Fluids Handling

Producing pharmaceutical water more efficiently

Phil Black - PII Editor 42 minutes ago

32 5 minutes read

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Dipl.-Ing. Nils Ern, Head of Engineering at the Syntegon subsidiary Pharmatec

Why membrane processes could become the preferred method for WFI production and what needs to be considered

Thanks to their energy efficiency and significant revisions to key pharmacopoeias, membrane processes have become an established method for producing Water for Injection (WFI) at ambient temperatures over recent years. Until recently, however, one key market remained excluded. This changed with the alignment of the Chinese Pharmacopoeia on 1 October 2025. The harmonisation of all major national standards could position membrane based processes as the preferred method for WFI production in the years ahead.

Water for Injection (WFI) is an essential component in pharmaceutical manufacturing, serving as the base material for injection solutions for parenteral use. To achieve this level of purity, contaminants such as microorganisms, ions and endotoxins must be removed. Acceptable limits are defined within national pharmacopoeias, which also specify the approved purification and treatment methods.

Until 2017, European requirements differed significantly from those in comparable pharmacopoeias such as the United States and Japan. Within the EU, distillation was the only permitted process for WFI production. While this method fully satisfies strict pharmaceutical standards, it is associated with high energy consumption and operational cost.

With increasing sustainability targets and rising energy costs across Europe, the revision of the European Pharmacopoeia represents a significant shift. It now permits methods equivalent to distillation, including membrane processes based on reverse osmosis and electrodeionisation combined with an additional ultrafiltration step.

In 2020, the World Health Organisation WHO recognised membrane processes as a suitable method for WFI production in Annex 3 of the WHO Technical Report Series TRS 1025. This guidance outlines key global principles and can be supplemented by national regulatory frameworks.

Increasing establishment

Since then, membrane processes have gained strong traction. Estimates indicate they already account for nearly 30 percent of WFI production globally. This is particularly notable given that the technology had not previously been approved for the Chinese market. The revision of the Chinese Pharmacopoeia in October 2025 has now aligned all major pharmacopoeias, paving the way for wider global adoption of membrane based WFI systems.

Looking ahead, the question is no longer whether membrane systems are viable, but whether they will become the dominant approach. For UK pharmaceutical manufacturers facing rising energy costs and stricter sustainability targets, the case is becoming increasingly compelling.

Two key advantages support this shift. Membrane based processes are both more economical and more environmentally sustainable than distillation. They remove the need for steam generation, reduce energy demand and lower associated operational costs.

However, due to the relative novelty of membrane based WFI production, close collaboration between planners, equipment suppliers and pharmaceutical companies remains essential to ensure compliance with stringent regulatory requirements.

Step one pretreatment

Pretreatment is the first critical stage in membrane based WFI production. Its purpose is to remove impurities that could damage downstream membranes or lead to fouling and deposits. Depending on raw water composition, a combination of pretreatment technologies may be required.

Multiple filtration stages are typically used to remove suspended solids. Total organic carbon TOC can be reduced using activated carbon adsorption, while microorganisms may be eliminated through oxidative chemicals or rendered inactive using ultraviolet radiation.

The design and sequencing of pretreatment steps should be carefully agreed between all stakeholders. From the outset, hygienic design principles must be applied. This includes the use of appropriate materials and surface finishes, minimising dead legs and ensuring continuous turbulent flow to reduce the risk of microbial growth.

Focus on sanitisation

Following pretreatment, water softening prevents hardness formers such as calcium and magnesium from creating insoluble compounds. While antiscalants can be used to increase solubility limits, they introduce additional validation requirements, as operators may need to prove their complete removal from the final product. For this reason, cation exchange resins are typically the preferred and more reliable solution.

However, water softening is also one of the stages most vulnerable to microbial contamination. To mitigate this risk, regular sanitisation of the resin is essential. This can be achieved using either chemical agents or hot water.

Chemical sanitisation generally requires lower capital investment but is less effective and only partially automated. In contrast, hot water sanitisation is fully automated, can be performed during operation and provides a higher level of process reliability. As a result, it is increasingly regarded as the standard approach in modern pharmaceutical water systems.

Hygienic design and hot water sanitisation ensure that microbiological limit values are complied with.

Reverse osmosis, electrodeionisation and ultrafiltration

Once softened, the water undergoes reverse osmosis (RO), which removes ions, particles and microorganisms. Depending on feed water quality, systems may be configured as single stage or two stage processes.

Dissolved carbon dioxide is not retained by reverse osmosis but can be efficiently removed using membrane degassing techniques such as air stripping. This ensures optimal downstream performance.

Continuous electrodeionization (EDI) then further reduces conductivity to below 0.2 µS per centimetre by combining membrane separation with electrodialysis. Finally, ultrafiltration removes endotoxins and bacteria, ensuring full compliance with pharmacopoeial limits.

To improve sustainability and reduce wastewater, the concentrate generated during ultrafiltration can be recirculated upstream of the reverse osmosis stage.

Continuous monitoring

Maintaining microbiological control throughout the process requires consistent and optimised system operation. Continuous operation offers the most effective protection against contamination, while oversized systems with intermittent operation should be avoided due to hygiene risks.

Modular system design is particularly advantageous, allowing capacity to be adjusted in line with demand. This flexibility helps maintain optimal flow conditions and minimises stagnation.

Robust monitoring strategies are equally important. Continuous measurement of TOC provides insight into organic contamination levels, while additional filtration stages can be introduced if required to further reduce TOC and inhibit biological activity.

Monitoring transmembrane pressure and conducting regular integrity testing also provide valuable data on membrane condition and filtration performance, enabling proactive maintenance and ensuring long term reliability.

syntegon pharmatec team — The experts from the Syntegon subsidiary Pharmatec can quickly and easily configure and expand the modular, turnkey MWFI systems to meet individual customer requirements.

A strategic partnership on equal footing

The increasing adoption of membrane based WFI systems demonstrates that pharmaceutical manufacturers can achieve significant energy savings and improve environmental performance when systems are correctly designed and operated.

Success depends heavily on selecting the right technology partner. Close collaboration is essential to define optimal system architecture and implement effective strategies to minimise microbial risk.

Partnering with a specialist supplier such as Syntegon provides access to advanced system design and in depth process expertise. Through its subsidiary Pharmatec, the company delivers turnkey membrane based systems that are modular, scalable and tailored to individual production requirements.

Extensive experience in pure media systems supports a collaborative approach, ensuring that solutions are both compliant and future ready. Under these conditions, membrane processes represent a valuable long term investment for pharmaceutical manufacturers and are well positioned to become the preferred method for WFI production across the UK and global markets.