http://www.onlinetmd.com/article/tmd0915-automatic-solution-compounding-processes
Thomas Doherty, chief technology officer at ARxIUM (formerly Intelligent Hospital Systems) based in Winnipeg, Manitoba, Canada, has nearly three decades of experience developing medical devices; aerospace applications for aircraft, spacecraft, and satellites; and naval command and control systems in a variety of platforms. He is also co-inventor of 12 patents for technologies deployed in RIVA, a fully automated intravenous (IV) compounding system for pharmacies that has completed nearly 4 million error-free doses across the world. The following are Doherty’s thoughts on automated compounding.
TMD: What is pharmacy compounding?
Doherty: Pharmacy compounding is the combining, mixing, or altering of a drug and other compounds to create specialized medications, often tailored to individual patients. Compounding can be either by hand (manual) or by highly specialized machines (automated).
TMD: Is there a significant risk to manual compounding?
Doherty: No one intends to make errors. The aseptic technique has become very refined, and for the most part, pharmacy technicians do a very good job. But humans are not perfect, and a very small oversight can have huge consequences. For example, in 2007, actor Dennis Quaid’s twin infants received adult doses of a blood thinner – 1,000 times stronger than a pediatric dose – because a pharmacy technician drew medication from a vial with a label that was almost identical to the vial that should have been used. Fortunately, both children survived. But last December, a woman in Oregon died after receiving an IV containing the wrong medication during an emergency room visit – even though the label on the bag listed the medication that was ordered by her doctor. This is why our goal has always been to design technology that could prevent exactly those types of errors.
TMD: How is automated compounding different, and what are the benefits vs. manual compounding?
Doherty: At its most basic level, automated compounding is simply the application of proven robotic technologies in the preparation of IV medications (syringes and IV bags). Available IV compounding technology not only duplicates the manual process, but does so with substantially more accuracy, efficiency, and repeatability.
Automated IV compounding systems remove the primary source of error – humans – from the compounding process. In fact, RIVA has completed nearly 4 million error-free doses. When you look at it from a liability perspective, hospitals really should explore available options to improve safety, especially if available at a reasonable cost. IV automation is commercially available, has proven benefits, and can be implemented cost-effectively.
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Automated compounding provides many advantages. Some systems – such as RIVA – already have features that would allow compliance with the Drug Quality and Security Act (DQSA). For example, RIVA provides an electronic audit trail documenting the details of every dose dispensed (including every vial used), an aseptic compounding chamber with ISO Class 5 air, and much more. The process is fully compliant with USP<797> compounding standards, also required by DQSA.
TMD: What kind of research was conducted prior to developing the RIVA compounding system?
Doherty: Automating the medication compounding process is far more complex than many people realize. A number of variables have to be taken into account, including admixture fluid weight, surface tension, specific gravity and viscosity, differences in the diameter of ‘standard’ syringes, the amount of force necessary for needles to puncture a vial stopper, and the list goes on.
To start, we did an analysis of manual compounding. For example, the preparation of a single dose of Vancomycin can involve as many as 42 process steps – from writing and inputting the order, selecting the vial, measuring and mixing the compound, and delivering and administering it to the patient. At that rate, preparing only 24 doses would require more than 1,000 process steps, and they all need to be performed correctly, every time. But, when you examine all the steps involved, there are a number in the compounding process alone where errors can lead to injury. Errors in preparation of IV medications can have significant consequences as they bypass all the body’s defense mechanisms and go right into the bloodstream. By the time you realize there’s a problem, it could be too late.
So, we looked at the processes for making compounded doses in syringes and IV bags in a pharmacy and asked, “What can go wrong?”
The fact is there are many things that can go wrong. Therefore, the goal of an ideal IV compounding automation system is to provide a solution to areas where a fault analysis shows a risk of failure can be mitigated or eliminated. We made a fault tree of all these things – wrong vial, wrong fluid, contaminated surface, and so on. That led us to begin developing a design that would not only mitigate all those failure points, but also have the system verify each step.
Some initial research for development of the RIVA system was done by engineers at the St. Boniface Research Centre in Winnipeg, who helped develop an early tabletop prototype of the system. This research informed the development and design of today’s RIVA system.
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TMD: How is automatic compounding designed to be safer?
Doherty: Our goal with the RIVA system was repeatability in IV production, which results in increased accuracy and reduced opportunity for contamination. Repeatability of process is an important concept, as you really want an IV dose to be made under the right conditions, and for those conditions to be the same for each dose made.
