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The FDA said Thursday it intends to regulate laboratory-developed tests (LDTs) that it deems as “high-risk” along the lines of Class III medical devices, positioning itself against academic medical centers and other developers of the tests, which have opposed efforts at imposing new rules.

The agency formally told Congress it will issue within “at least” 60 days a formal draft guidance laying out a detailed, risk-based framework for approving such LDTs [See “FDA’s LDT ‘Anticipated Details'” below]. FDA sought to soften the blow for LDT developers by urging them to offer feedback on the draft guidance, and saying it would phase in regulations over several years.

While FDA has long reviewed diagnostic tests, the agency has historically exercised only enforcement discretion over LDTs designed and used within a single laboratory, and had not sought to regulate their entry to market as is now required for Class III medical devices.

LDT developers hold to the agency’s traditional view that the tests are “laboratory testing services” and not medical devices subject to the Food, Drug, and Cosmetic Act (FDCA). At present, labs certified under the Clinical Laboratory Improvement Amendments (CLIA) waiver program may develop and use their own diagnostic tests internally, without FDA oversight.

Answering a GEN question during a briefing for reporters, Jeffrey Shuren, M.D., J.D., director of the FDA’s Center for Devices and Radiological Health (CDRH), said the planned LDT guidance is an effort to reconcile the interests of nonprofit academic medical labs with those of for-profit diagnostic developers.

“Our intent here is to put in place the right balance,” Dr. Shuren said, noting that academic labs can continue using an LDT without obtaining a premarketing approval (PMA) unless another entity has won FDA approval for that test.

“That’s our attempt to try to balance continuing those incentives—for example, the academic labs saying they want to be able to meet the needs of their patients when something [an approved test] is not there—but at the same time, also have the incentives for the conventional medical device diagnostic industry to also develop tests and facilitate innovation in both spaces,” Dr. Shuren said. “That also includes the development of companion diagnostics, which are absolutely critical if we’re going to advance personalized medicine in the U.S.”

FDA also issued a final guidance addressing development, review and approval or clearance of companion diagnostics (CDx). The final guidance—issued three years after FDA’s draft CDx guidance—encourages companies to identify the need for CDx during the earliest stages of drug development, and plan for simultaneous development of a drug and its companion test.

Dr. Shuren said FDA and the Centers for Medicare and Medicaid Services, which oversees CLIA, have long viewed LDTs as medical devices since the tests have entailed chemical reads, instruments and systems used to diagnose, cure, mitigate, treat, or prevent disease. “Labs have actually sent us submissions on their tests. We don’t regulate services, and even those labs acknowledge it, because they send us traditional kinds of tests for our review, asking us for our approval.”

During the briefing, FDA Commissioner Margaret A. Hamburg, M.D., cited “faulty or unproven” LDTs leading to over- or undertreatment for disorders that included heart disease, cancer, and autism. In April, the CDC expressed “serious concerns” about the potential for misdiagnosis due to false positive results from a Lyme disease LDT that used a culture method to identify Borrelia burgdorferi. CDC recommended that the diagnosis of Lyme should be left to FDA-approved tests.

“Just as drugs need to be safe and effective for treating diseases, medical devices used to help diagnose disease and direct therapy also need to be safe and effective,” Dr. Hamburg said. “Without premarket review by the agency, neither patients, nor their healthcare providers, or the FDA itself can be assured that these tests are accurate and reliable.”

FDA acted two weeks after lab directors from 23 academic medical centers urged the U.S. Office of Management and Budget not to release an earlier draft guidance submitted to OMB. “FDA regulation of laboratory developed tests would stifle the medical innovation occurring in academic medical centers today, and interfere with our ability to care for patients,” the lab directors wrote to Brian Deese, OMB’s acting director, on July 16.

Edward R. Ashwood, M.D., president and CEO of ARUP Laboratories and professor of pathology at the University of Utah School of Medicine, led the group in arguing that new regulations would add to the cost and time spent developing new tests while stifling innovative new tests that could deliver on the long-ballyhooed promise of personalized medicine.

However, NIH Director Francis S. Collins, M.D., Ph.D., said FDA’s planned LDT guidance would advance individualized treatment: “This is good news for all who are working to turn the dream of personalized medicine into a reality.”

The lab directors sent their letter two weeks after Sen. Edward J. Markey (D-CA) and four other Democratic senators urged OMB to release the earlier draft guidance. Joining Sen. Markey were Sens. Richard Blumenthal (D-CT), Sherrod Brown (D-OH), Dick Durbin (D-IL), and Elizabeth Warren (D-MA).

FDA’s LDT “Anticipated Details”
In a letter to the Senate Committee on Health, Education, Labor and Pensions and the House Committee on Energy and Commerce, FDA said it plans to begin premarketing approval (PMA) review requirements within 12 months after a final guidance for the highest risk devices and phase it in over four years for the remaining high-risk devices. The devices would stay on the market during FDA review.

The agency said its focus on “high-risk” devices will begin with LDTs with the same intended use as a cleared or approved companion diagnostic, followed by LDTs with the same intended use as an FDA-approved Class III medical device; and some LDTs designed to determine the safety or efficacy of blood or blood products.

FDA said it “intends to” publish priority lists for its review of high-risk LDTs within 24 months of a final guidance, and “moderate-risk” LDTs within four years.

Labs would have to begin registration, listing and adverse-event reporting for “moderate risk” LDTs, which would be deemed Class II medical devices, six months after a final guidance is set. PMA for these LDTs would begin five years after final guidance, and be phased in over four years.

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