By: Mitch Valdmanis and Ron Rob

One of the interesting challenges to solve in the design of IV automation is to create and maintain an environment where the compounding process can be carried out in air conditions compliant with ISO Class 5 and USP<797>. There are many factors to consider in the design – far too many to detail in a blog post – but some of the requirements with the greatest impact on the design were:

• Airflow throughout the compounding chamber must be laminar and uniform.
• Air particle counts must be lower than 3,520 particles per cubic meter (0.5μm or larger).
• All critical sites must be exposed to “first-air”.
• The air pressure in the compounding chamber must be positive (for non-hazardous drugs) or negative (for hazardous drugs) relative to the surroundings.
• All consumables must enter and exit the compounding cell via pass-through chambers.

Credit: flickr user brewbooks

Part I: Laminar Airflow

Certainly one of the greatest challenges in designing the RIVA air handling system was the establishment of laminar flow through the cell from top to bottom so that the entire compounding cell is continuously swept with clean air steadily moving in one direction. It is essential to avoid the creation of turbulent disruptions in the laminar flow that would introduce eddies or recirculation in the flow. This motion is best described as a rolling motion of the air. The issue is that if particulate is introduced in the air flow with recirculation, it becomes entrained in the rolling air mass and it remains there, slowly bleeding out over a long period of time. Fast moving flow alone is not sufficient to move particles downstream, a concept wonderfully illustrated by this kayaker caught in some turbulence on a river.

In poorly designed enclosures the time required for the environment to recover to ISO Class 5 conditions after some sort of breach or contamination, such as after the doors to the chamber are opened for cleaning, can approach or even exceed 15 minutes. Any particulate that is introduced in such an environment, even in small intermittent quantities, never really clears out during operation. By contrast, the RIVA air handling system has a recovery times ranging from 15 seconds after a cell door is opened in an ISO Class 8 environment (such as after regular cleaning) to 90 seconds from a worst-case scenario where the entire compounding chamber is artificially filled with smoke. It is truly astonishing to watch how the RIVA system is able to smoothly and quickly clear the air even while operating.

Many design considerations contribute to the laminar airflow. It begins with a patented diffuser at the top of the compounding area that evenly distributes the incoming HEPA-filtered air across the entire top of the compounding area. The air is extracted from the bottom of the compounding area into a return air duct that pulls air in around the entire periphery of the compounding area. Additional return air outlets are placed anywhere that the air needs to flow. The enclosures of all automation equipment are extended up to the internal diffuser to promote smooth air flow along the outer surface from ceiling to the floor. This avoids air from coming down and stagnating on the top of the equipment enclosure and then spilling over the sides as it moves downward. Such a spilling motion would create turbulent zones, disrupting the laminar flow.

Additionally, a cell like RIVA will have some equipment that projects into the air flow, such as temporary vial storage shelves shown in the figure below, which could have a turbulent zone below them if not handled appropriately. To keep flow in those areas laminar, they have been designed to have return air ducts in the structure behind them along with vents cut into the duct immediately below the overhang. Airflow is pulled into the vents, disrupting the formation of eddies and preventing recirculation. Where possible, the projecting equipment itself is also perforated to facilitate the smooth flow of air.

RIVA’s temporary vial storage shelves are perforated and vented to prevent air from recirculating below them.

Finally, the airflow over the interior faces of doors that are used to access the interior of the cell is designed to have a slightly higher speed to prevent the air flow from languishing and causing recirculation there, not unlike what is common in well-designed biosafety cabinets.

Achieving smooth, laminar airflow throughout the RIVA compounding cell was no mean feat, but it was critical to ensuring the safety and sterility of the millions of IV doses that have been prepared by RIVA to date. Any compromise to the design could lead to systemic turbulence in the airflow and greatly increase the risk of any particulate in the airflow infecting patient doses.

We’ll discuss the additional requirements identified above and the design challenges associated with them in forthcoming installments. Stay tuned!