The task of creating new medical devices may not seem like it would fall to chemists. Putting gadgets together is the domain of the inventive mechanical engineer--perhaps in cahoots with a physician desperate for a new tool. But that engineer and M.D. are increasingly turning for help to those trained in the behavior of materials and small molecules. Health care therapy by way of devices and diagnostics is shifting from the gross to the minuscule and entering the world of the chemist.
"We are, I think, being hit over the head with the point that there is a fusion now going on between the mechanical aspects of medical device design and the biochemical and biologic aspects of medical device design," says Paul G. Yock, a cardiologist at Stanford Medical School and cofounder of the Stanford Biodesign Innovation Program. "The poster child example is the drug-eluting stent"--a transformation of a purely mechanical device, the stent, to a combination drug delivery and mechanical implement.
The stent is a long-time staple of modern cardiology. Heart doctors use the narrow mesh coils to treat advanced cardiovascular disease. Surgeons insert stents in narrowed, diseased arteries to hold the arteries open. Unfortunately, about 20% of the time, the cells surrounding the stent become inflamed and replicate, and the artery narrows again.
The drug-eluting part came along when scientists added a thin polymer coating to the stent along with an antiproliferative and immunosuppressant drug that the polymer gradually releases to the surrounding vascular cells. The drug-eluting stent has significantly improved the performance of this device.
It's difficult to know how many of the roughly 100,000 medical devices in the U.S. started out in the mind of a chemist, but there are many hoped-for devices that could use a chemist's expertise. For example, many companies are creating devices that are essentially drug-delivery machines. "Sometimes drugs by themselves don't work well, or the device alone may not work. The integration creates a unique possibility for somebody who has strong chemical or biochemical skills to make an inroad," says Vartan Ghazarossian, president and chief executive officer of FlowMedica. In other areas, chemists can help create better artificial hips, knees, kidneys, and livers; biocompatible implantable devices such as heart valves and pacemakers; and biodegradable tissue scaffolding.
Many types of chemists can play a role in the creation and maintenance of a medical device.
Ghazarossian's company, FlowMedica, is creating a device to deliver drugs directly to the kidney. A year ago, Ghazarossian was at Imetrx helping design a device to target vulnerable plaques in heart disease. Through "a series of start-ups," Ghazarossian also helped promote and develop therapeutic drug monitoring and imaging devices, viral screening in blood, and a device that uses ultrasound to deliver drugs more effectively. Overall, he says, his career has been an "interesting evolution of trying to better understand and develop tools for local and regional drug delivery."
Ghazarossian has a Ph.D. in biochemistry from the University of Wisconsin, Madison, and says his chemistry background has always been helpful. As CEO and president, however, he is no longer working at the bench level. "The past several years, my role has been more on the management side, creating a vision for the company, managing that vision, and raising money." Ghazarossian enjoys the start-up environment. He enjoys finding a new vision, getting others excited about it, and developing it into a workable and clinically useful device. He especially likes that the device industry allows him to "see thoughts and ideas implemented very quickly."
A FELLOWSHIP program at Stanford University is teaching students a process that Ghazarossian knows well--the art of creating a new device. The Stanford Biodesign Innovation Program, founded in 2001, targets innovators and teaches them what it takes to choose, design, and develop a new medical technology. Yock and cofounder Joshua Makower say they hope that students leave with "a very systematic way of finding a need and characterizing that need so you really understand whether it is worth investing time and money in the solutions," Yock says. "Finding and understanding a need is more than half of a successful invention."
Makower and Yock accept a core group of four or five fellows into the program. This year, the group consists of two physicians and three engineers: biomedical, electrical, and biochemical. Makower believes that the more diverse backgrounds you have on the team, the better. "I can hardly think of a single discipline that would not potentially have value in medical applications." The fellows share one tendency: They "can't help themselves from innovating," Yock says.
Yock and Makower take seriously the proposition that students can design a product that will eventually reach the marketplace. "Inventors often come up with some of their best work early in their careers," Yock says. The fellows have access to a "faculty" of more than 110 CEOs, venture capitalists, product designers, regulatory specialists, reimbursement specialists, and patent attorneys doing this work in the real world. Four or five start-ups have already resulted from ideas that were conceived in the program.
The fellows start off in the hospital, where they are immersed in clinical work. Over several months, they come up with a combined list of at least 200 needs, which they then boil down to a dozen.
"In January, those top dozen feed into a bigger group," Yock says. In addition to the fellows, Makower and Yock form a class of 30 Stanford graduate students: 10 from engineering schools, 10 from the school of medicine, and 10 from the business school. Small teams form within the class, and each team takes on a need under the guidance of one of the fellows.
