💧 Water, water everywhere
If this line has been quoted far too many times, it’s because it is true. Even when it comes to simple drinking water, the production, storage and distribution process is hardly simple, as evidenced by potable water shortages and water-borne diseases in many regions around the world. But come to pharmaceutical grade water, and the challenges are further compounded. The difference between purified water and water for injection is the main crux of this article, but we will also cover all the different grades of pharmaceutical water and the need for these specifications in cleaning, sterilization, drug and vaccine production, and heat transfer in pharmaceutical operations.
As water is central to life, so is it to pharma operations. It is a critical resource with applications as a solvent for parenteral drugs, as a cleaning and sterilization agent in CIP/SIP systems, and for energy transfer by means of heat exchangers. Each of these processes requires a different grade of water – it could be purified water, water for injection, pure steam, or sterile water for injection. Using a particular quality of water is non-negotiable in not only pharma and biopharma but any sanitary industry. Failing to achieve internationally accepted standards can have dire consequences – at best, you may have to recall a potentially contaminated product and lose all the money invested in producing it; at worst, you may hurt the health or lives of the people who use your product. You don’t want to find yourself in either of these situations, so the only way to go is to understand the uses of purified water vs water for injection, to stick to specified guidelines as outlined by the European Pharmacopoeia, US Pharmacopoeia, or the Japanese Pharmacopoeia, and leave no room for error.
What’s the fuss about?
H2O. Despite its different forms, it is the very same compound; so what’s the big deal about the difference between purified water and water for injection and pure steam?
Water is far more than just its chemical composition. As with any other substance, it attracts contaminants which affect the quality of the pharma products that it comes in contact with. Water can collect impurities from the air, from the personnel who handle it, and any other foreign substance it interacts with. Such contamination can occur at any point during its life cycle, from purified water generation to storage and distribution. Of course, there are mechanisms to limit the exposure of pharma grade water to contaminants; high purity water is ordinarily produced on-site so as to minimize its interactions with potential contaminants. In cases in which sterile water has to be packaged for later use, the highest controls are put in place.
What’s more, even if the water is free of pyrogens and endotoxins, to be suitable for pharmaceutical applications, it needs to have specific temperatures, pressures and flow rates. This allows the biochemical processes occurring in pharma production to progress in the desired manner.
As you can see, how well you understand and work with purified water can make or break your success in the high purity world. So understanding the challenges, risks and benefits that come with appropriate water management is crucial. Especially when the consequences of lapses can be a matter of life or death for your final customers.
Before we get into the difference between purified water and water for injection, let us explore all the other grades of water that exist and the purpose that they serve.
Different grades of water
For starters, there is potable water. That is the ordinary water with minimal levels of purification that you would drink or use to cook with. While it is perfectly suitable to use for domestic purposes, it can hardly be used in pharmaceutical manufacturing settings. At best, it would be used for an initial rinse during equipment cleaning cycles. Also, potable water is the feed water which is then further processed to produce purified water, water for injection, and pure steam. By itself, potable water has far too many contaminants, including chlorides, bicarbonates and other minerals which could interact with active ingredients in the drug product and bacterial impurities which could affect the safety profile of the drug.
Then there’s pure steam. Pure steam is dry, saturated steam which is free of pyrogens and produced using specialized clean steam generators. As per the European Medicines Agency’s Guidelines on the quality of water for pharmaceutical use, pure steam should meet the specifications of water for injection when it is condensed. Where exactly is pure steam used? It finds its application particularly in the sterilization process, when pure steam is used to decontaminate storage and compounding vessels, process piping, and other pieces of equipment.
Finally, there’s also sterile injectable water. Sterile injectable water is among the highest levels of water purity you can achieve because this water is most commonly used as a diluent for dehydrated medical drugs; this means that this water is usually injected directly into the body and has a fast-track to the bloodstream, tissues and organs. According to the US Pharmacopoeia, sterile water for injection is non-pyrogenic, sterile, distilled water which is packaged as a single dose, ordinarily for intravenous administration when a drug product is added to it. The absence of bacteriostats, antimicrobial agents and buffers makes it ideal for parenteral administration. The only concern here is that sterile water for injection is extremely hypotonic, so it should never be administered unless a suitable solute is added to it.
Purified water vs water for injection
Finally, we come to the difference between purified water and water for injection. The European Pharmacopoeia, the US Pharmacopoeia, and all other important pharmacopoeias determine the specific properties of purified water vs water for injection.
Purified water is used to rinse equipment. It is used to produce oral and topical drug products. It is used in the granulation process for capsules and tablets. It is used as feed water for water for injection and for clean steam. So you can see that it is an important input in pharma production.
How is purified water produced? First comes pre-treatment: this includes a combination of all or few of the processes of chlorination, softening, and dosing. These steps are designed to get rid of bacteria and viruses, magnesium and calcium salts, and to break up silica, sulfates, and other precipitates in water. During the actual purification process, one or a combination of the methods of reverse osmosis, electro-deionization and UV disinfection is employed.
As for water for injection, or WFI, its main applications are in the production of small volume parenteral and large volume parenteral. Additionally, WFI is also used to clean any equipment or piece of packaging that the parenteral come in contact with: this includes caps, vials, ampoules, process piping, and more. Since parenteral are injected directly into tissues or the bloodstream – be it through subcutaneous, intramuscular or intravenous administrations – the water for injection used to make them is the purest pharma grade water out there.
Water for injection is prepared using either distillation or reverse osmosis & Post Ultrafiltration to eliminate endotoxins and pyrogens. It is generally prepared in bulk, and when it is further packaged as single doses for direct medical use, it is termed sterile water for injection. These extremely high purity waters are subject to testing for heavy metals, nitrates, appearance, conductivity, and bacterial endotoxins, with only very narrow allowances for the presence of aerobic bacteria.
Storage and distribution
The difference between purified water and water for injection extends beyond just the production process. The purified water vs water for injection battle continues in the arenas of storage and distribution. For purified water, the circulation loop of the water distribution system ordinarily operates in cold modes at temperatures within the window of 15 and 25°C. Water for injection, on the other hand, is maintained at a temperature of at least 80°C in circulation loops.
In storage and distribution systems for purified water, bacterial growth risks are minimized using UV disinfection at loop feed lines; all of these mechanisms must be completely drainable, free of dead legs, and equipped with heat exchangers to prevent excessive temperature increases in the system. For WFI storage and distribution, periodical sterilization at temperatures lower than 121°C with superheated water or pure steam is required.
Finally, it all comes down to equipment. If your equipment is not designed to support these stringently regulated processes, you are bound to be stressed out by the risk of contamination. Luckily, at TSA, all WFI and purified water storage and distribution systems are electropolished to less than 0.4 RA microns. Orbital-welded joints, video borescopes, and 316L stainless steel construction minimize contamination risk and maximize your ability to monitor and control your processes. At the end of the day, nothing is more important in pharma than quality, consistency and reliability. TSA’s high purity and process solutions give you all three. With two decades of experience, TSA is the trusted name and the ideal solution for all your high purity and process challenges, no matter how complex.