New Medical Devices Challenge Scientists And Regulators Alike

WASHINGTON -- Medical devices have been the most trouble-free of biotechnology's products; they have sailed smoothly through U.S. Food and Drug Administration review. But that situation is changing. These genetically engineered materials and technologies for treating and diagnosing disease are getting more complex. At the same time, Congress and the public are increasingly concerned that FDA is not being tough enough and that technology is inflating health care costs. Last month, FDA and the State of Maryland hosted the International Biotechnology Conference on Applications to Medical Devices and Perspectives for Future Development. At this meeting, the first of its kind, FDA leaders applauded biotechnology companies for the more than 350 devices, primarily genetically engineered diagnostic tests, that have passed muster at FDA in the last decade. And there's no end in sight. The integration of diagnostics, drugs, and devices is one of bio-technology's more promising applications, says Ralph Christoffersen, vice president for research at SmithKline Beecham Pharmaceuticals in King of Prussia, Pa. New materials and advances in electronics and molecular biology make possible therapies that were once just science fiction. At the same time, the new technology is expected to use in vivo imaging to make possible more precise monitoring of the body's processes and the effects of the drugs. But these advances could spell trouble if the government is not prepared to oversee them. "This rapid progress will almost certainly outstrip the ability of existing public and private leaders to assess and decide on appropriate policy," says Christoffersen. "It will certainly strain our current agencies and processes to handle applications of technologies." As an example, Christoffersen points to a self-regulating drug delivery system that could control diabetes better. It would allow doctors to implant an artificial pancreas that would secrete insulin in response to the patient's blood sugar levels. "Such an integrated system," he says, "has the potential to achieve one of the Holy Grails of medicine, i.e., to devise therapeutic interventions that are patient-specific, target-specific, and that deliver drug only as needed." Christoffersen envisions a similarly radical treatment for drug addiction. It would use an implanted artificial organ to release naltrexone only in the presence of morphine and, thus, block the effects of the narcotic that had been injected by the addict. But these treatments require greater integration of diagnostics, therapeutics, drug-delivery, and device-design expertise. Even when scientists perfect the technology for an artificial pancreas, for example, they still must determine how best to assess its long-term effects in the body and how long it can last. And no one is quite sure who should make those assessments. The artificial pancreas will be both a device - a casing that lets glucose and insulin seep through but keeps out the body's immune system components - and either a biologic or a drug, depending on how one defines the cell culture inside that makes and secretes insulin. As a biologic, both the drug itself and the manufacturing process need FDA approval. As such, the product could fall under the jurisdiction of any of three FDA centers, which regulate drugs, biologics, and devices. "It all depends on how the manufacturers present their claims," explains FDA's Jerome A. Donlon. He expects that where there is overlap, one center will take the lead and use the others as consulting experts. But the mere thought of a dual review is a nightmare for most drug companies. "Manufacturers are quaking from the thought of a review by two centers," says F. Alan Andersen, deputy director of science and technology for the FDA devices center. They worry that the centers will pass the product in question from one to another, leaving the manufacturer in the dark. "Joint jurisdiction between drugs and devices have created problems and inaction pending resolution of that issue," he adds. "The pitch being made is to avoid the slowest approach possible. If that is implemented as a concurrent review, then it saves time." To deal with these new technologies, FDA officials will have to reach across their traditional disciplinary boundaries. "It's incumbent on those of us in the state, federal, and local government to become more knowledgeable and not be swamped by the jargon," says Andersen. So far, the devices program seems to have done its work without attracting much attention. "Nobody ever thinks of the center for biological devices as having a role in biotechnology," says Elizabeth Jacobson, director of science and technology at the center. "We don't grow great big tomatoes, but we do get some of the in vitro diagnostics through the system." What worries Christoffersen, however, is that FDA has no policy to deal with these complicated products. "The possible results of such a situation are a bit ominous to contemplate," he says. "It is my fear that education is essential if general acceptance of these approaches is to be accomplished." But it's not enough for FDA to have its act together. Other factors could slow the flow of these technologies into the hospital, doctor's office, and drugstore. To date, most of those 350 devices already approved were seen as improvements to existing technology. Ninety-five percent slipped through under this grandfather clause, called a 510K application. But this procedure has been criticized recently in congressional hearings as a loophole in the regulatory process. "Many people do not believe that the federal regulations are adequate enough," says Dyan Brasington, director of economic development for Montgomery County in suburban Maryland. Congressmen, too, are wary. "They share all the vague concerns that the rest of the public shares," says Lesley Russell, a staff member on the House Committee on Energy and Commerce, which oversees FDA and other health agencies. "We should realize that biotechnology products are different," adds Arlene McLean, vice president for regulatory affairs at Centocor Inc., in Malvern, Pa. "The science is still developing. We don't know what the unknowns are." Bills in Congress reflect those concerns, along with a desire to slow escalating health care costs. New laws require that new treatments be evaluated in terms of cost-effectiveness as well as safety and efficacy. Also, legislation has been proposed to narrow the definition of 510K products and require FDA to look more closely at them. "I think the FDA can do the job, but we do need more resources," says Kiki B. Hellman, senior scientist at the FDA Center for Devices and Radiological Health. "We need more scientists who can handle the research." The number of biotechnology products entering the pipeline will increase exponentially, she predicts. Companies can help, too, says McLean. There should be more dialogue between industry and FDA scientists before a product enters the review process, she says. Others would like those discussions to include FDA's outside advisers, so that their concerns can also be addressed earlier in the review. Finally, they note, postapproval monitoring programs could help identify any unexpected findings. "We have some work to do before these wonderful ideas hit the marketplace," says Jacobson.

New Medical Devices Challenge Scientists And Regulators Alike

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