This video is a step by step instruction on how to achieve negative pressure per USP <800>. Per the chapter, the containment secondary engineering control (C-SEC) must be externally vented and maintain a certain number of air changes per hour and a negative pressure of 0.010″ to 0.030″ water column to the adjacent space. We walk through a nonsterile compounding hazardous drug room calculations and engineering methods for achieving negative pressure.
How to Achieve Negative Pressure for USP <800> Compliance
Video Transcript – Edited for better reading and additional context added.
Hello to all my compounding pharmacy friends and colleagues my name is Bryan Prince. I am a compounding workflow and lab design consultant and I specialize in USP 800 compliance. As issues come up, I like to share them with you the audience through these informational videos. I have spent a lot of time speaking with engineers about USP 800 compliance and how do we move air, what is negative pressure, and i think there is a little bit of a misconception about room pressurizations. The easiest way to achieve negative pressure in your USP 800 hazardous drug compounding rooms is to simply externally exhaust more air than what you supply.
I am going to show you some graphic examples in just a minute but essentially, we are going to walk through a quick room supply and exhaust calculation. The graphic example shows if you put “x” amount of air into the room it is x-times a percentage. There is no set percentage because it is based on the cube which is the room length multiplied times the room width multiplied by the room height. We will get deeper into that calculation but really the point of this quick video is to tell you and to show you as pharmacists and technicians and the designated person how to achieve negative pressure so that you can have conversations with your local general contractors, architects, engineers, and any of those folks that are going to come in on the project. The concept and math for room calculations is easy to understand, but the USP chapters have created a different animal here, so it is important you as pharmacists can have intelligent conversations with your contractors about the concept.
Let us walk through a graphic example together. I thought this would be a great compounding laboratory project to show you how to achieve negative pressure. What we are looking at here is a very standard two-dimensional architectural floor plan that I drew. Look at this room right here in the middle. It is going to be our USP 800 non-sterile hazardous compounding room. You can see coming in through the sliding doors here on the right we’ve got the pressure map labeled at negative pressure to 0.01 inches of water column to 0.03 inches of water column which means that this room is negative to its adjacent space. We would be measuring that differential via some sort of room pressure monitor to make sure that in fact you are maintaining that USP 800 standard. The USP 800 chapter does not clearly define the nonsterile HD room must have a continues differential room pressure monitor, but deductive reason would be to have it available to prove to the boards of pharmacy, accreditation organizations, or other regulatory that the compounding room is within USP chapters specifications.
This sliding door entering in the hazardous drug compounding room is infiltrating air from the hallway. You could prove that with a smoke study, but smoke does not give us a differential pressure range. Doors in a negative pressure room are going to infiltrate air or in a positive pressure clean room (not part of this design) exfiltrate air, which means that we are going to share air between rooms when designing compounding labs. In this design scenario some percentage of that air is coming in under or around the door and we account for that on the test and balance side of the equation. I wanted to show you this how we would handle this room.
These corner pieces here that I am highlight in blue are our low wall exhausts in this room design situation and I will show you a better perspective of those in a 3-dimensional rendering. What I did is I took this block which is representative of the actual floor dimensions and the square footage. 488.33 square feet is what it is showing, so I rounded it up to 490 to keep the numbers even. The ceiling height in that room is nine feet and confirmed with the client. I multiply the square footage times the
ceiling height to get the room’s cubic footage which is 4410 cubic feet. Now USP 800 defines for us in table two and table three, whether it is non-sterile or sterile, what our minimum number of air changes are
and I know that in an 800 non-sterile hazardous compounding room we must maintain a minimum of 12 air changes per hour. What we do now is take the 4,410 cubic feet and multiply it times 12 (the number of desired air changes per hour) and then divide that number by 60. Sixty is not actually shown here in the visual equation on the screen, but that is the number of minutes in an hour and that number never changes so it’s a constant factor in our equation.
