The FDA issued its to regulate laboratory-developed tests (LDTs), the agency said Monday.
LDTs are in vitro diagnostic products (IVDs) designed, manufactured, and used within a single clinical laboratory. They can be used to measure or detect markers like proteins, glucose, cholesterol, or DNA to help provide information about a patient's health, including diagnosing, monitoring, or determining treatments.
Historically, the FDA has generally exercised enforcement discretion for most LDTs, meaning it has not enforced applicable requirements. LDTs were certified under the (CLIA) and regulated by the Centers for Medicare & Medicaid Services, which did not require the tests to show clinical validity.
The final rule amends existing regulations and makes explicit that IVDs are medical devices under the Federal Food, Drug, and Cosmetic Act, including when the manufacturer of the IVD is a laboratory. It phases out the agency's enforcement discretion so IVDs manufactured by a lab largely would be treated the same as other IVDs.
"LDTs are being used more widely than ever before -- for use in newborn screening, to help predict a person's risk of cancer, or aid in diagnosing heart disease and Alzheimer's," FDA Commissioner Robert Califf, MD, said in a . "The agency cannot stand by while Americans continue to rely on results of these tests without assurance that they work."
A growing body of evidence indicates that some LDTs raise public health concerns because they don't provide accurate test results or don't perform as well as FDA-authorized tests, said Jeff Shuren, MD, JD, director of the FDA's Center for Devices and Radiological Health, in a press conference. That evidence comes from published research, the FDA's experience reviewing LDTs, news articles, and class-action lawsuits, he noted.
Comments posted on the helped shape the FDA's thinking, leading to a 4-year phase-out period of the FDA's general discretion approach, Shuren pointed out. "After this phase-out, the FDA generally will expect IVDs manufactured by either a non-laboratory or laboratory to meet the same requirements, though certain IVDs manufactured by a laboratory may fall within one of the agency's target enforcement discretion policies," he said.
Those discretion policies extend to LDTs that were marketed before the final rule was issued, certain tests that may help meet an unmet need, and LDTs approved by the New York State's Clinical Laboratory Evaluation Program (CLEP).
The FDA's final rule was met with mixed reviews. "We strongly support FDA's decision to regulate lab-developed tests because it is unconscionable that thousands of tests are being used by patients and consumers that have never been evaluated by independent experts to make sure they are accurate," said Diana Zuckerman, PhD, president of the National Center for Health Research in Washington, D.C.
"Unfortunately, this final rule has compromised on a crucial issue: it 'grandfathers' the thousands of tests -- some dangerously inaccurate -- that are already on the market, rather than requiring them to be proven to accurately diagnose serious medical conditions or genetic vulnerabilities," Zuckerman told 乌鸦传媒. "The previously proposed version of this LDT rule did not have that giant, deadly loophole -- a loophole that was also in the that Congress had considered on lab-developed tests."
Last month, several speakers at a House subcommittee hearing voiced concerns that, if the FDA proposed rule passed, labs would incur significant costs to meet compliance.
"While the final rule is a slight improvement to the proposed rule, it will still increase costs and decrease access to diagnostics and medical tests that provide information crucial for doctors to treat their patients effectively," Rep. Cathy McMorris Rodgers (R-Wash.), chair of the House Committee on Energy and Commerce, said in a . "At a recent hearing, we heard testimony about the harmful impact the rule will have on diagnosing and caring for patients. The FDA should abandon the rule, as it lacks the clear statutory authority to implement it."
Others saw the final rule today as a step forward. "The FDA is putting patients first by beginning to make many lab test developers prove their tests are accurate and clinically reliable before they are offered for use on patients," said Patricia Kelmar, JD, of the public advocacy group U.S. PIRG.
The agency also issued two draft guidances -- one about enforcement discretion for IVDs for an immediate response to an , such as an outbreak of an infectious disease, the other to provide insight into the FDA's thinking about the factors the agency intends to consider when developing a policy regarding enforcement discretion during a .