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.

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," reports Treadaway.