Quality Assurance – Potency and Stability Testing

Any pharmacy that compounds must have standard operating procedures in place that meet the standards set forth in USP chapters <795> (non-sterile compounding) and USP <797> (sterile compounding). One of the requirements for both of these enforceable guidelines is that the compounding pharmacy must conduct quality assurance testing of compounded preparations. Preparations dispensed from compliant pharmacies are tested for potency, microbial integrity, and chemical stability.

Potency testing is valid only for one compound for one point in time and is not stability-indicating. Potency test results cannot be used to establish beyond-use-dates for a preparation, even by the pharmacy that compounded the preparation. Nor can potency tests be used by other pharmacies to assign a beyond-use-date (BUD) for the same compounded preparation. Potency testing supplies both qualitative information (which verifies it is the correct chemical substance) and quantitative information (confirming the concentration of drug in the preparation). Potency is defined as a percent of label claim, of the concentration of active ingredients in a compounded preparation. Stability testing differs from potency testing in that it subjects the tested preparations to conditions of stress (similar to those that might be encountered in shipping, storage, handling, etc.) which allows pharmacists to assign reliable beyond-use-dates. The stability period, or BUD, is the time during which the compounded preparation retains at least 90% of the original concentration of active drug. Stability testing involves subjecting the dosage forms to different temperatures (usually from –20C to 37C), light exposure, and humid environments over a sample period of time. All samples are tested initially and then again at predetermined intervals to observe and quantify any degradation that may occur.

Both potency and stability tests must be validated, i.e., prove that the results of the test reflect the concentrations of only active parent drug and not a mixture of degradation products. Some analytical assays are incapable of distinguishing parent drug from degradation products, so while the potency results may be reported at 100%, the concentration of active parent drug may be considerably lower because the assay is also detecting degradation products that are not pharmacologically inactive.

In order to avoid this pitfall when assigning beyond-use-dates or conducting stability testing, compounding pharmacists can query analytical laboratories as to whether or not their assay methods are “stability-indicating”. Although many analytical laboratories will say they are utilizing a USP/NF method or a method used to detect drug in plasma, this does not guarantee that the testing is stability-indicating. Even if the assay method is taken from peer-reviewed literature, the analytical laboratory must revalidate the method using their own equipment and testing personnel to ensure that their methods accurately reproduce the accuracy of the published method. For this reason, the services of analytical labs that can provide true stability-indicating assays may be very expensive, but confidence in the results is well worth the investment.