|Trends & Perspectives|
In 1993, the Naval Medical Research Institute approached Helene Paxton, founder and president of In-tegrated Diagnostics, Inc. (Bethesda, MD), and asked whether her company could develop a reliable dipstick test for dengue fever. Although virtually unknown in the United States, the mosquito-borne tropical virus was on the rise in Central and South America. During missions in Haiti and Somalia, U.S. soldiers had come down with the disease in large numbers.
After a 1995 outbreak in northern Mexico, the first U.S. case in a decade was detect-ed, in Texas. Still, there was no commercial dengue fever test on the market, and only a select group of clinical labs could reliably detect the disease.
Although no money changed hands, the Navy loaned Integrated considerable expertise and resources, including access to serum banks, antigens, reagents, and advice on growing the viruses. By September 1995, the company had developed a test with sensitivity and specificity ratings in the 80—90% range. "The clinical test results were wonderful," says Paxton.
But since then, further development of Integrated's dengue fever test has stalled—and Paxton says the test may never be available domestically or for U.S. military use. The reason: an FDA decision that has sent shock waves through the IVD industry and set off a volley of protests to top FDA officials, members of Congress, and even Vice President Al Gore.
FDA decided that approval of Integrated's test would require a premarket approval (PMA) application rather than a 510(k) notice. That decision was confirmed last June, when the agency denied Paxton's appeal for a reversal.
Considering the longer time and greater costs involved in filing a PMA, developing the dengue test no longer makes fiscal sense, Paxton says.
"We're a small company. Our annual sales are only $1.7 million," she says. "To complete a PMA takes more than 24 months and costs between $250,000 and $1.5 million. But since dengue fever is not prevalent in the United States, there is no way for us to get a return on such a large investment."
Other diagnostic makers, including members of the Joint Council of Immunohistochemical Manufacturers (JCIM; Crestwood, MO), have taken up Paxton's cause. Arguing that ample predicate devices exist that justify use of the 510(k) process, the group believes FDA's ruling was arbitrary and capricious. "You've got one government agency asking for the test and another saying you can't market it," says Stephen A. Tillson, chairman of the JCIM executive board.
Worse still, there are inklings the decision could have a much broader impact on the IVD industry. At a July meeting sponsored by the Health Industry Manufacturers Association, FDA officials reportedly declared that the agency intended to issue a blanket order requiring PMAs for all new tests for emerging and reemerging infectious diseases. Such a requirement could have a devastating impact on a rich field for new IVD tools, Tillson says.
"Having worked so hard to eliminate the 'drug lag,' it is unconscionable for FDA now to create a 'diagnostic device lag,' a system that will deprive the United States of new diagnostic assays available throughout the rest of the world," Tillson said in a letter to acting FDA commissioner Michael A. Friedman.
JCIM has formally asked FDA to reverse its decision on Integrated's dengue fever test and to reconsider its new policy on emerging-disease diagnostics. The group has also asked Vice President Gore to intervene on industry's behalf. But so far, says Tillson, the council has gotten no response.
One top FDA official says the agency is sympathetic to manufacturers' worries and is trying to arrive at a fair and reasonable decision. "From FDA's perspective, the interesting thing about this test is that it is a very important device and its uses are new," says Steven Gutman, director of the Division of Clinical Laboratory Devices at FDA's Office of Device Evaluation. "The agency is doing a lot to try to make itself user-friendly, but the fact is we're cost-blind."
Paxton believes the agency is gun-shy because of a recent series of Lyme disease diagnostics that turned out to be less effective than billed. Gutman says FDA is trying to speed the dengue fever test approvals.
To keep the product moving toward approval, Integrated Diagnostics has decided to take it through FDA's recently established product development protocol (PDP) process. But Paxton sees little hope of the test coming through in the black. "We've already lost two years, and we're paying $4000 a month," she says.
Meanwhile, the company's product has now begun to be used—but in South America. According to Paxton, the test has just passed screening by the Brazilian National Institutes of Health.
And what of the U.S. military, which originally sought to have the test? They're using it only in "very controlled studies," says Paxton. "I'm afraid emerging-disease tests have fallen into a quagmire."