With New FDA Input, Momentum for LDT Regulation Accelerating

In what has been called a “critical milestone” towards enacting a comprehensive new oversight framework for diagnostic tests, the U.S. Food and Drug Administration (FDA) released its comments on the draft bipartisan bill crafted last year by Representatives Larry Bucshon (R-IN) and Diana DeGette (D-CO) on the House Energy and Commerce Committee.

While the Diagnostic Accuracy and Innovation Act (DAIA) was introduced back in March 2017, momentum seems to be building towards enactment of a new diagnostic oversight framework, possibly by the end of the year.

The draft bill, which was created with industry representation on the Diagnostic Test Working Group, established a new category of in vitro clinical tests (IVCTs) that includes both finished products (such as test kits), and lab test protocols (known as laboratory developed tests [LDTs]). In what can be seen as a compromise, the draft legislation included the creation of a new FDA center that would regulate test development and manufacturing, while lab operations would be overseen by the Centers for Medicare and Medicaid Services (CMS), which currently oversees CLIA-certified laboratories.

In early August, the FDA submitted 59 pages of comments on the DAIA. Reaction to the FDA’s Technical Assistance (TA) document was strong and swift. The clinical laboratory industry renounced the agency’s extensive comments as a dramatic departure from DAIA, with some calling it a rewrite of the bill, rather than a redlining. Representatives of the in vitro diagnostics industry, on the other hand, were pleased with the FDA’s direction.

“We note that rather than providing technical amendments to [the bill], FDA has drafted a distinctly different framework,” wrote the American Clinical Laboratory Association (ACLA) in comments to Congress. “ACLA recognizes that the FDA TA offers valuable insight into the priorities of FDA and certain concepts that could be incorporated into the Discussion Draft. However … ACLA believes that the framework set forth in the DAIA Discussion Draft should remain the starting point.”

Despite lingering deep divisions within the diagnostics industry, some congressional staff members say that lawmakers are pushing for action on the bill by the end of the year, with the House Energy and Commerce Committee expected to meet this fall to consider comments in response DAIA.

The FDA Weighs In
“The FDA supports the goal of legislation to create a predictable path to market for all in vitro tests (IVCTs) that is a risk-based approach consistent with the least burdensome principle for regulation and assuring necessary safeguards for consumers,” the agency wrote.

One area where the FDA has been praised was for its precertification program.

For a number of tests, the agency has signaled that precertification could be a least burdensome regulatory pathway. The process the agency outlines parallels its approach to authorization for 23andMe’s direct-to-consumer health risk tests. The agency wrote that for a group of tests using single technology or test method, or that have other shared elements (e.g., analytes, samples, purpose, intended population), the test developer would have to submit premarket review information for one test representative of the group of tests. Following precertification, the test developer could launch new tests that fall in that group without additional premarket review.

Despite praise for the precertification program, there were notable differences between the TA document and DAIA, which drew scrutiny from the clinical laboratory industry. A big difference includes narrowing of risk categories (DAIA allowed for a test to be characterized as low-, moderate-, or high-risk, and outlines the varying regulatory requirements based on the test’s risk level. However, the FDA dropped the moderate-risk category.) The FDA also eliminated calls for a strict review timeline in the draft bill and eliminated a new center for IVCTs, which it deemed unnecessary.

Industry Reaction
The FDA previously made clear that it believes increased regulation is needed as LDTs have become more complex, more broadly marketed, and increasingly risky to the patient and the public. Yet the clinical laboratory industry fundamentally questions the agency’s authority to regulate laboratory activities, which are currently overseen by CMS.

“ACLA has repeatedly asserted, and continues to assert now, that LDTs are not devices, and therefore FDA has no authority with respect to LDTs under current law that would be ‘retained’ under any new framework,” ACLA president Julie Khani wrote to Congress. She additionally stated that in addition to being “potentially duplicative and sometimes conflicting” with current CMS requirements, the FDA’s device regulations would be “unnecessarily costly and burdensome” for labs.

ACLA raised many objections in its 26-page comments. Specifically, the organization called “unacceptable” the FDA’s proposal that it can implement oversight provisions through guidance rather than regulation. ACLA said it bypasses “well-established notice-and-comment procedures, and fails to account for an economic impact analysis.”

Furthermore, the association “strongly opposes” the FDA’s revised definitions of analytical validity and clinical validity, speculating that the FDA intends to regulate IVCTs based on clinical utility. ACLA also objects to the FDA’s transition provisions and grandfathering provisions that could enable the FDA to “claw back” grandfathered tests “at its discretion without basis in meaningful standards.”

In comments to Congress, Pew Charitable Trust AdvaMedDx, which represents in vitro diagnostic tests, expressed support for FDA oversight of “all diagnostics” using a risk-based approach.

Takeaway: With lawmakers and some industry groups pushing for resolution by the end of the year, comprehensive diagnostic reform may soon become a reality. However, stakeholders and lawmakers must reconcile the notable differences between the FDA’s comments and the existing draft legislation.