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