The pharmaceutical industry has been using disposable containment technology for more than 10 years, and many applications have emerged during that time. Beginning with bulk bags and super sacks, options have multiplied to include flexible glove bags, flexible isolators, and flexible soft-wall cleanrooms. The technology’s containment capability has steadily improved to the point where it is comparable with traditional rigid systems. As a result, manufacturers have stopped seeing disposable containment as an ad hoc solution, and the technology increasingly incorporates thoughtful design and engineering. The future promises to bring more changes and new applications for disposable containment technology.
Huw Thomas, a principal pharmaceutical engineer at Foster Wheeler (Clinton, NJ), says multilayer flexible systems such as the one offered by ILC Dover (Frederica, DE) could point the way to further innovations. The company wrapped a small glove bag around the disconnection point of a continuous liner, and an operator double-ties or crimps and cuts the liner at the disconnection point inside the glove bag. “It’s the same principle as using a flexible liner inside a rigid glove box, which is a standard way of achieving nanogram-level containment,” Thomas explains. Multilayer flexible systems such as this can provide containment well below 1 µg/m3. “We’ve used this approach to ramp up containment on discharge systems,” says Thomas.
Connecting containers with heat sealing or crimping could be abandoned in favor of a zip-tight connection between two bags, Thomas remarks. This low-cost strategy has the benefit of simplicity and provides many potential applications. This technique “can convert a standard Tri-clamp into a well-contained, make-or-break connection,” he adds.
More and more, companies are manufacturing drugs in multipurpose facilities. Many new products are cytotoxic and hazardous. “These materials create such a high demand for cleaning between products that flexible disposable technology is the best solution,” according to Richard Denk, director of the pharmaceutical department at Hecht Technology (Pfaffenhofen, Germany). He predicts that pilot plants and contract manufacturers that must produce different products with the same equipment within one facility will increasingly use disposable containment.
Increasing production of high-potency products will make flexible containment kits more popular, says Thomas. Operators can attach these kits to standard equipment to improve containment whenever necessary. Several companies already use this approach. Rather than developing new high-containment equipment, Thomas says, equipment manufacturers could collaborate with containment vendors to provide low-cost containment kits to retrofit to existing equipment such as tablet presses and granulators.
Introducing a low-cost barrier system to a sterile manufacturing suite is another idea with great potential, according to Thomas. “A simple barrier between the aseptic zone and the operator would greatly add to the sterility assurance of that operation,” he explains.
Gene Fuchs, field marketing manager for aseptic transfer and drug delivery at Sartorius Stedim (Aubagne, France), says that disposable devices could be combined to change or eliminate traditional technology. For example, using rapid-transfer ports with disposable fluid paths eliminates the need for mouse-holes as a transfer system between classified spaces. In addition, disposable nozzle systems are replacing traditional spare filling nozzles for fillers. “Perhaps the most cost-effective change is the ability to reduce Class A space by using a fully disposable path from the holding vessel to the filling nozzle,” Fuchs says.
Technological advances now enable the industry to shift from an application-based to a systems-based approach to disposable containment, according to Fuchs. Disposables can be designed into the manufacturing process so that drug substance can be placed in a disposable bag, filtered, transferred into a cleanroom or isolator, and put into capsules using a disposable nozzle system.
Disposable containment also allows manufacturers to change the manner in which they design new facilities. For example, storing materials in disposable bags rather than in permanent vessels eliminates the need to include space to store vessels or wide hallways to transport them. This strategy also reduces the amount of cleaning required. Combined with isolators, disposable containment “is changing the entire fill-suite configuration,” Fuchs says.
Denk agrees. “Within the next 10 years, the design of process equipment, product-transfer systems, and facilities will be completely different from what we know today,” he says.