Calculating Supply CFM:
- Room width X (multiplied) Room depth = Square footage
- Cubic square footage X (multiplied) ceiling height = Cubic feet
- Cubic feet X (multiplied) desired number of air changes per hour / (divided by) 60
- Equals supply CFM at the ceiling diffusers to get desired air changes per hour
In our pharmacy example here, we get a minimum design criterion of 882 CFM and that is going to be our actual supply. Typically, the HVAC contractor or test and balance contractor would measure with a flow hood to confirm these numbers during mechanical equipment startup. In an ISO rated cleanroom the certification company would do the same to confirm and document the rooms are getting the correct number of air changes per USP. Some industry professionals have said “well on a negative pressure
room we actually want to measure the exhaust” to get a true air change calculation. That is correct but not always the easiest thing to do given duct layout, access points, drilling holes in ductwork, etc. Here’s some logic, if you are achieving 12 air changes per hour at the ceiling and we know that it requires more air out of the building to achieve negative pressure then of course you are going to be above 12 air changes per hour on the exhaust side. If you can hit it at the supply, you are going to maintain it at the opposing side, in theory. However, that last sentence will seem controversial to those follow ASHRAE and NEBB rules, so if you can get an exhaust duct downstream measurement from the negative pressure room, then please do so the test and balance documentation will be accurate.
If you have ever heard me speak on a webinar or conference or seen some of my videos you know that I tell you never design an engineer an HVAC mechanical system for a hazardous drug room or cleanroom to its lowest stated requirement. In this specific scenario we are discussing the minimum room requirement for air changes per hour would be 12 ACPH. If you design mechanical systems at its minimum USP specification, at some point during the year due to unpredictable seasonal and weather factors. Some factors may be controllable like the tightness of the building envelope (e.g. the compounding room) and some factors may not be controllable, but I tell folks that when you’re designing your 800 non-sterile (and sterile too) hazardous drug compounding room you actually would design it at 18 air changes per hour. Then people and process and July and August and all those other factors
will cause this room to settle somewhere in the middle which is great because then we are above our minimum number of 12 ACPH and we don’t have to worry about this room falling out of compliance specifications as stated on Table 2 in USP chapter 800.
In this video pharmacy example, we are looking at approximately 1300 cfm to achieve the desire number of air changes per hour. The geography of this pharmacy design project was a relatively stable area somewhere in the Midwest. They do not have a lot of fluctuations of relative humidity in the summer, which is great, so we ended up settling on a makeup air unit at 1200 cfm. I will do another video where I talk about sometimes you may want to go above that design CFM number depending on where you are located geographically. Let us just walk into this three-dimensional room and see how the 1200 cfm supply number fits into the equation.
As we walk inside this nonsterile compounding room through the sliding glass doors and we walk around
to this corner. Let us talk first about our supply air. As you see there are supply diffusers in the ceiling and I strategically spaced them out for good room dilution. I will do another video in the future that talks about how this ceiling profile is a chess match. Our design goal for a compounding space is to move the air from the ceiling down to the floor. We already know this design principle in a sterile cleanroom, but I want to carry this same air design thought process over to non-sterile room as well. Per USP 795 nonsterile compounding, which is also applicable, in USP 800 as a non-sterile standard we must clean that floor every day. So, if we’re dealing with powders in a non-sterile environment and technicians may breach containment from the containment primary engineering control (C-PEC) creating powder exposure then we want to make sure that we push that airborne particulate down to the floor with top to bottom airflow patterns. Maybe the micron size powder will statically charge to the floor maybe it will impact that floor so we can clean it at the end of the compounding shift. In the corner here of this model we want to send that sweeping air into this low wall exhaust grille and this just happens to be called a lattice style. I like these because they are easier to clean versus those horizontal grille slats which will cut your gloves and sometimes your fingers and they are just not easy to clean.
I used to tell folks that to achieve negative pressure your percentage to figure about fifteen percent because 0.01 inches of water column is not actually a lot of negative pressure. After getting some of these rooms into the market I have come to find that’s not necessarily true because based on the cube, based on the duct work, based on the height of the roof, and based on different factors that are sometimes not within our control that fifteen percent is not necessarily true. I have seen it as high as forty percent to achieve such a small minor negative pressure.
