From his perspective as vp, liquid pharma packaging, at Bosch Packaging Technology (www.boschpackaging.com), John Kirk sees a trend toward greater utilization of isolator technology for aseptic processing, for example in syringe filling. “In the past, this would have been done in a cleanroom. Today, the entire process is put inside an isolator.”
Another welcome advance is vendors’ interest in the science behind isolators. Bosch, for example, recently formed a process technology group to investigate how its products can improve productivity at customer sites. “It’s not good enough anymore just to build the machine, you have to understand the process.”
Like other top vendors, Bosch integrates its isolator systems directly into process machinery, so customers can acquire everything they need from a single source. “Customers can, of course, purchase equipment without the isolator,” Kirk notes.
Bosch’s integrated isolator-vial fillers come in a range of capacities. Bosch also offers its GLoveFIT glove-testing product for determining the integrity of isolator inlet gloves, and a decontamination system, SafeVAP, that uses industry-standard vaporized hydrogen peroxide.
Isolator technology is better established in Europe than in the United States and has been adopted primarily by small-molecule drug manufacturers. According to Sterling Kline, director of project development at IPS (www.ipsdb.com), larger biotech companies use isolators extensively in fill/finish areas. Early on, biotech companies were reluctant to adopt isolators due to regulatory uncertainties, primarily because cleaning cycles lasted as long as 18 hours. With the introduction of improved vaporized hydrogen peroxide sterilization by Skan (www.skan.ch), and more recently by Bosch, cycles have been reduced to three hours or less. Skan has performed extensive testing on various isolator materials for stability to peroxide sterilization.
Then there is the matter of priorities. “With the exception of the largest firms, biotech prefers to invest in manufacturing processes, not in isolators,” notes Jim Agalloco, president of Agalloco Associates (www.agalloco.com). “Smaller firms, especially, are not going to play around with exotic fill/finish technologies.”
Isolators increasingly make sense in biotech filling and finishing suites because the value of biologics per unit weight or volume is so high. Before blockbuster biologicals became commonplace, it was simply easier to process these products in classified rooms rather than invest in dedicated isolator technology. “Today, you just can’t afford to lose a batch,” Kline adds. Bristol-Myers Squibb (www.bms.com), for example, has introduced isolators to its fill/finish operations to reduce the potential for human error contaminating a batch.
Another positive trend for biotech isolators has been the migration from lyophilized products to liquid formulations, especially prefilled syringes. IPS typically specifies isolator-based vial- and syringe-filling equipment from Bosch and Inova (www.inova-ger.com), respectively. Groninger (www.groninger.de) also produces state-of-the-art filling equipment that is adaptable to isolator technology. “Most major companies are now building syringe lines within isolators,” notes Kline.
According to Andre Petric, product manager, material handling and containment, at Glatt Air Techniques (www.glattair.com), the need to contain process equipment through dedicated, integrated isolation units is growing among pharmaceutical companies. Glatt, for example, builds isolators around several equipment lines to provide a system where machine and barrier are married for the best performance. Among Glatt’s customers are manufacturers of pharmaceutical powders and oral solid-dosage forms.
Glatt’s small-scale isolator system for development work, Containment-Lab, is an array of modular isolators positioned sequentially for enclosing relevant operations: dispensing, wet granulation, fluid bed drying, sieving, tableting, and coating. Users may combine, add, or delete isolator modules as they modify processes. Each module contains a port for locking one module onto another without exposure to the ambient environment.
Never at a loss for a vivid analogy, Agalloco describes isolator-enabled unit operations in pharmaceutical manufacturing as “islands,” with processors striving to “ferry product from one island to another within the archipelago.”
For mid-sized pilot or large development-scale processes, Glatt offers its Glatt Process Coater-Granulator (GPCG2) system with a designed-in fluid bed processor. Larger processes and equipment, says Petric, serve as their own containment systems. “The machine itself is the isolator.”