Both pure steam and water for injection (WFI) are used in many areas of the pharmaceutical industry. Pure steam is mainly used for sterilizing tanks, filters and piping systems, as well as products in sterilizers. Moreover, it is used for air-moistening in cleanroom systems. WFI is used for the production of medicaments and intermediates, as well as for the final cleaning of equipment.
Quality has first priority with both the production of pure steam and WFI. Therefore, limit values are defined and, with the respective measuring technique, controlled and guaranteed. Production procedures are at least judged by their quality, but that alone is no longer enough. Because increasing energy costs lead to higher operation costs, GMP aspects have to be applied in reference to the pharmaceutical security and qualified and validated procedures with reference to process and control guarantee stability. Complete documentation and simple visualization systems that are matched to the user's requirements are becoming increasingly important, since water-treatment systems are, in general, "energy provision systems." They are not subject to daily variations, but must produce water of a constant quality over long periods of time. Service activities such as preventative maintenance and regular calibration work must be simple and practical, and must remain so in the future. This is supported by complete documentation and clear visualization concepts. The main emphasis is on quality-relevant data, but fault and alarm signals must be self-explanatory and easy to understand.
Since the specified water quality has to be achieved not only at the output of the water-treatment plant, but also at the points of use, due attention must be paid to the storage and distribution of the WFI produced by the water-treatment system. Integrated systems delivered in the form of turnkey projects guarantee comprehensive safety and compliance with the customer's requirements and with applicable pharmaceutical regulations.
If we take a look at the defined manufacturing processes with respect to the requirements of the applicable pharmaceutical regulations, we see that both the United States Pharmacopeia (USP) and the Japanese Pharmacopeia (JP) permit, in addition to the classical distillation process, a membrane process with at least two stages. In reality, therefore, processes such as reverse osmosis (RO)/electrodeionization (EDI) with a following RO or ultrafiltration stage are already in use, but the membrane technology does not yet offer the high safety assurances provided by the phase transition from liquid water to water vapor in the distillation process. This is particularly true in cases where the WFI is not used as final rinse water, but is actually used in the production process. This means that distillation systems, as required by the European Pharmacopeia (EP), are still widely used in the U.S. and Japan.
Two physically similar systems with completely different principles are used for distillation, namely vapor compression (VC) and multiple effect distillation (ME) systems. Both methods are based on the physical law that any particles, endotoxins, pyrogens or other contaminants remain in the water during the phase transition from water to steam. Unfortunately, large amounts of energy must be transferred to the water in order to achieve this phase transition and this input of energy causes the water to move rapidly. This is, in fact, necessary in order to transfer the heat from the secondary medium (normally hot steam) to the water to be evaporated. However, this movement of the water can cause droplets of fluid to be formed and carried away with the water vapor. These droplets may contain undesirable contaminants and must be removed from the water vapor. An optimally designed system ensures removal of the droplets, is as small as possible, consumes as little energy as possible, and incurs as little investment cost as possible. Lastly, water-treatment systems must ensure that they themselves are not a source of particles or dust caused by mechanical wear in fast-running components such as pumps, compressors and similar devices. Both processes must comply with these requirements.
VC systems are based on the principle of the heat pump with four cycles: evaporation, compression, condensation and expansion. In these systems, the water is evaporated at a low pressure (in some cases, in a vacuum) and at a correspondingly low temperature. It is then condensed again. One advantage of these systems is the small amount of heat required. From the pharmaceutical viewpoint, however, this can also be regarded as a drawback since higher temperatures would provide better protection against the growth of germs in the water. In addition, mechanically rotating compressors are critical components of such systems because they are generally installed on the "clean" side of the process and are thus in direct contact with the water being produced. Still, the amount of energy that can be saved, particularly in systems which produce large amounts of WFI (> 5000 l/h), is considerable. Another benefit of these systems is that they need no cooling water. They are used primarily for the production of "cold" WFI, i.e., in cases where the water for injection has to be delivered at low temperatures to the points of use. VC systems are not widely used in Europe at present, and this is probably due to the widespread use of warm production and storage and also to the customers' reservations with respect to the safety, maintenance and availability of these systems. Most of the VC systems in use today can be found in the United States.
Without a doubt, most plants use the ME process for the production of WFI, where the evaporation capacity is split between several columns (see Figure 1). Depending on the yearly production and energy cost, as many as eight columns can be used. It is yet to be determined whether the energy savings from minor heating and cooling needs justify the capital expenditure that accompanies an increased number of columns.
[FIGURE 1 OMITTED]
As in VC systems, ME systems vaporize the feedwater only once. Due to the fact that there is a pressure gradient between the individual evaporator stages (columns), and the fact that only the first stage of such a system is heated with externally provided energy (steam or electricity), the maximum pressure must be achieved in this stage. Heating steam at a pressure of 8 bar is common, resulting in a pressure of up to 7 bar and a temperature of more than 150[degrees]C on the pure-steam side of the first column. Sufficient heating steam pressure is still the precondition for using seven or more columns, as there needs to be enough pressure to reach the necessary temperature gradient for the whole system. The water vapor produced by the first column is condensed in the second column, and the heat it releases vaporizes some of the feedwater. This process is repeated in the following columns, where the pressure gradually drops and the temperature falls to about 100[degrees]C. The pure steam leaving the last column enters a condenser cooled by the incoming feedwater, which flows in the opposite direction. At the end of the process chain, the WFI produced by the second and subsequent columns and the condensate produced by the condenser are cooled again to the necessary WFI outlet temperature of about 85[degrees] to 100[degrees]C.
This principle means that less heating and cooling energy is needed as the number of columns increases. If there are seven or more columns, and if cold feedwater is used, cooling water is unnecessary because the feedwater is sufficient for condensing the water vapor and cooling the final product.