The control of microbial growth in systems for producing United States Pharmacopeia (USP) Purified Water is of critical importance to pharmaceutical manufacturers. It is also of critical importance to the United States Pharmacopeial Convention Inc. (USP) organization, as evidenced by the sheer number of pages dedicated to the control of micro-organisms in the proposed USP 23 General Information chapter 1231 "Water For Pharmaceutical Purposes" (1).
If a water purification system is designed, operated, and maintained properly, it will not be plagued by microbial contamination. However, if special attention is not dedicated to the control of microbial growth, problems will very likely result. Neither the proposed (USP 23) nor the current (USPXXII) specifications for USP Purified Water have established a limit for microbial concentration. However, the General Information chapter in both cases gives a "recommended action limit" of 500 colony-forming units per milliliter (cfu/mL) for the feedwater and 100 cfu/mL for the final product water. Despite the fact that these action limits are not necessarily required, most pharmaceutical manufacturers strive to maintain microbial concentrations below these recommended action limits. This article will address the methods for operating and maintaining a USP Purified Water system to continuously meet the objective of 100 cfu/mL.
Typical Purified Water Systems.
A typical USP Purified Water system may consist of several processing steps, each designed to provide further purification of the water. The first step of a typical system, based on two-pass reverse osmosis (RO) technology, is usually a multi-media filter followed by a water softener to remove insoluble particles and hardness ions, respectively. Next, a bisulfite (HSO3) injection system may be used to remove chlorine. The central purification process is then the two-pass RO system. The final step is to pump the purified water to a heated or ozonated recirculating loop.
Feedwater: The first task of system design is to evaluate the feedwater. When microbial contamination is a concern, it is important to measure the residual disinfectant in the feedwater and obtain a baseline microbial count. This baseline microbial count and disinfectant concentrations should be monitored over each season of the year to determine the possible range encountered from season to season. The disinfectant residual should be high enough to maintain a microbial concentration at or below the USP-recommended action limit of 500 cfu/mL. The typical city water supply contains between 0.2 and 1.0 parts per million (ppm) of free chlorine (or chloramines) and, in most cases, is adequate to control microbial concentrations in the feedwater to the USP Purified Water system.
Pretreatment steps: As mentioned above, the first processing step is usually filtration with a multi-media filter containing gravel, manganese greensand, and anthracite. The primary purpose of the manganese greensand is to remove iron, but it also serves as a very good particle filter. The anthracite provides a "light" layer that is easily backwashed, alleviating much of the load from the greensand, allowing the sand to perform more effectively. These two media types together are effective at removing suspended solids at sizes as small as 5 to 10 micron (µm).
The second processing step is typically water softening, using ion-exchange softening. The water softener is used to remove hardness (calcium and magnesium) from the water, replacing these with sodium ions. Removing hardness protects the RO system by keeping hardness scale from forming on the membrane surface. It is best to not control scale by acid addition, which has the disadvantage of increasing the free carbon dioxide (CO2) by shifting the bicarbonate to carbonic acid that, in turn, dissociates into CO2 and water. The resulting carbon dioxide will pass through the membrane, producing a high-conductivity product water as the CO2 re-associates with the water to reform ionic bicarbonate.
- Courtsey: M/s Aquazone Systems & Engineering