Laboratory directors have long opposed FDA regulation of their operations. Credit: © grzegorz knec/Alamy

The US Food and Drug Administration (FDA) has told Congress that it intends to enforce its oversight over laboratory-developed tests (LDTs). On July 31, the agency announced that it will publish draft guidelines on how it will regulate LDTs. The FDA has sidestepped bringing laboratory tests under its control for years, but the rapid expansion of genotyping technology and widespread genomic testing, among other things, have increasingly brought the existing regulatory framework into question. FDA now plans to subject laboratory services firms to similar rules as those currently governing in vitro diagnostics sold as kits.

Reaction to the FDA proposal was predictably divided. AdvaMed, a medical technology trade group, “welcomes the publication of the draft framework on a risk-based approach to the regulation of LDTs,” says executive director Andrew Fish. On the other hand, the American Clinical Laboratory Association (ACLA) expressed concern that “another layer of regulation could stifle diagnostic innovation and ultimately jeopardize patient access to timely and effective treatments,” and urged the agency to exercise caution.

Debate over regulation of LDTs—tests developed by and performed in laboratories, as opposed to tests manufactured and distributed as kits—has raged since the early 1990s, when FDA first claimed the authority to regulate them. At the time, the agency said it would exercise “enforcement discretion” and declined to act. Since then, laboratory tests have mainly fallen under the Clinical Laboratory Improvement Amendments (CLIA) pathway. But CLIA rules, implemented in 1988, focus on a laboratory's processes for performing tests; not on the nature of the tests themselves. They do not assure an LDT's safety and effectiveness, require adverse event reporting or provide a means for removing a test from the market if it is deemed unsafe.

Laboratory-developed tests have become increasingly complex, propelled by sequencing and bioinformatics. Tests now include cancer therapy selection, for instance. This is a higher-risk use similar to that of in vitro diagnostics, Jeff Shuren, director of the FDA's Center for Devices and Radiological Health, noted in a press briefing on the guidance. The new rules aim to level the playing field for in vitro diagnostics manufacturers, whose diagnostic products are expected to undergo a premarket review process to determine safety and effectiveness. “Numerous stakeholders have claimed that the current system of uneven oversight has a negative effect on innovation,” Shuren said.

Among the first class of LDTs to be reviewed will be those with the same intended use as FDA-approved companion diagnostics. Laboratories running such tests will have to submit a premarket application 12 months after the final guidance date (which would be sometime after October 1, 2014, following a public comment period). FDA will set up advisory panels to assist it in classifying other LDTs into risk-based categories, with other high-risk devices phased in over the next four years, followed by another four-year phase-in for moderate-risk devices. Low-risk LDTs, those for purely forensic use, and certain tests for transplantation are exempt from the new rules. FDA will also require only notification rather than review for some tests, including LDTs for rare diseases, otherwise unmet needs, and those used in hospitals or clinics for diagnosing or treating their own patients.

Regulating LDTs that compete with FDA-approved companion diagnostics (a category that now includes cancer tests around KRAS, EGFR, BRAF, ALK and Her2) is a significant undertaking by itself, says Danielle Pambianco Showalter of the health care consultancy ADVI in Washington, DC. “Think of how many labs across the country are running KRAS tests,” she says. “Then extrapolate to other companion diagnostics.” With the in vitro diagnostics road becoming a more popular route for developing companion diagnostics, “by the time this plays out there will be a fair number more on the market,” she says.

FDA has “made a big splash” and put “a lot of momentum” behind the guidance, says Bruce Quinn of the law firm Foley Hoag in Boston. But with a definite proposal now on the table, Congress could weigh in on FDA's authority or attempt to curtail implementation through its control of the FDA budget. “It's definitely not a done deal,” Quinn says. “It could be that only a few segments of this survive, or that [implementation] is delayed for several years while FDA regroups and tries another approach,” he says.