Pharmaceutical Robotic Applications
by Bennett Brumson, Contributing Editor
Robotic Industries Association Posted 04/01/2002
In the world of pharmaceuticals, there is a vital role for robotics to play in the complicated processes of research and development, production, and packaging. Justification for robots ranges from improved worker safety to improved quality. Speeding up the drug discovery process is another benefit of robotics. A number of robot manufacturers have products specifically designed for this industry.
R & D Robots
'In high throughput screening (H.T.S.), millions of compounds are tested to determine which leads could be drug candidates. There is a need for the use of robotics to test these millions of compounds,' said Dr. Al Outhouse, senior applications scientist at CRS Robotics of Burlington, ON.
Prior to the widespread use of robotics in the drug discovery process, scientists would screen compounds manually, pipetting by hand. It would take three to five years to go through enough samples to find promising leads. Up until the 1980's, scientists could screen little more than 30 drug candidates a week. With robotic H.T.S., there is the potential to screen up to 100,000 compounds in a day.
Researchers can screen an entire sample collection in approximately three months. Those leads are then chemically modified, often using robotics, until a compound with the desirable attributes is found. Robotically operated equipment in pharmaceutical research labs enables the handling of hundreds of thousands of synthetically created compounds as well as natural products.
'As part of the drug discovery process, robotics assist in creating pharmaceutical libraries and can do laboratory testing, such as urinalysis and blood testing,' declared Ben Sagan, director of packaging and food processing accounts at Kuka Robotics of Sterling Heights, MI.
Using laboratory robotics, new experimental procedures are eliminating human tedium and miscalculation in washing and transferring. This includes experiments in radioactive, fluorescent, and luminescent analysis. Laboratory robots have been engineered to handle liquids along with fully integrated systems consisting of multiple robot arms, pipetting stations, incubators, plate washers, and reagent detectors.
Other tasks that robots perform in pharmaceutical research and development are of sample preparation work. This consists of liquid handling robots that gently shake candidate compounds. The robots move trays to different positions where processes are performed and sample experiments are examined. Some experiments require that the temperature be carefully controlled, with the robot moving samples in and out of an oven for a specified incubation period.
To maintain profitability, pharmaceutical users of robotics have directed their efforts to high density assay layouts. This is made up of small wells where liquids are examined in batches of 384, 864, 1536, 3456, or 9600. The benefit of this format has been to reduce assay volumes to the sub-microliter level, essentially making the system a low-volume liquid material handling application.
Image 1For pharmaceutical production, the robots of choice tend to have a relatively low payload capacity, usually no greater than four kilograms. Some payloads are as little as 100 grams, which includes test vials and a small amount of a compound being scrutinized. For example, a CRS robot for drug discovery, the CataLyst-3, has a payload of one kilogram. Typically, there is not a need for pharmaceutical robots to have a long reach, so the CataLyst-3 has 660 mm of reach, including a gripper, to perform the laboratory tasks demanded of it.
There are some differences between pharmaceutical production and other robotic manufacturing applications.
'Pharmaceutical production is essentially a material handling problem. The main difference is there are tight software interfaces, where 60 to 70 different devices need to be connected to the robot. There are tighter time constraints in performing screening operations,'said Dr. Outhouse. 'Most of these experiments were developed manually. It was a challenge to make them fit into a robotic environment,' he added.
'Pharmaceuticals require more speed, precision and faster cycle times than typical robotic operations. In auto production, cycle times are generally greater than four seconds. In pharmaceutical applications, cycle times are usually less than four seconds,' asserted Tom Sturrup. Sturrup is a regional sales manager at Flow Automation, based in Burlington, ON.
Another difference between general robotic manufacturing and pharmaceuticals is the requirement for cleanliness.
'Maintaining a clean room environment that is Class 100 or better is a challenge. This is done through purging. The air in a workcell is cleaned and kept at a higher pressure than outside air, so dirt cannot come inside. There is extensive use of stainless steel in the enclosures which are easy to clean,' said Steve Olson, robotic sales engineer at Automated Concepts, Inc. (ACI) of Council Bluffs, IA.
The other major function that robotics plays in pharmaceuticals is the production of medical devices.
'Most of Flow's focus is medical device assembly. We use two-axis pick and place robots for this application. We assemble test kits for Bayer and intravenous bags for Baxter Health Care,' said Tom Sturrup.
