An annoyance for many, a real health threat for some. Just the sort of problem an inventor wants to solve. In 1932, an engineer named Arnold Sutermeister noticed what happened when diesel oil hoses developed pinhole leaks. High-pressure streams of oil shot out, and workers handling the hoses essentially had their hands injected with oil.
Liquid could be its own needle.
Sutermeister and a medical student collaborated on a needle-free injector. Other devices followed. Hypospray, one brand, was also the name for a futuristic injector used in episodes of Star Trek.
The U.S. military developed needle-free injectors capable of vaccinating 600 soldiers an hour and used them widely from the 1950s through the 1980s. But these so-called multiuse-nozzle jet injectors, or munjis, could pick up a little blood from one arm, carry it on the nozzle, and inject it into the next arm. A hepatitis-B outbreak in California in the mid-1980s was tied to the use of a munji at a clinic. The devices were largely retired.
Needle-free injectors with disposable cartridges instead of a fixed nozzle, like the PharmaJet, were next. Following the emergence of AIDS, the need was urgent. The annual number of needle sticks of U.S. health care workers has been estimated at as many as 800,000. And in developing countries, PATH has estimated, half of all needle injections are unsafe. Some syringe designs, to be sure, improved following the AIDS crisis. Shields and retractable features were added to reduce sticks. Autodisable features were added to prevent reuse. However, these syringes are more expensive -- roughly 7 cents to 38 cents apiece -- and not all the safeguards are foolproof. Simple 6-cent (and even cheaper) needles are still widely used. And needle reuse remains a big problem, says Darin Zehrung, a PATH vaccine official.
Callender, with Umbaugh's design in hand, decided her cartridges had to be made of polypropylene, because its low cost would give PharmaJet a better chance of matching needle prices. It's hard stuff to work with, though, and in clinical trials in Cuba in the late 1990s, some of the cartridges leaked when under the 3,000-pounds-per-square-inch pressure needed to propel medicine into the skin. Word got around. "The device was not ready for prime time," says Royals, who joined PharmaJet a few years later. "That left a bad taste in some people's mouths."
The Food and Drug Administration approved the device's use in 2004. But it was too big, awkward, and ugly. "Nobody would buy it like that," Callender says. With nearly $1 million sunk into the business, Callender was still really at the beginning.
Some plastics experts told Callender she would never get a reliable cartridge from polypropylene. But without it, PharmaJet might as well have folded. Callender went looking for a design engineer who could make it work, and in 2004, she met John Bingham. He had run a tool-and-die shop and an injection-molding shop and had designed consumer and industrial products. A medical device? Never. Callender and Bingham were introduced over iced tea on the back deck of a mutual friend's house. It was supposed to be a get-to-know-you meeting. But Callender was anxious about her plastics problems, and she cut to the chase. "I handed him the injector and syringe [cartridge]," she says. Bingham studied it. Callender waited. "He said, 'Hmm, I can see some problems with this and how I would fix it.' " Callender decided on the spot: He's my guy.
Bingham dropped most of his other work. Getting the cartridge's opening right -- about three hairs wide, Bingham says -- was especially tricky. To prevent leaks, the molds had to be perfect. Finally, Bingham found the right plastics molder, and the cartridges came out consistently. "I met her and just had to help the lady," Bingham says. "She was going to rid the world of needles."
Bingham also began redesigning the injector, simplifying and shrinking it and the docking station used to cock its spring between injections. An FDA official suggested Callender also comply with a new international standard for needle-free injectors. She agreed to, learning only later precisely what that entailed: 60 injectors tested for durability to 30,000 cycles. In his workshop, Bingham rigged an elaborate, Rube Goldberg contraption that cocked and fired five injectors at a time, roughly every eight seconds. Bingham wore out a compressor powering the setup. It took 45 days. The injectors made it.
Around the time she found Bingham, Callender also went looking for scientific help -- someone to design and oversee animal studies, then human studies, to demonstrate the injector's efficacy. She met Royals, a veterinarian by training, at a biotech conference where he was exhibiting his consulting firm. They talked for an hour. Callender walked around for a while, then came back to Royals's booth and declared: "I think we're supposed to work together."
He asked for an injector and a week to evaluate it. "I injected my dog, first thing," Royals says. "The most impressive thing was he did not respond. I began to investigate it on friends-and-family dogs. Same reaction. We did horses that throw up a rodeo when they see a needle. No reaction." Royals signed on, too.
His access to an animal necropsy lab at Colorado State University's vet school was a big help. Dressed in old clothes, Callender and Royals would go in, pull out whatever roadkill or other carcasses had arrived, and inject them. "Horses, cows, dogs, cats, leftover mice," Callender says. "You come out smelling, but we gained a huge amount of valuable information at almost no cost." Later, Royals arranged to have much of PharmaJet's human testing done overseas. That saved the start-up millions of dollars.
But, as Sam says, "eventually you run out of money." Todd tried fundraising, without any luck. Was PharmaJet finished? Then the Callenders' daughter, Heather Potters, came to the rescue. Potters had been working in private equity in Eastern Europe for 15 years. She had money connections from Wall Street to Warsaw. She pulled together a prospectus, and she and Callender hit the road in December 2005. "She said, 'Put on your roller skates. It's going to change dramatically,' " Callender says.
