Inside Machines: Vision-guided robots automate vial, syringe filling
Machines that are typically used to fill vials, syringes and other containers for pharmaceutical manufacturers rely on dedicated machinery having hard automation. Consequently, the machinery is normally capable of filling only one type of container. This is acceptable when producing long runs using one container, but inflexible when pharmaceutical manufacturers need to package the same drug in multiple types of containers, such as vials, syringes and intravenous (IV) bags. Other “short run” needs include product packaged for clinical trials, production of smaller scale, personalized medications. Since most automated filling systems rely on exact positioning unique to each container size and type, filling different container formats requires the manufacturer to purchase multiple filling machines, or tolerate lengthy changeovers when switching between container types.
Automated Systems of Tacoma Inc. (AST) has developed a new vision-enabled flexible robotic filling system that can handle a wide range of container types and sizes, and can be switched from one size or type to another in about 30 minutes. Vision systems in AST’s AseptiCell enable robots to “see” the drug product containers they’re filling, so the end-of-arm tooling can fill and stopper the containers without requiring them to be precisely positioned. The flexibility of this robotic filling system can dramatically reduce the cost and space required to process any product that requires frequent changeovers, such as preclinical and clinical products, personalized medicines, orphan drugs, vaccines, etc.
Limits of conventional filling
Conventional filling equipment used in pharmaceutical applications allows for container size changes, but little else. For example, if a contract manufacturing organization (CMO) wants the ability to fill vials, they would purchase a monoblock style filling system that is capable of filling multiple sizes of vials only. The CMO would not be able to use this same system to fill syringes or IV bags, and thus need substantial ongoing capital investments to expand their manufacturing capabilities. AST was asked by a life science research company to develop an alternative to conventional pharmaceutical filling machinery. The company wanted one machine that could fill and finish all their small-scale clinical trial products on a single flexible platform.
The basic concept is a system that positions ready-to-use “nests” of a particular container within the operating envelopes of two robots. A Cognex In-Sight Micro vision system is used to precisely locate each container and stopper and provide the robots these locations prior to processing. This approach allows for rapid changeover from one container type or size to another by loading a new robot program, replacing the products carriers, and instructing the robot to change out the end-of-arm tooling. The system uses disposable materials on all process-contacting parts, which also reduces the changeover time and eliminates the risk of cross contamination.
Integration of vision and robotics
The biggest challenge in developing the AseptiCell was integrating the robot and vision system to provide the high levels of accuracy and speed required by the application. “We had developed a number of machines in the past using machine vision,” said Josh Russell, project engineer for the Life Sciences Group at AST. “We have found that it can be very difficult to integrate robots with vision systems. We were hoping to find a new approach that would simplify that task and enable us to focus on optimizing the productivity, robustness and flexibility of the machine.”
AST called in Brian LaFave, automation engineer for Olympus Controls, because of his company’s long experience in developing vision applications. “I took a close look at the application and came to the conclusion that integration between the vision system and robot was key,” LaFave said. The Staubli TX-60 HE six axis industrial robot was AST’s first choice for this application, because of its ability to withstand aggressive cleaning and bio-decontamination required for the application. “Mounting the vision system on the robot arm made it essential for the vision system to be small, light and have very simple cabling. I felt that the Cognex Micro In-Sight 1100 would be perfect for the task,” LaFave added.
The Cognex In-Sight Micro system comes equipped with pre-configured drivers, ready to use templates, and sample code for communicating with most robots. Cognex also supports the most commonly used open-standard Industrial Ethernet and Fieldbus communications protocols for trouble-free connection to PLCs and a wide range of automation devices. The Cognex In-Sight Micro 1100 provides resolution of 640 by 480 pixels in an enclosure measuring only 30 mm by 30 mm by 60 mm. It also includes a non-linear calibration tool that enables mounting at angles of up to 45 degrees from the object to be inspected. The Cognex Micro supports Power over Ethernet (PoE) to provide power and network communications on a single standard networking cable.
