A pharmaceutical water system that it is in compliance at all times and produces the intended quality of water, should be properly monitored and controlled with a variety of parameters and instruments. When planning the system, breaking it into three sections – pre-treatment, purification, storage and distribution – simplifies the design process and will allow the system to be engineered to meet the facility’s demands.
Pre-treatment
The source water is a significant determining factor in what pre-treatment technologies will be utilized. While the pharmacopeia requires, at a minimum, that the source water be safe for human consumption, the ionic and organic profile of that water will vary depending on the source used, ground water or surface water. This should be known and taken into consideration when deciding on the pre-treatment system. A typical pre-treatment system incorporating several removal technologies and the parameters that should be incorporated into the system to monitor performance and contaminant removal is shown in below figure.
This system includes filtration (multi-media and cartridge filters), softener (to reduce hardness), Granular Activated Carbon (GAC - for organic removal) followed by additional filtration at a smaller micron rating, UV treatment (for inactivation of microbial contaminants) and then the addition of acid, alkali or sodium bisulfite to adjust the pH and remove chlorine.
Many of the pre-treatment processes involve the physical removal of contaminants so monitoring will utilize pressure and flow to determine maintenance and replacement schedules. Further in the pre-treatment module, pH and ORP are the controlling parameters for the adjustment of pH and determining the removal of chlorine or other oxidants.
Purification
The purification section will vary depending on the water type being produced for the specific pharmaceutical applications and the capacity required, plus any future expansion requirements. In general, if the intention is to produce WFI the purification will include reverse osmosis and either deionization or electrodeionization followed by distillation. The inclusion of UV oxidation is for inactivation of bacteria, and in some systems there may be ultrafiltration, but it would only be installed before the last purification process. Filtration after the water has been treated is strongly discouraged by the regulators as it may be a potential site for microbial growth.
The entire purification process is shown in below figure with the parameters that should be incorporated in the system. The purification process is the part of the pharmaceutical water system that determines the quality of the water and the type of water that is being produced. This is also an area of a pharmaceutical facility that will be audited by regulators and inspectors (the water system is one of the most audited aspects of a pharmaceutical facility).
The measurement parameters utilized in the purification process are not only used to control the performance of the system, but are also the measurements that must be reported to confirm the quality of the water being produced. Control and system monitoring of the process will or should include; flow, pressure, temperature, bioburden, pH and ORP. However, these parameters are not part of the required tests for the pharmacopeia, but they are critical to the proper control of the purification system. In addition, there will be conductivity and TOC measurements installed on the system, not only for control and monitoring, but also as regulatory control points. For WFI and PW there are conductivity, TOC and microbial contamination limits that must be monitored and reported. While off-line testing is still permitted, the pharmacopeias are encouraging the use of on-line testing and cautioning that off-line testing can be a source of false test results.
Storage and distribution
- stainless steel Grade 316 L (low carbon)
- polypropylene (PP)
- polyvinylidenedifluoride (PVDF)
- perfluoroalkoxy (PFA)
- unplasticized polyvinylchloride (uPVC) used for non-hygienic designed water treatment equipment such as ion exchangers and softeners
