1 february 2017

New WFI Monograph Teases with Cost Reductions

Shaun Summers is the Pharmaceutical Market & Key Account Manager at Veolia Water Technologies.

Orion Pharma Article

The most significant development of 2017 in the sphere of pharmaceutical water is the revision of the European Pharmacopeia (Ph. Eur.) Monograph 169 Water for Injection (WFI). It will allow the industry more choice in the production of Water for Injection (WFI) – but will that really give cost reductions?

What has Changed?

Previously, the Ph. Eur. required WFI to be produced by distillation, but the revised monograph will allow, from April 2017, production “by distillation … or by a purification process that is equivalent to distillation. Reverse osmosis (RO), which may be single-pass or double-pass, coupled with other appropriate techniques such as electro-deionisation, ultrafiltration or nanofiltration, is suitable”. It also reinforces the ISPE Baseline® Pharmaceutical Engineering Guide on Water and Steam Systems in respect of operation and maintenance procedures, including monitoring of conductivity, TOC and microbial contamination. This brings Ph. Eur. in line with the US and Japanese pharmacopoeias however what does it mean for pharmaceutical engineers?

Hot or Cold?

At first glance, membrane systems appear to have lower costs than distillation systems in terms of both capital investment and operation. They are also significantly smaller, which means savings in installation space. In fact, producing WFI by membranes is only marginally more expensive than techniques currently employed for producing Purified Water, so it may be worthwhile considering a membrane system to produce WFI and using this for all purposes where Purified Water or better is required.
RO Pharma Article
Of course, the reason that distillation was originally specified for WFI is that the phase changes from liquid to vapour and back is a very effective method of purification and the operating temperature of a multiple effect still ensures that the product water is compliant with microbial and endotoxin limits. This makes distillation reassuring from the operational viewpoint and, for those companies who need, or simply prefer, to store and distribute hot WFI, it’s the automatic choice.

Another factor to consider is that RO systems typically operate at ambient temperature and this can lead to the formation of biofilms. These are notoriously difficult to remove and, because they protect microorganisms from disinfection chemicals, can result in rapid re-growth and proliferation, as well as increasing the likelihood of microbiological by-products, such as endotoxins, throughout a system.

There is a further factor against change from distillation and that is the requirement, written into the Monograph, that notice must be given to the supervisory authority of the manufacturer before implementation of a membrane system for both new and existing drug manufacturing protocols. This will involve extensive validation procedures and associated documentation.

Cost vs Risk

Your choice of WFI production method is ultimately about finding the correct balance between cost and risk. On the basis of capital cost alone, membranes will usually win. The direct cost of utilities (power and water) are generally higher for distillation but add in the cost of regular sanitisation of the membranes plus multi-point in-line monitoring of TOC, conductivity and possibly rapid microbiological testing and the difference may not be so great. Then there’s the operational risk of microbiological contamination. What is the real cost of having to decontaminate your distribution system, not forgetting lost production? Distillation techniques have traditionally been considered less risky than RO based systems, which may be susceptible to biofilm formation. However, a membrane system such as Orion, that can be heat sanitised, can control the formation of biofilms and, when coupled with real-time microbial control, offers a low risk solution. The operating cost savings offered by this type of RO based system are highly attractive, and we expect an increasing number of customers to be adopting this approach as a way to reduce operating costs without affecting the integrity of the system.

Minimising Risk

Any system for WFI production - regardless of technology - must be well designed by an experienced company in line with the current regulatory guidelines, correctly installed and then monitored and maintained to a high standard. At Veolia we have over 30 years of pharmaceutical water experience and our range of Orion RO based systems and Polaris distillation units are market leaders in the production of WFI.

Click to download a concise guide to the revised European monograph for Water for Injection (WFI)