There’s been a “new” term that’s been introduced with the revision of USP <795>, Water Activity. There’s an entire 2 page USP Chapter about water activity now too that you should read (USP Chapter <1112> Application of Water Activity Determination to Non Sterile Pharmaceutical Products). Oddly enough, this is not a “new” term altogether, it’s actually been used in the food industry for some time. So what is Water Activity exactly and what does it tell us?
In technical terms (click for source):
The water activity (aw) of a food is the ratio between the vapor pressure of the food itself, when in a completely undisturbed balance with the surrounding air media, and the vapor pressure of distilled water under identical conditions. A water activity of 0.80 means the vapor pressure is 80 percent of that of pure water. The water activity increases with temperature. The moisture condition of a product can be measured as the equilibrium relative humidity (ERH) expressed in percentage or as the water activity expressed as a decimal.
Water Activity (aw) in Foods – FDA website
Most foods have a water activity above 0.95 and that will provide sufficient moisture to support the growth of bacteria, yeasts, and mold. The amount of available moisture can be reduced to a point which will inhibit the growth of the organisms. If the water activity of food is controlled to 0.85 or less in the finished product, it is not subject to the regulations of 21 CFR Parts 108, 113, and 114.
Let’s simplify that a little, water activity is the amount of water in a particular compound or product which influences whether microorganisms can grow in that product. This doesn’t necessarily mean that if you have some water in a product that it will definitely have high water activity though. There are interventions that can reduce the water activity of a product.
“Things” that influence water activity
The Water Activity of a compound can be reduced by:
- Temperature (lowering temp decreases Aw – i.e. storage conditions)
- Adding preservatives or antimicrobial agents
- Reducing the amount of water in product
Water activity is among a few other attributes that can all have an “antimicrobial” effect: “low or high pH, absence of nutrients, presence of surfactants and the addition of antimicrobial agents, help to prevent microbial growth. However, it should be noted that “more resistant microorganisms, including spore-forming Clostridium spp., Bacillus app., Salmonella spp. and filamentous fungi, although they may not proliferate in a drug product with low water activity, may persist within the product.” (USP Chapter <1112>). (I bolded this, not in original USP chapter)
An interesting side note, <1112> also mentions examples of food that generally have very low water activity: dried fruit, syrups (maple!) and pickled meats and vegetables, which are all inherently self preserving. Again, just to make the point that this knowledge has been around for quite some time and has traditionally been used to control microbial deterioration of food.
USP Chapter <51> Antimicrobial Effectiveness Testing
Water Activity is one of the analytical tests you’d perform when doing a stability study as part of determining Antimicrobial Effectiveness. In USP Chapter <51> Antimicrobial Effectiveness Testing, it states:
For the purpose of the test, aqueous is defined as a water activity of more than 0.6.USP <51> Antimicrobial Effectiveness Testing
Generally speaking, if it’s determined that your product or preparation has a water activity below 0.6, you may not have to perform Antimicrobial Effectiveness Testing. As noted above though, some microorganisms can still persist in products with Aw below 0.6 (Clostridium, Bacillus, Salmonella, and Fungi), so be cautious. This decision should be based on a risk analysis and a determination to eliminate <51> testing should be made VERY carefully.
I highly suggest you check out this new and extremely short USP Chapter to learn more about Water Activity. USP Chapter <1112> is part of the Compounding Compendium, which is filled with EVERY USP Chapter that has to do with pharmaceutical compounding; and it’s only $150. (I’m truly not advertising for this, NOR do I get any money for putting this here…but if you’re doing any compounding, this is a reference you MUST HAVE.
Always happy to help! #keepraisingthebar
About the Author:
Seth DePasquale is a Board Certified Sterile Compounding pharmacist and co-founder of LyceumCE; an ACPE accredited provider of Continuing Pharmacy Education. Lyceum specializes in creating engaging video-based courses to help you with complying with the latest standards. Seth is a 2002 graduate of Albany College of Pharmacy in Albany, NY and is a Registered Pharmacist in New York, Kentucky, Michigan, Oklahoma, Texas, West Virginia, Virginia, Alabama, Tennessee, Mississippi, Arkansas, Nebraska, Louisiana and Oregon.