Water conforming to the regulation of water for injection in Chinese Pharmacopoeia
Water for injection refers toChinese pharmacopoeiaWater specified under water for injection.Water for injection is distilled water orDeionized waterThe water obtained by distillation is weighed againdistilled water。in order toEffective controlMicrobial contaminationAndSimultaneous controlBacterial endotoxinLevel,Purified waterThe design and manufacturing of water for injection system have two major characteristics: first, more and more disinfection/sterilization facilities are used in the system;Second, the pipeline distribution system has evolved from the traditional water supply pipeline to the circulating pipeline.
The preparation, storage and distribution of water for injection shall prevent the breeding and pollution of microorganisms.Tanks andTransmission pipelineThe materials used shall be non-toxic and corrosion resistant.The design and installation of pipelines shall avoid dead corners and blind pipes.Storage tankAnd pipes shall be cleanedsterilizationPeriod.Water for injection storage tankVentsHydrophobicity of non shedding fiber shall be installedSterilization filter。Water for injection can be stored at 80 ℃ or above, at 70 ℃ or below 4 ℃.
Pipes used for pretreatment equipment of water for injection are generallyABS engineering plastics, also adoptedPVCPPR or other suitable materials.However, the distribution system of purified water and water for injection shall adoptChemical disinfection、pasteurization、Thermal sterilizationAnd other corresponding pipe materials, such asPVDF、ABS、PPREtc., preferablystainless steel, especially the 316L model.Stainless steel is a general term. Strictly speaking, it is divided into stainless steel and acid resistant steel.Stainless steel is a steel that is resistant to weak medium corrosion such as atmosphere, steam and water, but is not resistant to chemical corrosive medium corrosion such as acid, alkali and salt, and has stainless property.
In addition, the effect of flow rate in the pipe on microorganismreproductionImpact.WhenReynolds numberWhen Re reaches 10000 to form a stable flow, it can effectively cause adverse effects on the growth of microorganismsenvironment condition。On the contrary, if water is not noticedsystem designAnd details in manufacturing, resulting in low flow rate, rough pipe wall or blind pipe in the pipeline, or the structure is selectednot suited toValve, etc,microorganismIt is entirely possible to rely on the resultingobjective condition, build your ownhotbed- Biofilm brings risks and troubles to the operation and daily management of purified water and water for injection systems.
Operation mode
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The regular cleaning and disinfection of the pipeline distribution system shall be considered for the operation of the purified water and water for injection system. There are usually two operation modes.
One is to make water like a productBatch No, i.e. batch operation mode.The "batch" operation mode is mainly for safety reasons, because this method can separate a certain amount of water during the test period until the test has reached a conclusion.
The other is the "once through" operation mode of continuous water production, which can be used while producing.
daily management
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The daily management of the water preparation system includes operation and maintenance, which is very important for verification and normal use. Therefore, a monitoring and pre maintenance plan should be established to ensure that the operation of the water system is always based onControlled state。These include:
⑤ Key water treatment equipment (including main parts), pipeline distribution system andOperating conditionsThen moremanagement。
Basic Requirements
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The WFI system is composed ofWater treatment equipment、storage device, distribution pump, pipe network, etc.The water production system has the following problems:raw waterAnd the possibility of external pollution caused by external causes of the water preparation system, and the pollution of raw water is the most important external cause of the water preparation systemPollution source。American Pharmacopoeia, European Pharmacopoeia andChinese pharmacopoeiaIt is clearly required that the raw water for pharmaceutical use should at least reachdrinking waterOfquality standard。If notDrinking water standardPre purification measures shall be taken first.becauseEscherichia coliIt is an obvious sign of water pollution, so there are clear requirements for E. coli in drinking water internationally.Other contaminating bacteria are not subdivided“Total number of bacteria”It means thatBacteriaThe total limit is 100 pieces/ml, which indicates that there are alsoMicrobial contaminationThe main contaminating bacteria endangering the water production system areGram negative bacteria。Others such asStorage tankOfExhaust portNo protective measures or poor qualityGas filter, water backflow from the polluted outlet can also lead to external pollution.
In addition, there is internal pollution during the preparation and operation of the water preparation system.The internal pollution is closely related to the design, material selection, operation, maintenance, storage, use and other factors of the water pollution system.Various water treatment equipment may become the internal pollution source of microorganisms, for example, microorganisms in raw water are adsorbed onActivated carbon, deionized resinFilter membraneAnd other equipmentBiomembraneMicrobes living in the biofilm are protected by the biofilm, generallydisinfectantIt doesn't work.Another source of pollution exists in the distribution system.Microorganisms can be generated on pipe surfaces, valves and other areascolony of bacteriaAnd reproduce in large numbers there to form biofilm, thus becomingpersistencePollution source.Therefore, some foreign enterprises have strict standards for the design of water preparation system.
Processing equipment
① The pretreatment equipment for water for injection can be equipped according to the quality of raw water, and it is required to meet the drinking water standard first.
③Activated carbon filterIt is a concentration area of organic matter to prevent bacteriaBacterial endotoxinIn addition to automatic recoilSteam disinfection。
① The United States Pharmacopoeia (24th edition) stipulates that "water for injection must be made byEnvironmental Protection AssociationorEuropean CommunityOr the drinking water required by Japanese laws is distilled or purified by reverse osmosis ".
