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Robotic fill/finish systems reduce human intervention, improve flexibility, and allow more gentle handling of containers.
The population of robots working on parenteral fill/finish lines is increasing rapidly. The expansion mirrors growth in biotech products, particularly self-injected therapies, which require autoinjectors that can deliver a safe, effective, and consistent experience. Robotic systems excel at maintaining aseptic conditions and protecting operators from toxic substances. In fact, Comecer Group has offered robot-equipped systems to handle radiopharmaceuticals for more than a decade.
Robots not only provide precise, consistent handling, but also offer a high level of flexibility so systems can accommodate a wider range of containers and components with minimal or no change parts. “Flexibility is crucial for high-value, relatively low-volume products,” says Eric Petz, senior marketing manager at Vanrx Pharmasystems. “Batches are smaller, so you can’t have long changeover and startup times,” he explains.
Robots also can reduce or eliminate glass-to-glass and glass-to-metal contact, which are major causes of container failure. But the most important benefit robots provide is improved quality due to minimization or elimination of human intervention, the biggest source of product contamination. To prevent contamination, regulatory agencies worldwide are looking for less human intervention, and original equipment manufacturers (OEMs) are working on ways to remove operators from the process. “It’s all about risk mitigation,” says Simon Cote, principal engineer, Technical Customer Support at West Pharmaceutical Services. In fact, “I would be highly surprised if the industry doesn’t incorporate more robots,” he says.
West Pharmaceutical Services is adding a robotic system to its equipment lineup with the purchase of a dual-robot, customized KCP 5060 Flexible Filling system from Bausch + Stroebel Machine Co. The base model, which was shown at INTERPHEX 2017, features cleanroom-compatible robots that reach upward to perform their tasks. Mounting the robots below the containers maintains sterile laminar air flow across product-contact surfaces, protecting product from potential contamination. Capable of handling vials, cartridges, or syringes in bulk or nested format, the system is equipped with four processing stations to perform filling, closing, sealing, and inspection. The system is compatible with vaporized hydrogen peroxide (VHP) for decontamination of the work area including the robots. The compact machine, which occupies less than 14 feet of linear space, operates at speeds up to 1200 units per hour, a rate particularly well-suited for self-therapy products. Container size ranges include vials from 16–52 mm in diameter with heights up to 94.5 mm, syringes from 0.5–20 mL, and cartridges from 6–14 mm in diameter with heights from 40–90 mm.
Biotech products have been a driving force behind robot-equipped fill/finish systems. When the founders of Vanrx Pharmasystems couldn’t find a filler for small volumes with sufficient flexibility, they studied automation. Inspired by the use of robotics in the semiconductor industry, they began designing a robotic fill/finish system from the ground up. The resulting machine needs no glove ports, relies on ready-to-use containers and closures, and eliminates aluminum crimp caps, a common source of particulate contamination. “There’s no intervention the robots can’t perform,” explains Petz. “All sources of jams have been eliminated,” he adds.
Because containers never leave the nest, there’s no potentially damaging container-to-container contact. Press-fit closures, also supplied in nests, streamline the capping and lyophilization process. In addition, Petz says, “Conventional [parenteral] filling lines are generally custom-designed. This one is standard and scalable.” Designed to be deployed worldwide, the standardized system simplifies validation and standard operating procedures. Scalability shortens time to market and maximizes the patent protection period for brand owners.
The Vanrx system performs filling and closing with nested groups of containers and closures. An operator loads nests into the carousel and closes the door. At the conclusion of a vapor hydrogen peroxide sterilization treatment, the chamber is aerated, and Tyvek lidstock is removed from the nests. Containers are filled and closed and shuttled back to the carousel.
Vanrx has installed systems at two contract manufacturing organizations, Singota Solutions and AB BioTechnologies. “Two more systems will be installed in the United States this year,” reports Petz. He predicts, “It’s a technology that is going to be widely adopted. We’re seeing a wide uptake.”
Lines from Luciano Packaging Technologies also demonstrate the advantages robots can bring to fill/finish operations. In one example, robots transfer product and load preformed pouches. “The ability to manipulate and transfer uniquely and/or irregularly shaped syringe products … significantly decreases the complexity of the mechanism required for manipulations like inverting, placing, and spacing … while maintaining a high degree of orientation and control,” says Larry Luciano, president of Luciano Packaging. “The robots also provide the ability to re-direct product into alternate paths.”
Other OEMs, including M&O Perry Industries, ESS Technologies, Marchesini Group, and MG America, offer robotic fill/finish systems. The NSF nested syringe filler from M&O Perry Industries features a Yamaha robot. Capable of filling powders, liquids, or powders and liquids, the system also can handle vials. The robot controls powder filling and achieves speeds up to 40 units per minute. Higher speeds are possible by adding fill needles.
