One of the most common issues a cleanroom will encounter is inconsistent temperature and humidity parameters. Because of the varying weather conditions and atmospheric pressure outside the building, conditions inside the building also fluctuate. As a very dry and cold room with low pressure, a cleanroom is susceptible to natural laws of vapor transmission. These laws dictate that vapor goes from warm to cold and moist to dry, which means moisture is attracted to the cleanroom. When a cleanroom has a temperature of 65 degrees Fahrenheit and a relative humidity of 45%, then the cleanroom is attracting warm vapor from other spaces. When it is hot and humid outside (or raining) in the summer, atmospheric conditions are trying to equalize with the building. If the cleanroom’s HVAC system is not engineered specifically to deal with extreme conditions, which are geographic-specific, then the cleanroom is going to struggle to maintain consistent temperature and humidity conditions.
Case in point is one pharmacy cleanroom project where we were called in to do a forensic analysis of the temperature and humidity problems. In such instances, we often don’t know who was first to the original cleanroom design team, but in this case, the architect was first to the party. Although the architect had designed a couple of “healthcare projects,” like a series of surgical centers, a chiropractor’s office, and even an outpatient facility, designing a compounding pharmacy that adheres specifically to USP compliance standards may have been a stretch given the architect’s resume.
The architect thinks the cleanroom might need an air-handling system of its own, which is correct. As sharing a common air handler that needs to maintain a strict temperature typically below an office and/or retail space is not a good idea, the architect hires a mechanical engineer to do the specifications, the duct size drawing, and the appropriate mechanical sheets, so the permit set of prints can be submitted at a later date to the city for a building permit. The architect compiles all the drawings and sends them out for bid to local general contractors (GC). The lucky general contractor is awarded the bid for the job and now the GC hires the HVAC contractor, commonly referred to as the “mechanical contractor.” The mechanical contractor is responsible for purchasing HVAC equipment, including the air-handling system for the cleanroom.
In late February, the pharmacy project is completed, and the cleanroom’s new air-handling equipment is started up in the middle of March. A test, adjust, balance (TAB) contractor is hired by the mechanical contractor to make sure the cleanroom’s fan filter units (FFUs), cascading room pressures, return CFMs (airflow), and exhaust CFMs are appropriately balanced to the space. Finally, a certification company comes in and measures airflows for air-change-per-hour (ACPH) calculations, aerosol challenges the HEPA filters, and gives a certification report that the cleanroom complies with USP standards.
Now April rolls around and a nice warm spring only slightly changes the temperature set points inside the cleanroom, requiring some adjustment to the thermostat. Spring and fall are considered a “should season” because they are in between peak seasons where we see extreme seasonal conditions. As we coast into May, the pharmacy notices the cleanroom’s humidity is starting to fluctuate based on outside conditions and even the time of day. This is due to these days seeing thirty-to-forty-degree temperature swings from morning to afternoon, but despite this, the cleanroom is in compliance 90% of the day. By June, the pharmacy can’t control the humidity more than half a work shift. Even though someone is constantly playing with the thermostat trying to find the sweet spot and driving the thermostat cooler, the humidity continues to be a problem and moisture starts to form on the glass.
What is the problem with the HVAC system?
When the target temperature in the cleanroom is reached, the thermostat signals the air-handling compressor to cut off. The compressor is responsible for temperature control as it controls the flow of gas through the outdoor coil and indoor coil to remove heat. At some point during the design phase of this project, the architect or engineer asked the owner, “What temperature do you want to target in the cleanroom?” After putting on a rear tying gown, bouffant, double shoe covers, and double gloves, pharmacy technicians all agree that 65 degrees Fahrenheit is a good target temperature. That temperature was what the engineer used as a target for cooling load in the space, considering the size of the rooms and some minor heat gain from lighting, people, and processes.
When the unit’s compressor is off, the air-handling unit’s internal blower will typically also shut off, but the fan filter units (FFU) located in the ceiling of the cleanroom are still demanding the supply air. This could be causing temperature fluctuations if the HVAC unit is cycling on and off frequently (short cycling). Let’s assume someone had the foresight to turn the thermostat fan to “ON” so it runs all the time and the air-handling unit is delivering a constant supply of air to the FFUs. If the compressor is off and moisture is present on the coils, then the internal blower is pushing vapor downstream into the cleanroom, which would account for the fluctuations in humidity. Keep in mind a cleanroom is changing air every 90 to 120 seconds on average, so there is a significant amount of air moving. Fluctuating temperatures and humidity from a cycling compressor will show up every time.
What is the solution to our pharmacy’s temperature and humidity issues in the cleanroom?
Both temperature and humidity should be satisfied independently in a cleanroom. A dedicated make-up air unit (MAU) does exactly that by using temperature and humidity logic to keep the compressor running almost all the time. If the temperature in the room is satisfied but the humidity is not, as detected by a humidistat (which measures room humidity much like a thermostat measures temperature) in the cleanroom, a hot-gas bypass or digital-scroll technology kicks in to satisfy the room’s humidity by keeping the compressor working. A supply air sensor located in the ductwork is sending temperature feedback to the system and the humidistat is sending humidity information back to the system, creating an efficient design parameter logic loop with stable airflow and pressure. A dedicated MAU built specifically for these controlled and critical environments must be specified in the design criteria by either the architect or mechanical engineer, so that your cleanroom has a guaranteed compliant environment. Therefore, you should not use a standard “DX” package or split unit with common specifications like “2-ton” or “4-ton” to effectively or efficiently run a cleanroom. Standard DX HVAC equipment was not built to actively control humidity as an independent variable.
USP <800> has allowed us to take a deep dive into mechanical engineering as it specifically relates to air handlers because, up to this point, we have been dealing with positive-pressure cleanroom environments where recirculating 100% of the air is common. Recirculating air makes it somewhat easier to overcome temperature and humidity issues. Externally venting air out of the building per USP <800> now creates an entirely new layer of engineering mystery. The one thing we have learned about externally venting air out of a building is that it requires the absolute replacement of that air back into the equation. Single pass air is difficult not only as a concept to grasp but also to engineer in real life because normal HVAC systems recirculate 90-100% of their air so they only need to cool a degree or so per pass thru the unit an average of 6x per hour. This is a new evolution for architects and/or engineers and mechanical contractors to conceptualize and realize that newer air-handling equipment with updated technology must be implemented into the design criteria because we never want to lose control over a cleanroom that runs all day every day. As you can see from this real-life example, someone on the project team needs to take ownership of the performance of the equipment because you, as the pharmacy owner, do not want to pay twice for someone else’s mistake.
About the authors:
Bryan Prince, MBA is a compounding workflow and lab design consultant specializing in USP <800> compliance. With more than 15 years of construction management and pharmaceutical containment technology experience, Bryan has gained extensive knowledge of chemical-handling techniques, safety strategies, and facility design. Bryan has published numerous articles on compounding pharmacy workflow design and has spoken at conferences on USP <800> throughout the U.S. for several compounding related companies, groups, and associations. Email: firstname.lastname@example.org
Shawn Valandra is an Environmental Filtration Consultant and owner of SVE Industrial Air Filtration Solutions based in Phoenix, AZ. He has spent two decades providing clean air solutions to commercial and industrial facilities including 503A and cGMP manufacturers. Shawn has provided air-handling design solutions to multiple compounding pharmacies for USP compliance. Email: email@example.com