CRB Caption - Modern ambient water for injection (AWFI) generation system

Modern ambient water for injection (AWFI) generation system [Image courtesy of CRB]

The pharma industry is in the process of moving toward ambient water for injection (WFI).

Despite changes to regulations almost five years ago that allowed for alternative methods of generating WFI, the industry has been slow to fully embrace the shift away from traditional distillation despite the significant advantages of membrane-based WFI generation.

For companies with legacy distillation systems, the investment in new equipment for ambient WFI can be significant. Given its history, many pharmaceutical companies are familiar with the traditional distillation method.

In this article, industry experts from CRB, Chris Carlson and Jarrod Wrampe, describe the considerations to keep in mind when choosing between membrane-based WFI and traditional distillation for pharma applications.

Pro for membrane-based WFI generation: European regulations support it

Chris Carlson, process utilities engineer at CRB, highlights the significance of membrane-based WFI generation, stating that it became a big topic in 2017 when the European Pharmacopoeia updated their monographs. European regulators decided to permit the use of membranes as an alternative method for WFI generation in cases where it could be proved equivalent or superior to distillation.

The advantages can be significant for companies that can move away from distillation. “The big benefit of membrane-based WFI generation is energy savings,” Carlson said. Distillation requires a steam source, which is often natural gas.

Membrane-based WFI generation also tends to offer savings in terms of capital costs and operating and utility costs. It also has less of an environmental impact than distillation. The equipment associated with the process also tends to be relatively compact.

There are other considerations to keep in mind, however. “Are you using the water for injection hot or ambient?” Carlson asked. For companies using hot WFI, distillation could make more sense than heating the water after the reverse osmosis stop.

Con for membrane-based WFI: China’s regulations don’t allow it

China’s monograph still requires distillation to generate water for injection (WFI). Alternative methods are not allowed. However, there are rumors that this may change in the future. “However, there are rumors that they are looking to change the verbiage [of its regulations] to allow alternative methods,” said Jarrod Wrampe, director and market team leader at CRB.

Companies considering a switch to membrane-based WFI generation should thus determine whether the company sells its products in China. If not, the company should assess how it uses water in its processes and determine if membrane-based WFI generation would be a more cost-effective and energy-efficient option for operations conducted at ambient or cold temperatures.

When making this decision, pharma companies should also identify their regulation and process needs and the type of pharmaceutical water to suit their process requirements.

Membrane-based WFI generation often but not always best choice

While membrane technology can offer advantages, it may not always be the best choice. For large-volume situations, the total cost of ownership for vapor compression stills can be competitive or better than for membrane-based WFI generation.

Some of the biggest WFI producers in the world are IV bag manufacturers, as they use it to fill their products. “It’s largely done with vapor compression stills because of the sheer volume they have to create,” Wrampe said. The water itself is not hot but instead comes off the still at an ambient temperature. “That is a unique situation where vapor compression distillation allows them to use electricity instead of natural gas to generate steam while also producing WFI at a temperature closer to what is needed for the process at the same time,” Wrampe said. “There are conversations on what the right application of membrane technology is. Is it always the right answer? Not necessarily.”

It’s also worth noting that distillation equipment has limitations regarding its footprint. In a case study from CRB, the footprint of a distillation system was about two times larger than that of a membrane system, taking into account factors such as the inclusion of pretreatment onboard and additional equipment required for distillation. The membrane system’s smaller footprint is partly due to having pretreatment included on a single skid.

“It’s important to remember that for multiple effect distillation specifically, but sometimes vapor compression too, the pretreatment for that is exactly what we would put in for a membrane system,” Wrampe said.

Distillation can also become expensive, requiring water pretreatment to work as intended. Each situation requires careful analysis to determine the best approach, particularly when considering commercially available off-the-shelf options.

Distillation systems can pose burn risks

“As we design distillation systems, we make sure that everything is well-insulated to ensure safety,” Wrampe said. “There should be no hot surfaces.”

But once a plant is up and running, maintenance staff may take equipment apart and not properly reassemble it. “Hot surfaces may be left exposed,” Wrampe said. CRB has noted in its hazard analyses for clients that burn incidents related to distillation equipment are common. “Whether that’s specific to distillation equipment or just hot equipment in general, burns happen multiple times in a given year,” Wrampe said.

Membrane-based WFI offers sustainability advantages

When distillation is used to generate water for injection, a lot of plant steam is required, which is usually produced from natural gas, as mentioned earlier. “However, with membrane systems, we can use electricity to heat the water if there are minimal hot use points in the system,” Carlson said. “This allows for cleaner energy generation options, including the possibility of purchasing cleaner produced electricity. With natural gas, we don’t have the option to choose a cleaner energy source.”

In the face of changing regulations and sustainability concerns, pharma companies must weigh the pros and cons of membrane-based WFI generation and distillation to find the best approach for their specific needs.