Sodium azide (NaN3), a colorless-to-white crystalline solid that is odorless and moderately soluble in water, is the most prevalent inorganic compound used as an antibacterial and antimicrobial agent in bulk reagents and stock solutions in the in vitro diagnostics (IVD) industry. If you were to review the composition of almost any phosphate-buffered saline formulation or any other stock solution that needs to have a prolonged shelf life used in the industry, there is a very high probability you will find sodium azide in a percentage by volume varying between 0.1%-0.05%.
Sodium azide does present significant safety concerns, however, as it is considered a potentially deadly chemical by the CDC and others. Some of the pictograms found in sodium azide safety data sheets warn that it can be explosive and toxic, and it is considered a health and environmental hazard. Additionally, sodium azide possesses the National Fire Protection Association’s (NFPA) highest rating of a 4 on the health scale.
When considering its use, it is critical you understand the entire process in which sodium azide will be used and everything with which it will come in contact. For example, if your process will place the compound in contact with strong acids, it will produce hydrazoic acid, which is a colorless, volatile, and explosive liquid at room temperature and pressure. In addition, hydroazoic acid has a pungent smell, and its vapor can cause violent headaches in exposed personnel.
As an example of sodium azide’s explosive power, it is often used along with oxidizers and other agents in passenger car airbags. These chemicals are intended to explode at the moment of a collision to inflate and deploy the airbag. This same type of explosion occurs upon heating the sodium azide to approximately 300°C. It is therefore important to understand the entire process in which sodium azide will be used so that you can ensure proper material handling and maintain appropriate personal protective equipment to mitigate potential risks.
One should also understand sodium azide’s antibacterial and antimicrobial properties and the impact they could have on your products. An antibacterial is an agent that destroys or suppresses the growth or reproduction of microorganisms, and an antimicrobial is an agent that kills microorganisms or inhibits their growth. Sodium azide has properties that suppress or inhibit the growth of organisms; it is not a sterilant and as such does not provide a log reduction in organism colony forming units (CFUs).
To understand whether sodium azide is appropriate for your products, you need to determine what types of organisms your products are most susceptible to. This information can come from your facilities’ environmental monitoring data, similar product bioburden and/or sterility testing, or any other testing performed on the manufacturing environment, similar products, or the components/equipment used in the manufacturing process. Having organism identification will be an additional benefit in this process beyond just the types of organisms. Sodium azide is excellent at inhibiting most gram-negative bacteria; however, gram-positive bacteria (streptococci, pneumococci, lactobacilli, etc.) are resistant to sodium azide and can leave your product at risk. When evaluating use of sodium azide as a potential preservative, it is recommended to verify your findings through performing and gathering data from USP <51> Antimicrobial Preservative Effectiveness (APE) testing.
Based on the fact that sodium azide inhibits the growth of organisms and doesn’t provide a log reduction, it is also recommended that you use sterile sodium azide to minimize the risk of contaminating your products.
In addition to determining the effectiveness of sodium azide, you should also determine how to engineer controls to minimize the severe hazards associated with the compound as you scale to routine manufacturing quantities to ensure a safe environment for your employees. To ensure this is set up correctly, you can turn to the safety data sheet (SDS), the Occupational Safety & Health Association (OSHA), the National Institute for Occupational Safety & Health (NIOSH), and other sources to ensure proper storage, ventilations, personal protective equipment, etc. as it pertains to purchasing, receiving, storing, using, and disposing of sodium azide. These are the actions most commonly taken today by most of the IVD industry. Another option that not many are aware of or consider is to instead utilize a pre-diluted solution to lower the toxicity; a side benefit to this is that it will also be ready to use, saving time and preventing employees from having to dilute the sodium azide themselves.
Sodium Azide is hazardous. It is lethal. It is explosive and has the potential to off-gas in dangerous ways. However, all of these risks can be managed through understanding the chemical and the role it will play in your process and products. Such understanding can help you employ the appropriate administrative and engineering controls to ensure employee safety.
Consider the process outlined here and then take advantage of some of the solutions available today that can mitigate your risks by using pre-diluted versions of sodium azide, by using sterile versions, and by doing the analysis and work in advance to ensure optimal outcomes. All employees should have a safe work environment, and safe handling of sodium azide is a great place to start.