How the robotic filling system works
The AseptiCell is designed to fill and finish pre-sterilized syringes, vials, IV bags and other ready-to-use containers and medical devices. This multifunctional capability saves money and cleanroom space by eliminating the need for upstream equipment required for washing, depyrogenation and sterilization of the containers and stoppers prior to filling. The containers are purchased clean, sterile and ready to use, with each tub of product containers wrapped by two sterile layers of material. Operators remove one sterile layer when the containers are brought into the cleanroom, and the second layer is removed when the containers are loaded onto the machine.
The ready-to-use tubs of containers and stopper components contain fixtures called “nests” that hold each container and stopper in an upright position for filling and stopper placement. Using sterile glove ports, the operator removes the nest from the tub and places it on a turntable conveyor in the material ingress area of the AspetiCell. The doors of the sealed aseptic processing area open automatically and the material moves into this area.
Two Staubli robots in the aseptic processing area contain all of the tooling required to: fill containers, purge the container of oxygen by filling it with nitrogen to avoid infiltration, apply stoppers, and heat seal an IV bag. The processing tasks can thus be apportioned as desired between the two robots by the robot program. AST designed the system to have built in redundancy, so if one robot should go down, the machine can still operate at 50% of its full capacity using the functional robot arm.
Each robot moves to the approximate position of the first stopper and then to the container to be processed. The Cognex In-Sight Micro 1100 vision system acquires images of each. The fine circle tool is used to determine the exact position of the container and stopper, and then reports the location (relative to the robot tool center position) to the robot controller.
Challenge of syringes
Syringes represent the greatest machine vision challenge because of the placement of the syringe stopper. There are two proven methods of placing the stopper within a syringe: mechanical and vacuum placement. Mechanical stopper placement, the more challenging of the two, requires placing a thin-walled stainless steel straw concentric to the inside of the syringe barrel with minimal clearance between the two and pushing the stopper through it using a pushrod. The vision systems accurately locates the position of the container, so as to not scrape the sidewall of the syringe or, worse yet, damage or break it with the straw. If higher accuracy had been needed, it could have been achieved with one of several other Cognex vision system models that offer a resolution of 1,600 by 1,200 pixels.
The robot controller uses the position information of each container and stopper provided by the vision system to precisely position the several sub-tools on the robot arm for subsequent operations. For vial filling, the filling sub-tool dispenses the sterile pharmaceutical product into the vial. Then, another sub-tool on the end of the arm picks up a stopper and places it into the mouth of the vial. A third sub-tool applies an aluminum crimp cap with a flip off cap, sealing the stopper to the vial.
After every container has been filled and sealed, the turntable conveyor indexes the finished product to the material egress area (see illustration). While the nest of containers is being processed, the operator passes the tub through the barrier between the material ingress area to the material egress area. The operator places the nest containing the finished product containers back into the tub prior to removal from the system.
To change from one type of container to another, the operator de-energizes the robot, places the robot end-of-arm tooling inside the aseptic processing area, and makes the sterile fluid connections on the tool. The operator then installs the product carriers for the product to be filled, and selects the proper program from the touch screen interface. The robot will automatically change the tooling so the operator never needs to get close to the robot or the sterile product containers and stopper components.
Handling potent compounds
The AseptiCell is ideally suited for handling highly active and potent compounds, such as those used for cytoxic cancer therapies and vaccines. The AseptiCell design protects manufacturing personnel from the risk of exposure to the active pharmaceutical ingredients, and eliminates the greatest potential source of product contamination: human contact with the filling system. All processing operations are preformed within a sealed enclosure called an isolator.
A vision-guided robotic filling system “is the simplest solution for any organization looking to increase their product and container filling capabilities without purchasing multiple machines dedicated to a particular product or container type,” says Russell. In this case, the solution fits within a 12- by 16-foot cleanroom and costs far less than the machines that it replaces, he says.
Also read from Control Engineering:
– Edited by Renee Robbins Bassett, a Control Engineering contributing editor. Reach her at firstname.lastname@example.org.