Medical Device Link.

Because clinical trials deal with human health, the accuracy of drug delivery is of utmost importance. "As pharmacists, we must be certain that we're not only delivering the correct drug, but also the correct amount of medicine for every dose the patient takes," says Dan Beechuk, who has worked in the clinical trials area for 35 years and has managed the Clinical Pharmaceutical Operation of Pfizer (Ann Arbor, MI) for the past 20 years. For a long time, though, he was convinced that there was a way to improve packaging speed without sacrificing accuracy, and he even worked with students from an engineering school to look at the possibility of using robots for mechanical placement.

Traditional methods for creating clinical trial packages with multiple substances required several steps and manual assembly. First, each drug was blister packaged in its own tray. If there were three different drugs or three different strengths of the same drug, then three different sets of trays were created, handled separately, inventoried, stored, then cut into strips, and hand assembled into the final configuration on a unit-dose card according to the trial regimen. Besides the time-consuming manual assembly, a substantial amount of handling was involved in this process.

The Trialpack robot-based blister packaging system from Zurich-based Fleximation—represented in the U.S. exclusively by Klöckner Medipak (Clearwater, FL)—was the solution for Pfizer. Installed at the end of 1999, the Trialpack system incorporates a Klöckner Medipak EAS unit-dose blister packager and a robot- based filling system, capable of accurately placing up to four different products in complex, double-blind, randomized clinical trials.

The idea for the Trialpack system was the feasible solution to a common problem. "While I was working for another robotic company," explains Matthias Vogelsanger, founder and president of Fleximation, "I worked on a custom robotic filling system for clinical trial blister packs for a Swiss pharmaceutical company. I realized there was a real need for an even better, commercially available system." And so he created the Trialpack system. Exceptional flexibility, safety, on-line quality control, and fast and easy setup for the small batch sizes typical of clinical trials were his design parameters, along with keeping special tooling at a minimum to make the system more affordable.

"Klöckner Medipak's EAS unit-dose blister packager was already the preferred machine for clinical trial packaging operations," notes Vogelsanger. "The EAS machine also offered inexpensive tooling and the ability to configure packs via software." And so, Klöckner Medipak became the exclusive North American representative of the Trialpack system in March 2000.

Currently, Pfizer's Clinical Pharmacy Operation's blisters are standardized on Pentapharm alfoil PVdC- coated vinyl film from Klöckner Barrier Films. The Packaging Development division of the company selected Klöckner materials more than 10 years ago, when the first Medipak EAS machine was acquired there. "We wanted to take the conservative route and pull all of our clinical trial products in high-barrier materials," explains Monica Schiksnis, manager of package development.

While clinical trials have varying complexities and therefore distinctive packages, Pfizer's Clinical Pharmaceutical Operation's packaging engineer Rick Klepek estimates that for a package with a medium complexity level it generally takes a total of 3 days and 2–3 people to produce, handle, inventory, and cut up the trays, and another 2 people to hand assemble the final unit-dose packages. This compares to the approximately 6 hours that Trialpack requires to do the same job. "Up until now we've had two operators on the new robotic system, one to watch the machine and keep the product and material levels full, the other to inspect every blister," says Klepek. "But the truth is the machine is totally automatic, and we can cut down to one operator."

"The new robotic Trialpack system actually takes more time to create each unit-dose package with multiple drugs than a conventional blister packaging machine takes to create a tray of one type of drug," says Beechuk. "But it is eliminating all those subsequent steps and handling, as well as the manual assembly of cards that gives us the big time savings. With the robotic system, we can work with the different drugs simultaneously and create the final package in one step." In addition, the unit-dose package also helps ensure compliance with the trial regimen, explains Beechuk.

Instead of allocating, inspecting, and cutting apart trays of single product, the preparation process before a production run using the Trialpack system includes half an hour of designing the packing pattern on PC-based software. This consists of defining the pattern of tablets and capsules and the wording to be printed (such as morning, noon, evening, and day 1, day 2, etc.). The production file is then loaded onto the Trialpack system. Using system prompts, the operator can load up to four different tablets and capsules into safety-locked feeders. The feeders require no change parts to accommodate different types of products, so setup time is less than 20 minutes.

The product travels on conveyors from the feeders to the robot with a vacuum-operated gripper, which locates each tablet or capsule on the conveyor using information from the integrated vision system and places it in the appropriate blister cavity. The robotic feeder can handle up to 54 products per minute; however, the complexity of the pattern and the number of days of the particular clinical trial govern the speed of the machine at any point in time. Each blister cavity is checked before placing product inside, and correct placement is verified with the vision system using data from the production file. If the system detects an error, it automatically rejects the blister package. All errors and other quality-related events are automatically logged to provide full documentation for every batch. The system can also print information on the foil-lidding material on the back of the blister.

Not only is the system saving time and labor costs, but "we're also running at 98% and higher efficiencies, some days 100%," says Klepek. "On two production runs this past week, one of 300 packages, the other of 240, we had zero scrap. The only time we've had any waste was during QA tests when we tore apart packages to check them."

"Now that we're part of Pfizer, we're going to get even busier," predicts Klepek. "With the efficiency of the Trialpack system, we'll be able to bring Pfizer's clinical trials in-house." Klepek estimates this will cut the cost of packaging Pfizer's trials in half.

As for Beechuk, who had the vision to pursue a more efficient, robotic solution: "We always thought robotics were the way to go. We're pleased that we finally have a machine that allows us to have a very sophisticated model for handling as complicated a study as we can design, one that lets us handle more than one drug at a time and one that can do it accurately and reliably."