13 Water Systems For Pharmaceutical facilities Mark Keyashian 1.0 INTRODUCTION Common, everyday water is a major consideration in a pharmacer tical plant. The final product or any of its intermediate materials can only be as contaminant-free as the water available at that stage. Water may be an ingredient or used principally to wash and rinse product contact components andequipment. Water is also used to humidify the air, to generate clean steam for sterilization, to cool or heat, as a solvent, for drinking and sanitary uses etc. To better control this critical media, the pharmaceutical industry has defined two additional types of water purified water and water for injection both of which are highly regulated. Special attention to a good understanding of the water systems in a pharmaceutical facility are essential 2.0 SCOPE This chapter is an overview of the water systems used in a pharmaceutical facility. It will help bring about a better understanding ofhe they are generated stored and distributed ar t equipment is involved Starting with raw water as it is sourced, this chapter will 590
Water Systems For Pharmaceutical Facilities Mark Keyashian 1.0 INTRODUCTION Common, everyday water is a major consideration in a pharmaceutical plant. The final product or any of its intermediate materials can only be as contaminant-free as the water available at that stage. Water may be an ingredient or used principally to wash and rinse product contact components and equipment. Water is also used to humidiethe air, to generate clean steam for sterilization, to cool or heat, as a solvent, for drinking and sanitary uses, etc. To better control this critical media, the pharmaceutical industry has defined two additional types of water: purijied water and water for injection, both of which are highly regulated. Special attention to a good understanding of the water systems in a pharmaceutical facility are essential. 2.0 SCOPE This chapter is an overview of the various water systems used in a pharmaceutical facility. It will help bring about a better understanding ofhow they are generated, stored and distributed and what equipment is involved. Starting with raw water as it is sourced, this chapter will: 590
Water Systems for Pharmaceutical Facilities 591 Take the reader step-by-step through various treatments to generate different types of water. 2. Outline applicable cGMP's(current Good Manufactu ing Practices 3. Point out some potential pitfalls to watch for In addition, for a better all around understanding, an overview ofhow these systems are designed and some of the more important design parameters will be discussed 3.0 SOURCE OF WATER Water supply to the plant is either ground water(wells), surface water(lakes, rivers), or city water. Raw water is typically contaminated with salts, oils, various organic substances, calcium, clay, silica, magnesium, manganese,aluminum, sulfate, fertilizers, ammonia, insecticides, carbon dioxide and of course, bacteria and pyrogens. a city water treatment plant removes most of these impurities, but adds chlorine or chloramines and fluoride. Table I summarizes the level of contaminants by type of raw water Table 1. Contaminants by Type of Source Water Tap Water Surface Water Ground Water Particulates 3-7 Dissolved Solids 1-5 5-10 Dissolved Gases 3-5 7-10 5-8 Organics 3-8 0-5 Colloids 0-5 3-8 0-4 Bacteria Pyrope 7-9 6-9 0=None 10= Very High
Water Systems for Pharmaceutical Facilities 591 1. Take the reader step-by-step through various treatments 2. Outline applicable cGMP’s (current Good Manufactur- 3. Point out some potential pitfalls to watch for during In addition, for a better all around understanding, an overview ofhow these systems are designed and some ofthe more important design parameters will be discussed. to generate different types of water. ing Practices) installation and start-up. 3.0 SOURCE OF WATER Water supply to the plant is either ground water (wells), surface water (lakes, rivers), or city water. Raw water is typically contaminated with salts, oils, various organic substances, calcium, clay, silica, magnesium, manganese, aluminum, sulfate, fertilizers, ammonia, insecticides, carbon dioxide and, of course, bacteria and pyrogens. A city water treatment plant removes most of these impurities, but adds chlorine or chloramines and fluoride. Table 1 summarizes the level of contaminants by type of raw water. Table 1. Contaminants by Type of Source Water Tap Water Surface Water Ground Water Particulates 3-5 3-7 4-9 Dissolved Solids 2-5 1-5 5-10 Dissolved Gases 3-5 7-10 5-8 Organics 1-4 3-8 0-5 Colloids 0-5 3-8 0-4 Bacteria 1-2 6-9 2-5 P yrogens 7-9 6-9 2-5 0 =None 10 = Very High
