Purified water has many uses throughout the biologics, pharmaceutical, and medical device industries – from cleaning equipment after manufacturing, to heating and cooling for sterilization and sanitization, to providing the base constituent of life-sustaining therapies. Because of the many uses for highly purified water, there are many ways to use the IMD-W system, an instantaneous microbial detection system for pharmaceutical grade waters.
The IMD-W system has been designed specifically with flexibility of use in mind. The system may be used in a laboratory setting for the testing of individual samples, and also can be placed online for continuous monitoring.
The IMD-W system’s fluorescing particle counts show a high level of correlation to conventional CFU cultured counts across a wide dynamic range.
The IMD-W’s 405nm laser intersects the water flow path. Particles within the flow path are determined to be inert or biologic, based on the presence or absence of autofluorescence.
Filling Line Cleaning /Clean-In-Place (CIP)
Typically, the filling line conveyor belt and other ancillary equipment are considered product contact surfaces for the purposes of pharmaceutical, biologic, and medical device manufacturing and, for that reason, need to be as clean as the product itself. Residual API or sugars, for instance, may harbor microbial growth which could compromise sterility in the cleanroom. Therefore, water used for cleaning filling lines, conveyor belts, and other machinery should be rinsed down to bulk purified water levels with zero chemical residuals. The IMD-W system can facilitate the process by determining the water’s microbial count prior to these cleaning processes, either by assessing grab samples from the clean water line, or for CIP processes, through direct online connection.
Pretreatment and Reverse Osmosis (RO) Effectiveness
Sampling of the purified water generation process, near or at the end of the pretreatment, is performed to confirm water quality inputs into Water-for-Injection (WFI) or Purified Water (PW) generation systems. Here, the IMD-W system can be used to monitor continuously the post-RO filtered water, much as online conductivity and TOC instruments are used. When combined, these data will help paint a picture of the pretreatment water generation process, support the development of schedules for critical system cleaning and sanitization, and lead to a better understanding of the microbial nature of that process throughout water production.
Storage Tank Sampling
Water within storage tanks usually is re-circulated to reduce the chances of microbial adhesion and biofilm formation. Even in these closed systems, changes may occur in not just the microbial quality of the water, but also in the integrity of redundant filters and gaskets. An IMD-W system can be very useful in monitoring these loops on a continuous basis to assure that microbial levels are low or to maintain a constant baseline. Potential contamination from gasket and filter changeouts may be monitored in real time, and the resulting data used to support the decision to bring a water generation system back into production. Finally, continuous monitoring of recirculating storage tanks allows for greater understanding of microbial proliferation in the system being monitored, if any exists. These data can provide a concrete rationale to justify water hold-time recommendations.
Water System Validation
Validation of a purified water system typically is performed upon installation of the line, or when there are modifications to it. Every sample site is sampled, each day, for a period of a month or so during validation. This is a very work-intensive process using traditional methods, requiring those involved to wait each day for updated results from the past several days, and then to make adjustments to the line until counts are right. By using an IMD-W system, this iterative adjustment process can be greatly accelerated as a result of IMD-W’s instantaneous microbial feedback on each water sample collected.
Routine Water Sampling
After water system validation has been completed, it is possible to reduce sampling requirements based upon schemes to monitor Critical Control Points (CCP) or through risk analyses of the validation data. In this situation, an online IMD-W system installed at each CCP can deliver continuous monitoring capability. Generated data can be sent to a central location and monitored remotely, much like data from online conductivity and TOC analyzers are managed. In this way, the IMD-W system can accelerate actions to mitigate risk and reduce investigation costs, driven by data collected in real time while offering a means to enhance process understanding.
The IMD-W system’s advanced signal processing algorithm discriminates a biological particle by using three different signals.