Antimicrobial Effectiveness

Revisions to USP <797> mandate that aqueous, multiple-dose CSPs undergo AET in accordance with USP <51> once per formulation in its specific container-closure system. However, the compounder may rely on published literature or results from an FDA-registered facility if the following conditions apply:

1. The formulation, both in strength and ingredients, is equivalent to the reference formulation.
2. The container closure-system is equivalent to the one tested.

In lieu of testing each formulation for AET, a compounder may perform a bracketing study for any given formulation of varying strengths. This approach tests antimicrobial effectiveness in a formulation at the lowest and highest active pharmaceutical ingredient (API) concentration and the results would extend to all formulations compounded within the tested range, given that all other excipient concentrations remain the same.

For example, if a compounder formulates drug product X at a concentration of 1, 5, 10, and 15% in the same container-closure system, then AET can be performed on the 1 and 15% concentrations to satisfy the requirements of the chapter.

As with the previous version of the chapter, multiple-dose CSPs must be discarded 28 days after initial puncture unless otherwise specified by the manufacturer, but never to exceed the BUD.

Non-preserved aqueous and topical ophthalmic CSPs that are prepared as Category 2 or 3, labeled for single-patient use, and labeled to be discarded within 24 hours after opening at room temperature or 72 hours when refrigerated, do not require AET.