592 Fermentation and Biochemical Engineering Handbook Regardless of the source, the first step in knowing or designing a system is to obtain a complete analysis of the supply wate Table 2 is an example water analysis. Please note that a water analysis on a sample obtained at the city treatment plant may be significantly different from one obtained at the site Table 2. Typical Water Supply Analysis It Plant Feed Color Alkalinity 10 mg/L 3.2 mg Potassium 3. 1 mg/L 0.04 27 mg/L Nitrogen(nitrate) 0.002mg/L SDI(fouling index) Usually, immediately upon entering the plant, supply water is split into potable water and process water. This is done by using an air break or back flow preventers. This is a precaution against process contaminants backing up into potable or city water and vice versa. Often a break tank is used as the air break since it also provides storage capacity for demand surges
592 Fermentation and Biochemical Engineering Handbook Regardless of the source, the first step in knowing the water supply or designing a system is to obtain a complete analysis of the supply water. Table 2 is an example water analysis. Please note that a water analysis on a sample obtained at the city treatment plant may be significantly different from one obtained at the site. Table 2. Typical Water Supply Analysis Item Plant Feed Turbidity Color Alkalinity Hardness (as CaCO,) Calcium Magnesium Sodium Potassium Iron Manganese Sulfate Chloride Nitrogen (ammonia) Nitrogen (nitrite) Nitrogen (nitrate) Copper SDI (fouling index) PH 0 0 8.8 16 mgk 38 mgk 10 mgk 3.2 mg/L 23 mg/L 3.1 mg/L 0.04 mg/L 0.03 mg/L 27 mgk 49 mg/L 0.05 mg/L 0.30 mg/L 0.002 mg/L 0.002 mg/L 25 Usually, immediately upon entering the plant, supply water is split into potable water and process water. This is done by using an air break or back flow preventers. This is a precaution against process contaminants backing up into potable or city water and vice versa. Often a break tank is used as the air break since it also provides storage capacity for demand surges at the use points
Water Systems for Pharmaceutical Facilities 593 4.0 POTABLE WATER Potable water, also called drinking or tap water, is used for sanitary purposes such as drinking fountains, showers, toilets, hand-wash basins cooking, etc. If the water supply to the facility is from a public system such as city water, the maximum contaminant levels, are set by the Environmental Protection Agency(EPA)Standards, Title 40 CFR, Part 141. Table 3 is a highlight of a typical water supply standard. Primary drinking water regulations, Appendix I outlines the existing and proposed U. S.EPA drinking water maximum contaminant levels Table 3: Minimum Potable Water Standard Appearance chloride 250 ppm Sulfate 250 ppm 0.05 mg/L Fecal Coliforms 1/100 ml(Proposed: 0/100 ml) Other Microbes Total Dissolved Solids Chromium Hexavalent 0.05mg 0.7mg 0.2mg Mercury 0.002mgL 00l1 Chlordane 0.003mg Endrin 0.0002mgL 0.0001mg/L Heptachlor Epoxide 0.000mg/L 0.004mgn 0. 1 mg/L 2,4,5-TP(Si 0.01mg Specific 10,000 ohms/cm(typically) H 6.5-8.5
Water Systems for Pharmaceutical Facilities 593 4.0 POTABLE WATER Potable water, also called drinking or tap water, is used for sanitary purposes such as drinking fountains, showers, toilets, hand-wash basins, cooking, etc. If the water supply to the facility is from a public system such as city water, the maximum contaminant levels, are set by the Environmental Protection Agency (EPA) Standards, Title 40 CFR, Part 141. Table 3 is a highlight of a typical water supply standard. Primary drinking water regulations, Appendix I outlines the existing and proposed U. S. EPA drinking water maximum contaminant levels. Table 3: Minimum Potable Water Standard Item Specification Appearance 1 Turbidity Unit Chloride 250 ppm Fluoride 1.4 to 2.4 mg/L Sulfate 250 ppm Lead 0.05 mg/ L Fecal Coliforms Pyrogens Not Specified Other Microbes Not Specified Total Dissolved Solids 500 mg/L Arsenic 0.05 mg/L Barium 1.0 mg/L Cadmium 0.010 mg/L Chromium Hexavalent 0.05 mg/L Chloroform 0.7 mg/L Cyanide 0.2 mgL Mercury 0.002 mg/L Nitrate 10 mg5 Selenium 0.01 mg/L Silver 0.05 mg/L Pesticides 1/100 ml (Proposed: Oh00 ml) Chlorodane 0.003 mg/L Endrin 0.0002 mg/L Heptachlor 0.0001 mg/L Heptachlor Epoxide 0,0001 mg/L Lindane 0.004 mg/L Methoxychlor 0.1 mg/L Toxaphene 0.005 mg/L 2,4-D 0.1 rngL 2,4,5-TP (Silvex) 0.01 mg/L Specific Resistance 10,000 ohmdcm (typically) PH 6.5-8.5
594 Fermentation and Biochemical Engineering Handbook Please note that the proposed EPA drinking water standards reduces the coliform count from l to o per 100 ml. All types of water discussed from this point on will fall under the category process water 5.0 WATER PRETREATMENT After the break tank, process water is treated using various equip ment and technologies depending on its intended use and the water analysis Some of the technologies are: multimedia filtration, water softening, acti ated carbon adsorption, UV treatment, deionization, ultrafiltration, reverse osmosis. final filtration and distillation Figures I and 2 depict two alternative equipment trains for treating However, these diagrams are not all inclusive. For example, if the analysis shows a high concentration of insoluble iron oxides, the first step would be to inject a flocculent agent and then filter. Cle be removed by the softener or the Fig. I system Potable bution Figure 1. Water pretre
