Earlier this month, five democratic U.S. Senators sent a letter to the Office of Management and Budget (OMB) regarding the regulation of laboratory-developed tests (LDT). In this letter, Senators Edward J. Markey (D-MA), Richard Blumenthal (D-CT), Elizabeth Warren (D-MA), Sherrod Brown (D-OH), and Dick Durbin (D-IL) called on the Obama administration to release a draft guidance that FDA submitted several years ago to ensure appropriate oversight of LDTs.

“FDA has developed what the agency has referred to as a ‘risk-based’ draft guidance on how the agency will exercise its authority over LDTs, while recognizing the unique circumstances of the laboratory community,” said the letter. “For years, this draft guidance has languished at OMB, causing continued unpredictability and uncertainty for industry, clinicians, patients, and the general public. I therefore urge you to take prompt action in releasing this draft guidance on the regulation of LDTs, to ensure appropriate and efficient oversight of diagnostic tools can move forward in an open and transparent manner.”

Industry analysts generally supported the Senators’ letter, while maintaining a wait-and-see stance until OMB releases FDA’s draft guidance on LDTs.

“The LDT topic is long overdue for discussion, but unfortunately no real meaningful discussion will take place until OMB releases the FDA draft. Nothing is gained by OMB sitting on it,” said Bradley M. Thompson, JD, an attorney at Epstein Becker Green (Washington, DC). “It’s time for OMB to let its hostage go, and for the rest of us to roll up our sleeves and figure out a sensible, uniform, risk-based approach to ensuring the safety and effectiveness of all laboratory diagnostics.”

Thompson added that while he is looking forward to see the LDT topic discussed, he gave the following summary of his main concerns:

The two systems for IVDs and LDTs cannot both be right. One risk-based system for everyone is needed, whether that is a CLIA system, FDA system, or something in between.

The American Clinical Laboratory Association (ACLA) has made a number of comments in the press about the medical value of LDTs, their safety, and the benefit of a flexible CLIA system that can allow innovators to respond quickly to medical need. Thompson agrees with a lot of what ACLA is saying, but none of it answers the question: how can both systems be right? He believes a single, optimal system is needed that all diagnostics innovators, whether in labs or IVD companies, can work within to get innovative diagnostics to patients more quickly.

Equal regulation does not necessarily mean identical regulation. Just as IVD manufacturers are subject to different controls depending on the products they make, labs may be subject to different requirements that accommodate their specific manufacturing activities. For example, the detailed labeling requirements of 21 CFR §809.10 may not be needed for tests that are manufactured for use solely in-house, where a site-specific vernacular could provide clearer instructions to employees than traditional IVD labeling. However, the basic regulatory framework in which labs and IVD manufacturers would operate must be the same.

A couple of weeks later, in a one-two counterpunch, more than twenty laboratory directors at prominent academic medical centers also sent a letter to OMB urging it not to release FDA’s guidance for LDTs. Spearheaded by Edward R. Ashwood, MD, president and CEO of ARUP Laboratories (Salt Lake City, UT), the letter stated that FDA regulation would add another cumbersome layer to the already heavily regulated approval process for LDTs.

“FDA regulation of laboratory-developed tests would stifle the medical innovation occurring in academic medical centers today, and interfere with our ability to care for patients,” said the letter. “For all of these reasons, in the best interest of the relevant agencies, Congress, stakeholders, and the American people, we collectively urge the Administration not to proceed with issuance of any guidance or regulation under which LDTs would be regulated by the FDA as medical devices.”

Analysts like Thompson agreed with quite a bit of the lab directors’ letter, with the notable exception about LDTs not being medical devices. They also agreed that many LDTs have played a very important role in patient care.

“But that’s not the issue. The issue is whether it makes sense to anyone to have two completely different regulatory approaches that depend simply on the entity that makes the test,” said Thompson. “More to the point, IVD manufacturers sell their products to CLIA-regulated laboratories. So why on earth is there a separate and different set of FDA regulations that apply to IVD manufacturers? If CLIA is by itself a sufficient regulatory scheme, why don’t we rely simply on CLIA for all tests regardless of where they originated? In this discussion, we simply have to get beyond talking about whether LDTs are helpful or not. They are helpful. Indeed, in many cases they are so helpful that we ought to basically rely on CLIA for the necessary safeguards. It simply makes no sense to have the dual standards.”

These dueling letters have made it abundantly clear that the various interested parties have very wide differences of opinions on the regulation of LDTs. At the same time, these parties agree that LDTs are valuable and have a lot to offer as clinical diagnostic tools. But since LDTs are used on human beings, a potential misdiagnosis by a faulty LDT that could lead to harmful treatment decisions is not worth the risk. Therefore, some form of government oversight and regulation of LDTs is necessary. The question is what is the appropriate level of LDT regulation.

An earnest debate on that question could begin if OMB releases FDA’s draft guidance on LDTs. The Senators’ letter noted that, “Once this draft guidance is released, it will be open for public comment before being finalized by the FDA.” The public comment period could be an opportune time for the various interested parties to voice their opinions and air their differences. FDA would hopefully take these comments and reach an equitable solution to the LDT issue.

For more information about the regulation of LDTs, please access the series of blogs on this topic that I’ve posted these past few weeks.