Medical Device Link.

Originally Published PMPN November 2004

Filling Equipment

The H510 from Optima Machinery Corp. employs servo technology and can be used in a barrier isolator or a RABS system.

by Jenevieve Blair Polin
Contributing Editor

“Increased speed and accuracy, simplicity of maintenance, and ease of operation” are some of the advantages of a new generation of pharmaceu-tical filling equipment, says Gary Lowden, sales manager, ProSys (Webb City, MO). Servomotors, once an expensive option found only in high-end equipment, are rapidly replacing cam-driven motors in all levels and types of fillers—for tubes, syringes, ampules, vials, and powders.

SERVOS SERVE UP ADVANTAGES

“We are forced by our customers and regulatory agencies to have a lean, clean system that can be cleaned and maintained easily. Everything on top, including the top plate of our filling machines sold to the United States, is solid stainless steel, mechanically polished or electropolished. All mechanical components, including servo drives, are underneath the tabletop plate,” says Uwe Kellerman, vice president, pharmaceutical applications, for Optima Machinery Corp. (Green Bay, WI). This design is suitable for use within a barrier isolator or a restricted-access barrier system (RABS) setup.

“Getting rid of as many electromechanical components as possible, like gears, belts, and motor drives that can generate particles under the top plate, and replacing them with servo technology,” is one of the keys to achieving cleanliness goals, says Ron Nicholas, Eastern sales manager, National Instrument Co. (Baltimore).

“With cam-driven motors, two metal contact parts rub against each other or rotate around each other, which definitely generates particles,” says ProSys’s Lowden. ProSys recently introduced the RT60 servo-driven squeeze-tube filler, complementing its line that includes the higher-end RT85 and RM110 models. “That cam and the cam follower may or may not be enclosed and shielded from the environment, whereas the servo-motor and actuator by design are enclosed. The possibility of particle generation is going to be much less, which is key for a cleanroom.”

“Servo drives help maximize yield,” adds Bernie Conlon, director of sales and marketing, IWKA PacSystems Inc. (Fairfield, NJ). “The flexibility they offer allows machines to operate with peak performance even under difficult conditions. For example, with mechanically driven machines, the dosing characteristics of the pump were tied to the profile of the cam. With these systems you had to slow down the machine to handle difficult products. With servo-driven pumps, you can tailor the pumps’ dosing characteristics specifically to each product and keep the machine running at maximum speed.”

Greater electronic sophistication increases the quality control aspects of the machinery as well. “Because servos are feedback loops, in essence, they report on every single operation they perform. That allows for a much easier user interface for sending error messages, documenting problems, and reporting on machine functions,” explains National Instrument’s Nicholas.

Many pharmaceutical manufacturers, Nicholas adds, are marrying the latest filling system PLCs to PC networks or in-house SCADA (supervisory control and data acquisition) systems. “Ethernet connections and data highway systems have made that very viable. A customer may want to document machine faults, output, errors, and speed as part of its validation package,” he says. National Instrument can offer this capability as an addition to the control system of the Filamatic Model MNB 2000 modular compact monobloc systems.

“Servos also provide an advantage when there is a need to integrate multiple machines,” says Conlon. “Since servo machines are electronic, information such as product position and machine timing can be easily communicated from one machine to another. This allows for a simpler transfer of products from the filling machine to downstream machines.”

SLOWER, SMALLER, BETTER?

“Getting away from mechanical systems and moving to the more precise servomotors with feedback reduces indexing time, which allows us to get better speed out of the machines,” points out Matthew Gingerella, sales manager for M&O Perry Industries (Corona, CA). Nevertheless, M&O Perry now offers servo technology in a compact, economical system—the P1500-series powder filler with a maximum rate of 50 bottles a minute—for customers just starting to automate production.

“We’re finding that instead of increased speeds, people want lower speeds and more-compact units,” reveals National Instrument’s Nicholas. “There’s an increasing demand for units that can be used for limited production, pilot plants, and clinical lots, especially from biotech companies that have very-high-value products and limited volume requirements. They don’t need to fill hundreds of vials a minute. They need precision, clean environments, and lines that run at 20 to 30 a minute,” Nicholas stresses.

To meet this demand, National Instrument recently introduced the three-function Mini-Monobloc. This machine is a cut-down version of the full MNB monobloc line, occupying about a third of the space with its 2 ¥ 4-ft configuration.

“It has the same capabilities as our full-scale machines. The only things we’re sacrificing are speed and bottle- size capability,” Nicholas says.

Reducing the footprint of a filling machine is particularly important in the front-to-back dimension, points out Warren Roman, president, IMA USA (Bristol, PA). IMA, he says, has redesigned its F200 and F2000 liquid- filling systems within the past two years “to be containment friendly. The width of the machine front to back has been reduced to less than a meter.” A shallow, in-line design increases accessibility to the unit, whether it is in a barrier isolator or a RABS system.

