Many pharmaceutical products require ultra-purified water as part of their makeup. This water for injection (WFI) is purified through multiple steps to achieve a level where it consists of virtually nothing else but hydrogen and oxygen atoms. It requires a multi-step process to achieve water with this level of purity. Once this has been accomplished, the water must be continuously “polished” to maintain purity. It is even more critical for WFI systems than other, less-pure water systems to ensure that the entire system and its sub-components are free from bioburden and other organic contaminants.
Traditional Purification Methods and Their Challenges
The first step in the process of making WFI is reverse osmosis (RO) where the water is forced through a membrane by pressure to remove salts and minerals that occur in municipal water supplies. This filtered water is moved into the next stage where any remaining impurities, including mineral ions, are removed by passing the water through a bed of resin beads composed of organic polymer chains which will bind with any negatively or positively charged particles. This process removes substances such as ammonia, boron, silica and carbon dioxide. The complete process results in purified water that is suitable for pharmaceutical use
Historically, the process of generating WFI has required distillation as an essential step with the two major still designs being Vapor Compression and Multiple Effect. In either design, feedwater is boiled and the resulting steam is condensed back to liquid form. The water is kept at an elevated temperature of 80°C (176°F) throughout the system to kill off any bacteria and prevent the build-up of bioburden – masses of biological colonies residing on interior surfaces of piping, tanks and other components. However, maintaining the water temperature has the downside of being energy intensive, adding to the cost of production.
Electrodeionization (EDI): A Modern Alternative
In mid-1970s, the first steps were taken in developing a new process called electrodeionization (EDI), which is also known as continuous electrodeionization (CDI). The goal was to achieve a system where the only consumable was electricity and the use of chemicals was greatly reduced or eliminated. However, these early systems remained expensive and difficult to maintain. It was only recently that technological and regulatory hurdles were overcome to make EDI systems more commercially viable while being as clean as traditional, “hot WFI” systems.
Challenges in Ambient WFI Systems
Even with these breakthroughs, ambient WFI systems are still expensive and complex. Since the high temperature that kills bacteria in a distillation-fed, hot WFI system is not present in an ambient WFI system, ambient systems can be more susceptible to the buildup of bioburden. This has come as a surprise to some operators who have converted their traditional, hot WFI systems to an ambient temperature WFI operation. In a traditional WFI system, filtration chemistry and high temperature are utilized to prevent a build-up of biomass. A common error among operators of EDI systems is not realizing that the new ultrafiltration (UF) filters need to be changed more frequently. As a result, bacteria can spread throughout the system, requiring a complete shut down and thorough cleaning and sanitization procedure.
Risks in WFI System Conversions
Another issue arises from the design of the WFI system itself. A simple conversion of replacing a traditional WFI system with an EDI unit can lead to unforeseen complications and bacterial growth. Simple factors such as an improper gasket size or tightness, a dead leg with low water flow, an improper slope, or just the lower temperature of the water can set up conditions where bacteria can breed.
Validation and Ongoing Maintenance for EDI Systems
Even with relatively few stainless steel internal components itself, a new EDI unit will need to undergo pre-commissioning treatment regardless of whether it is a component of a new system or replacing a traditional deionizer. Operators will still need to consistently monitor and sample the system’s throughput on a schedule that meets the specific requirements of the technology and take into account the different behavior of bacteria at ambient versus hot temperatures. “We’ve always done it this way” can become a recipe for contamination.
Astro Pak’s Approach to EDI System Cleaning
Because of the sensitivity of EDI units to chemistry and heat, many surface remediation service providers have been reluctant to take on jobs cleaning this new technology. However, Astro Pak has worked with manufacturers of various EDI systems to develop a process based upon its five-stage bioclean process. When a WFI system is taken offline because of bioburden, Astro Pak looks at the entire system as a whole. Starting with the point where municipal water first enters the system to begin treatment, bacterial test results (including bacterial species and counts), trending data and the cleaning methods attempted to date are used to determine how much of the system has been impacted and what the best course of treatment is required to completely eradicate the biofilm and bacteria.
Derouging the stainless steel segments of the entire circuit is often a first step as the crystalline structure of the iron oxide provides a safe harbor and nutrients for many bacterial species. Remediation solutions range from replacing membranes and filters, checking fittings and gaskets, to passivating the stainless steel to strengthen its resistance to future corrosion. Astro Pak will assess and work with any combination of water purifying equipment to develop the most effective bioremediation possible while still maintaining safety and chemical compatibility.
