Water Activity USP <795> Changes

Beyond-use dating in the newly published USP <795> guidelines set to go into effect December 2019 have made big changes to the recommended maximum beyond-use dates for different types of formulations.

One of the biggest changes is a new focus on microbial growth and preservative efficacy. The guidelines specify aqueous preparations as those having a water activity (Aw) greater than 0.6, and only preparations with an Aw less than or equal to 0.6 are considered nonaqueous or solid dosage forms.¹

Water activity is a measurement of the ratio of vapor pressure of the substance in question when at equilibrium with the surrounding air to the vapor pressure of distilled water under identical conditions.² For example, a water activity of 0.6 means that the vapor pressure of the substance in question is 60% of that of pure water. Water activity should not be mistaken for water content. Water content is a measure of how much water is in a particular substance by weight or volume, whereas water activity is a measure of water that is available for reaction or accessible to microbes. Even items with relatively low water content can still have relatively high Aw.

Water activity is a fairly reliable measure of a microbe’s ability to grow in a particular substance. Generally, bacteria can grow at Aw greater than 0.85, and fungi such as yeasts and molds at Aw greater than 0.6.^3,4 Newly published USP <795> guidelines consider anything with an Aw equal to or less than 0.6 to be nonaqueous, and therefore can be given longer recommended maximum beyond-use dates without necessarily having a preservative.¹ Water activity is also a useful reference parameter when considering how much water is available in a substance to act in chemical reactions, potentially resulting in degradation of active ingredients in that substance.⁵

This new focus on Aw not only means a change in beyond-use dating guidelines, but also a new focus on preservatives and how to select one for a particular compounded preparation. The frequently asked questions page on USP’s website clarifies that these new guidelines do not require compounders to measure Aw for particular compounds and that these markers are intended to be used as a guide.⁶ It refers to General Chapter 1112 (Application of Water Activity Determination to Nonsterile Pharmaceutical Products) which provides a list of approximated Aw for various products.^6,7 If Aw is not tested for a water containing preparation such as a cream or suspension, the Aw should be assumed to be greater than 0.6 and, in the absence of an appropriate study, the beyond-use date should be consistent with the maximum beyond-use date listed in table 3 of new USP 795 guidelines.¹ In the absence of explicit data on a particular compound, General Chapter 1112 provides a good resource for justifying an assigned beyond-use date.

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