“We have a machine capable of 600 a minute, which we have sold here in the States,” adds Roman. “But that is a particular high-volume product line. I find most of the demand right now is for the 300- to 400-a-minute machine.”

One of the attractive features of the 300- to 400-a-minute fillers, Roman says, is “the ability we have to do 100% IPC at 300 vials a minute.” Advanced electronics, he adds, allow the machine to “report all the tares and weights, everything that is important from the quality point of view.”

Kevin Constable, senior equipment engineer for Wyeth Pharmaceuticals (Collegeville, PA), says Wyeth is awaiting delivery of one isolated filling line for vial liquid filling and lyophilization of potent and solvent-based compounds. Wyeth chose scalable equipment, with the intention to scale from clinical trials into commercial manufacturing. “We looked for smaller-scale equipment that could work around clinical processes and could handle small lots but was built around a process that mimics manufacturing. We can launch from these lines, because we can scale up from lots of 2000 to lots of up to 100,000,” Constable explains. This flexibility will allow Wyeth to start commercial production while building a facility that can handle larger volumes if necessary, he adds.

COMPONENTS LIMIT SPEED

The high-speed MNB from National Instrument has a multiservo axis.

Jorge Ferreira, a mechanical engineer, specifies and customizes process and filling equipment for pharmaceutical clients. Ferreira is senior consultant, Technology Group, for Washington Group, International (Boise, ID), an integrated engineering, construction, and management solutions company. He also sees a marked trend toward medium-speed machines. “In the past, everybody wanted to run 500 a minute or more, but those machines typically ran effectively at the design speed for short periods of time (10 minutes or so), resulting in very poor overall performance.

“With high-speed machines running at close to 600 a minute, the biggest problem was actually the dependence on good, accurate components, the vials and stoppers. The companies that make the components are not making them to the precision that a high-speed filler requires. The components caused a lot of problems in the handling. The approach lately has been to choose a machine able to run consistently at 300 a minute. These machines can compensate for components being slightly out of tolerance or have a wider tolerance, which keeps overall costs down,” he says.

Improved component handling has almost doubled the production output on the SCF Hypak filling system, an ultra-high-speed syringe-filling ma-chine from Inova Pharma Systems. The company redesigned a key feature in conjunction with its customer, Baxter Pharmaceutical Solutions LLC (Bloomington, IN), a division of Baxter Healthcare, the largest manufacturer of prefilled syringes in North America.

Lee Karras, Baxter Pharmaceutical Solutions’ vice president of contract services, explains: “By improving the handling of the nests in which the Hypak syringes are supplied, we have reduced the nest-handling time from 12 to 8 seconds. The result has been to increase the filling speed from 300 to more than 500 Hypak syringes a minute.

“The biggest advantage is getting twice the production capacity for the same square footage,” he says. Furthermore, “The products that we fill don’t see any conditions that are different compared with the 300-a-minute filler. The pumps, the needles, the speed, the means of dispensing are the same. The only change was in the nest handling.” Baxter uses this system primarily for filling vaccines.

In June 2004, Inova Pharma Systems delivered one of these systems to a U.S. customer. This system has an output of 500 syringes a minute, in a 100-nest configuration. This rate, explains Kellerman, “is possible only because of advanced technology and the new, improved, nest handling.” In this system, he says, all motions are performed by servomotors.

“For the first time ever, at least in our applications, the pumping system, in-cluding the rotation of the pumping, is also servo driven. This results in filling accuracy across the board of all filling stations of ± 0.25%, and fill volumes of as little as 0.15 ml,” Kellerman adds. The system is available with either positive-displacement pumps or a time-and-pressure fill system.

Like other equipment manufacturers, Marchesini Group (Bologna, Italy) has seen a demand for smaller, slower machines in some niches. At an October open house at its facility in Bologna, Marchesini introduced several completely redesigned pieces of filling equipment. These incorporate brushless motors, a form of servo technology.

One introduction was the most recently redesigned Millennium 120 tube filler. This machine has only one filling head and fills a maximum of 120 tubes a minute, compared with the 200-tubes-a-minute rate of the dual-head Millennium 200 introduced two years ago.

The design, however, is more sophisticated. “Every movement is performed by a brushless motor,” explains Pietro Tomasi, Marchesini’s commercial director. This form of servo technology allows filling volume precision of ± 1%.

“We are targeting multinational companies that need a machine on which it is easier to do a changeover, a machine that is easier to clean and easier to operate because it is controlled by a PC,” Tomasi adds. “It is not always the case that the customer wants to go up to 200 a minute. Some need 60, 100, 120, 200, so we are completing our range of new machines with this one.”

Marchesini also introduced high-end, fast alternatives in October. One is an FSP 10-needle syringe filler from Corima (Siena, Italy), a manufacturer that Marchesini acquired in 2003. With this acquisition, Mar-chesini offers equipment for filling ampules, syringes, vials, and bottles. Marchesini integrates Corima fillers with its own cappers, cartoners, and other equipment for a complete packaging line.

