Above and Beyond USP Chapters <795> and <797>
Aim for CGMP-like environmental monitoring standards in your 503A compounding pharmacy
By Gina Shaw – Pharmacy Practice News November 10, 2021
If your hospital or health system has a compounding pharmacy, it’s almost certainly classified as a 503A facility, permitted to do small-batch compounding, primarily for individual prescriptions, and is governed by your state board of pharmacy and USP General Chapters <797> and <795>. Your environmental monitoring and other practices are not required to meet the much more rigorous Current Good Manufacturing Practice (CGMP) regulations demanded of large-batch 503B outsourcing compounding facilities. So, why would CGMP be relevant to environmental monitoring in your 503A facility?
“There are many reasons why you should design an environmental monitoring program for your 503A that exceeds USP <797>,” said Tenille Davis, PharmD, BCSCP, the pharmacist-in-charge at Civic Center Pharmacy, in Scottsdale, Ariz., during a session on “quality built in” at the 2021 Compounding Pharmacies Grand Salon, held virtually. “First, it improves patient safety; but also, it comes closer to what the FDA is looking for during inspections. Some observations on 483s issued by the FDA are beyond <797> requirements. Knowing what the FDA would like to see can help you build a more robust program and give you more control of your space, which improves patient safety.”
One way to do that is by increasing the frequency of your surface and air sampling. The proposed revised USP Chapter <797>—released to much fanfare on Sept. 1 (see page 1)—requires only two sampling points per year for 503A compounders. (By comparison, 503Bs must sample at least once per shift.) “The chapter tells us that we have to trend data, but you can’t trend data with two air-sampling points a year,” said Abby Roth, the senior director of business operations for Critical Point LLC, who moderated the session. “If you are doing sterile-to-sterile compounding, we suggest that you do both air and surface sampling at least monthly.”
“Twice a year is not enough to trend anything,” Dr. Davis agreed. “If you’re only doing surface sampling every six months, it will take years and years to see trends. The more testing you can do, the more data points you have to trend your results and mitigate any sort of problems.”
Taking as much of your sampling and testing in-house as possible can help you conduct more testing without the added expense and delays of using an outside certification company. “Many 503As are outsourcing their testing to outside companies, which makes it difficult to react in a timely manner if you have an actionable exceeded level,” Ms. Roth said. “Sometimes the certifier can’t come in for another two weeks to resample, which means that depending on what the excursion was, that may mean you’re now operating at a reduced beyond-use date. It puts a lot of strain on your organization to not have control over the sampling.”
Once you’ve invested in your own air sampler, all you have to pay for on a regular basis are the sampling media, Dr. Davis said. “Those are really inexpensive, and it allows you to have more control of the process and get more data points.”
You can also improve your sampling procedures with guidance from supplemental resources, such as the Controlled Environmental Testing Association’s (CETA) Application Guide CAG-009, “Viable Environmental Monitoring for Sterile Compounding Facilities” (bit.ly/3uNvddM); USP’s Chapter <1116>, “Microbiological Control and Monitoring of Aseptic Processing Environments” (bit.ly/3oGGkEn); and the FDA’s Aseptic Processing Guideline (bit.ly/3BlpSNt).
“USP <797> tells you what to do, while documents like these can help you with how to do it,” Ms. Roth said. “CAG-009 will provide information to fill in the gaps. For example, the chapter doesn’t talk about how to ship samples to a lab or get into specifics about control plates, or things an org might run into if they’re outsourcing the analysis of their samples to a lab. While <1116> focuses on the limitations of environmental monitoring, what it’s meant to do and things like what you should look for in air samplers.”
Once you have more environmental monitoring data and can actually look for trends, what information are you actually looking for? It shouldn’t just be whether or not action limits for viable microorganism colony-forming units are exceeded. “If there are increasing numbers of colonies over time, even if action levels aren’t exceeded, that should be a red flag,” Dr. Davis said. “Are you seeing continued growth in the same area? That tells you it’s a hot spot you need to monitor and develop an action plan for what to do if those kinds of trends continue.”
What do you do if action levels are exceeded? “You need an out-of-specification plan: How do you investigate your results; what do you do to remediate them; and how often do you retest?” Dr. Davis asked. “A lot of pharmacies are just checking boxes. They don’t want growth in the buffer room, so they clean the location three times with bleach and then retest. Maybe it doesn’t grow anything, but that doesn’t solve any underlying problems.”
Instead, Ms. Roth recommended repeating sampling for five days to determine whether the result is a trend or a one-off, while assessing other factors such as air pressure differentials and personnel involved. “If you have the same finding five days in a row, you have a clear problem you need to think about fixing,” she said. “Use data to figure out how to mitigate contributing factors so they don’t keep happening. Do you need to retrain people in handwashing and garbing, for example? Do you need to change up your cleaning products or increase fingertip testing?”
Ms. Roth cautioned that environmental monitoring has its limits. “It’s a snapshot in time. What’s here now might not be here 15 minutes from now or five days from now,” she said. “And it’s a tool, not a box check for chapter compliance. You can’t use environmental monitoring as a sterility test for your compounded sterile preparations. Just because you recover organisms in your buffer room, anteroom or even your ISO [International Organization for Standardization] 5 primary engineering control, that doesn’t mean that everything produced during that time is contaminated. The way you build quality into your operations is what gets to be important. Has your organization implemented a really good hand hygiene and garbing program? Does everybody comply? Does everybody know how to use the primary engineering controls? Do you have good material handling procedures? All those things will mitigate the risk that even if we do recover something in that space with environmental testing, it will reduce the chance that your compounded preparations were contaminated.”
Above and Beyond USP Chapters <795> and <797> – Pharmacy Practice News
