Equipment Fills Drug Industry's Needs
Advances in technology enable filling machinery and parts to meet ever-changing production demands.
by Erik Swain, Senior Editor
Pharmaceutical companies demand a lot from their filling equipment. They want precise accuracy to ensure that the proper dosage has gone into the package. They want enough speed to be able to run the line efficiently and the ability to adjust speeds during a cycle. And they want the flexibility to accommodate different package sizes and different product consistencies.
An operator adjusts a powder filling and closing machine from Bausch + Stroebel Machine Company, Inc., inside an isolator.
Although it may seem challenging to incorporate all of these demands into fillers, suppliers have found ways to accomplish this task. Advances in valve, pump, and servomotor technologies have speeded progress.
With new drugs becoming more biosensitive and more expensive, and with increasing regulatory pressure to ensure a repeatable filling process, filling accuracy has become extremely important. Ron Keller, president of Keller Packaging Engineering Group LLC (Wayne, NJ), notes that pharmaceuticals is one of the few industries that need to guard against overfilling as much as underfilling.
"If every drop is worth $50, you want to limit the waste," says Paul Chimino, sales engineer at Bausch + Stroebel Machine Company, Inc. (Clinton, CT). "If the drug you are filling is of high potency, there has to be an accurate amount," or there can be adverse consequences for the patient. As a result, he says, net-weight filling has become a popular technique in pharmaceuticals because this is the best method to ensure that each fill produces the same amount of drug.
What is especially important for drug companies to consider, Keller says, is how a machine's fill accuracy is determined. Some ways of measuring inspire more confidence than others.
"You must question potential filling machine manufacturers and have them explain what they mean by their advertised fill-weight accuracy percentages," Keller wrote in a self-published newsletter. "For instance, are they claiming a ±1% fill accuracy at one, two, or three sigma? Include a specification that states the desired sigma level in filling-equipment purchase orders. Density, moisture content, particle size distribution, and manufacturing scheme all contribute to fill-weight variations."
Positive shutoff, for example, is important in both filling and form-fill-seal operations. According to Jim Victoria, an application specialist with EFD Inc. (East Providence, RI), "A valve with a fast, clean cutoff will prevent overfilling, and in form-fill-seal operations, it will eliminate drooling that could affect the integrity of the heat seal and cause leaks."
SERVOS HELP SPEED
The key to the recent advancement of filling equipment is servomotors, experts say. "A lot of the increased capabilities can be tied into the implementation of servo-driven machinery," says John Mueller, president of Prodo-Pak Corp. (Garfield, NJ). "We can communicate with the machines and do things we were probably not able to do before."
One example of an advance brought on by servo technology is the ability to pump at different speeds during the same cycle, says Goran Adolfsson, president of Norden Inc. (Branchburg, NJ). "You can start slow, then pump fast, or start fast, then pump slow. And if you have a servomotor on the lifting function, that enables you to have an infinite combination of lifting versus pumping action."
Servomotor-driven pumps have meant improved quality in the liquid-filling process, says Barrie Phillips, president of Infinity Packaging Systems (Bloomington, IN). "You can control the fill cycle in terms of accelerating and decelerating the pumps to reduce foaming," he says. "This eliminates the unnecessary whipping of the product while in the pump. It allows us to be extremely flexible with product viscosities."
Servo technology has been a big help, especially since the advent of liquid drugs whose viscosity changes with temperature. This characteristic has presented a challenge.
"With these drugs, if the room changes 1ºC and the viscosity changes significantly, they will fill differently than they would otherwise," says Jack Lysfjord, vice president–technology and international sales at Bosch–TL Systems Corp., (Minneapolis), a member of the Bosch Group. "You have to measure the temperature of the product as it goes into the filling system and compensate by adjusting the time. It's all done electronically."
Servomotors also help with adjustments from job to job, says Barry Campbell, regional sales manager at Cozzoli Machine Co. (Plainfield, NJ). "With electronics, you can make adjustments for different heights, which makes for a no-tool changeover," he says.
If a filler is going to be handling multiple products, it will have to do so safely and efficiently, and be documented as doing so, or FDA and customers might express concern about contamination. One way to handle this concern, says Chimino, is "to have a separate set of sized parts and pumps for each individual drug. If you have one set for product A and a completely different set for product B, that helps defend against cross-contamination. In a lot of cases, you would be dealing with different size vials, so you would need different parts anyway. While you run one product on the machine, you can sterilize the parts for the other product, so there will not be a lot of downtime."
One of the biggest improvements in filling equipment technology, notes Alioscia Bassani, vice president, Capmatic Ltd. (Montreal-Nord, QC, Canada), is that machines are now "very, very easy to take apart, to assemble all the parts, and to clean."
The FSM-2700C filler from Bosch–TL Systems operates at speeds up to 150 vials per minute and at fill volumes from 0.5 to 500 ml.
And, if there are no moving parts in the filling system, adds Wallace Noonan, national sales manager of Adtech Filling Systems Inc. (Hulmeville, PA), the system can be cleaned and sterilized in place, which makes for even more efficiency. "Moving parts have cracks and crevices that are difficult to clean and sterilize," he says.
Even if the filling machine will run the same product for its entire life, it still needs to be able to accommodate different package sizes. This has become especially important in tube filling, says Norden's Adolfsson. "Tubes are now available in larger sizes than ever and in smaller sizes than ever," he says. "What we've had to do on the larger sizes is develop machines with larger pitches, and consequently they have larger pumps and larger sealing systems. On the smaller side, we've had to develop automated systems for feeding the tubes into the filler. Instead of pushing the tube out, they pull the tube out by the tail, so there is no physical impact that could damage the tips."
Also, Adolfsson says, drug companies demand flexibility because "they have to buy equipment long before they know if a drug is going to be successful. If a drug turns out not to be what they hoped it would be, they want to use the machine for something else if they can."
In addition to accuracy, speed, and flexibility, a variety of other needs are met in new pharmaceutical filling equipment, Lysfjord says. For example, he says, peristaltic pumps can handle radioactive products, and rolling diaphragm pumps "get rid of the piston-to-cylinder shear effect."
What the next great need will be is not known. Some think it will be related to syringe filling, which is perceived as being a fast-growing market. Regardless, if recent history is any indication, when the drug industry demands it, equipment makers will figure out a way to supply it.