Jason Davies is a combination M.D./ Ph.D. (biophysics) student in this year's class. He describes what the teams do with their chosen need: They perform a market analysis. They go through the scientific literature. They look at reimbursement and patent issues. "We investigate any area that might tell us, 'Is this a real clinical need or is it not?'"
Davies says a number of the ideas have to be set aside. His team discarded a need to create a device for diagnosing brain aneurysms because it wouldn't have been cost-effective.
That is exactly the point at which a need should be discarded, Yock says. "It is so of ten the case that somebody starts with a very incomplete and often distorted idea of what a need is, invents a technology, and from then on, it becomes a technology chasing an actual need. It's backwards."
Only after a need has been thoroughly validated do the fellows and graduate students start designing. They come up with a number of designs and mock-up prototypes, and they make "elevator pitches" to each other about how one design is best. Davies' team members have designed a device for preventing bone fractures that they think is especially promising.
The team of developers and business managers who work with innovators is extraordinarily important. "We have a myth, in America especially," Yock says, "about these brilliant lone inventors, which is absolute rubbish. Almost all good inventions come from teams. The really great inventors understand that, and they surround themselves with people who invent as a team."
Chemists are vital members of such teams. For example, Kishore Udipi, director of polymer research at Medtronic Vascular, is working on creating a second generation of Medtronic's drug-eluting stent. He directs the research of formulating new biocompatible polymers that release the drug at a different rate.
Udipi received his Ph.D. in polymer science from the University of Akron, in Ohio. Subsequently, he worked at Philips Petroleum and Monsanto doing polymer research. "Although most of my career I have worked on engineering applications of polymers, during the past six years at Monsanto, I was working on biomaterials. I have seen a steady shift in polymer research, both in academia and in industry, from engineering applications to biomaterials."
Medea Myhra is a formulation chemist at Coloplast in North Mankato, Minn. Coloplast was founded in Denmark in 1957 after a nurse, Elise Sørensen, conceived of the first disposable ostomy bag (a device for patients who have the colon brought through an opening in the abdomen called a stoma). She approached a plastics manufacturer, and when his wife, also a nurse, told him of the great need for such a bag, he started producing polyethylene bags that adhered to the skin around the patient's stoma.
Coloplast has since expanded its product line to include skin health, breast care, continence, and wound care products in addition to ostomy devices. Myhra works in the skin health division, in R&D, "also known as product development." She is always looking for ideas for new skin care products. One of her first projects was a hand sanitizer for Danish hospitals. In addition, Myhra is a "product champion" for existing products, including Sween Cream, which is a moisturizer used on dry skin conditions such as those created by radiation therapy. She deals with any technical questions that arise about the product.
Myhra earned a B.A. from Gustavus Adolphus College in St. Peter, Minn., in general distributive science with an emphasis in biology and chemistry. "In college, I was premed. I decided not to be a doctor, but this is getting closer."
Richard Gniewek at Ventana Medical Systems formulates reagents for automated clinical laboratory systems. He works primarily in product development, helping move products from R&D into manufacturing. Many Ventana products automate antibody staining, and Gniewek works mainly on those products. His background is in immunochemistry. He earned a Ph.D. in biochemistry from the University of Texas medical branch.
Gniewek says, "It is always a challenge to come up with new ways to stabilize the biologicals in such a way that they give high-quality results."
GHAZAROSSIAN, Udipi, Gniewek, and Myhra often deal with the challenges of meeting government regulations. Both the U.S. Food & Drug Administration and European regulating bodies are strict in requiring companies to prove safety and efficacy of their medical devices. "We rely a lot on what our regulatory department people say to guide us," Gniewek says, "but it is important for everybody to understand the impact of those regulations and what it means to quality and the bottom line."
Hybrid devices that combine technologies (such as adding a drug) have to go through an especially rigorous approval process. "The performance requirements in biomaterials for biomedical applications are very high," Udipi says. "After all, the polymer that you synthesize will end up in someone's body someday. And it is expected to last there for a long time without any adverse reactions from the body."
The challenges of creating new medical devices may be larger than ever, but the rewards are still great. "Having that immediate impact on the patient to improve quality of life or even save a life is very gratifying," Gniewek says. "It's like raising a child who then goes out in the world and contributes."
And Makower says there is "tremendous, tremendous clinical need" for new products. "Wherever you look, you find a clinical problem that has not really fully been addressed." He encourages anyone to enter the field and focus their energy and creativity on finding and addressing those needs. No need to be a physician, he says. "I find that some of the most interesting ideas come from people who have previously not been exposed to or even trained in the particular clinical discipline, but bring a unique technical background and perspective to the problem"--somebody like a chemist.