Purified water, microbiological control

Regulatory expectations for microbial bioburden for nonsterile pharmaceutical products are reviewed using the FDA guide to inspections of microbiological quality control laboratories [2], purified water systems [27], topical products [28], and oral solutions and suspensions [29]. 

Now that we have determined what processes the facility will be used for, we can finalize utility requirements. The following utilities are required for our solid-dose facility heating, ventilation, and air conditioning (HVAC), hot and cold water, steam, electrical service, compressed air, vacuum systems, dust collection, chillers, effluent stream, and purified water. For the more specialized processes or special material handling, we may need specialized gases and breathing air. Purified water is one of the more difficult utilities to maintain the quality of. From a source of potable water, a series of treatments must be performed to control microbiological quality. Typical treatment options include carbon filters, reverse osmosis, and UV radiation. 

Water quality is usually defined in terms of chemical and bacteriological purity, particulate matter content, and endotoxin levels. Potable water is normally from the municipal water system, which may have been treated with chlorine to control microbiological growth. Soft water and deionized water have undergone ion exchange or similar treatment to eliminate unwanted ionic species, such as Mg2+ and/or Ca2+. Purified water, water for injection, and other types of water meeting compendial specifications are produced by ion exchange, reverse osmosis, distillation, or a combination of such treatments. 

The pharmacopoeias deal with ingredient water of two types. Purified Water and Water for Injection. The principal difference in biological quality between the two types of water is that Water for Injection is specified to be pyrogen-free (less than 0.25 Eu of bacterial endotoxin per mL). Only water of Water for Injection quality may be used to dissolve, dilute, or compound parenteral products, because endotoxins may pass through 0.22 pm sterilizing filters. Control of bacterial endotoxins is achieved in the first instance through control of microbiological contamination. 

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