Since the early days of combining chemical ingredients to synthesize medicines, high-purity water has become an essential component in various pharmaceutical manufacturing processes. In the production of biologics derived from living organisms, the role of water for injection (WFI), the highest quality water in compendial monographs, is even more critical as it is often a component in creating the drug substance itself.
Due to the need for compliance and reliability, the industry has traditionally produced WFI through distillation, a steam-heated purification method that is effective and robust but also costly and energy-intensive. Today, we explore the benefits of an alternative method based on advanced membrane systems for producing WFI at low temperature, highlighting how this “cold WFI” approach can drive not only efficiency and compliance but also long-term sustainability and safety.
A compelling alternative to distillation
Modern cold WFI systems, based on reverse osmosis (RO), electrodeionization (EDI), and ultrafiltration (UF) technologies, utilize semi-permeable membranes under pressure to remove impurities from water, avoiding the need for heat to convert water to steam and condense it back to its liquid form.
Here are some key advantages of membrane systems for producing cold WFI:
1) Capital and Energy Efficient
Membrane-based technologies are associated with lower equipment outlays than distillation systems, which require extensive pre-treatment to mitigate scaling and corrosion risks. Because of its energy efficiency, operating membrane systems at ambient temperatures is also more cost-effective because they avoid the expense of raising the water to vaporization temperatures. All in all, membrane systems are an attractive option to both optimize capital budgets and reduce operational costs, leading to accelerated returns on investment.
2) Robust Microbial Control and Monitoring Programs
Since cold WFI generation systems do not operate at high temperatures continuously, they rely on an automated hot-water sanitization cycle to prevent biofilm build-up. Similarly, distribution loops are sanitized through intermittent ozone exposure. Meanwhile, low-temperature WFI storage tanks are self-sanitized through consistent exposure to ozone, typically generated on-site with an electrolytic generator. Ozone acts as a strong oxidizing agent that, when dissolved into water, instantly neutralizes biological matter (bacteria, viruses, and other pathogens), ensuring tight microbial control. To this end, the latest advances in online analytical instrumentation enable microorganism testing and analysis that detect bacteria and endotoxin in real-time, in addition to chemical impurities such as conductivity and Total Organic Carbon (TOC), hardness, and chlorine.
3) Consistently Compliant Water
The advanced membrane technologies used in cold WFI systems produce water quality that exceeds that specified in compendial standards, to allow for a margin of safety against any impurities that may be collected before the point of use. The final ultrafiltration membrane barrier is particularly effective at removing residual organic impurities and microbial contaminants, especially bacterial endotoxins, guaranteeing depyrogenated water that ensures the integrity of pharmaceutical products.
4) Faster, Low-Temperature Sanitization
Thanks to ozone-based sanitization of cold WFI storage and distribution systems, costly downtime and interruptions are significantly reduced compared to hot systems, whose heat-based disinfection requires a longer time to allow temperatures to rise. Continuous tank ozonation extends cycle runs and reduces the frequency of loop sanitization, which features lower downtime, minimal energy consumption, and wastewater generation. Thus, cold WFI systems have higher uptime, faster return to production, and less disruptive sanitization cycles.
5) Electricity-Driven Operation
Unlike distillation systems, electricity-driven processes, such as membrane-based cold WFI generation, can readily replace heat, a major driver of on-site emissions through fossil fuel combustion in natural gas-fired boilers. By capitalizing on renewable energy sources, cold WFI generation provides greater energy security with lower volatility, paving the way for long-term, all-electric, zero-emission manufacturing operations.
6) Space Saving Design
Thanks to a simplified layout that features a complete assembly fully integrated with a built-in reservoir, cold WFI systems are compact and require less floor space compared to traditional distillation units, which rely on utility boilers to produce and distribute the steam they depend on. This is particularly advantageous for facilities with limited space, allowing for more efficient use of the available area or decreasing the physical footprint of a new building.
7) More Safety with Less Maintenance
By eliminating the need for routinely heating water, membrane systems contribute to a safer working environment. With no risk of direct contact with hot surfaces, bursts, or spillages, there are no burns or need for insulation, jacketing or labeling. Concerning maintenance, the lack of heating elements and reduced mechanical complexity means that membrane systems are less prone to breakdowns and can operate continuously for extended periods. This reliability is essential for maintaining production schedules and avoiding costly interruptions. Low operating temperatures are also less conducive to rouging, which avoids re-passivation, while reducing the wear and tear on components such as fittings, elastomers, and gaskets.
The transition from traditional hot distillation to low-temperature, low-energy membrane systems for producing WFI is underway and represents a revolution in pharmaceutical water purification. With benefits spanning building design, system operation, monitoring and maintenance, it is easy to see why modern pharmaceutical manufacturers choose the value offered by cold WFI systems that ensure compliance, drive efficiency, and gain competitiveness and productivity.
