Typical Multi-Effect WFI Still
Water for injection by definition is water that is intended for use in the manufacture of parenteral (i.e. injectable) drugs whose solvent is water. The USP (United States Pharmacopeia) defines this as highly purified waters containing less than 10 CFU/100 ml of Aerobic bacteria. These waters should also have fewer than 500 ppb of total organic carbon, fewer than 0.25 EU/ml endotoxins, and a conductivity of less than 1.3uS/cm @ 25 C.
Now that we have the textbook definition out of the way, we’ll spend the rest of this blog post delving a little deeper into WFI, how it’s made, and common pieces of process equipment used to make up WFI.
To begin, let’s start by looking at how Water for Injection is made. The USP allows WFI to be produced by one of two means; either distillation or reverse osmosis. Prior to making it to the still, however, supply water has to go through extensive pretreatment. Pretreatment usually includes various filtration steps, removal of chlorines through the use of activated carbon beds, and percolation of water through ion exchange resins to remove residual ionic compounds.
What is the purpose of all this pretreatment? By pretreating the water, we effectively reduce the conductivity of the water, as well as the level of organic contaminants.
Once the water makes it through these pretreatment steps, it goes to the still. What happens in a WFI still? Distillation, of course. When water is distilled, it heated until it is a vapor, stripping the heavier ions, particulates, and endotoxins from the water. There are both single and multiple effect stills and which one is best for you is determined by how much WFI you are trying to generate. There are also vapor compression stills available that can make WFI. Regardless of what kind of still you are using, the basic process is the same- the water vapor is passed through a series of tubes and recondensed, resulting in WFI.
You can also get WFI from a process called reverse osmosis. In reverse osmosis, or RO, water is forced through a semi-permeable membrane and the pores in that membrane reject dissolved ions, salts, and organic compounds. This is filtration on a molecular and ionic level. The quality of water, temperature, PH, and flows rates are all critical in RO as the membranes used can foul easily. Reverse osmosis systems rely on booster pumps to increase pressure across membranes, storage tanks, and sophisticated controls for bulk WFI preparation. RO systems are capable of producing 600-50,000 gallons per day of WFI.
So what is done with WFI after it is produced to ensure the water stays at water for injections quality? It either needs to be used quickly (usually same day) or put in a state that allows it to maintain its efficacy. How do you make sure WFI stays as WFI? You need to minimize microbial growth. This is accomplished by maintaining it at high temperatures and keeping it in motion. Normally WFI is kept at 90 degrees C and recirculated through a distribution loop at a minimum velocity of 5 feet per second.
To ensure there is no contamination of entering or building up in the distribution system, the piping is normally highly polished, at least 20 Ra, often with electropolish. Any ventilation or vent filters are usually sterile membranes of at least 0.2 uM. Vent filter, commonly found on tanks, are often heat traced or steam jacketed. Why is that? Well, when WFI comes in from the still, it can be very hot. The heat can cause it to flash off and enter the filter. Once the steam makes contact with the vent filter, which if not heat traced will be cooler than the tank, the vapor will recondense and cause the vent filter to blind. When you go to pump that tank out, you would then pull a vacuum and could cause the tank to collapse.
Other common pieces of equipment used to ensure system integrity include double sheet shell and tube heat exchangers and weir type diaphragm valves. EPDM is probably the most common gasket material we see in a WFI system.
Because the conductivity of WFI is so low, it is considered “ion hungry”, ready to leach ions out of any surface it comes in contact with. That makes the water very abrasive. That means we use centrifugal pumps with single or double mechanical seals and hard seal faces, the most common and robust being either silicon carbide or tungsten carbide.
So to recap, what is WFI? WFI is highly purified water that contains less than 10 CFU/100 ml of Aerobic bacteria. These waters should also have fewer than 500 ppb of total organic carbon, fewer than 0.25 EU/ml endotoxins, and a conductivity of less than 1.3uS/cm @ 25 C.
Why is this important? Well, because as the name implies, WFI is the water, combined with active ingredients used to make drugs that are injected into our bodies. It is also used a the final rinsing agent for any component that comes in contact with the drug such as vials, ampules, caps and stoppers. How do we make it?
Through a series of steps aimed removing ionic and organic contaminants with the final steps being distillation or reverse osmosis.
Once we make it, what do we do? Keep it hot and moving, use it or lose it. We store and transport WFI using ultra high purity process equipment like highly polished tubing, diaphragm valves, sanitary centrifugal pumps with single of double mechanical seals, and double sheet shell and tube heat exchangers.
Any questions? If so, contact a Holland Sales Engineer today.