In April 2017 the European Pharmacopoeia Water for Injections (WFI) monograph was updated. For the first time this allowed manufacturers of WFI in Europe to choose between distillation systems (hot WFI) and Reverse Osmosis (RO) based membrane (cold WFI) systems. This has opened up a real opportunity for pharmaceutical manufacturers, as - using tried and tested technologies - cold WFI can offer a more cost effective solution, which makes use of existing systems and helps significantly lower energy usage.
The update to the monograph was a significant change and brought Europe in line with other major regional pharmacopoeias such as the United States Pharmacopeia (USP) and Japanese Pharmacopoeia (JP) that have long allowed non-distillation methods.
The regulations state the requirement for a ‘purification process that is equivalent to distillation’ and recommends a reverse osmosis (RO) system coupled with electro-deionisation and a suitable secondary filtration process. The membrane-based system achieves compliance with the WFI standard with these three primary technologies and as such it is sometimes referred to as a RO / CEDI / UF solution.
Reverse osmosis uses a semi-permeable membrane to remove up to 99% of the dissolved solids, particles, colloids, organics, bacteria and pyrogens from the feed water. Continuous electro-deionisation (CEDI) is a highly efficient, chemical free process for creating low conductivity water. The system uses electricity, resins and ion exchange membranes to separate dissolved impurities (ions) from water. Ultrafiltration (UF) uses membrane filters with microscopic pore sizes of 1 to 10 Nanometre (nm), which can remove particles as small as protein macromolecules.
The change in regulations was initially greeted with caution by some in the industry - both among manufacturers and customers. This is despite the fact that the recommended technology has been commercially available for decades and has been used extensively in other areas of the world for highly purified water production with low endotoxin levels in line with WFI water specifications.
However, since 2017 we have seen growing confidence in producing WFI using this method. Part of the reluctance is due to the increased risk of contamination in cold WFI systems if not managed correctly. This concern has been reduced to some extent with a better understanding of how these risks can be mitigated as well as an increasing body of best practice advice developing within Europe.
Also, as manufacturers look at a comparison of the available options it often becomes clear the size of cost saving that can be achieved with cold WFI methods. As there is no need to heat the water, the energy costs associated with producing WFI can be reduced significantly. This cost saving becomes more attractive as the market for pharmaceutical products and ingredients becomes more competitive. Many businesses are more willing to take on the measures required to mitigate these risks to achieve a more cost effective output.
The membrane systems also have other benefits such as a lower capital cost as an existing pure water equipment can be enhanced to produce WFI. The systems also typically have a smaller footprint, ideal if space on site is limited.
While distillation and RO based systems each have advantages, ultimately the decision will come down to the available budget, perceived risk versus cost, the experience of those in the organisation and existing systems and the end user’s product.
At Veolia Water Technologies UK (VWT UK), we offer a range of products for both hot and cold WFI applications including Polaris and Orion.
To learn more about cold WFI watch our recent webinar. Alternatively contact a member of our team to discuss your WFI requirements.
