Many states are requiring stability studies of compounded formulations to be subjected to more stringent testing. They are now including, not only Beyond Use Dating (BUD) information, but container enclosure, pH, accelerated exposure to heat and humidity to determine breakdown of actives, and the effectiveness of the antimicrobial additive to everything from creams and gels to solutions and injectables.
We at Compounder’s International Analytical Lab, are attempting to keep the cost of such test as low as possible, so as to not impose such a financial burden on compounding pharmacies. We are now offering Antimicrobial Effectiveness Testing (AET), either as a stand alone test or as part of meeting the requirements of Stability Study testing.
The AET is very involved, labor intensive and takes 28 days to complete. We follow USP exactly to conduct the test. It requires a total of 55 mls of sample and we realize that is a lot of sample, but it is what is stipulated by the USP. The test determines the effectiveness of the antimicrobial agent in a formulation by inoculating it with three bacteria, one mold and one fungus and incubating it for several days. The microorganisms are dictated by the USP. We watch the growth of the microorganisms inoculated into the sample at baseline, seven days, fourteen days and twenty eight days, by plating on agar plates a mixture of the sample and saline. The microorganism count should decrease at each time point. At the end of the twenty eight days, there should be little to no growth observed. That demonstrates that the microbial agent is effective in preventing microbial growth for twenty eight days. The USP has determined that if the microbial agent is effective that long, it should be effective until the end of the BUD. This is not only applicable to sterile products but to non-sterile creams, gels and solutions that could spoil or that could support microbial growth over time.
As more states require proof of the effectiveness of the microbial agent, it is important to be aware of this requirement, even though your state may not require it yet, you may ship to a state that does. Most stability studies should also include an AET during the stability testing.
Is a separate fungal test necessary if a sterility test is done?
There are two school of thought on this. One says most fungi will be exposed in a two week sterility test. While that may be correct, the operative word is MOST fungi. The other school of thought is that in order to be absolutely sure, one should do a separate fungal test run concurrently with the sterility test. The reasoning is that bacteria prefer a soy based broth in which to grow while fungi much prefer a starcher environment such as a potato dextrose base. We recently had a situation in our lab which proves this point. A client sent in a sample for sterility and fungal testing. The sterility test passed. The fungal test did not demonstrated growth until several days after the sterility test was completed. The tests were repeated using different media lot numbers and the results were the same. Had a separate fungal test not been run, the standard sterility test would not have picked up on the fungal growth. When CSP's are to be invasively introduced into the body, due vigilance has to be the operative word.
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