Filling Adapts to New Market Needs
Filling innovations mark todayï¿½s technology.
A dual-barrel filling machine from Turbofil eliminates air in syringes.
There have been many opportunities for innovation in filling in the past year. Some large drug makers are outsourcing the total packaging process to contractors. Also, more generic drug companies are entering the market. Because both generics and contract shops tend to run very high-mix, short-run production, equipment manufacturers are moving more toward developing highly flexible systems to help these operations.
With lines that change over from product to product come concerns about contamination of both product and workforce as well as the increased need for product traceability. All of these issues and more are making the pharmaceutical and biomed filling area one of the fastest expanding markets for equipment manufacturers.
Moving to servo-controlled filling systems is providing high flexibility in all areas of filling. Servo-driven systems allow the user to save all process routines for instant recall.
Aylward Enterprises LLC (New Bern, NC) has designed servo-driven equipment that meets any flexibility need for oral solid-dose pharmaceutical filling. “Our equipment provides instant start-up after changeover,” says Matt Neumann, vice president of sales and marketing. “We basically eliminated all the adjustments.”
From highly viscous to watery liquids, ProSys (Webb City, MO) handles them all. Its servo-driven filling equipment has the ability to move viscous product and give an air-free, bottom-up fill for different-shaped containers. The control software gives the equipment the ability to vary how the material is flowing out of the metering system into the container as it is filled at high speed.
“This provides a great deal of flexibility,” says Don Sonntag, division manager. “Being able to change how the product flows into the container can create a perfect match between the container profile and the flow profile. It accomplishes a good, clean cutoff after filling.”
One contract manufacturer with a very tight time frame and a high-risk application discovered the value of servo control when it called upon ProSys. The firm needed a customized automated tube filler for a unique HDPE squeeze tube that included an applicator tip and a “side button” for release of oral (morphine) medication.
“Using ProSys’s standard RT 60 as a base model, we were able to customize a machine to address the small fill volume, the unique tube characteristics, and high-accuracy requirements of government-regulated product,” Sonntag says. “The control system was easily expanded to provide government reporting requirements needed for the controlled substance–classified filling material.”
Unique containers are seen more today, whether developed to grab market share or to improve the effective use of a pharmaceutical or biomedical product. Tony Miller. marketing coordinator, Bosch Packaging Technology’s Pharma Unit (Minneapolis), notes that in some instances, it is not the container itself, but how it needs to be presented, that is the issue. “Most of the new prefilled syringe projects we are seeing are now nested products, and we have had to develop a new line of machines to meet the demand,” he says.
Highly specialized container shapes are the norm for the growing analytical instrumentation area. Machines test biofluids for disease and other critical issues. To do this, reagents are needed. Because the companies that make the analytical equipment also sell the reagent (in the specialized containers) to the labs, they create them in odd shapes, so no other reagent can be used in their specific machine.
Filamatic Div. of National Instruments LLC (Baltimore) specializes in liquid-filling equipment and has firsthand knowledge of filling reagent containers. “Odd shapes are difficult to handle, load, and orient and are very specialized for each customer,” says Jack Grosskopf, director of engineering. “With our long history, we take unique containers in stride.”
One analyzer customer took customization a step further. “It decided to remove all operator interfaces from every aspect of the process to ensure total sterility and product safety,” Rudy Arn, president and CEO, says. “So not only was it an odd-shaped container, we had to put verification stations after every operation.”
The product had a foil seal that went over the top of the container once it was filled. Two different labels went onto the container, and both were serialized. The Filamatic system had to keep track of the printing as well as the application to make sure every single vial had its personal traveler for every aspect of the process.
Another growing area is in the dual-syringe market where two different drugs or materials need to be put into side-by-side syringes for specific medical use. There are issues to monitor, such as air in syringe fills and cross-contamination. Because of these fears, this application has typically been either manual or semiautomatic. Turbofil (Mount Vernon, NY) has completely automated this process.
When dispensing, the machine must maintain a strict ratio between the two syringe compartments. If the fill level is off in any way, such as an air pocket dropped into the product, it will throw off the accuracy in the mix ratio.
“We have been able to solve all the problems using servo-controlled off-set nozzles to eliminate the chance of cross-contamination,” says Eli Uriel, general manager. “Using a proprietary vacuum chamber for evacuating the air answers the additional issues. In the end, you get increased throughput and fewer rejects. Our customers have been very happy.”
Managing Difficult Liquids
Miller notes that Bosch has encountered many types of products and, in general, more viscous, sticky, or stringy products, are the most challenging to work with. “It makes accurate dosing of the product slightly more difficult,” he says.
Sonntag agrees, adding that these materials are particularly difficult to fill at higher speeds. “It’s a challenge for many filling machines to accomplish the speed the customer wants with an accurate and repeatable fill and also get a good cut off,” he says.
He goes on to say that to meet this challenge, ProSys developed a patented servo-metering system for dispensing highly viscous and stringy materials that can now run consistently at any speed and can deliver precision cutoff.