The Model SF20 TaskMate robotic aseptic syringe filling and capping system from ESS Technologies integrates a FANUC robotic cell with an OEM-supplied restricted access barrier system. A FANUC LR200iD clean class robot receives syringes from a flexible feeder and uses vision and a mechanical gripper to pick the syringe and place it on the filling station. The second FANUC LR Mate 200iD robot picks a cap from the tray and places it into the torque station. A servo-driven pick-and-place unit transfers the syringe from the fill station to the torque station. Capped syringes descend a divided chute to a discharge/reject bin. Fills range from 50 µL–60 mL at speeds up to 15 syringes per minute. The machine also can handle vials and various cap styles. Changeover generally can be accomplished in less than 15 minutes.
Marchesini’s Extrafill syringe filling and stoppering machine features a robotic de-lidding station, monobloc design, and two tub opening and syringe filling/stoppering stations. Up to three more stoppering stations can be added to boost output to 12,000 syringes per hour. Dosing range is 0.1–50 mL.
The Steriline RVFCM50 filling and capping machine, supplied in the US by MG America, handles vial sizes from 2 mL–100 mL without changing format parts. Rated at up to 3000 vials per hour, the system can be integrated with an RA-V4 rotary vial washer, ST2 CCS depyrogenation tunnel, and EDM-C external decontaminating machine.
Beyond the fill/finish operation, robotics play a role in inspection and secondary packaging of parenteral products. Robotic inspection systems can overcome problems with limited floor space. “A typical, commercially available manual inspection line for two operators that includes automatic de-nesting and re-nesting is a linear line using three machines for the primary operations and is in the order of 40 feet long,” explains Luciano. “The LPT robot cell [HPI-30M nested syringe inspection machine] is only 10 feet long because the robot is able to perform multiple operations-de-nesting, syringe presentation for flange inspection/rejection, and labeling path transfer or re-nesting. In this case, the robot is picking five syringes from the Hypak that supports a matrix of 10 staggered rows of 10 syringes per row. And since there is extra spacing between each tub, there are four different pick positions and 12 different re-nesting positions, so you can see how the programmable flexibility of the robot (in combination with a servo-indexing Hypak conveyor) is helpful in reducing mechanical complexity.” If higher speeds are needed, manual inspection can be replaced by automated vision systems, and a second robot can be added for discharging.
An example of a robot-equipped line for secondary packaging functions was shown by Marchesini Group at CIPM Qingdao (April 19–21, 2017, Qingdao, China). The customizable line integrates a deep-draw FBZ 320 thermoformer with a continuous-motion BA 400 Argento cartoner (see Figure 1). Operating at up to 240 cartons per minute, the system thermoforms trays, loads syringes and vials, and cartons filled trays. A centerpiece of the thermoformer is a four-axis Robomaster system. Positioned between the forming and sealing stations, it picks syringes or vials and places them into trays. Infeed options include plug-in belts and vibrating tables.
Many robot providers offer cleanroom models compatible with hydrogen peroxide sterilization for parenteral fill/finish applications. When designing robotic equipment, the first consideration is whether a robot is the best option. “You don’t want to use robots where simple mechanics could accomplish the task,” says Massimiliano Cesarini, global sales manager, Isolation Technology Division at Comecer.
A primary consideration when specifying a robotic fill/finish system is speed. “Robot lines are typically slower,” says Gregor Deutschle, business development manager at Schott North America. Batch size is another consideration. Shorter runs mean more frequent changeover. “Robots eliminate a lot of change parts and star wheels,” notes Deutschle.
Robots also replace traditional container handling mechanisms. “Eliminating turntables and infeed belts definitely helps reduce glass-to-glass contact,” he adds. As a result, robots can provide gentler handling and may be especially well-suited for polymer containers, which scratch easily.
End-of-arm tooling (grippers or end effectors) must be carefully designed to optimize handling. Factors to consider include weight, which directly impacts speed, and arrangement of pneumatic and vacuum lines and sensor wires so performance is not impacted by movement of the arm. The end effector also must handle the product without marring or other damage. Vacuum is a common choice, but may not work with all surface areas and product orientations. Nevertheless, “Vacuum is usually the gentlest,” says Luciano. However, vacuum may not provide enough support for the container(s). In that case, a rigid guide may need to be added.
Finally, programmability must be considered. Many of today’s robots do not rely on proprietary programming languages, but can be easily programmed from a library of functions or by simply moving the arm through the path it needs to take.
When referring to this article, please cite it as H. Forcinio, " Robots Package Parenteral Products," Pharmaceutical Technology 41 (5) 2017.
About the Author
Hallie Forcinio is Pharmaceutical Technology’s Packaging editor, firstname.lastname@example.org.