Water Systems for Pharmaceutical Facilities 595 60 MULTIMEDIA FILTRATION Multimedia filtration(also called prefiltration, sand filtration or multilayered filtration)is mainly aimed at removing sediments and suspended matter. Suspended contaminants are trapped in small crevices and, as a result, water turbidity is improved. A number of media are distinctly layered with the coarsest on top so the suspended matter is collected throughout the according to siz The filter beds need to be backwashed periodically as the back pressure increases; however, backwashing removes the filter from use. To avoid downtime, often a dual filter bed system is installed During construction, the filtration unit should be installed before all the walls are erected so it can be kept upright, in which case the filters can be charged by the vendor before shipping. This would reduce chances of damage to the internals during loading. The unit, of course, should be inspe thoroughly upon receiving. Before shipping, the vendor will often disconnect controls to minimize potential damage. Sufficient time should be allowed to reconnect all of these. Finally, to avoid bacteria building up, start-up should be delayed until a constant water flow is assured
Water Systems for Pharmaceutical Facilities 595 Figure 2. Water pretreatment 6.0 MULTIMEDIA FILTRATION Multimedia filtration (also called prefiltration, sand filtration or multilayered filtration) is mainly aimed at removing sediments and suspended matter. Suspended contaminants are trapped in small crevices and, as a result, water turbidity is improved. A number of media are distinctly layered with the coarsest on top so the suspended matter is collected throughout the depth of the filter according to size. The filter beds need to be backwashed periodically as the back pressure increases; however, backwashing removes the filter from use. To avoid downtime, often a dual filter bed system is installed. During construction, the filtration unit should be installed before all the walls are erected so it can be kept upright, in which case the filters can be charged by the vendor before shipping. This would reduce chances ofdamage to the internals during loading. The unit, of course, should be inspected thoroughly upon receiving. Before shipping, the vendor will often disconnect controls to minimize potential damage. Sufficient time should be allowed to reconnect all of these. Finally, to avoid bacteria building up, start-up should be delayed until a constant water flow is assured
596 Fermentation and Biochemical Engineering Handbook 7.0 WATER SOFTENING Water is softened to remove the scale-forming hardness elements Soft water is required for boilers, water heaters, cooling towers, reverse osmosis systems, etc. Softening is an ion-exchange process which replaces almost all of the metallic or cations by sodium ions and sometimes, the anions with chlorine ions. Therefore, a constant supply of salt is required a softener may be used in conjunction with a deionizer on certain water supplies to provide softened water for use in regeneration. This will prevent the formation of insoluble precipitates within the deionizer resin bed It is important to note that softening does not remove silica, which forms a very hard scale that is not easily removed In addition, softening does not remove chloride which can cause stress corrosion cracking in stainless A freshly regenerated resin bed is in the sodium(Na)form. When in service, sodium cations are exchanged for undesirable quantities of calcium(Ca*), magnesium (Mg*), and iron(Fe)ions. Sodium ions already present in the raw water pass through the process unchanged. Upon exhaustion of the resin, as indicated by unacceptable hardness leakage, most systems are designed to go automatically into regeneration. It should be noted that although the water is softened, the total dissolved solids content remains unchanged. Further, the effluent contains the same anions as the supply water. Softeners can be a microbial concern. a dark and moist column interior can provide a growth environment. The regeneration cycle which uses concentrated brine solution and a backwash cycle aids in reducing the bioburden. Softeners should be regenerated based on a time clock set for twice weekly regenerations and on a volumetric flow of water, whichever is shorter. Since the regeneration cycle removes the softener bed from opera tion,a dual bed system is often specified 8.0 ACTIVATED CARBON Activated carbon has long been used as an effective means of removing organics, chlorine, chlorates, other chlorine compounds and objec tionable tastes and odors. The organics removed include pesticides, herbi- cides and industrial solvents for which activated carbon has diverse capacity Typically, carbon filters are operated at a flow rate of 1-2 gpm/ft'ofactivated carbon
