Technical problems and improvement measures of pharmaceutical pure water system

Technical problems and improvement measures of pharmaceutical pure water system

1. In the pure water system, reverse osmosis is the core equipment in the water system, and the work of reverse osmosis localization has also been increasingly valued. However, with the increasing application of reverse osmosis technology, the problems that arise are becoming increasingly serious. The main reasons are as follows:
     1.1 Due to the different quality of raw water, the full set of imported equipment lacks technical demonstration and process modification, and is copied and pasted, which is not suitable for my country's actual situation. Therefore, the reverse osmosis influent must be pretreated according to the different quality of raw water to meet the equipment's requirements for influent water quality.
     1.2 Some companies with poor technical capabilities do not understand the reasonable selection of membrane elements and their number of reverse osmosis devices, the reasonable arrangement of membrane elements, etc., causing some membrane elements to operate under abnormal conditions.
     1.3 The quality of domestic membranes is not up to standard. The quality of the membrane directly affects the removal rate of salt and other impurities. The Filmtec composite membrane produced by Dow Chemical Company in the United States can maintain a stable retention rate of more than 90%.
     1.4 Lax operation management. When the system is running, the pressure must be within the working pressure range that the membrane can withstand to prevent over-intensity and overload operation, which will cause mechanical damage to the membrane and lead to leakage. When the reverse osmosis system runs for a period of time, the water production volume decreases sharply, the water quality deteriorates or the pressure difference increases, it means that the membrane needs to be cleaned. At this time, the machine should be switched to the cleaning state to allow the system to clean itself and restore the function of the membrane.

1.5 The whole system cannot reach the low of ro membrane elements
II. Technical improvement measures
2.1 Design of mechanical filter
    The main reason for the low normal utilization rate of imported equipment is that the pretreatment equipment does not take into account the characteristics of poor raw water quality in my country, the mechanical filter is not thoroughly backwashed, the upper filter sand is agglomerated, and the SDI (pollution index) increases, causing the membrane to be blocked and affecting the operation of the system. RO devices generally require SDI < 4 (each membrane element manufacturer has different requirements for SDI). To meet the above requirements, technical improvements and improvements should be made in the following aspects:
2.1.1 Selection of mechanical filter
      Combined with the raw water quality and equipment material and filler in my country, it is recommended to use a double-layer filter. From the perspective of the filtration mechanism, it should be from large to small, but in fact, mechanical filters are retained by the finest sand layer on the upper layer, so the uppermost sand is easy to clog and agglomerate, and the head loss increases rapidly. Adding natural manganese sand is to remove iron and manganese (because the pharmaceutical industry mostly uses underground deep well water). Generally, the low-valent iron ions and low-valent manganese ions in the water are oxidized into high-valent iron ions and high-valent manganese ions by oxidation method, and the dissolved divalent iron or divalent manganese are oxidized into insoluble trivalent iron or tetravalent manganese compounds, and then removed by adsorption filtration to achieve the purpose of reducing the iron and manganese content in the water. The effect is good in practical application.
2.1.2 Backwashing of mechanical filters
      Mechanical filters are difficult to backwash because of the large specific gravity of quartz sand filled inside. The unstable operation of many systems is due to the neglect of the thorough and clean backwashing process. The backwashing devices set on the system cannot meet the requirements of backwashing intensity. This is a problem existing in many water treatment equipment manufacturers and engineering companies. According to our company's experience in engineering practice, the backwashing effect of mechanical filters after fouling is very obvious by using the method of repeated flushing with air and water. The sand layer is cleaned very cleanly and the performance is restored well. The specific measures are:
① When designing the backwashing device, the backwashing pump and pipeline must meet the requirements of the backwashing volume, and the backwashing intensity is 12~15L/(s•m2);
② Use compressed air to scrub the filter material to remove the sludge and other materials on the surface of the filter material. The intensity is 18~25L/(s•m2),
2.1.3 Selection of internal filler
       Internal filler, according to its different drainage structure, can choose different particle sizes of quartz sand, but the particle size of the top layer of quartz sand should be 0.3mm. The natural manganese sand for removing iron and manganese should be mainly manganese oxide. Natural manganese sand filter material with a manganese content (in terms of MnO2) of not less than 35% can be used for both groundwater iron removal and groundwater manganese removal; natural manganese sand filter material with a manganese content of 20%~30% is only suitable for groundwater iron removal; manganese ore sand with a manganese content of less than 20% is not suitable for use (this filler is actually implemented due to the quality of the raw water).
2.2 Application of activated carbon adsorption
       The activated carbon adsorber has two main functions: ① adsorbing some organic matter in the water, with an adsorption rate of about 60%; ② adsorbing residual chlorine in the water. For users who directly extract groundwater, activated carbon can be cancelled. If the hardness is high, a water softener should be used. Activated carbon must be used for surface water, because the bactericide and active residual chlorine in the water have strong oxidizing properties and will damage the RO membrane. According to the RO system water inlet requirement, residual chlorine <0.1mg/L, so activated carbon is used to adsorb residual chlorine. In addition, the removal of residual chlorine by activated carbon is not a simple adsorption effect, but a catalytic effect on its surface, so there is no problem of adsorption saturation of activated carbon, but only carbon loss.
2.3 Selection of coagulant

