Aspergillus, Bacillus, and Cladosporium – The Importance of Genus Identification
The revised USP <797> standards for compounded sterile preparations (CSPs) have arrived, and they're causing a stir in the pharmaceutical world. Adherence to the new standards will require more effort from compounding pharmacies, especially in areas such as documentation. These Standard Operating Procedures (SOPs) are even more important when you consider that the revised language leaves a lot of previously defined areas open to interpretation.
In this post, I’ll talk about the importance of genus identification. As always, make sure you defer to your risk assessments, state regulations, and relevant Authority Having Jurisdiction (AHJ) when designing a quality sterile processing program.
What is Genus Identification?
If you have anything at all to do with USP <797> adherence, you probably know this already, but it can’t hurt to do a quick level set. At a high level, genus identification refers to the process of classifying organisms, specifically bacteria and fungi, to the genus level.
The way taxonomy works is that there are different levels of organization that start with kingdoms such as animals, plants, bacteria, etc. and then go down all the way to orders, families, genera, and species. Each species has a genus name and species name. Different species of the same genus possess many characteristics in common, and we can use these characteristics to determine the genus. We can also use DNA sequencing to determine the genus or species because phenotypic features (observable characteristics) are determined by genetic material and, with further distance in the relationship, we have more differences in the DNA. We can even go into sub-species level like strain identification and so forth with DNA analysis.
OK, that’s enough of a biology lesson for today. Let’s get into what this all means for USP <797> compliance.
What Do the Revised USP <797> Standards Say About Genus Identification?
The former standards identified certain groups of organisms that triggered immediate action, regardless of the number of Colony Forming Units (CFUs). For example, molds like those of the genus Aspergillus were previously defined as highly pathogenic microorganism and would trigger an environmental sample to be out of compliance. If you recovered even one CFU of Aspergillus on a plate, you needed to take action immediately.
That language has been replaced, but the revised USP <797> standards are not completely silent on the matter of genus identification. Section 6.2.3 (Viable air sampling data evaluation and action levels) and Section 6.3.3 (Surface sampling data evaluation and action levels) both say that an attempt must be made to identify any microorganisms recovered to the genus level with the assistance of a microbiologist.
We could get into a discussion on what they mean by a microbiologist, but we can do that in a separate post. My point here is that the standards do call for genus identification. To be fair, they are written in such a way that they could be interpreted to mean that genus identification is only required if action levels are exceeded, but is that really the case?
USP <797> is About More Than Checking the Boxes
Furthermore, Section 6 begins with this paragraph:
“An effective microbiological air and surface monitoring program provides information on the environmental quality of the compounding area. In addition, an effective microbiological air and surface monitoring program identifies environmental quality trends over time, identifies potential routes of contamination, and allows for implementation of corrective actions to minimize the risk of CSP contamination.”
Again, the emphasis is mine, but the word effective is used more than 30 times in the revised standard.
Just because the explicit language around Aspergillus and other pathogens of concern was replaced doesn’t mean these pathogens are any less dangerous than previously considered. The revised USP <797> standard is simply more of a framework for ensuring patient safety, with the onus put on compounding pharmacies to do their own risk assessment and define SOPs that address identified risks.
In addition to determining the level of risk present, genus identification can also help identify the source of the contamination. For example, a Micrococcus luteus colony may point to a personnel problem, such as a gowning issue or an excessive shedder. Aspergillus, on the other hand, is a common mold that can come from almost anywhere, including the HVAC system or incoming supplies. If you know where the contamination is likely to come from, it’s easier to address the problem.
If the goal is to protect patients and the onus for creating an effective USP <797> program is placed on the pharmacy, it seems prudent to perform genus identification on all samples relative to assessed risks and take appropriate corrective action before they impact patient safety.
Have Questions?
If you’re still working your way through the changes to USP <797> and what it means to have an effective environmental monitoring program, you’re not alone. We’re fielding questions daily from our customers and will be sharing answers to many of them in future posts. In the meantime, don’t hesitate to reach out to us with your own questions. Our accredited microbiologists and USP <797> compliance team members are happy to help.