596 Fermentation and Biochemical Engineering Handbook 7.0 WATER SOFTENING Water is softened to remove the scale-forming hardness elements. Soft water is required for boilers, water heaters, cooling towers, reverse osmosis systems, etc. Softening is an ion-exchange process which replaces almost all ofthe metallic or cations by sodium ions and sometimes, the anions with chlorine ions. Therefore, a constant supply of salt is required. A softener may be used in conjunction with a deionizer on certain water supplies to provide softened water for use in regeneration. This will prevent the formation of insoluble precipitates within the deionizer resin bed. It is important to note that softening does not remove silica, which forms a very hard scale that is not easily removed. In addition, softening does not remove chloride which can cause stress corrosion cracking in stainless steel. A freshly regenerated resin bed is in the sodium @a+) form. When in service, sodium cations are exchanged for undesirable quantities of calcium (Ca++), magnesium (Mg++), and iron (Few) ions. Sodium ions already present in the raw water pass through the process unchanged. Upon exhaustion ofthe resin, as indicated by unacceptable hardness leakage, most systems are designed to go automatically into regeneration. It should be noted that although the water is softened, the total dissolved solids content remains unchanged. Further, the effluent contains the same anions as the supp 1 y water. Softeners can be a microbial concern. A dark and moist column interior can provide a growth environment. The regeneration cycle which uses concentrated brine solution and a backwash cycle aids in reducing the bioburden. Softeners should be regenerated based on a time clock set for twice weekly regenerations and on a volumetric flow of water, whichever is shorter. Since the regeneration cycle removes the softener bed from operation, a dual bed system is often specified. 8.0 ACTIVATED CARBON Activated carbon has long been used as an effective means of removing organics, chlorine, chlorates, other chlorine compounds and objectionable tastes and odors. The organics removed include pesticides, herbicides and industrial solvents for which activated carbon has diverse capacity. Typically, carbon filters are operated at a flow rate of 1-2 gpm/ft3 of activated carbon
Water Systems for Pharmaceutical Facilities 597 Since chlorine is removed from water by the carbon, extra care is quired from here on to protect against bioburden growth. Carbon bed themselves are good breeding grounds for bacteria. To keep the system in check, a recirculation system as depicted in Fig 3 is recommended. The constant recirculation avoids water stagnation and reduces viable bioburden Figure 3. Activated Carbon Activated carbon is manufactured by heating selected or other higher carbonaceous material in the absence of ctivation"process burns out impurities and produces a honeycomb-like structure containing millions of tiny pores. The structure provides a large total surface area that enables the carbon to adsorb(attract and hold to the surface)large quantities of contaminants. Chlorine, or its related elements are first adsorbed on the surface of the pores where they react with the carbon to liberate chloride. Because of this reaction and deterioration of chlorine the capacity of activated carbon for chlorine removal is exceedingly high. In addition to chlorine removal and adsorption oforganics, the granular carbon is an effective filter. Although removal of turbidity will shorten the carbon life by blocking pores, the carbon will function as an excellent filter. Particle removal down to 40 microns can be achieved with freshly backwashed beds
Water Systems for Pharmaceutical Facilities 59 7 Since chlorine is removed from water by the carbon, extra care is required from here on to protect against bioburden growth. Carbon beds themselves are good breeding grounds for bacteria. To keep the system in check, a recirculation system as depicted in Fig. 3 is recommended. The constant recirculation avoids water stagnation and reduces viable bioburden growth. Filtered Water 5 Mlcron Fllter 0 I Drain Figure 3. Activated Carbon. Activated carbon is manufactured by heating selected grades of coal or other higher carbonaceous material in the absence of oxygen. This “activation” process burns out impurities and produces a honeycomb-like structure containing millions of tiny pores. The structure provides a large total surface area that enables the carbon to adsorb (attract and hold to the surface) large quantities of contaminants. Chlorine, or its related elements, are first adsorbed on the surface of the pores where they react with the carbon to liberate chloride. Because ofthis reaction and deterioration of chlorine, the capacity of activated carbon for chlorine removal is exceedingly high. In addition to chlorine removal and adsorption of organics, the granular carbon is an effective filter. Although removal of turbidity will shorten the carbon life by blocking pores, the carbon will function as an excellent filter. Particle removal down to 40 microns can be achieved with freshly backwashed beds of carbon