 Various coagulants and polymer flocculants are added before the mechanical filter to remove suspended matter, colloids and other impurities in the water. However, if they are added blindly without considering the actual water source, not only will the water quality not be improved, but on the contrary, substances harmful to the RO membrane will be brought into the water due to the agent itself or the impurities contained in the agent. There are many problems in the water treatment systems of domestic pharmaceutical factories. Therefore, the choice of agents is very particular. According to the characteristics of RO membrane:
① Avoid using aluminum salts as coagulants. Aluminum salt coagulants make aluminum gels easy to be produced during the coagulation process, which are difficult to clean after entering the RO surface;
② Cationic polymer flocculants should not be used. RO membranes are anionic, and cationic polymer flocculants are easy to combine with the membrane to form a polymer membrane that is difficult to clean. If the above situation is not taken seriously, the membrane life will be shortened at best, and some membrane elements will be scrapped at worst. At the same time, the compatibility between agents should not be ignored. If ST polymer flocculants are selected, they should be used with ArgoAF150ul.
2.4 Technical discussion on reverse osmosis (RO) system
2.4.1 Importance of security filter
The main purpose of the security filter is to ensure that the RO water does not damage the membrane assembly. Generally, the filtration aperture is 5μm. The filter element is replaced according to the pressure difference before and after. The pressure difference is controlled within 58.8kPa. At present, domestic systems all use wire wound or PP cotton disposable filter elements. Even if the pressure difference before and after is not large, the use time of the filter element should not be too long, because the filter element is easy to breed bacteria. It is recommended to use 14~15t/(h•m2) (m2 is the filter element filtration area.)

2.4.2 Configuration of large flow flushing
In the process of reverse osmosis water separation, the membrane surface contains many pollutants. Since the water separation direction is 90° to the water flow direction, the pollutants on the membrane surface can be removed by a large amount of flushing. In fact, the original domestic assembly equipment ignored the cleaning device, while the imported equipment was equipped with a cleaning device. According to our company's engineering practice application experience, the use of PLC automatic control of large flow flushing system is conducive to the extension of the service life of RO membrane.
2.4.3 Selection of chemical cleaning liquid
           Under normal operation, the RO system only needs to be cleaned 3 or 4 times a year, and different agents should be used for different pollution. Domestically, citric acid and EDTA are generally used as the main ingredients, but the cleaning effect is often poor, while the imported cleaning solution has obvious cleaning effect.
2.4.4 Design of reverse osmosis device
RO device design calculation has a set of complex calculation methods. At present, all foreign membrane component manufacturers have developed special software. As long as the designer determines the plan based on the raw water quality report and the performance of each membrane component, and then inputs the raw water quality into the computer, the program software will verify the feasibility of the preliminary plan. If it does not work, a warning will be issued, and it will be informed which part of the design is unreasonable. In addition, the designer should pay attention to the various protection measures that should be equipped in the design according to the requirements in the membrane component manual. The membrane technologies used in pure water manufacturing mainly include early electrodialysis, reverse osmosis (RO), nanofiltration (NF), ultrafiltration (UF), and microfiltration (MF). Compared with traditional water treatment technologies, its working principle has the advantages of simple process, convenient operation, easy automatic control, low energy consumption, no pollution, high impurity removal efficiency, and low operating cost. In particular, the combined use of several membrane technologies, supplemented by other water treatment processes, such as quartz sand filtration, activated carbon adsorption, degassing, ion exchange, UV sterilization, etc., provides an effective and reliable means to remove various impurities in water and meet the needs of the pharmaceutical industry for pure water.

