The Right Technique Economical Production of WFI

Safety is the top priority in WFI (Water for Injection) production, but cost efficiency is also an important consideration. Intelligent media flow configurations provide the answer.

Related Vendors

EDL Anlagenbau Gesellschaft mbH

Pörner Ingenieurgesellschaft mbH

ProMinent GmbH

The European Pharmacopeia (EP) stipulates that distillation must be used to produce water for injection (WFI). The American Pharmacopeia allows distillation and other suitable methods. At the current state of technology, this means reverse osmosis in combination with EDI systems and ultrafiltration. It is no secret, however, that thermal systems are the solution of choice in the US. When the HPW water quality grade was introduced in 2002, the EMEA Quality Working Party cited the reasons why thermal treatment is preferred. In 2008, the EMEA published the Reflection Paper on Water-for-Injection prepared by Reverse Osmosis, which reaffirmed the concerns relating to the safety of the RO process. It is feared that defects in the RO membrane or leakage could allow pathogens to pass through. The paper also criticizes the lack of methods to test integrity which makes validation difficult. In addition, biological deposits in areas with poor flow and endotoxin contamination can cause microbiological problems.

Assessing system efficiency

The first factor to consider in the selection of a WFI production system is daily volume and peak demand. This information can be used to determine the hourly throughput of the distillation system and the capacity of the storage tank. As product volumes increase, users tend to look more closely at process cost and system efficiency. The costs are broken down into capital investment costs and ongoing operating expenses.

Media supply is another major issue. What sources of primary energy are available (steam or electricity)? What cooling media are available? Can a distillation system be deployed which eliminates the need for cooling water? It is also important to ensure that sufficient volumes of the media are available and that there is enough space (footprint, room height, etc.).

Choosing the right solution

Energy-saving technology is not available on single-stage distillation systems (apart from simple feedwater preheating and insulation), which is why these systems are generally unsuitable for industrial-scale applications. The range of WFI applications is generally restricted to labs, pilot production and pharmacies. Most of the systems have electrical heating, and the energy costs are higher compared to systems with steam heating. Cooling water consumption is also disproportionately high.

Multi-stage pressurized column distillation units are the most widely used solution in the pharmaceutical industry. The systems operate with heating steam at 3–8 bar and have between three and ten columns. Efficiency increases as more columns are added at constant throughput. Increasing heat exchanger surface area reduces energy consumption. As the heating steam pressure increases in the first column (variable between 3 and 8 bar) and the temperature rises, system performance increases because there is a larger temperature differential that can be distributed.

Reduced stand-by costs

The WFI is unpressurized when it leaves the system, and it has a temperature of 85–95 °C. Systems with six stages or less require cooling water. No cooling water is needed on systems with seven stages or more. A special feature of falling film systems is the low volume of water which is present in the system during the ongoing process and which is automatically removed from the system when it is shut down. Following a cold start, the units are back in production within ten minutes, which reduces stand-by costs. On a WFI system rated at 1000 l/h, these costs can add up to € 40,000 over a 15 year period. Pharmastill falling film technology is very energy efficient due to the optimal coupling between the hot liquid WFI and the feedwater.

The efficiency (kilogram of heating steam per volume of WFI produced) of multi-stage WFI systems with more than six columns is comparable to that of thermocompression systems. Thermocompression is the most economical method for production of cold distillate or optionally hot distillate. The key component on the system is the turbine compressor (heat pump) which condenses the vapor from the heated feedwater and raises the temperature from 100 °C to about 140 °C. The energy released by the condensed steam during condensation is used to heat and vaporize the feedwater.

No need for cooling water

The energy extracted from the hot WFI, incondensable gas and concentrate is fully exploited to pre-heat the feedwater, and that is another key feature which contributes to overall system efficiency. With this type of process, there is no need for cooling water. Users do not spend money on cooling water, and the installation and maintenance costs are also lower. Large heat exchangers minimize the velocity of the rising steam, ensuring excellent droplet separation. This type of system will work well with water that has only been softened.

The incondensable gases also rise at low velocity, and they can be effectively removed. As a result, the use of water that has only been softened can also go hand in hand with distillate of assured low conductivity.

The results of a risk analysis for a distillation system must contain explicit specifications for the materials and finishes as well as a definition of the process parameters. Experience shows that the process temperatures should be kept as low as possible to effectively minimize rouging. The system should be designed to eliminate additional droplet separation baffles and cyclones as far as possible. Thermocompression is virtually the ideal solution for meeting this requirement.

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