598 Fermentation and Biochemical Engineering Handbook Carbon beds are backwashed to remove carbon fines and suspended matter which have been filtered by the bed. Backwashing does not regenerate the carbon. Sanitizing and some degree of regeneration can be effected by passing low pressure steam or hot water through the carbon bed. The degree of regeneration is limited and the carbon must be replaced periodically (once every 1-2 years). Steam is of course more effective than hot water for sanitization, but it does cause some carbon degradation 9.0 ULTRAVIOLET PURIFICATION In high purity water systems, UV light is often used in-line to control microorganism contamination. Use of uV as a disinfectant is somewhat controversial. In the authors opinion, UV as an added measure is worth- while; however, it should not be totally relied on to keep the water clear of bacterial contaminants, UV systems cannot correct for a poorly designed water system. Also, note that UV kills microorganisms and hence generates pyrogens, 2) In most cases, microorganisms can be filtered out, while pyrogens cannot be To be effective UV radiation at a wavelength of 2537 a must be applied. A minimum dosage of 16,000 microwatt-seconds per cm2 must be reached at all points throughout the water chamber. appendix ii is a summary statement by the Department of Health, Education and Welfare on the use of uv as a disinfectant During construction and installation, extra care should be taken in handling the UV unit. The UV lamp sleeves are made of quartz, since glass filters UV radiation, and are very fragile. The same is true in the start-up the lamps can break when the unit is first pressurized. It is recommended that spare lamps be kept on hand. Lamps also get broken during start-up if they are turned on when there is no flow. they get hot before the flow is established and then cold water causes them to break. Finally, avoid looking directly at the lamps while they are on. UV radiation can cause eye damage a port equipped with a thick glass cover is provided to visually check the 100 DEIONIZATION Deionization is the process of removing the dissolved ionized solids from water by ion exchange. Ion exchange can be defined as a reversible exchange of ions between a solid (resin) and a liquid (water). The major
598 Fermentation and Biochemical Engineering Handbook Carbon beds are backwashed to remove carbon fines and suspended matter which have been filtered by the bed. Backwashing does not regenerate the carbon. Sanitizing and some degree of regeneration can be effected by passing low pressure steam or hot water through the carbon bed. The degree of regeneration is limited and the carbon must be replaced periodically (once every 1-2 years). Steam is of course more effective than hot water for sanitization, but it does cause some carbon degradation. 9.0 ULTRAVIOLET PURIFICATION In high purity water systems, UV light is often used in-line to control microorganism contamination. Use of UV as a disinfectant is somewhat controversial. In the author’s opinion, UV as an added measure is worthwhile; however, it should not be totally relied on to keep the water clear of bacterial contaminants. UV systems cannot correct for a poorly designed water system. Also, note that UV kills microorganisms and hence generates pyrogens.[21 In most cases, microorganisms can be filtered out, while pyrogens cannot be. To be effective, UV radiation at a wavelength of 2537 A must be applied. A minimum dosage of 16,000 microwatt-seconds per cm2 must be reached at all points throughout the water chamber. Appendix I1 is a summary statement by the Department of Health, Education and Welfare on the use of UV as a disinfectant. During construction and installation, extra care should be taken in handling the UV unit. The UV lamp sleeves are made of quartz, since glass filters UV radiation, and are very fragile. The same is true in the start-up; the lamps can break when the unit is first pressurized. It is recommended that spare lamps be kept on hand. Lamps also get broken during start-up if they are turned on when there is no flow. They get hot before the flow is established and then cold water causes them to break. Finally, avoid looking directly at the lamps while they are on. UV radiation can cause eye damage. A port equipped with a thick glass cover is provided to visually check the lamps. 10.0 DEIONIZATION Deionization is the process of removing the dissolved ionized solids from water by ion exchange. Ion exchange can be defined as a reversible exchange of ions between a solid (resin) and a liquid (water). The major
