Pharmaceutical manufacturers take cleanliness seriously. The slightest
contamination—especially of an injectable drug—can literally be deadly. Even
less serious consequences of contamination can damage a company's reputation and
lead to financial catastrophe. A pharmaceutical manufacturer's greatest fear,
says one expert in the field, is the recall of a product.
And cleanliness isn't the only exacting requirement for pharmaceutical manufacturers. Measured quantities of packaged drugs must be extremely accurate, not only for proper dosage, but because some drugs are so very expensive. Some biotech drugs, for example, cost as much as $3,000 for a small vial, and wasting even a milliliter is like throwing money away.
But those stringent requirements for cleanliness and accuracy aren't limited just to pharmaceutical manufacturers. The machines used in pharmaceutical manufacturing have to deal with them, too. Large, complex liquid filling machines, for example, must never allow a product to become contaminated, and they typically have to dispense and weigh liquids to an accuracy of less than 1%. To complicate matters, they have to meet these criteria while filling vials, syringes, or ampoules that are whizzing along at an eye-blurring rate of hundreds per minute.
How can engineers ever design machines for such exacting requirements? Some of the answers can be found in the FLM 4080 pharmaceutical liquid filling machine from Bosch Packaging Technology. To improve cleanliness, its designers scrapped the conventional physical structure. To improve its filling accuracy, they designed a new method of weighing pharmaceutical products as they're packaged. The engineers—some in Minneapolis and others in Crailsheim, Germany—also came up with new ways of working together while separated by an ocean and six time zones.
Clean Machine: Bosch's liquid filling
machine mounts tools on a vertical wall in a unique way, ensuring that
downward-flowing purified air doesn't strike a large surface and disperse
any contaminating particulates.
The cleanliness requirement for pharmaceutical liquid filling machines is especially difficult. The packaging of pharmaceutical liquids occurs in very clean environments where pure, filtered air flows around vials or other containers as they're filled to keep out any possible contaminants. That purification scheme falls short, however, if the airflow strikes any surfaces where particulates may have settled, thereby dispersing them into the air. Early pharmaceutical filling machines, for example, had large horizontal bases, like tables, with filling equipment on top. Downward flowing pure air, when striking a table surface, could kick up particulates and create air turbulence, causing some of the particulates to get into the vials being filled by equipment on the table. To alleviate this problem, later filling machines raised the vials by a foot or so from the table's surface, thus separating them from most, but not all, of the disturbed particulates.
Turning the Tables
Bosch's new filling machine tackles the cleanliness problem by literally turning the tables. Its designers scrapped the conventional horizontal table with equipment on top of it, and instead created a vertical back wall, with equipment mounted on the wall and extending from it. Thus, there's no large, horizontal surface where particulates can accumulate and get stirred up by the forced airflow. "It's as if you had a vial in your hand and you're extending your arm out away from this wall," says engineer Al Peterson, Bosch Packaging's manager of product development in Minneapolis. "The vial is in the middle of the downward airflow, so that it experiences as much as possible the fresh air right out of the filters rather than any recirculated air."
Bosch's machine also takes an innovative approach to improve liquid filling accuracy. Traditionally, liquid filling machines have monitored fill accuracy by weighing a sample of filled vials as they move along the packaging line. Checkweighing—the process of weighing an empty container, then filling it, and then weighing it again—determines the quantity of liquid in each sampled vial. With the FLM 4080, however, Bosch changed how checkweighing occurs.
Conventional liquid packaging systems use two different load cells for checkweighing. A robot pulls an empty container out of the "upstream" packaging line, puts it on a load cell to measure tare weight, and then puts it back in the line, where it moves through the filling zone. Another robot then pulls the filled container out of the line "downstream" and puts it on a second load cell to measure gross weight. The problem with that scheme, says Peterson, is that it introduces error by weighing the empty vial and the full vial on two different load cells.
To improve checkweigh accuracy, Bosch engineers created the Twin Check weighing system, which measures both tare and gross weights on the same load cell. As before, a robot takes empty vials out of the upstream line and weighs them. After it places the vials back in the line, however, the robot continues with them through the filling step. "It actually carries them through the filling system without letting go of them," says Peterson, "and then brings them back to the same upstream load cell. You don't get the error of weighing on two different load cells." Also, says Peterson, Twin Check weighs more vials per minute than other checkweigh systems on the market, sampling about 3% of all vials versus a standard 1% to provide even better verification of accurate filling.
To design and integrate the many different components of the FLM 4080, Bosch drew on the expertise of its engineers in both Germany and the U.S. The vertical wall concept, for example, originated with TL Systems Corp., which Bosch acquired several years ago and which is now part of Bosch Packaging's North American operation. In Germany, a major design module was a new infeed "unscrambler," which converts a large, swirling mass of empty vials to a high-speed, single-file march through the packaging line. All together, about 25 German and American engineers worked on the project.
The key to working together, while speaking different languages and separated by six time zones, was modular design. Modularity, says German engineer and project director Stefan Baaman, "made it possible to talk about different functions separate from the overall design." "We split up duties by module," says American engineer Peterson. "We would be designing for several months on, say, the stoppering module, and they would have other modules to design." Modularity also made it possible for engineers to concentrate on customer requirements they were most familiar with. "It made sense to split the design work between Germany and the U.S.," says Baaman, "because of the very different markets and customer requirements in different geographical areas."
Good tools, consistently applied, also helped the project along. "We all used the same design software, the same CAD system," says Peterson, "and we exchanged engineering files across the ocean in both directions every night. It really made it possible to do complex design as a team—the fact that we could see their work and they could see our work on a daily basis." Also, says Baaman, having a 3D CAD system made it easier to see and discuss pictures of components, not only among engineers, but with sales and marketing people.
The design team did encounter obstacles, however. "If we wanted to have a workshop," says Peterson, "there was a nine-hour flight each way. The jet lag got to me. I was trying to stay awake on three or four hours of sleep." For the Germans, says Baaman, "Language was the most difficult thing, so we used a lot of pictures. Sometimes a picture can say much more than words."
All of the German engineers spoke at least some English—designated the primary language for the project from the beginning—but not everyone was fluent. "That gave us a break," says Peterson, "but it created a little difficulty for a couple of the engineers on their side of the ocean." The solution, Peterson adds, was side discussions. "They would go into a huddle and speak German for five minutes and then come back to the main discussion in English."
And the group accomplished a lot. Lead mechanical engineer Steve Bougie notes, for example, that Bosch customers are now taking accurate sample weights in a way that no other equipment in the world can do. As for cleanliness, Kirk says that the vertical wall "changed the playing field a little bit." Kirk also notes that sales of the FLM 4080 so far have exceeded forecasts.
More significant than technical and financial achievements, though, says Kirk, is the human aspect. "Even though the stakes are very high financially," he says, "it's always in the back of your mind that these machines are really helping people. The products produced on these machines truly are saving lives."