2.5 Design of EDI device
            edi In my country's domestically produced pure water systems, especially the early pure water systems, edi ultrapure water equipment and ultrapure water processes are a new type of desalination technology that combines ion exchange technology (electrodialysis), ion exchange membrane technology and ion electromigration technology. It cleverly combines electrodialysis and ion exchange technology, uses high voltage at both ends of the electrode to move the charged ions in the water, and cooperates with ion exchange resins and selective resin membranes to accelerate the movement and removal of ions, thereby achieving the purpose of water purification. In the edi desalination process, ions are removed through the ion exchange membrane under the action of the electric field. At the same time, water molecules produce hydrogen ions and hydroxide ions under the action of the electric field, and these ions continuously regenerate the ion exchange resin to keep the ion exchange resin in the best state. Edi ultrapure water equipment can effectively remove all ions in the water, and the outlet water resistivity can be stabilized at more than 15mΩ.cm. It has continuous operation, no chemical pollution, and high water utilization. It has broad application prospects in the high-purity water preparation process. The conventional application of EDI device is to replace the traditional mixed ion exchange technology (MB-DI) after the reverse osmosis system to produce stable deionized water. Compared with the mixed ion exchange technology, EDI technology has the following advantages:
①Stable water quality
②Easy to achieve full automatic control
③No shutdown due to regeneration
④No chemical regeneration required
⑤Low operating cost
⑥Small plant area
⑦No sewage discharge.
2.5.1 The development history of high-purity water treatment technology:
The first stage: pretreatment -> cation bed -> anion bed -> mixed bed
The second stage: pretreatment -> reverse osmosis -> mixed bed
The third stage: pretreatment -> reverse osmosis -> EDI device
Reverse osmosis (RO) technology is a method of removing ions from water by membrane separation. Although the reverse osmosis system removes 95%-98% of ions in water, it cannot fully meet the requirements of high-purity water in pharmaceutical production. Its subsequent process must use ion exchange equipment. In recent decades, mixed bed ion exchange technology has been used as the standard process for ultrapure water preparation. However, since it requires periodic regeneration and uses a large amount of chemicals (acids and alkalis) during the regeneration process, it is difficult to meet the acid-free and alkali-free pure water system. Because traditional ion exchange has become increasingly unable to meet the needs of modern industry and environmental protection, EDI technology combining membranes and resins has become a revolution in water treatment technology. The desalination rate of EDI facilities can be as high as 99%. If reverse osmosis equipment is used to perform preliminary desalination of water before EDI, ultrapure water with a resistivity of more than 15-18M Ω. .cm can be produced after EDI desalination. This technology uses the electro-regenerative ion exchange desalination process to replace the traditional mixed ion exchange desalination process. Ion exchange resin and selective ion membrane are used to achieve high desalination effect, and the combined process with reverse osmosis can stabilize the water quality to reach high-specification pure water of 15~18M Ω· CM.
2.5.2 Working principle of EDI ultrapure water membrane block:
EDI membrane stacks are composed of a certain number of units sandwiched between two electrodes. There are two different types of chambers in each unit: the fresh water chamber to be desalted and the concentrated water chamber to collect the removed impurity ions. The fresh water chamber is filled with a mixture of cation and anion exchange resins, which are located between two membranes: a cation exchange membrane that only allows cations to pass through and an anion exchange membrane that only allows anions to pass through. The resin bed is continuously regenerated using direct current applied to both ends of the chamber. The voltage decomposes the water molecules in the incoming water into H+ and OH-. These ions in the water are attracted by the corresponding electrodes and migrate through the cation and anion exchange resins in the direction of the corresponding membrane. When these ions pass through the exchange membrane and enter the concentrated chamber, H+ and OH- combine to form water. This generation and migration of H+ and OH- is the mechanism by which the resin can achieve continuous regeneration.
1. When water enters the EDI system, the main part flows into the resin/membrane, while the other part flows along the outside of the template to wash away the ions that pass through the membrane.
2. The resin intercepts the dissolved ions in the water.