Another machine that debuted in October is the Marchesini Steril 400 sterile filler. It fills 500–600 vials a minute and is suitable for use in bar-rier isolators. The latter machine features CIP/SIP and checkweighing capabilities.

Component handling has also evolved. “Pick-and-place technology is old technology,” Tomasi asserts. “Now we are using robotic technology.” At its October open house, Marchesini launched a series of robots, one of which is called RoboVision. This robot uses a camera to detect the positioning of the needed components and a robotic arm to grasp and orient them properly for feeding into the next piece of process equipment.

M&O Perry has also found packaging components to be a limiting factor in small-scale automation. Many pharmaceutical manufacturers fill preassembled and presterilized cryovials from Nalge Nunc International (Rochester, NY). One option is to purchase the Nalge Nunc cryovial caps and tubes packaged separately. “When somebody wants to move to auto-mation, once they get past the hand-filling production phase, then we can supply our Model P1600, which is a beginning filling machine for use if they purchase the cryovials with the cap and the tube separate,” Perry’s Gingerella notes.

Another option, says Nicholas, is a National Instrument Mini-Monoboc machine designed specifically for precapped and presterilized plastic microtubes and cryovials. These preassembled sterilized containers are transferred from plastic bags from the outside environment via a feed chute directly into a vibratory feed bowl that, like the rest of the machine, is contained in a Class 100 HEPA environment. “By use of all-servo-driven components, the screw cap is removed from the vial, the vial is filled, and the same screw cap is replaced on the vial and torqued, all in a 2 ¥ 4 in. footprint,” Nicholas explains.

FILLING CHALLENGES

The cold fill—the product that must be kept at just slightly above the freezing point (2–8°C)—is one of the greatest challenges for filling equipment. The product must be kept within the specified temperature range at every step of the manufacturing process, from formulation to filling and beyond.

“With every small stop of the machine, the temperature of the product has the tendency to rise, from 2° to 4°, to 8°C, and, for a longer-span fill, then up to room temperature,” Kellerman points out. If the temperature rises, he adds, “the density of the product changes, and therefore the fill characteristics and ultimately the fill accuracy.”

Inova Pharma Systems has countered this tendency by recirculating the product through the manifolds back to the receiving vessel, which is kept chilled. Suspensions present another challenge. “We’ve done some products that are like sand,” IMA’s Roman laughs ruefully. “The engineer gives me a vial, shakes it up, and says, ‘Here is the suspension,’ and puts it on his desk, and within seconds it’s already coming out of suspension.”

“To keep the product suspended, you have to recirculate it even during the fill back to a tank with a mixer in it,” Kellerman offers.

“It is impossible to recycle everything that is in the system,” adds IMA’s Roman. “There’s some product in the needles, for instance. You need to tell the machine to reject a certain number of vials upon resumption of operation after a shutdown of a specified duration.”

PUMP OPTIONS

Some manufacturers are seeing an emerging demand for machines that are not locked into one filling system. “We offer not only our volumetric filling systems but also the option of having multiple interchangeable filling systems on the same machine,” says National Instrument’s Nicholas. “Sometimes we integrate other manufacturers’ filling systems if a custom-
er requests it.” He adds that some pharmaceutical manufacturers, for instance, prefer peristaltic systems, “because they eliminate many cleaning issues.” Another option is a rotary piston system for extremely small fill volumes.

In July 2004, NJM/CLI Packaging Systems International (Lebanon, NH) introduced volumetric rotary gear pump modules for the FLX 1200 liquid filler. This filler’s modular design uses interchangeable mobile filling- pump modules on caster wheels.

The qualities of the suspension or the viscosity of the product may determine which is the best filling equipment for a particular application. “Different products lend themselves to or require different solutions to their particular problems,” explains IMA’s Roman. IMA, he adds, offers a choice of positive-displacement, time and pressure, and peristaltic pumps.
Choice of pump may be especially important for biotech drugs, Roman continues. “A lot of the biotech product molecules are long chains. Sometimes you need a particular pumping system so that you don’t break or shear the chains of the molecules.”

READY TO UPGRADE?

Tomasi says customers with older models of Marchesini equipment can incorporate some of these innovations without tossing out their whole process line. “Some machines can be retrofitted, and sometimes we even buy back the old machines to replace with new ones,” he reveals.

ProSys also has retrofitted some of its earlier-model equipment with new technology and has even retrofitted lines of equipment from other manufacturers. “Depending upon the model, or complexity, or access to it, it can actually occur fairly smoothly,” Lowden says. Many customers, though, are finding the advantages of a new system very tempting.

“Five or six years ago, the use of servo componentry could have created a premium of 25–35%. Today, with the way technology has expanded, it’s maybe a 5% premium,” explains Lowden. “Now our customers are saying, ‘Wow, 5% more, and it gets me 15% more speed, I can change over faster, and it’s more accurate?’ Easy sale.”

Copyright ©2004 Pharmaceutical & Medical Packaging News