Design Considerations for Water for Injection (WFI) Distillation Systems for Improving Quality, Project Performance, and Equipment Life Cycle Cost Reduction was featured in the September/October 2015 issue of Pharmaceutical Engineering® magazine.

This four-part series presents and discusses a number of key requirements and design, quality, and engineering considerations that have high importance in end-user usability, cost control and end-product quality that help manage risks in Water for Injection production and processes.  Part three reviews:

  • Should you expand your current facility or build a new one?
  • Typical Utility Connections for WFI distillation systems
  • Efficacy of High Temperature and Particle Separation of WFI Process
  • F0 of WFI Process

Expand Existing Production or Build a New Facility?

A new facility gives more freedom in equipment and process design in comparison to upgrading or expanding existing production capacity. With existing equipment, the impact of existing validation-procedure requirements on the upgrade process must be considered; having to redefine validation procedures due to major equipment upgrades can be time-consuming as well as resource-consuming.

When a completely new facility and equipment are being designed, it is recommended to discuss with management any expansion plans that may help prepare for increased capacity, such as reserving extra space for additional equipment or sizing the unit so that there is extra space for future use. A backup plan in terms of ensuring available capacity using duplicated processing units or dividing capacity over two or more units can be worth the investment in true 24/7 operating production facilities that allow minimal or no downtime. Duplicating equipment is a big investment, but it may be just a fraction of lost production capacity in a situation where there is prolonged downtime. Dividing the WFI production capacity from one big central unit to two smaller units may increase the investment cost but never by a factor of two. This solution can guarantee the minimum of half-capacity at all times and provide flexibility for planned downtime arrangements, such as periodic preventive equipment maintenance.

Along with the redundancy scenario considerations, it is important to acknowledge that a simpler system is better and more reliable. Do not fall into the trap of over-engineering that can compromise the reliability of the system and have negative implications on the quality of production. Unnecessarily complicated processes require more maintenance, more spare parts, more validation, more testing, and more documentation and can lead to an increased number of welds, connections, and ports that can compromise the WFI process.

If pure steam is required, consider whether an independent unit is needed or should the distillation unit be equipped with a pure steam generator operation, simultaneous steam generation, or a simple pure steam outlet port. One has to remember that a pure steam generator operation isolates the rest of the unit and produces only pure steam at the time of use. Simultaneous operations are typically not designed for central autoclave pure steam supply but for other smaller needs.

A combination-type unit means that the WFI is still equipped with a significantly bigger first column followed by a number of smaller distillation columns to be able to run steam generation for larger steam header systems with distillation simultaneously and without risk of process fluctuations.

Typical Utility Connections for WFI Distillation Systems

The following utilities are typical for WFI distillation systems:

  • Feed water to unit (ambient temperature, sufficient supply pressure)
  • Cooling water (supply pressure and temperatures according to open- or closed-loop system)
  • Plant steam supply (typically three to eight bars, depending on the system)
  • Atmospheric drain connection for blowdown and other reject waters
  • Plant steam condensate return to heating system
  • Three-phase electrical connection
  • One-phase electrical connection (typically in case of additional peripheral devices)
  • Ethernet connection wiring from the unit’s control system to the facility BMS system for data collection and remote start/stop
  • Dry contact wiring for possible handshake signals (for example, from the pretreatment system or WFI storage tank)

With multiple-effect water distillation systems, the steam utility line size may be bigger compared to a vapor compression steam connection. On the other hand, the electrical-connection power requirement for cable and main fuse size for a vapor compression system is significantly bigger. Multiple-effect systems require three-phase electricity merely for the feed-water pump and control system, while a vapor compression system requires high electrical power for its compressor. Cooling-water connection size and need depends directly on the cooling-water loop temperatures available, as well as the number of effects applied to the MWS or the cooling-water needs of the vapor compressor.

Efficacy of High Temperature and Particle Separation of WFI Process

The greatest means of risk mitigation with high-temperature distillation systems that employ separation of impurities is the safety they provide from contamination by microorganisms or their particles. Just as important is the removal of nanometer- or smaller-size particles that could affect patients when they are injected into the body. Microbial contamination in WFI cannot be detected by any sensor during on-line production. Conductivity of water can be one indicator of WFI quality and low conductivity to indicate sufficient quality of WFI, along with periodical off-line sampling for endotoxins. However, overlooking the highest risk of microbial contamination by small particulate presence in WFI can cause risks affiliated with patient safety – and especially with patients who have an infection or who are undergoing treatments that lower their resistance. Therefore, any considerations of not having sufficient microbial-controlled WFI production should be ruled out.

F0 of WFI Process

Heat is an effective means of microbial control. Heat sterilizes the water through the different stages of the heat distillation process, starting with heating up the feed water in the condenser, going through column pre-heaters in each stage and finally ending in the first column, which operates with plant steam and exposes incoming water to the highest temperature. Following the route of feed water to flash vaporization and condensing to final distillate takes place in each column, ending at the condenser outlet, typically at 95°C to 99°C for the MWS. Typical maximum operating pressure for plant steam is eight bar, and this respectively equals to a temperature of 175°C. The WFI processing temperature or the exposure temperature of feed water and WFI throughout the process of MWSs is typically between 143°C and 175°C. In comparison, the typical operating temperature in processing WFI with vapor compression technology is significantly lower: between 100°C and 105°C. This means that in a multiple-effect distillation process, the F0 exceeds the equal sterilization batch exposure time significantly, where the vapor compression distillation process does not reach F0 = 15 at any stage of the process. Water dwell time in this process is too short, and the temperature too low.

Since the exposure time of water passing through the equipment is measured in seconds instead of minutes, the high temperature in exposure is critically important to achieving acceptable sterility levels that ensure a Sterility Assurance Level (SAL) of 10-6.

This is a key element for safety of any such production, and calculating the F0 value for the WFI system is critical. The heat exposure of water is not only estimated in the highest temperature of the first column but the F0 accumulates in every part of the process where the exposure temperature exceeds 100°C.

The F0 accumulation is exponential, and this shows when looking at water exposure in the WFI process at higher temperatures than the reference point of 121.1°C. For example, in the first column the feed-water temperature can rise to 170°C when running at eight bar of plant steam pressure. To achieve the same F0 at 160°C that equals to 15 minutes at 121.1°C, only 0.12 s is required. See the time/temperature correlation table for reference (Table B).

WFI Distillation Systems Table B

By:  Juha Mattile, Sr. Product Manager for Steris Finn-Aqua High Purity Water & Team, VHP Sterilization and Effluent Decontamination systems and Mike Parkka, Project Manager for Steris Finn-Aqua

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