② The European Pharmacopoeia (1997 edition) stipulates that "the water for injection is the drinking water or purified water that meets the statutory standards and is distilled by appropriate methods.
③ The Chinese Pharmacopoeia (2000 Edition) stipulates that "this product (water for injection) is the water obtained by distillation of purified water".
It can be seen that purified water for injection is the preferred method recognized by the world through distillation, while clean steam can be used in the same setDistilled water machineOr separate cleaningSteam generatorget.
③ Equipped with measurement, recording andAuto-ControlconductivityWhen the conductivity exceedsSet valueAutomatic steering for drainage.
container
The general requirements for water storage containers are to prevent the formation of biofilm, reduce corrosion, and facilitate the disinfection of storage tanks with chemicals;The storage tank shall be sealed,Internal surfaceBe smooth and helpThermal disinfectionAnd chemical disinfection and can prevent the formation of biofilm.
There are usually two methods for the tank to compensate for the change of water level:respirator；Another method is to use nitrogen filledAutomatic control systemDuring peak water consumption, the nitrogen supply volume after aseptic filtration automatically increases to ensure that the storage tank can maintain positive pressurewater consumptionThe hourly air supply is automatically reduced, but a small positive pressure is still maintained outside the storage tank. The advantage of this is to prevent water from flowingoxygen contentTo preventcarbon dioxideEnter the storage tank and prevent microbial contamination.
Requirements for storage tank:
① Adopt316L stainless steelProduction, inner wall electropolishing and passivation treatment;
② 0.2 μ m installed on water storage tankHydrophobicityAnd can be heated and sterilized or jacketed;
③ Able to withstand at least 121 ℃ high temperature steam disinfection;
⑤ If nitrogen is filled, 0.2 μ m hydrophobic filter must be installed for filtration.
Pipeline distribution system
The construction of pipeline distribution system shall consider that the water can circulate continuously in the pipeline and can be cleaned and disinfected regularly.The system with continuous circulation is easy to keep normalrunning state 。
The outlet water of the pump shall be designed as "turbulent flow" to prevent the formation of biofilm.The pipeline installation of the distribution system shall have sufficient slope and drainage points, so that the system can be completely drained when necessary.water cycleThe distribution and discharge system of shall avoid low flow rate.Diaphragm valveEasy to removevalve bodyDissolved impurities and microorganisms are not easy to reproduce.
The requirements for the pipeline distribution system are:
③ The valve is made of stainless steel poly IVethyleneDiaphragm valve, sanitary chuck connection;
④ The pipeline has certainInclinationIt is convenient to drain water;
⑤ The pipeline is arranged circularly,backwaterThe parallel connection or series connection method can be used to flow into the storage tank, and the series connection method is better.At the point of use valve“Blind tube”Segment length, forheating system It shall not be greater than 6 times of pipe diameter,Cooling systemIt shall not be greater than 4 times of pipe diameter.
⑥ The pipeline is sterilized with clean steam at 121 ℃.
Delivery pump
① 316L stainless steel (immersion part), electropolishing and passivation treatment;
③ The lubricant is purified water or water for injection itself;
④ The accumulated water can be completely drained.
heat exchanger
heat exchangerIt is used for heating or cooling water for injection, or for cooling and condensing as clean steam.The basic requirements are as follows:
① Made of 316L stainless steel;
② Designed according to sanitary requirements;
③ Electropolishing and passivation treatment;
④ The accumulated water can be completely drained.
Performance characteristics
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The difference between purified water and water for injection still lies in the water preparation process. There are various options for the preparation process of purified water, but each countrypharmacopoeiaThere are limited conditions for the preparation process of water for injection. For example, the United States Pharmacopoeia clearly stipulates that the preparation process of water for injection can only be distillation and reverse osmosis, while the Chinese Pharmacopoeia stipulates thatProduction processIt must be distillation.These are used by countries to ensure the quality of water for injection according to their actual conditionsnecessary condition。 The principle for selecting the preparation method of pharmaceutical water In addition to controlling chemical indicators and particulate pollution, the pharmaceutical water system must effectively treat and control microorganisms andBacterial endotoxinPollution.The purified water system can use reverse osmosis, while the water for injection system uses distillation more often, and the distilled water machine is often used to distribute the purified water systemCirculation loopMain water points in (water circuit).
As for the choice of source water for pharmaceutical use, the USP has greater flexibility. According to its provisions, water for injection can be made from drinking water by distillation or reverse osmosis. It does not require enterprises to use purified water as source water to prepare water for injection.Of course, the drinking water standards in the United States are different from those in China.Experts believe that this flexibility of the United States Pharmacopoeia gives "clauses" a wide range ofApplicabilityFrom its discussion on the pharmaceutical water system, its control of water quality is not limited to the previous projects and indicators, but also extends to the design, construction, verification and operation monitoring of the system.
Distillation method is adopted for domestic water for injection, which is certainly the same as domestic water for injectionReverse OsmosisThe quality status quo.It should be pointed out that different distilled water machines have different requirements for source water, and different models of distilled water machines can use purified waterDeionized waterThe deep soft water is the source water, and the standard injection water is prepared.On the other hand, the preparation of purified water with water that meets the drinking water standard as the source water, or the preparation of water for injection with purified water that meets the standard, does not necessarily ensure that the effluent meets the specified standard, which is related to the performance of the selected equipment.It should also be pointed out that the quality of source water must be monitored, and the water intake point should avoid pollution sources as far as possible.