As we conceptualized RIVA, we recognized that it needed an engineered environment to protect fluids and interfaces. RIVA is designed so materials don’t go directly into the compounding chamber, which prevents outside air from getting in. Implementing this design feature was a challenge. It required segmentation of the inventory, separate airflow control, and isolation of the compounding chamber. These kinds of details are important because without attention to such areas, the production process for an IV has variability, and if there is variability, there is not repeatability.
Additionally, we have to make sure ISO Class 5 laminar air moves across critical areas at the right velocity. You need to have fans of a certain size and design to move air that quickly. To do this, we patented ceiling designs and membranes that prevent airflow from being turbulent right at the ceiling where it originates. We also needed to pull air away at the bottom or it would be turbulent there – we had to balance the pushing and pulling of air, while keeping the velocity adequate to sweep all the air away. If it is too gentle, dust or particulates can hang in the middle of the chamber – so we designed it to change the air quickly. In fact, if the chamber is breached, it will automatically stop compounding, reject the dose, and then refill the chamber with clean air in less than a minute.
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There were other items we considered in the design that may not seem as important, but are key to a successful automated process. For example, RIVA doesn’t store inventory under the area where fluid transfers occur because there is always a chance for a drip. If you look at other automated compounding systems, you’ll see some store inventory in these areas. A drop might fall and no one would ever know.
Another example is surface sanitization. One of the failure points in the process is that if critical surfaces, such as a vial stopper, aren’t sanitized properly, they could contain bacteria. When that surface is punctured with a needle, the bacteria will get into the fluid, so we use UV lighting to kill bacteria on the vial stopper and laminar airflow to ensure any particulate doesn’t land on other critical surfaces.
TMD: Can you explain how each RIVA is manufactured?
Doherty: When manufacturing a system like RIVA, the design the design behind it needs to have some tolerances so that we can fine-tune the alignment and physical interfaces during assembly.
One of the main components of RIVA is the robotic arm, which is purchased pre-assembled and then we teach it the specifics of interacting with its environment. This teaching of the physical interfaces adjusts for any of the tolerances of the assembly when subsystems are built and installed. When you think about it, the robot is a flexible transportation system – it moves a syringe from the inventory to a station, removes the cap, and then weights it at another station. While at that station, a camera looks at it so we can align the slope and bevel of the needle the same way. Then the robot takes it off and hands it to a fixed station where it is gripped at the barrel, plunger, and needle to make sure all those things are straight and aligned. So, the robot moves things around – precisely and quickly, but all the automation is done by fixed units around the cell.
TMD: What is the process for installing RIVA at a pharmacy?
Doherty: Each RIVA is fully assembled at the factory, and then taken apart and transported to the customer. Once on location, the robot is again re-taught as there are slight variances when reassembled. The process is relatively straightforward as in many cases the positions of items are fixed relative to a reference point. Once the robot learns the unique physical position of an interface area, the rest of the interactions become defined.
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TMD: Does RIVA need to be installed in a cleanroom?
Doherty: When someone compounds a medication manually, that person works under a laminar hood in a cleanroom to minimize the risk of contamination. RIVA is a self-contained system that does not necessarily need to be installed in a cleanroom – if the room it is placed in meets certain basic attributes.
TMD: Do you think more pharmacies will be using automation in the future?
Doherty: Absolutely. It’s going to come to the point that a pharmacy is going to have to justify not using automation. The awareness of the risks that the facility is accepting by not using automation are only going to increase as more pharmacies implement the technology.
ARxIUM
www.arxium.com
About the editor: Elizabeth Engler Modic is editor of TMD and can be reached at 216.393.0264 oremodic@gie.net.
Clearly, the NECC meningitis outbreak continues to resonate among health care providers and policymakers. The Drug Quality and Security Act (DQSA), passed by the U.S. Congress in 2013 in response to the NECC tragedy, provides enhanced rules for preparing and tracking compounded medications. The law allows compounding pharmacies to voluntarily register with FDA as outsourcing facilities (hospitals that participate in Medicare are required to purchase CSPs only from registered outsourcing facilities) and undergo enhanced inspections.
Automated compounding provides many advantages. Some systems – such as RIVA – already have features that would allow compliance with the Drug Quality and Security Act (DQSA). For example, RIVA provides an electronic audit trail documenting the details of every dose dispensed (including every vial used), an aseptic compounding chamber with ISO Class 5 air, and much more. The process is fully compliant with USP<797> compounding standards, also required by DQSA.
TMD: How is automatic compounding designed to be safer?
There were other items we considered in the design that may not seem as important, but are key to a successful automated process. For example, RIVA doesn’t store inventory under the area where fluid transfers occur because there is always a chance for a drip. If you look at other automated compounding systems, you’ll see some store inventory in these areas. A drop might fall and no one would ever know.
TMD: Does RIVA need to be installed in a cleanroom?
