The packaging is a double-foil structure: the polyvinyl chloride–foil laminate blister plus a foil-overwrapped multipack.
This design protects the sensitive powdered insulin from moisture before use and enables the product to have a two-year shelf
life. The blisters are arranged on six-count, perforated cards. Each blister contains a small well that holds a precisely
measured amount of insulin powder, which is white to off-white in color. Each blister also is notched and printed to aid in
proper placement in the inhaler. Printing is color-coded according to the dose: green for 1 mg and blue for 3 mg. In addition,
raised bars provide a tactile dose indicator: one bar for 1 mg and three bars for 3 mg. Because some powder remains behind
in the blister after dispensing, they are overfilled to compensate and ensure that the proper 1- or 3-mg dose is delivered.
Five blister cards (30 doses) are packed in a thermoformed polyethylene terephthalate (PET) tray. Each tray contains a desiccant
and is sealed with PET lidstock. The sealed tray, in turn, is placed in a foil pouch with a desiccant.
Goals for the handheld inhaler design required that it dispense the powder in a high-efficiency operation with little or no
waste, deliver a very high concentration of insulin with only one puff, and protect the moisture-sensitive powder from humidity.
Designed to be refilled and reused for one year, the inhaler weighs approximately 4 oz. The device is roughly the size of
an eyeglass case and consists of three major subassemblies: the base unit pump, the suspension chamber, and the insulin-release
unit. The latter is replaced every two weeks by the patient. The suspension chamber also can be replaced. In addition, the
unit partially disassembles to permit weekly cleaning. Essentially mechanical in operation, the device does not rely on electronics
and therefore needs no batteries or electricity. Nearly all of the parts in each subassembly are injection molded.
In use, the patient inserts a blister into the inhaler and pumps the handle to draw air into a cylinder where it is compressed.
The patient then presses a button and the insulin-release unit pierces the blister, releasing compressed air and sending a
smoke-like cloud of fine powder into the clear suspension chamber. When the patient sees the cloud, he or she puts the mouthpiece
in his or her mouth and inhales normally to draw the aerosolized powder deep into the lungs. After removing the mouthpiece,
the patient holds his or her breath for five seconds and then exhales normally.
Because manufacturing the delivery system fell outside both companies' expertise, the partners turned to Tech Group, (Scottsdale, AZ,
http://www.techgroup.com/) about six years ago. This company became par0t of West Pharmaceutical Services (Lionville, PA,
http://www.westpharma.com/) in 2005. The injection-molding specialist and contract manufacturer helped develop an automated assembly process for the
device and installed and validated the equipment as well as the quality system. This project was completed in advance of regulatory
clearance so the plant would be ready to ramp up to commercial-scale production as soon as approval was received. "The device
is part of the NDA so it is treated like a pharmaceutical from a regulatory perspective," explains Mike Treadaway, general
manager of drug delivery devices at Tech Group. "All of the development and validation work [for device production] was done
the same way it would be for a drug," he adds.
Several different materials are used: engineering resins for internal components, an acrylonitrile butadiene styrene (ABS)–polycarbonate
blend for the outside and clear ABS or styrene–acrylonitrile for the suspension chamber. Some parts require two-shot molding.
This sequential molding technique produces a part made of two different materials by injecting one material and then another
into the mold to create, for example, a rigid part with an integral flexible gasket. Approximately 15 injection-molding machines
are needed to produce the many intricate parts required for the device. "There also is a lot of precision involved in assembly,"