Massimo Pannini, product manager for the Marchesini Group SpA (Bologna, Italy; for USA Div., West Caldwell, NJ), notes that some of the newer high-viscosity or foaming liquids are normally considered the most difficult to dispense. However, an analysis of specific project specifications will typically suggest a very easy technical solution. “We have introduced filling using electromagnetics and flowmeters that help reduce vial filling times and provide high dosing accuracy and filling precision over all material types,” he says.
Issues With Solids
While gelatin capsules and coated tablets are relatively stable, uncoated tablets leave dust that builds up on the machinery. This dust can affect the visual inspection of fill accuracy on some systems.
To counteract the dust issue, Service Industries (Rolling Meadows, IL) developed an electronic system based on sensor-array and infrared lighting for its SureFill 300. “We use an array of optical sensors lined up across the slat,” says president Joel Gray. “For an 80-cavity slat, there are 80 sensors looking to make sure each cavity has a tablet in place. There is a hole in the bottom of each slat cavity. An infrared light shines up through the hole as the slat goes by, and the sensor above immediately knows that if the light gets through, there is no product in that cavity, so the fill will be rejected.”
Dust often brings up the need for operator protection, requiring operators to “gown up” to work near the filling process. One such customer came to Aylward for this reason. Its products contained a high quantity of active material. They basically had to shield the operator completely from contact with the product during filling and packaging.
“We provided a system that shielded off the operators from the moment the product entered the system to the time the bottle left the filler,” Neumann says. “Tests have proven that with our equipment and product-containment system, they were able to completely do away with gowning. This saved the company a great deal of time and expense.”
Addressing Sterility, Tracking & Traceability
Example of a full filling and packaging system from Marchesini Group SpA.
The Optima Pharma Group, headquartered in Germany and with a U.S. facility in Green Bay, WI, has a finger on the global pulse of the prefilled syringe market. Matthias Poslovski, technical sales director, says that while the basic styles of syringes have been relatively stable, what is new is in the area of safety: the automatic snap-on feature that protects nurses or patients after syringe use. “Customers have come to us needing a machine that can assemble the syringe into such safety devices directly after filling,” he notes.
There is also a growing need for complete traceability. One of these is the area of removable labels on syringes. “A doctor can administer the product and then peel this label off the syringe and paste it onto patient charts for traceability of not only to what was administered, but back to the actual lot code of that particular syringe.
“We are finding that more and more we are taking over the full range of the prefilled syringe process,” Poslovski says. “For syringes and vials, for instance, we are doing the washing, sterilization, and inspection, and then the filling, stoppering, labeling, safety device assembly, and magazining.”
One very interesting application Marchesini recently addressed concerned a line of liquid bottle filling in a sterile environment for Immucor, a Georgia-based company that specializes in pretransfusion diagnostics. Immucor makes and distributes products used by transfusion centers, blood banks, and clinical laboratories to test blood components prior to patient transfusion.
“The line was required to fill and process 10-ml reagent vials in a sterile room situation,” Pannini says. “Keeping all aspects of the process completely contamination-free was the prime criterion.
To address this application, Marchesini developed a bottle-filling and -capping machine, the ML661, for the sterile room that was fitted with a CIP/SIP (clean in place/steam in place) unit for washing and sanitizing. The system is a linear single-block machine with robotized machine movements and brushless-motor control of the filling syringe stroke and valve opening. Balcony structure is in place for correct laminar flow according to CGMP directives. Filling takes place in-line with a continuous-tracking motion. At the end of washing, purpose-designed sensors establish whether another sanitizing cycle is required. Once filled and closed, the vials arrive at a labeler.
Running at 200 vials/min, this new Marchesini liquids line allowed Immucor to double production compared with other lines already installed.
IMA Safe (Bristol, PA) focuses on equipment for blister packaging, tablet counting, cartoning, end-of-line equipment, and tube-filling machines. Darren Meister, sales director, says that higher accountability is a key issue. “For solid-pharmaceutical traceability, inspection systems we are looking at [examine] product color, broken or rogue items, and count verification. On the safety side, containment solutions for operator exposure include fully contained monobloc machines,” he says.
IMA is addressing these changing trends by offering new equipment and upgrades to existing equipment. “For tablet inspection, we not only offer infrared optical sensors for our electronic tablet and capsule counters, but also EFS (electrostatic field system) detection systems that create an accurate assessment of tablet parameters, including size, shape, and weight, during the counting process as tablets are being fed into containers,” he says.
The growing clinical trial market requires a bottle-filling process that addresses very small quantities, extremely fast changeover, and completely accurate product count. Because the end product will go into clinical studies at labs and in medical test groups prior to product approval by FDA, these must be completely accurate and fully documented.
“FDA requires more and more testing, the tests are drawing out longer, and you cannot trust manual product counting anymore. It has to be precise and absolutely traceable,” Neumann says. “Aylward developed a completely new bottle-filling process that addresses the clinical area. This is for very small quantities and extremely fast changeover for lines up to 50 bottles a minute. We guarantee the 100% count needed by this market.”
Looking to the future, contributors to this feature all agree that the trends covered here will be continuing in the coming year. They will change how the pharmaceutical manufacturer is approaching the filling process, and this will be a boon for filling equipment manufacturers. Each opens up more market opportunities for new equipment.