Water Systems for Pharmaceutical Facilities 599 portion oftotal dissolved solids is mineral salts, such as calcium bicarbonate, magnesium sulfate, and sodium chloride. Since deionization requires the removal of all ions, both the negatively charged anions and the positively charged cations, materials capable of altering both are required. These materials are known as cation exchange resins and anion exchange resins The ion exchange resins are contained in pressure tanks, and the water to be deionized is forced through the resins. Typically, deionizers are either dual bed or mixed bed systems Dual-bed models have two separate resin vessels, the first being a cation unit followed by an anion unit. Cation resin collects the positively charged cations such as calcium, magnesium or sodium and exchanges them for hydrogen. The discharge from the cation tank is very acidic There are two types of anion units. Strong base anion resin units remove all anions including silica and carbon dioxide Removal of silica and CO, are specially important prior to distillation in a unit such as a wFI still They typically produce a deionized water with a ph greater than 7. Weak base anion units are used when removal of silica and carbon dioxide are not required. Mixed bed units contain both the anion and the cation resins in one vessel. Mixed bed discharge pH is typically around 7.0, neutral After a time, the resins are exhausted and must be regenerated This is done with a strong acid and a strong base. Cation resin is typically regenerated with hydrochloric or sulfuric acid. Anion resin is normally regenerated with sodium hydroxide. A neutralization tank is generall necessary to adjust the ph before waste effluent from regeneration can be discharged into the sewer. The neutralization tank and system should be laced close to the DI(deionization) system, this is due to the fact that strong acid and base solutions will have to be piped between thetwo systems. Before hookup, all lines should be flushed. For obvious reasons, mixed bed deionizers are more difficult to regenerate The quality or degree of deionization is generally expressed in terms of specific resistance(ohms)or specific conductance(mhos). Ionized material in water will conduct electricity. The more ions, the more conduc- tivity and the less resistance. when ions are removed, resistance goes up, and therefore the water quality is improved. Completely deionized water has a specific resistance of 18.3 megohms centimeter During construction, the DI system should preferably be positioned before all the walls are erected so the skid can be kept upright, in which case the vessels can be charged with the resins by the vendor before they ar shipped. This would reduce chances of damage to the internals during loading. Again, sufficient time should be allowed to reconnect all the control
Water Systems for Pharmaceutical Facilities 599 portion oftotal dissolved solids is mineral salts, such as calcium bicarbonate, magnesium sulfate, and sodium chloride. Since deionization requires the removal of all ions, both the negatively charged anions and the positively charged cations, materials capable of altering both are required. These materials are known as cation exchange resins and anion exchange resins. The ion exchange resins are contained in pressure tanks, and the water to be deionized is forced through the resins. Typically, deionizers are either dual bed or mixed bed systems. Dual-bed models have two separate resin vessels, the first being a cation unit followed by an anion unit. Cation resin collects the positively charged cations such as calcium, magnesium or sodium and exchanges them for hydrogen. The discharge from the cation tank is very acidic. There are two types of anion units. Strong base anion resin units remove all anions including silica and carbon dioxide. Removal of silica and CO, are specially important prior to distillation in a unit such as a WFI still. They typically produce a deionized water with a pH greater than 7. Weak base anion units are used when removal of silica and carbon dioxide are not required. Mixed bed units contain both the anion and the cation resins in one vessel. Mixed bed discharge pH is typically around 7.0, neutral. After a time, the resins are exhausted and must be regenerated. This is done with a strong acid and a strong base. Cation resin is typically regenerated with hydrochloric or sulfuric acid. Anion resin is normally regenerated with sodium hydroxide. A neutralization tank is generally necessary to adjust the pH before waste effluent from regeneration can be discharged into the sewer. The neutralization tank and system should be placed close to the DI (deionization) system, this is due to the fact that strong acid and base solutions will have to be piped between the two systems. Before hookup, all lines should be flushed. For obvious reasons, mixed bed deionizers are more difficult to regenerate. The quality or degree of deionization is generally expressed in terms of specific resistance (ohms) or specific conductance (mhos). Ionized material in water will conduct electricity. The more ions, the more conductivity and the less resistance. When ions are removed, resistance goes up, and therefore the water quality is improved. Completely deionized water has a specific resistance of 18.3 megohms centimeter. During construction, the DI system should preferably be positioned before all the walls are erected so the skid can be kept upright, in which case the vessels can be charged with the resins by the vendor before they are shipped. This would reduce chances of damage to the internals during loading. Again, sufficient time should be allowed to reconnect all the control