A Breath of Fresh Air
Posted on December 3, 2015
By: Mitch Valdmanis, Senior System Designer
Part III: Of Pass-through Chambers and Control Systems
In parts I and II of this series we described how RIVA has been designed to achieve ISO level 5 air cleanliness by sealing the compounding chamber, filtering incoming air, and maintaining laminar airflow inside of the cell. So far so good, but if we can’t allow entry of 0.5 µm diameter particulate into the compounding chamber, how are we to get any consumables into the chamber and products out? More importantly, how do we transfer inventory into and out of the system without undoing all of the work to get the airflow clean and laminar in the first place? The answer is the use of pass-through chambers.
The use of pass-through chambers to segregate two separate spaces is hardly a novel idea, but incorporating them into a fully automated compounding system did pose some particular design challenges. All consumable entry into and product and waste removal from RIVA occurs through pass-through chambers, however the consumable entry pass-through provides a particularly interesting case study of intertwined requirements, dependencies, and features, as illustrated in the flowchart below. Ultimately, the result is that the inventory pass-through requires active airflow management to maintain cleanliness, but we get to that result from multiple directions.
As with so many of the design decisions made during RIVA’s development, the primary driving force in this case was maximizing patient safety. From this starting point, we head down two paths: fully automating the compounding process, and adhering to USP<797> which are the suggested standard operating procedures (SOPs) in this case. The SOPs recommend minimizing exit and entry to the direct compounding area (DCA) to minimize the potential risk of contamination of the DCA. One way to minimize entry/exit is to provide large inventory capacity within the compounding cell, maximizing the compounding time between inventory loads. As it happens, providing large inventory capacity also helps achieve the full automation goal, for the exact same reason, no less.
So we’ve determined that maximizing inventory capacity is beneficial for multiple reasons. How do we provide a large inventory space that remains ergonomically accessible to the operator, while ensuring that all inventory is loaded via a pass-through chamber? Make the inventory space the pass-through chamber itself! RIVA’s inventory storage is contained in two rotating carousels with multiple, vertically oriented inventory racks located around the periphery of each carousel. Storing inventory in the pass-through chamber is our first direct requirement for airflow in the pass-through, since a constant stream of clean air must be passed over the stored inventory from dedicated HEPA filters.
Now a slight detour: For the inventory carousels to act as a pass-through chamber, an opening to the compounding cell must be provided that does not open a direct airflow path to the exterior when a door is open. To store a large amount of inventory while keeping it readily accessible to the robot, the interior opening should be as large as possible, but from the USP<797> SOPs, we recall that we want to minimize the risk of contamination in the compounding chamber. A large opening from the pass-through to the compounding chamber provides a potential contamination path. Any particulate in the pass-through could get into the compounding chamber when open. A large opening high in the cell has greater potential to expose particulate from the pass-through to critical sites in the compounding cell. Put these two thoughts together – large opening; minimal contamination risk – and the only viable solution is again to provide active airflow through the pass-through to evacuate any particulate from the pass-through before it has the potential of contaminating the cell. By removing the contamination risk, we can go ahead and make the opening as large as necessary.
The third path to airflow in the pass-through chamber goes through cell pressure management. Specifically, RIVA was designed to be able to compound either antibiotic or hazardous drugs. One of the primary differences between compounding hazardous or non-hazardous drugs is the relative pressure of the compounding chamber – positive for non-hazardous drugs, negative for hazardous drugs. But it’s not quite that simple. To, yet again, minimize contamination risk from the pass-through to the compounding cell, the pressure in the pass-through should always be slightly lower than the pressure in the compounding cell so that air flows from the clean area to the dirty area. That means when compounding non-hazardous drugs the pass-through is less positive, and when compounding hazardous drugs the pass-through is more negative. How can we manage this? You guessed it, by providing active airflow in the pass-through chamber that can be controlled separately from the airflow in the compounding cell. The addition of the vestibules over the loading doors that provide HEPA-filtered air over the loading door to further minimize the risk of particulate ingress during loading when the external door is opened.
This leads us nicely to the final discussion point for this series on the airflow in RIVA: controlling the airflow. There are many, potentially competing factors to manage in controlling the airflow through an aseptic compounding chamber. As mentioned above, the pressure in the compounding chamber must be maintained positive or negative, depending on the nature of the compounds, and the pressure in the pass-through chambers must be maintained lower than the compounding cell. The flow regime of the air (i.e., laminar or turbulent flow) is highly dependent on having a uniform velocity of the airflow. Specifically, laminar flow may become suddenly turbulent if the flow velocity is increased. On the other hand, USP<797> specifies minimum airflow velocities to prevent disturbances such as thermal buoyancy from warmer items causing a reversal of the airflow. A minimum air change rate, which is also dependent on airflow velocity, is required for compounding sterile preparations to ensure timely purging of any particulate that may arise in the process. RIVA’s airflow control system continuously monitors air pressures and velocities, adjusting the intake and exhaust fans to maintain proper conditions for sterile compounding.
That wraps up our whirlwind tour of some of the design considerations made to keep the airflow through RIVA free of whirlwinds. The importance of maintaining clean, laminar airflow in direct compounding areas may not get the appreciation it deserves since it can’t be visibly seen during normal operation. I hope this series has provided a new or renewed sense of the criticality of properly managing the airflow in all sterile compounding activities.
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