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Design Considerations for WFI Distillation Systems Part 1

Juha Mattile
Mika Parkka

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 three-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 one will review:

  • Design considerations from the perspective of different distillation methods
  • Systems with WFI product against back pressure

WFI production is a critical part of any parenteral drug process. There are several factors that need to be considered when selecting WFI production methods, such as capacity, future needs, storage, and quality control. This article discusses, among other things: concentrating on the end-user perspective when designing WFI distillation systems, evaluating different possible configurations, the latest available technologies, setting criteria and overall requirements, and the implications with regard to pharmaceutical production processes.

WFI Distillation Systems Technologies

This article also discusses design considerations from the perspective of different distillation methods. It focuses on the requirements of the European Union, but these methods can be applied to North America as well. The methods specifically in question are multiple-effect distillation and vapor compression distillation. In general, both of these are considered common technologies, but for clarity it is beneficial to highlight some major differences between them. Vapor compression technology was originally designed for desalination processing. The process utilizes preheating and heat recovery along with the core, which uses the latent heat of steam by superheating vaporized feed water via the compressor, providing energy efficiency as well. The compressor operates by using electrical energy between approximately 15 kW to 20 kW per hour per produced 1,000 kg/h of WFI water. Multiple-effect water still (MWS) uses general plant heating steam for heating in the first stage of the process, after preheating the feed water by condensers evaporating the pure steam to WFI. Next in the process, preheaters and several column stages (there are typically six to eight columns for today’s energy-efficiency requirements) vaporize pure steam and generate WFI. One major difference in these two technologies is the processing temperature. Vapor compression technology typically distillates in lower temperatures (for example, 105°C) and ends with room-temperature WFI (between 25°C and 35°C), where the multiple-effect water-distillation process utilizes nearly the maximum temperature provided by the heating steam (typically between 150°C and 170°C, depending on the used plant steam pressure) and ends with WFI (typically between 85°C and 95°C). More specific comparisons between these two technologies can be found in several Pharmaceutical Engineering articles covering this topic. See the schematic-diagram examples for typical WFI water pretreatment, WFI generation, and WFI storage systems (Figures 1 to 3).

Design Considerations for WFI Distillation Systems Design Considerations for WFI Distillation Systems Design Considerations for WFI Distillation Systems


Determining the Daily and Maximum WFI Quantity

The daily quantity of WFI or pure steam required for any parenteral drug process typically plays a significant role in the overall manufacturing process. If a high volume of water is continuously needed, the entire manufacturing process may depend on the kind of equipment used and the available storage capacity. In instances of the occasional use of water, the necessity of equipment may be less, especially if the required amount of WFI in bulk can be obtained from outside sources. In cases where a minimal amount of WFI, such as 1,000 liters per week, is needed, in-house control of WFI production may still be preferred or probably cost less than purchasing it. Knowing the WFI usage will allow for optimal design of the process. This knowledge will help to determine the proper size of the WFI holding tanks, holding time, and energy required to maintain temperatures (especially in the most common situation of WFI storage at temperatures of 80°C or higher) to ensure the availability of a consistent supply of WFI for the facility. It is essential to monitor the operating interval, counting back to the capacity needs in the process, how many shifts per day, and immediate peak needs.

System with WFI Production against Back Pressure

One safety precaution to ensure the quality of the WFI in the tank is to use a nitrogen blanket at slight overpressure. This measure minimizes the possibility of having air pockets as a source of contamination in the vessel. The challenge for the WFI distillation systems is overcoming the positive pressure that is present in the WFI tank. If the WFI distillation systems has the possibility to naturally produce WFI at a positive pressure, this can eliminate having to add a distillate transfer pump, tank, valves, and other instrumentation, which may complicate, add cost, and create a risk of contaminating the supply system. Most WFI equipment either relies on gravity feed, meaning the outlet needs to be higher than the WFI tank inlet, or requires a WFI pump. The multiple-effect distillation process can, however, be designed to push distillate up to five meters of H2O (0.5 bar) of back pressure naturally and without the use of an additional pump. This can eliminate having to raise the unit or condenser and does not require an additional pump in the system.

Define the available floor space and room height, bearing in mind the required service clearances around the system. Equipment should be designed so that there is service clearance from at least two sides of the equipment. Ensure the route for transporting the equipment onsite.

No one wants surprises when building a new facility or expanding/renovating. In order to avoid unexpected setbacks, study the entire route before bringing in the new equipment. It is always easier to break old equipment into small parts; new equipment often requires a similar process but in reverse. It is also important to remember that this equipment may be heavy, especially when full of water. This needs to be taken into consideration when calculating the floor load design and plans. The equipment area requirements and any maintenance clearances need to be considered when repairing or replacing components. Anything brought in-house may have the benefit of being tested as a whole – including all functions, sensors, and calibration. Any equipment that is physically disconnected from wiring may require recalibration. Be sure to consider this in the Site Acceptance Testing (SAT) or onsite validation cost. Having documented proof that sensors and analyzers were tested and verified at the supplier’s facility before delivery at Factory Acceptance Testing (FAT) and not disconnected after that can significantly reduce the onsite SAT and qualification timeline and cost. The cost of modification at the supplier’s facility compared to onsite work is estimated at only 1:3.

Following the ASME BPE Standard

The ASME Bioprocessing Equipment (BPE) standard is an excellent tool for designing a sanitary process. The content is specific to material selection, types of applicable components, piping dimensions, types of connections, surface finishes, mechanical assemblies, and cleanability and process applications in general. The intention of the standard is to help with designing new equipment but also not to limit any new technologies in case they are novel and not noted in the specification. It’s important to understand that there are always a number of required physical properties or methods that cannot be applied simultaneously and rule each other out in some cases. It is encouraged and beneficial to demand a statement from the vendor and see where the expectations, requirements, and available offerings meet and agree. Some examples might help to explain this: One such example is welding a pipe branch with 2D maximum dead leg using orbital welding. This may not be possible in the case of small-diameter pipes, such as outside diameter (OD) inch and OD ¾ inch, since the 2D branch length is less than 20 millimeters, which is typically required to fit into an orbital weld machine clamp.

This is acknowledged in the ASME BPE as not being an absolute requirement. However, this may still be achieved by using hand welding; the dead leg minimum requirement can be reached but by using hand welding instead of the generally preferred orbital welding. Surface roughness is better in orbital welding than in hand welding; that’s why it is preferred. Pipe bending vs. number of welds is also an interesting point of discussion. Even with the best of the bending machines, some of the inner surface finish is lost in an elbow bend; what is achieved, however, is not having two welds in the pipe. This is a far better alternative than adding to the number of welds or components in the process piping. Any other excess connections, such as clamps or flanges, may be avoided in the same way. Drainability of equipment: It is not required to slope a pipeline that is 250 millimeters long or less. In other words, sloping is required for pipeline runs that are longer than 250 millimeters. Especially with large-diameter pipes, this may typically be achieved by forced sloping against tubing physical properties if bending vessel connections or adding sloping parts to flange joints is not feasible. However, this is not allowed due to the risk of weld leaks and pressure vessel safety, so this rule can conflict with the ASME Pressure Vessel Code, which always takes priority. There are many more examples of design considerations based on ASME BPE. While some direct assumptions may not be possible based on the ASME BPE standard, prioritizing the features that are the most desirable or appropriate for the processes and applications is important.

Catch up on the rest of the WFI Distillation Systems series:

In July, the ISPE Training Institute will be conducting a manufacturing efficient, product quality and GMP compliance training focusing on: