The FDA has finalized its regulatory rule that aims to bring laboratory-developed tests more in-line with how the agency oversees other diagnostics.
At its heart, the 528-page final rule (PDF) looks to make clear that in vitro diagnostic tests are to be considered medical devices like any other under the Federal Food, Drug & Cosmetic Act, the decades-old law that grants the agency its authorities.
In the past, the FDA made allowances for tests that were developed for limited use within a laboratory, and did not require them to clear the agency’s review process. Commonly referred to as LDTs, they were originally categorized as a product with lower risks compared to mass-marketed diagnostic kits, because they were typically produced in small volumes using common lab equipment.
However, when the FDA proposed this regulatory change last fall, the agency said the risks have since become higher: Too many developers are now approaching LDTs as an alternative pathway to the market—one that would let them pursue an initial commercial launch with new technologies before subjecting them to federal review—and these tests are now reaching a broader and more diverse population of people.
“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 said in an agency statement Monday. “The agency cannot stand by while Americans continue to rely on results of these tests without assurance that they work.”
“The final rule announced today aims to provide crucial oversight of these tests to help ensure that important health care decisions are made based on test results that patients and health care providers can trust,” Califf added.
Further, the FDA said it is “aware of numerous examples of potentially inaccurate, unsafe, ineffective or poor quality IVDs offered as LDTs that caused or may have caused patient harm, including tests used to select cancer treatment, aid in the diagnosis of COVID-19, aid in the management of patients with rare diseases and identify a patient’s risk of cancer.”
The final rule outlines a plan for the FDA to phase out its previous regulatory approach over the next four years — after which the agency said it will generally expect diagnostics to meet the same requirements, no matter where they are made.
However, the agency said it will adopt select enforcement discretion policies for specific categories of LDTs. That includes forensic tests designed solely for law enforcement use as well as LDTs developed within the Department of Defense and the Veterans Health Administration.
In addition, the FDA said it would generally not require premarket reviews of LDTs that are approved by the New York State Clinical Laboratory Evaluation Program—as well as LDTs that are manufactured and performed by a laboratory integrated within a health system, “to meet an unmet need of patients receiving care within the same healthcare system,” measures that were in part requested by the American Hospital Association last year.
The agency also plans to grandfather in LDTs that were on the market before its rule was finalized, including newer versions with minor changes.
“Today’s action is a critical step toward helping to ensure the safety and effectiveness of LDTs, while also taking into account other public health considerations, including continued access to critical tests patients rely upon,” said Jeff Shuren, director of the FDA’s Center for Devices and Radiological Health.
“Through targeted enforcement discretion policies for certain categories of tests manufactured by a laboratory, we expect patients and health care professionals will continue to have access to the tests they need while having greater confidence that the tests they rely on are accurate,” Shuren added.
The FDA also published two new draft guidance documents alongside the rule, to help outline the agency’s thinking on how it will approach tests responding to the outbreak of an infectious disease, for example, as well as during other public health emergencies.
Previously, the medical device industry association AdvaMed—and its AdvaMedDx division covering in vitro diagnostic test makers—generally supported (PDF) the FDA’s authority to regulate LDTs, while also reiterating its calls for Congress to instead pass the VALID Act to update diagnostic regulatory oversight with a risk-based framework. AdvaMed also called on the FDA’s phase-out period to work to minimize disruptions to clinical studies and the marketing of about 3 billion specimen collection systems in the U.S.
“We appreciate FDA’s commitment to ensuring the safety and effectiveness of in vitro diagnostic tests, regardless of their source, which is what today’s rule would accomplish,” said AdvaMed President and CEO Scott Whitaker. “We hope this rule is just the first step toward comprehensive reform of the framework for diagnostic test regulation overall, which the VALID Act would accomplish through Congress. This reform is critical to supporting the continued innovation of safe, effective, and high-quality diagnostic tests.”
The American Clinical Laboratory Association, meanwhile, has maintained that “LDTs are not medical devices and regulating them as such would be harmful to patients and would severely hamper innovation in the next generation of diagnostics.”
“ACLA has grave concerns about this rule as a matter of both policy and law,” said ACLA President Susan Van Meter. “The rule will limit access to scores of critical tests, increase health care costs and undermine innovation in new diagnostics. The rule also exceeds FDA’s statutory authority, as Congress has never granted the agency authority to regulate laboratory-developed testing services offered by laboratory professionals. We are disappointed that FDA has continued down this path.”