With the European Pharmacopoeia updating its guidelines in 2017, manufacturers now have a choice of methods beyond the traditional distillation systems to produce water for injection (WFI). Here we look at what the options are and what customers need to consider when making their choice.
For many years distillation has been the only WFI option for biopharmaceutical businesses who operate in, or supply their products to, Europe. This changed in April 2017 when the European Pharmacopoeia amended its guidance to bring it in line with United States Pharmacopoeia (USP) and Japanese Pharmacopoeia (JP) where other methods have been permitted for many years.
The revised standards allow manufacturers to choose between distillation and an alternative purification method that would produce water of an equivalent quality. This includes membrane systems such as reverse osmosis (RO) coupled with a suitable secondary membrane system such as ultrafiltration (UF). As with distilled water, continuous electrodeionisation (CEDI) is then utilised after the RO to achieve the conductivity specification.
Distillation turns water into vapour to remove bacteria and endotoxins. The vapour is then condensed to create purified water. In contrast to this ‘hot purification’ process, a reverse osmosis membrane system with secondary membrane does not require heat and so is referred to as a ‘cold WFI’ system.
Choosing the right system
As both approaches will produce water that meets the specified standard for WFI, the decision will depend on factors such as the operational requirements, existing equipment and systems, available space, budget and the previous experience of those in the organisation.
Distillation is a very effective method of purification and for some the high operating temperatures are reassuring from an operational perspective. Also, for applications where it is necessary to store and distribute hot WFI, distillation is an obvious fit.
However, cold systems also have several advantages. The heat source used in WFI distillation systems is most commonly steam. This means that the plant has to be engineered in compliance with the EU Pressure Equipment Directive. As a result, the capital cost can be significantly higher than that of RO plant.
Also, as most pharmaceutical manufacturers will already be using purified water it is possible to take advantage of this to simplify the production of WFI water. For example, if the facility already has RO or CEDI water purification, a secondary ultra-filtration (UF) membrane system can be added to the stream to produce WFI without the need for heat. This means that the operating cost of producing WFI through filtration can be lower when compared with water purification by distillation, often making it only marginally more expensive than purified water. As this is the case, some customers are using membrane systems to produce WFI water that is then used for all purified water applications as well.
Furthermore, where space is limited, a membrane system may be preferred as they typically have a smaller footprint. Some customers also view the ambient operating temperature as a benefit as it eliminates some health and safety factors that have to be considered with distillation systems.
However, with a cold WFI system customers have to be aware of the possibility of the formation of biofilms within the equipment due to the ambient temperature operation. These are difficult to remove and protect microorganisms from disinfection chemicals, which can result in increased endotoxin levels in the system. Therefore, the risks are mitigated by modern RO/CEDI/UF systems that can be frequently hot water sanitised to prevent the risk of biofilm forming.
What systems are available?
At Veolia Water Technologies UK, we have developed a number of distillation and filtration systems designed specifically to meet the needs of water for injection applications.
Polaris is our range of high-capacity distillation systems for the production of WFI. Polaris offers a number of configuration options with both steam and electrical heating. These include single- and multi-effect distillers, vapour compression distillers, clean steam generators and combi units for simultaneous water and clean steam production. The highly efficient, POLARIS MED (Multiple Effect Distillation) features a dry column design, using falling film technology and utilising a baffle system. It is designed to maximise droplet separation for excellent decontamination performance and optimised heat transfer to provide high efficiency and rapid start-up.
(Photo of the Polaris MED)
For those looking for a cold WFI system our Orion product can provide a solution. Orion is a skid-mounted, multi-technology purified water generation system. It combines softening, reverse osmosis and continuous electrodeionisation technologies and can be fully or partially hot water sanitised. This means it is ideal for pharmaceutical grade water and by the addition of a UF module it will produce cold WFI. We offer three models of Orion that deliver flow rates from 0.5 to 20 m³/hr. All Polaris and Orion systems are backed by our comprehensive range of service, maintenance and support packages.
(Photo of the Orion)
The system that is right for your organisation will depend of on a number of factors. Our expert team will be able to look at your existing system as well as your current and future requirements to advise you on the best WFI solution for you.
For more information about Cold WFI please Learn More.
About the Author
Ranj Rihal started as an internal sales engineer for the export department in the early 90's and within a couple of years he was prompted to Project engineer, concentrating on packaged desalination systems. Thereafter with the company moving under US Filter, he concentrated on Project Managing pharmaceutical purified and WFI water systems. In the late 90's he moved into the role of a Senior Design Sales Engineer, producing proposals for all markets initially then concentrating on the Pharmaceutical market. In 2007 he moved into the Pharmaceutical Competence centre supporting the global VWT business units (BUs). The role evolved onto his present position of developing the pharma market globally by supporting all of the VWT BU's in both developed and developing regions.