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ARL offers two potency test options, non-cGMP and cGMP, for determining the concentration of the active pharmaceutical ingredient (API) in compounded preparations.

USP <797> states compounders must ensure products maintain labeled strength within monograph limits. The difficulty with determining limits (specifications) for compounded preparations is that there may not be a monograph to reference. In these cases, ARL assigns the specification by choosing them from a monograph that is closest to the product being tested. When there is not a monograph for a similar product, ARL defaults to 90%-110% per <797>.

For potency testing with respect to HPLC, IC and/or GC methodologies, ARL verifies by way of system suitability that we are capable of performing the analysis. The verification focuses on:

1. Multiple injections of the reference standard for calculation of %CV

2. Verification of retention time of the standard and the sample

Now is the time to prepare for proposed changes to USP <797>.

Over the next few newsletters, we will highlight proposed changes to sterile compounding testing requirements and how ARL can help your pharmacy meet USP standards. 

We begin with Personnel Qualification and Environmental Monitoring Requirements for Compounded Sterile Preparations (CSPs) Categories 1 and 2. 

The sampling quantities defined in USP <71> Sterility Tests are determined based upon statistical probabilities of identifying contamination, should it be present, given various article and batch sizes. The specific direction to follow is found in tables 2 and 3 in the chapter. Table 2 defines the minimum volume per test article to be inoculated into each sterility media type. Since there are two types of media used during a USP <71> sterility test, tryptic soy broth (TSB) and fluid thioglycolate medium (FTG or FTM), the quantity noted in the table represents half of the per-article test volume needed to complete a USP <71> compliant sterility test. Table 3 defines the minimum number of articles of a final product to be tested based on the batch size of the lot being assessed. Complying with the sampling guidelines in USP <71> provides the recommended level of stringency for sterility testing of compounded pharmaceutical products and is the minimum acceptable quantity to test to ensure confidence in a “Sterile” result.

Mycoplasmas are a fascinating group of extremely small bacteria with unique characteristics and growth habits. There are over 120 species of Mycoplasmas found in and on a variety of animal and plant hosts. They possess no cell walls, are fastidious in their growth requirements, and are the smallest type of self-replicating prokaryotic organism. Their lack of a cell wall makes them resistant to antibiotics like Penicillin, which target cell wall synthesis in other bacterial organisms. Mycoplasmas are parasitic and commensal bacteria that commonly colonize cell lines and tissue cultures in the lab environment, and the epithelial lining of the respiratory and urogenital tracts in humans. Their parasitic nature is a result of their inability to produce a number of factors required for growth, hence their association with living cells and tissues.

In 2022, Compounding Today ran a series of articles on pharmaceutical compounding errors. These articles are captured in an 11 part series. See the links below for access to content.

Aaron Thompson, MS

Forensic Technology Leader

In compounded preparations, water activity refers to the water in a drug product freely available to participate in reactions such as hydrolysis or provide an environment that supports microbiological growth. Measuring water activity is important because many drug products include water in their formulations and are sensitive to water exchanges with the environment.

Quality assurance programs are essential to establishing standards for compounded preparations. One of the most important elements in a QA program is identifying the root cause of a failure and implementing a corrective action to prevent a future failure, also known as CAPA (Corrective and Preventative Action).

USP <795> states that compounders shall adhere to general principals of compounding which includes adequate procedures and records exist for investigating and correcting failures or problems in compounding, testing, or the preparation itself.