出口、过滤器元件前后安装压力表 (PI)；
onlydirectly mounted membrane type connections shall be used.
只能使用直接安装的膜式连接。
7.1.2Pressure indicator transmitter (PIT):
压力表变送器
for monitoring the system pressure in various points.
用于在不同的点监视系统压力。
7.1.3Conductivityindicator transmitter (CIT):
电导率仪变送器
formonitoring the non-compensated conductivity and;
用于监测无补偿电导率;
CITshall be used at: RO feed, RO permeate/product streams, inter-stage for DoublePass Reverse Osmosis (DPRO), CDI/EDI/CEDI product.
CIT应用于：RO进水、RO渗透/产品流、双通反渗透 (DPRO)、CDI/EDI/CEDI输出。
7.1.4Flow indicator transmitter (FIT):
流量计变送器
formonitoring the flow rate and;
监测流速;
flowindicator transmitter (FIT) shall be used at: permeate/product/reject streams.
流量计变送器 (FIT) 应在渗透/产品/排出处使用。
7.1.5 Quantityindicator transmitter (QIT):
水量变送器
for monitoring the total volume entering the system.
用于监视进入系统的总水量。
7.1.6 Free chlorine indicator and transmitter (CLIT):
余氯检测变送器
for monitoring the free chlorine level before and after the chlorine removalstage.
用于监测氯去除阶段前后的余氯水平。
7.1.7Temperature transmitter (TT):
温度变送器
formonitoring water temperature and;
用于监测水温
temperature transmitter (TT) shall be used at: inlet and outlet of heat exchangers, feed water,
应在热交换器进出口和进水口使用温度变送器 (TT)
PW/WFI product water and RO reject.
PW/WFI产品水和 RO排水。
7.1.8 Level transmitter (LT):
水位变送器
formonitoring the supplied water storagetank level.
用于监控供水储罐的液位。
7.2Parameters for measuring, alarming. storing and graphing from onlineinstruments
在线仪器的参数监测、报警、存储和绘图
Table 2 lists the parametersthat shall be measured, alarmed, storedand graphed.
表2列出了应测量、报警、存储和绘制的参数。
Level of criticality
关键程度
Water inlet
进水
Pre-treatment
预处理
RO feed
RO进水
RO reject
RO排水
RO permeate
RO渗透
CEDI permeate
CEDI渗透
Shall
必须
-
Chlorine
余氯
Temperature
温度
ESC amps
ESC电流
UV Dosage
UV剂量
Chlorine
余氯
Conductivity
电导率
Flow
流量
Temperature
温度
Pressure
压力
Conductivity
电导率
Temperature
温度
Flow
流量
% Rejection
排水比例
Conductivity
电导率
Temperature
温度
Flow
流量
Should
应该
Chlorine
余氯
-
Flow
流量
Pressure
压力
-
Pressure
压力
Pressure
压力
May
可以
Temperature
温度
Flow/Quantity
流量/进水量
Pressure
压力
Flow
流量
Pressure
压力
pH
Conductivity
电导率
-
TOC
Conductivity shall be measured uncompensated at 25℃
电导率监测应在25℃下无补偿
8 System design
系统设计
8.1Specification of feed water
原水标准
Examples of feed water categoriesare in Table B.l.
表B.1中列出了不同原水类别的示例
8.2 System selection table based on feed water quality
基于原水质量的系统选择表
8.2.1 TableC.1can be used for systemselection and guideline.