UPDATED: FDA announces intention to comprehensively regulate lab-developed tests

The FDA announced July 31 that it intends to issue a draft guidance soon that would require moderate- and high-risk diagnostics to obtain 510(k) or premarket approval, regardless of their place of origin, putting an end to a battle to regulate laboratory-developed tests (LDTs) that's been waged for several years. The planned draft guidance on the regulatory oversight of LDTs had been held up by the White House Office of Management and Budget since 2010.

FDA Commissioner Margaret Hamburg

FDA Commissioner Margaret Hamburg cast the move as a win for patient safety and personalized medicine during her announcement of the planned regulatory reforms.

"Just as drugs need to be safe and effective for treating diseases, medical devices used to help diagnose diseases and direct therapy need to be safe and effective. These devices need to be accurate and reliable," she said. "We're aware of faulty or unproven LDTs that could cause patients to be over- or undertreated for things like heart disease, cancer patients to be exposed to inappropriate therapies or not get appropriate therapy, incorrect diagnosis of autism, unnecessary antibiotic treatment based on faulty diagnoses, and exposure to avoidable harmful treatments."

Currently, diagnostics carried out by clinical laboratories are regulated under the Clinical Laboratory Improvement Amendments (known as the CLIA rules), while those tests whose machinery and reagents are distributed as in vitro diagnostic kits are regulated by the FDA. While the CLIA rules regulate a lab's testing process, the tests themselves are not scientifically validated to regulators under CLIA, leading to uncertainty as to their safety and efficacy, Jeffrey Shuren, the director of FDA's device arm, the Center for Devices and Radiological Health, said during the conference call.

"Even in cases where we've seen the (lab's) data, the data didn't actually support that this is an accurate test. But then they'll turn around and say 'but I'm an LDT so I can still go ahead and market it," Shuren said.

Furthermore, the two-track system unfairly favors providers of LDTs over FDA-regulated manufacturers of testing equipment, Shuren said. Conventional diagnostic medical manufacturers "generally obtain premarket approval or clearance before packaging their tests into kits for use in multiple labs or healthcare facilities. They also register with the FDA, list their devices, report adverse events, and comply with Good Manufacturing Practices (regulations). They are concerned that their laboratory competitors are currently not doing any of this, which creates a disincentive to develop new tests. Why comply with regulations, if your competitor does not?" he asked.

The FDA hopes to reform the system by ending its policy of "enforcement discretion" for LDTs adopted in 1976, under which the agency opted not to regulate the tests even though it claims to have the authority to do so.

The plan calls for a phase-in of the 510(k) and PMA requirements over 9 years following the issuance of a final guidance, the FDA said in its required notification to Congress. For the "highest risk" LDTs, enforcement of the premarket review requirements will occur 12 months after the issuance of the final guidance. These include diagnostics with the same intended use as an already cleared or approved companion diagnostic; Class III, generally PMA-approved diagnostics; and "certain LDTs for determining the safety or efficacy of blood or blood products."

Enforcement of the requirements for the remaining LDTs deemed "high risk" will be phased in over the following four years. And "moderate risk" Class II devices requiring a 510(k) will be phased into the new regulatory system over the subsequent four years.

The FDA said it will continue to apply enforcement discretion of review requirements for LDTs deemed low risk or Class I. It will also opt not to enforce review requirements for LDTs for rare diseases or unmet needs, those used for law enforcement purposes, certain LDTs for transplantation and traditional LDTs that existed prior to the issuance of FDA's original enforcement discretion policy in 1976.

The FDA's intentions are far from being implemented, however. During the call, the agency said it will consider comments on its looming draft guidance and hold a hearing on the topic as well. The draft guidance is at least two months away, because Congress took the unusual step of mandating a notification of intent for this guidance at least 60 days prior to its publication. And the time gaps between draft and final guidance run into the months, or even years.

But having fought to get to this stage since 2010, and even before that, expect the FDA to act with urgency and push for implementation sooner rather than later.

- read the release
- here's the notification to Congress describing the upcoming guidance (PDF)
- get more commentary from the FDA

Editor's Note: This article has been updated with some quotes from the FDA's announcement over conference call.

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