In the pharmaceutical industry, water for injection (WFI) is used to synthesise parenteral medications as well as for cleaning and other production activities. The quality criteria for WFI are particularly stringent because it might be integrated into final medication compositions. WFI has traditionally been made by distillation, however pharmacopoeia monographs in the United States and Japan have authorised alternate procedures as long as the same quality is obtained.
High Quality Standards
WFI quality standards have long been standardised in the United States, Europe, Japan, and China. At 25 °C, WFI must have a conductivity of less than 1.3 microSsemens per centimetre (mS/cm). Bacterial levels must be less than 10 colony-forming units per 100 millilitres (cfu/100 mL) and endotoxin levels must be less than 0.25 international units (IU)/mL in order to qualify. In all three compendia, total organic carbon (TOC) must be less than 0.5 mg/L. Europe and China require an extra maximum nitrate limit of 0.2 ppm, which the US and Japan do not now demand.
Distillation is used to make WFI
Multiple-effect distillation (MED) and vapour compression distillation (VC) in big stainless-steel equipment have typically been used to create WFI in pharmaceutical production plants. Boiling water and allowing the steam to pass through a long column or evaporator are the basic steps in this process. Water with impurities cools faster and returns to the distillation "pot," whereas the purified stream travels further up the evaporator before being condensed to produce water that fulfils WFI conductivity, TOC, bio burden, and endotoxins standards. This process is repeated numerous times in the case of MED to increase device efficacy and capacity.
Distillation is an excellent approach for eliminating bacteria and endotoxins because it includes heating the water. Furthermore, the WFI produced by this approach is hot, and distributing water at a high temperature once the purification process is complete reduces the possibility of microbial contamination.
Membrane Filtration for WFI
Reverse osmosis (RO) has been around for more than a century. However, it has only been legal in the United States for a little more than 30 years for the manufacturing of WFI. Despite the USP's endorsement of membrane-based WFI, only a few companies headquartered in the US — and selling only to US clients – deployed RO systems for WFI generation, owing to the European monograph's distillation restriction. Highly Purified Water, which meets the same quality specifications as WFI in terms of conductivity, TOC, bio burden, and endotoxin but may be generated using membrane filtration technology that is equal to distillation, was added to the European monograph in 2002. WFI, on the other hand, could only be made through distillation until 2017. The acceptance of this approach for WFI production is likely due to the gathering of more than a decade of data on the safety and quality of RO-produced water.
Benefits of RO for WFI
The decision to select RO (or distillation) for WFI production requires consideration of several factors.
1. The first is capital cost. A typical traditional MED system takes up a large amount of plant floor space and consumes a significant quantity of energy for steam generation and cooling, contributing to high operating costs. A MED WFI still can range from $300,000 to $600,000 (depending on capacity), which does not factor in the cost for the rigorous pre-treatment requirements necessary to protect the equipment. Vapour compression distillers can require significantly less pre-treatment and can be competitive in larger scale WFI production; however, cost and space constraints can be a challenge.
2. In contrast, membrane systems generally do not require steam or cooling. Sanitization of the RO membranes and piping can be accomplished using an electric heater, but steam can be used if available. Since the membrane WFI generation system is the terminal process the space requirements for the MED can be eliminated. There is also potentially less welding required and less stainless steel used in their production, allowing for faster delivery. Some existing facilities that already have an RO system installed for the generation of purified water may choose to retrofit the purified water system with a terminal UF filter. Once revalidated, the system could provide WFI water for applications that require WFI or purified water.
3. WFI produced using RO is particularly attractive for new facilities that rely on single-use technologies and do not require water for steam-in-place operations. In these plants, the use of an RO WFI production can result in the elimination of the need for a boiler, which can provide a significant reduction in capital expenditures, which are coupled with the savings from the eliminated MED. If for some reason a MED unit is later determined to be required or preferred, the membrane WFI can easily function as adequate pre-treatment for the WFI still.
Pharmaceutical manufacturers considering the use of RO for WFI production can benefit from the experience of an engineering and design firm.