At the time of this writing we are seeing proposed chapter revisions for USP <795> nonsterile compounding and USP <797> sterile compounding. On December 1st of 2019 we will see a harmonization of the two chapters with USP <800>, which includes both sterile and nonsterile compounding for hazardous drugs. It’s important to understand that the intent of the chapters is to separate nonhazardous from hazardous compounding and nonsterile compounding from sterile compounding. The Reference-1 example on the right shows a four-quadrant explanation of the four aspects of compounding. One question we commonly get from compounding pharmacies is, “will separate rooms be required”? Without getting deeply immersed into all the semantics and dissecting the chapters line by line, the simple answer is ‘yes’. The intent of this blog post is to give a topical dissection of the four rooms, their engineering requirements, and how to achieve those requirements.
The area where we compound nonsterile (nonhazardous) drugs falls under USP <795>. The proposed revision does not actually require a separate room, but it does require “Areas related to nonsterile compounding must be separated from areas not directly related to compounding”. That separated area can be a counter or section designated for nonsterile compounding. That means the counter or space cannot be used for anything else, meaning no one can use the space as a desk or for dispensing.
However, it is important to note that, “Any weighing, measuring, or other manipulation of an active pharmaceutical ingredient (API) or added substance in powder form that could generate airborne contamination from drug particles must occur inside a containment device such as a containment ventilated enclosure (CVE) (i.e., powder containment hood)”. This should signal that the days of open bench compounding of powders without engineering controls are behind us now.
Sterile compounding of nonhazardous drugs as we currently know it will not really change as it relates to engineering controls. ISO class-5 primary engineering controls are still required and cleanrooms with a dedicated ante and buffer will still have positive pressure greater than .02 water column. The cleanroom will be required to have HEPA filtered air from the ceiling and have 30 air changes per hour. The ante room can be an ISO Class 8 (or greater) rated room and the buffer room must be an ISO Class 7 rated room.
A cleanroom for nonhazardous sterile compounding can recirculate the room air, which has always been the case, but new languages states “The ACPH of 30 can include recirculated HEPA-filtered air, but at least half (a minimum of 15 ACPH) must be HEPA-filtered fresh air”. It will be interesting to see if the final chapter revision keeps this language because opening an outside air damper on a make-up air unit at 50% could cause pressure relationships to change and balancing the cleanrooms will be an interesting challenge for ‘test and balance’ companies. Additionally, the air handler for the cleanroom will have to condition that additional outside air to the temperature requirement of 20-degrees Celsius (which is now a “must” and not a “should”) as well as the humidity below 60%. Some pharmacies might discover that their current air handling system was not designed for these specifications and will have to consider replacing their existing units.
USP <800> (nonsterile)
Nonsterile compounding of hazardous drugs must be “physically separated from other preparation areas” which is a dedicated room, under negative pressure (.01 to .03 inches of water column) and maintain at least 12 air changes per hour. Most packaged commercial air handlers will turn the air in a room four to six times an hour, so it is highly unlikely the pharmacy’s current air handler will keep up with the demands of USP <800>. The containment secondary engineering control (C-SEC) is the room and must be “externally exhausted” which translates to a one-pass air. To dissect this further, the expectation of the chapter is that no air is recirculated back into the air handler. The air will be introduced into the hazardous drug room and then exhausted out of the building in a single pass. This will take a dedicated make-up air unit (also called “dedicated outside air unit”) to achieve the engineering standard set forth in the chapter. There are no specific temperature targets and an expectation to maintain below 60% relative humidity.
The challenge with achieving this engineering standard is finding a rooftop location to place a new unit, coupled with possibly reinforcing the building’s roof structure to support the weight of the new unit (usually weighing more than 700 pounds). For those pharmacies with “A-frame” roofs a split-package unit might be the solution, with the unit’s condenser located outside the building and air handler in the interstitial space between the ceiling and roof. Again, the interior unit’s location and weight will be a consideration based on the pharmacy’s existing structure.
USP <800> (sterile)
For the most part, the cleanroom looks and feels much like the USP <797> cleanroom in that the ceiling provides HEPA filtered air and achieves 30 air changes per hour, with matching ISO standards. The main difference is that the hazardous drug sterile compounding room is under negative pressure (versus positive) and is fully exhausted with no opportunity for recirculation.
Again, it is very unlikely that the air handling system for the pharmacy’s current USP <797> cleanroom is going to be able to be utilized in the USP <800> cleanroom. Most USP <797> cleanrooms recirculate some percentage of the air introduced into the ante or buffer rooms and now the hazardous drug buffer will require 100% make-up air, so essentially the air handling and engineering controls are just too different to work together. A dedicated make-up air unit providing 100% outside air with specific temperature targets below 20-degrees Celsius (68 degrees Fahrenheit) and below 60% relative humidity is not typically a “standard” packaged unit and is engineered specifically to the zip code and local climate. If you are working with a local architect and engineer on a facility remodel and/or build-out of a new facility, make sure the project team fully understands these principles during the design phase.
If your pharmacy is planning a facility remodel or new build-out and needs help understanding more about the four design-engineering aspects of compounding, please call Encore’s Customer Service team at 800-454-2304. Encore Scientific offers a design-consulting package that corresponds with your pharmacy’s business model and works with your local project team to dissect the USP engineering compliance. If you have any questions or comments about the content of this blog, please email email@example.com.