Back to this current scenario of twelve hundred cfm on the makeup air unit to supply the air. For exhaust in this room we do the calculations at 15% to 20% to 25% above the 1,200 cfm and we estimate the exhaust calculation about 1600 cfm. This low wall exhaust grill in this corner is going to carry about 750 to 800 cfm. The test and balance company will back into this exhaust number so these CFMs are approximate numbers that we give to the engineers and/or the HVAC contractors so they know what ranges they are working with because the duct sizing is all contingent on how much air, duct distance, and what pressure we’re going to move that air through the ductwork. Now let me pan around to show you what the other low wall exhaust looks like in the opposing corner. Based on the exhaust CFM we have a large low wall exhaust grille and there’s ductwork hiding behind this framed drywall. I do not typically like to move more than 500 to 800 cfm through each low wall exhaust. I do not like to get up to a
1,000 cfm because you’ll find sometimes if the duct work is not properly sized or you’re moving air too fast, that the low walls will actually start to whistle and nobody wants to work in a compounding room where your walls are whistling because that then gets to be a little bit old.
Let us go up to the roof now to talk about how we are achieving negative pressure. Let us rewind and restate that I told you that we are putting the air supply in at the appropriate number of air changes and I showed you how to figure that. Then we moved down towards the floor got these two low wall exhaust ducts and they notice how they join into this red duct. I colored it red just to show you that is exhaust because I felt like the color would make it easier to differentiate in the model. The red exhaust line goes up above our flat commercial roof line. If your pharmacy has a pitched roof, we must make changes and to how we do this, but for the sake of this model we used a typical flat roof structure. That exhaust transition above the roofline goes into an optional HEPA filter. I will do another video in the future that talks about optional HEPA filtration. Just know that it is not required for USP 800 compliance. HEPA filtration prior to exhaust was in an earlier draft version of the chapter on hazardous drugs but did not make it to the final version. From there the exhaust air into our utility set blower, which is generating the negative pressure. Some people call this a snail shell blower which could be a belt drive or a direct drive. On top of the blower is our stack height. The stack height is typically based on a local stack height requirement, so this does vary. I have seen the requirement as low as 36 inches, 48 inches above the roofline and even 10 feet in upwards of 20 feet, so it varies all over the country based on local building code requirements.
This larger box here labeled make-up air unit (MAU) is what is supplying that original 1200 cfm of supply air into the compounding room via the ceiling mounted diffusers. I have mentioned before an important point in other videos and white papers worth mentioning here, that if you constantly and consistently throw air out of a building per USP 800 via the containment secondary engineering control (C-SEC) then you must replace that air. The C-SEC is the cube of the compounding room we figured earlier, and it is externally vented that means you are throwing perfectly good air out of the building. It is important to note that you cannot “peter and paul” this airflow scenario and pull it from other places from around the building. That engineering design not going to work long-term, or your entire building is going to go negative, so in this situation especially with 1200 cfm which is a fairly significant amount of air we did in fact put the makeup air unit on top of the roof to do the entire supply of the compounding room. I’m just going to rotate this around you see we supply in we get our proper number of air changes and then with those low wall exhaust grilles, again moving the air from the ceiling down to the floor, and then exhausting it out of the building. You will notice that if we add up 800 CFM here at this low wall exhaust grille, plus 800 CFM from the other corner, that is 1600 CFM total. Remember I told you this makeup air unit was 1200 CFM, so again we’re pulling out more air than what we’re putting into the space and that is what is achieving negative pressure per USP chapter 800 compliance standards as state in Table-2 and Table-3 in the hazardous drug chapter.
I appreciate you joining me on this video. Sometimes this can be more confusing or less confusing so ask if you have any questions certainly give me a call at 228-239-6842 or email me firstname.lastname@example.org and thank you again for joining me on this video.