FDA's LDT Webinar; Avalere FDA White Paper; Geopolitical Molecular Strategies

On May 14, 2024, the FDA held a webinar to educate the public on its intentions for rapidly regulating lab-developed tests.   FDA has posted materials:

• The FDA webinar home page is here.
• The video archive is here.
• The 19-page deck is here.
• The 15-page transcript is here.

One highlight you might not have been aware of yet.  FDA cuts some slack for LDTs that have no IVD equivalent.  But, when a test is endorsed by 510(k), by de novo, by PMA, OR BY New York State approval of a similar test, that will tend to close out enforcement discretion [transcript p 13].   This is one of the remarks highlighted for us by Avalere's excellent white paper on the FDA rule, which Avalere released May 20 and it includes learnings from the FDA webinar.

• Find the Avalere document here.
• Avalere has some first-class graphics.
• Avalere writes, "If a lab runs a test that is similar to a test approved by the NYS CLEP enforcement but does not meet the standards of the test approved under NYS CLEP, the similar test will be subject to the phaseout policy." [see also transcript p 13]

FDA states it plans to enhance its staffing via the FDA 2027 user fee act [see transcript p 12/13], but since applications for tests must be filed by 2027 or early 2028, the time from Congressional action to hiring and training seems a severe mismatch.  FDA also remarks it may enhance its third-party review program, but that too requires large amounts of dollars and manpower with highly specialized training, in the thousands.

Devil in Details

In many cases, the devil is in the details and not on the slides or explicit in the transcript.  For example, when a CLIA lab modifies an IVD, will that modification trigger a new local FDA approval?   Not if it does not "significantly affect the safety or effectiveness of the test."  I don't think anyone designs modifications in order to harm the safety of a test.   

Another question (page 7) on the competitiveness or innovativeness of smaller labs was stonewalled with an oblique response from FDA.

Shifting GeoStrategic Advantages x 2

The FDA rule, if carried out as proposed, would give an advantage to NY State labs, which have until now borne the weight of heavier NYS regulatory costs.   

Similar, from a "grand geostrategy" perspective, MolDx's recent announcement of a broader new policy for pathologist genomic test orders gives an advantage to genomic labs in MolDx states.  If you are a lab in a MolDx state, their new and creative article A59741 will be used as the standard if you are audited, for pathologists and their patients in all 50 states.   But, molecular labs being audited for their order forms in non-MolDx states (say, Pennsylvania) might find their order forms scrutinized under locally harsher review rules, regardless of where their patients live.

AI Corner

I asked Chat GPT 4 to write an op ed from the perspective of an industry columnist who is writing in a lab trade journal.

FDA's Ambitious LDT Regulation Plan: A Leap Before Looking?

In a webinar held on May 14, 2024, the U.S. Food and Drug Administration (FDA) laid out its grand plan to bring Laboratory Developed Tests (LDTs) rapidly under the FDA's control. The initiative, a phased enforcement of regulations long offered exemptions, promises to standardize what has been a rapidly evolving healthcare sector. But as the details of the webinar unfolded, we saw the agency's roadmap appear less like a path to safety and innovation, and more a march into bureaucratic uncertainty.

The webinar, ostensibly to brief us on the FDA's final rule for LDTs, sketched a troubling narrative: an agency possibly overreaching beyond its current capabilities, with a plan that could stifle innovation. For an industry that thrives on agile responses to emerging health challenges, the specter of heavy-handed regulation looms large.

During the session, the FDA meticulously outlined the phaseout of enforcement discretion—a policy that had allowed LDTs to be developed and used without the same regulatory hurdles faced by other in vitro diagnostics (IVDs). The shift aims to treat LDTs, many of which now employ complex technologies and cater to national markets, as traditional IVDs, ensuring they meet comprehensive safety and efficacy standards.

Later, as the floor opened to questions, the FDA's responses—or lack thereof—on several critical issues were telling. Inquiries about the agency’s capacity to implement these sweeping changes were met with vague assurances rather than concrete plans. Questions regarding the impact on small laboratories and innovation received broad, generalized answers that seemed to sidestep the specific challenges these entities face.

Particularly telling was the agency’s response to concerns about resources. With a major upscaling of regulatory activities planned, the FDA anticipates enhancing its staffing through the FDA 2027 user fee act. Yet, the timeline and logistics of such an expansion beg scrutiny; ramping up a workforce skilled enough to handle the complexities of modern LDTs is no minor feat. The concern here is not just the scale of hiring but the training and integration of new staff to manage a highly specialized and burgeoning field.

The FDA also hinted at expanding its third-party review program to manage the workload, but again, details were sparse, raising questions about the feasibility of outsourcing such critical assessments. The underlying message was clear: while the agency’s intentions might be in the right place, its preparedness is not.

From the perspective of many industry stakeholders participating in the webinar, the FDA’s plan feels like a grand vision limited by a lack of quantitative planning. The approach risks not only overwhelming the FDA's current capabilities but also burdening a well-functioning part of healthcare, especially with the rapid advances in oncology. The shift could cut back the pace of medical advancements and complicate the regulatory landscape to a degree that will quickly discourage smaller startups and spinouts from pursuing breakthroughs.

As we parse through the FDA’s ambitious regulatory overhaul for LDTs, the balance between ensuring safety and nurturing innovation is vital to preserve. We don't need a precarious gamble, predicated more on hopeful outcomes than on assured readiness. The medical community, and indeed the patients we serves, deserve a plan as robust at its foundation as in its aspirations.