USP <800>: The Why, What, Who and How to Compliance
Last month compounders that handle hazardous drugs (HDs) received a reprieve from the United States Pharmacopeia (USP) (https://www.cdc.gov/niosh/topics/antineoplastic/pdf/hazardous-drugs-list_2016-161.pdf); an extension of the implementation date for USP chapter <800> to December 1, 2019. The reasoning behind the delay according to USP’s website is, “to align the official date of General Chapter <800> with the official date of the next revision of General Chapter <797>.”
Despite the seemingly good news, if you haven’t already started the process for implementing compliance with the newest chapter I wouldn’t procrastinate any further because the planning, budgeting, construction, and implementation process is time consuming. In this article I’ll be outlining the reasoning behind the chapter’s intent as well as a strategy for implementation. While many articles focus on specifics for compliance, this article will give you our real world experience to quickly get up to speed with USP <800>.
First, let’s get one misconception out of the way. If you’re a retail/community pharmacy and you’re worried about having to purchase engineering controls (hoods and HVAC equipment) and build a cleanroom you have an “out” for complying with USP <800>; it’s written into the chapter on page 2 in Section 2. Simply stated, for dosage forms like tablets and capsules that are intact and will not be further manipulated there is no need to comply with the engineering standards. However, you do have to perform a risk assessment documenting there is no personnel or environmental exposure while handling the solid dose forms, and of course repeat the risk assessment process every 12 months per the chapter’s requirements.
The risk assessment process may seem intimidating or overwhelming but fear not, we have multiple sources for how to perform one. I’ve written (https://pharmacyinspection.com/save-500k-hacking-usp/) about this actually and how to easily get this done. Additionally, here’s an article that walks you through the process step by step and only introduces one form for accomplishing the risk assessment: https://learn.nuaire.com/white-papers/hazardous-drug-risk-assessment
Additional resources on the topic of risk assessment:
https://www.pppmag.com/article/2012 (written by Patti Kienle and Kate Douglass)
Why is this USP <800> chapter so important and what makes it more difficult than others to accomplish? The handling of HDs was addressed to some degree in USP <797> but without much direction. The new chapter gives medical personnel a codified way for handling these drugs properly so as not to contaminate ourselves, our work environments, our patients and other products. While many state boards of pharmacy are deciding to what extent they will be adopting this newest standard (https://naspa.us/2017/08/usp-800-adoptions-state/), we would like to suggest the implementation in spite of what your state may decide. While the data for contamination from various HDs is sparse, I contend that exposure to POWDERS specifically, whether they’re “hazardous” or not isn’t healthy because every chemical that we handle has some occupational exposure risk. This point alone specifies the need for Primary Engineering Controls (PECs – commonly referred to as “hoods” – powder containment and/or biological safety cabinets). The take-away here is that whether your state will enforce or not is irrelevant, it’s my opinion that pharmacies have a duty to protect their personnel to some degree and depending on what dosage form your compounding with (i.e. powders) you should really be using the proper containment protocols.
To accomplish what USP <800> is asking us to do, for those of us doing high risk sterile HD compounding especially, it requires us to potentially do some major renovations. We need to turn our rooms themselves (in addition to our PECs) that we compound in from positive pressure to negative pressure. There are numerous ways to accomplish this going by directions from the chapter but essentially what you need to know is that rather than pushing air OUT of our rooms, we’re actually pulling air into them. This is done via the hoods or low air exhausts in an attempt to keep any hazardous material away from the operators handling them and adjacent rooms. The one thing I will caution everyone is that along with air being pulled into these spaces that also means that particles that carry bacteria, fungi and humidity could be pulled into what should be an extremely clean environment. The one thing I learned from this project is that you should ensure that you have clean air in the adjacent space(s). Again, this can be accomplished in a number of ways. The really long explanation of how we accomplished this is on my site https://pharmacyinspection.com/dangers-usp-800-cautionary-tale-2/ but to summarize we made sure:
1.We weren’t exhausting TOO much air (pulling too much air into our space) and
2.The air that was being pulled in from adjacent spaces was HEPA filtered. We actually made the area directly outside of our ante room a HEPA filtered environment as well to help clean the air.
Of course there’s more than one way to accomplish this and the next section explains probably the biggest factor in assessing your needs and the best solution for compliance.
When my pharmacy decided to undertake this project back in 2015, I don’t feel like there were many resources for us to turn to. Looking back, we made a whole lot more errors than necessary. Had we done a little more planning in selecting our contractors and consultants we would’ve saved a lot of money and caused us so much less frustration and sleepless nights. The good news for those reading this is two-fold: you can learn from our mistakes and you have more time.
How should you go about determining who to use? Interview. Ask for references, call those references. Ask other pharmacies around you and if the cleanroom builder operates nationwide call somewhere far. I really like the International Journal of Pharmaceutical Compounding’s (IJPC) listserv for asking questions like this. Social media sites like LinkedIn may be of benefit too, but let me give additional caution because there is a lot of bad information out there as well. As pharmacists we need to start sharing more of this information because the meaningful collaboration can and will save us money and time.
If you haven’t already read in detail what it may take to get compliant I would make yourself familiar. While you don’t need to know how to build and install a cleanroom I highly suggest you know at least what’s going on. It may save you some headaches and make you educated enough to ask intelligent and coherent questions as to why your contractors are doing what they’re doing. This will serve you well in the planning stages especially as some may try to sell you unnecessary extras and drive up the cost of the build or even the long term maintenance and operating costs of your new cleanroom. A good example of this is trying to build rooms above the necessary ISO class that’s required or a biologic safety cabinet that exhausts 100% of the air as opposed to recirculating some of its own air back into the room. If someone is suggesting you build an ISO 5 room, tell them to take a walk; it’s not necessary and will drive up the costs tremendously. There are only a few situations where that is absolutely necessary and most likely you’re not doing those tasks (lyophilization to name one).
For further reading on the specifics of the engineering controls needed for complying with USP <800> check out this article on NuAire’s site by Bryan Prince: https://learn.nuaire.com/white-papers/facility-and-engineering-controls-using-usp-800-guidelines
There is so much to be said and discussed on the topic of USP <800> that Bryan and I started a podcast together to dig deeper into the issue of compliance and compounding quality. We encourage you to listen to our Pharmacy Inspection Podcast (http://pharmacyinspection.libsyn.com/); the first few episodes have been dedicated strictly to USP <800>. Our goal with the podcast is to share industry knowledge through our own experiences and those who we interview within compounding pharmacy.
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About the Author: Seth DePasquale is a compounding pharmacist and Co-owner of BET Pharm, LLC. In 2017 he started writing on compounding pharmacy compliance through his website pharmacyinspection.com and subsequently also started producing a podcast with his co-host Bryan Prince.
Contributing Author to this article: Bryan Prince is the owner of Lab Red Pharmacy Consultants LLC and specializes in compounding safety, workflow, and USP <800> design. Bryan has published numerous articles and been the invited speaker at compounding conferences throughout the U.S.