Other pharmaceutical products produced by robotics include Hepa filters, syringes, and inhalers. One method by which syringes are kept surgically sterile is through the use of gamma radiation. ACI's Steve Olson explains:
'The robot moves packs of syringes through gamma radiation, to sterilize them. A robot takes the syringes off a pallet and puts them on a conveyor to be radiated. Another robot at the other end repalletizes the boxes. This keeps people out of a radioactive area while maintaining sterility.'
Vision systems are an integral part of research and development pharmaceutical robotics.
'Our vision system helps in code identification of cell cultures. These cultures can contain up to 100,000 vials holding cell samples. The system must keep track of them and the vision system can identify potentially useful compounds,' stated Kaz Naganuma, industry marketing manager for health care at Cognex Corporation, Natick, MA.
Pack 'em up, Stack 'em up
Like other products, pharmaceuticals need to be packaged and inspected after production. Often, medications are packaged in blister packs to protect cleanliness and to help patients keep track of their daily dosages.
'The robot fills blister packs with single or multiple dosages, then moving those that have been filled and places them in a box. The robot can palletize at five to seven picks per minute, up to 20 boxes at a time. Blister packs are filled every two seconds with 12 to 18 dosages per pack,' said Steve Olson.
A vision system inspects each blister pack to make sure they were filled with the proper amount of tablets and scans for broken ones. If the system detects a blister pack that was filled incorrectly, it diverts that one off the conveyor line.
'The packaging process is pretty fast, but not as fast as bottling beverages. The speeds have to be kept relatively low, about 30 per minute, to prevent tablets from breaking. Pediatric products can be packaged at 30 to 60 per minute, while big selling items such as Tylenol can go as fast as 200 to 300 pills per minute,' said Sagan.
Using a specialized gripper, 15 to 20 bottles at a time are clasped and put into cartons. With specialty items or test kits, the speeds are somewhat slower. The example Sagan used to illustrate this was lice shampoo.
'Lice shampoo has a special applicator. When consumers need more of this type of shampoo, they do not need another applicator, so there are some packages that have them and some which do not,' he said. It is a similar process for inhalers and other products.
'The robots we use can fill 50,000 bottles per day,' says Mike Seidl, marketing manager at AutoMed, Vernon Hills, IL. A Seiko robot accumulates both the medications and empty bottles. The robot sorts prescriptions before they are put into a conveyor line for a pharmacist to check. The prescription is mailed out to a pharmacy or to an individual customer.
Up to 16 bottles can be filled simultaneously in the AutoMed system. The bottle is labeled, moved to the correct filling zone and is filled. The bottle is inspected using a digital image. Finally, the bottle is capped. The robot picks and places it into a sorting zone. Using a conveyor, the bottle is moved on to a pharmacist, who checks it. If there is supposed to be an inhaler included, the bottle is moved to an area where that is inserted.
A feature that pharmaceutical packaging has that is not common in other manufacturing is the need to track an item once it leaves the production facility.
'The major difference is traceability. With traceability, a vision system is used to perform tasks like date lot coding, which has a data file to track a specific bottle. The system uses photos in some cases, to be able to find a bottle of pills after it left the factory if there is a recall or if there was tampering,' Sagan pointed out.
Vision systems play other roles in pharmaceutical packaging application.
'The need for tracking includes date and place of production, as well as language. There is no need to send instructions in French to Korea, but must have both English and French in Canadian markets. Also, the rules of packaging pharmaceutical varies from one country to the next. Vision systems help track this,' said Ben Sagan.
The Cognex vision system aids in meeting new Food and Drug Administration (F.D.A.) rules for electronic pharmaceutical records.
'21 CFR part 11 mandates good packaging and laboratory practices. Our vision systems assists in compliance. There is a requirement to provide information in the testing protocol. The Cognex In-Sight vision system complies with 21 CFR part 11,' said Naganuma.
The 1999 rule provides criteria under which F.D.A. will consider electronic records to be valid as are paper records, and electronic signatures equivalent to traditional handwritten signatures.
The outlook for pharmaceutical robotics is healthy.
'CRS is investing new ultra high H.T.S. systems which could screen compounds at a rate of two to ten times the current rate,' prophesized Dr. Outhouse. Also, there is a shortage of pharmacists to fill orders, which shows little sign of being alleviated. Robots are ready to fill part of that shortfall.