3. Under the action of the electrode, the anions move toward the positive electrode and the cations move toward the negative electrode.
4. The cations pass through the cation membrane and are discharged from the resin/membrane.
5. The anions pass through the anion membrane and are discharged from the resin/membrane.
6. The concentrated ions are discharged from the wastewater flow path.
7. Deionized water flows out of the resin/membrane.
2.5.3 EDI ultrapure water membrane block inlet water quality requirements
        The following standards are the minimum water inlet conditions for the normal operation of the EDI system. In order to achieve long-term stable operation of the system and obtain higher water quality, the system design should be appropriately improved.
1. Pretreatment process setting:
Generally, it is a first-stage reverse osmosis + softener, or a two-stage reverse osmosis.
(1) TEA (total exchangeable anions, including CO2 in CaCO3) ≤ 25ppm
Limitation of ionic impurities in raw water:
TEA<25ppm, calculated as CaCO3
TEC < 25ppm, in CaCO3
Generally, the total load of exchangeable anions (TEA) is greater than the total load of exchangeable cations (TEC) because of the ubiquitous CO2. Therefore, the system design is usually based on TEA. TEA includes all anions and substances removed by EDI in the form of anions.
(2) Raw water hardness
The limitation of raw water hardness is to prevent scaling in the EDI membrane stack. The OH- ions produced by electrolysis in EDI maintain a high pH value on the concentrated water surface of the anion membrane, which can form calcium and magnesium scale (carbonate, hydroxide). The cathode surface is also a high pH location because the regeneration of OH- ions is related to the electrolysis of water. These scales can be removed by chemical cleaning methods.
Raw water hardness limit operating conditions
When the inlet water hardness is <0.1ppm, the maximum recovery rate of the system is 95%; when the inlet water hardness is 0.1-0.5ppm, salt needs to be added to the concentrate to adjust the conductivity of the concentrate, and the maximum recovery rate of the system is 90%, and regular cleaning is required. When the inlet water hardness is above 0.5ppm, it is recommended to add auxiliary equipment to reduce the hardness.
EDI raw water hardness can be reduced by the following methods:
-Use RO membrane with higher desalination rate
- Use double-stage reverse osmosis
- Softening RO permeate
(3) Variable metal Fe, Mn < 0.01 ppm
High-valent ions such as iron and manganese will poison the ion exchange resin in the membrane stack, which is much more serious than the poisoning phenomenon of iron and manganese ions in the mixed bed. Since the total amount of resin in the membrane stack is much less than that in the mixed bed, the time for the resin to be completely poisoned will be many times shorter than that in the mixed bed. Therefore, the iron and manganese content of the influent water should be strictly controlled.
（4） CO2<5 ppm
Because carbon dioxide exists in different forms at different pH values, CO2 is the primary cause of poor water quality. CO2 is converted into HCO3- in the membrane stack. It will also be converted into CO32- at high pH near the anion exchange membrane. The CO2 content will significantly affect the quality of the produced water. If the TEA including CO2 exceeds 25ppm, the membrane stack will not be able to produce high-purity produced water. The amount of CO2 can be reduced by adjusting the RO inlet pH or using a degasser.
(5) Conductivity
Conductivity is a comprehensive indicator of the total amount of ions in water, but it can only be used as a reference indicator for the quality of EDI influent water and cannot directly represent the quality of pure water. The main reason is that conductivity cannot truly reflect the content of weak electrolytes in water, such as carbon dioxide. The carbon dioxide content of RO produced water with a water output of 5μs/cm may be 1ppm or 5ppm.
(6) Soluble silicon: ≤0.5ppm
Silicon is an impurity that must be controlled in many power generation and semiconductor devices. Usually, most of the active silicon is removed by RO. The residual silicon in RO produced water can be effectively removed by EDI.
(7) Organic matter (TOC): ≤ 0.5ppm
（8）H2S: ≤0.01 ppm
(9)SDI：≤1.0
(10) PH：5-9
pH value is an important indicator affecting the carbon dioxide in the inlet water. When the total hardness of the inlet water is low, the water quality of the produced water can be improved by appropriately increasing the pH value.
(11) Residual chlorine: ≤0.05 ppm
The oxidation of residual chlorine on ion exchange resin will cause permanent damage to the resin.
(12) Oil or grease: cannot be detected

2.6 Selection of ultraviolet disinfection device and membrane filter
Ultraviolet disinfection device can kill bacteria in water, and then remove the dead bacteria through membrane filtration. These designs can use conventional products and will not be described here.