Webinar Panelists Strongly Debate FDA's LDTs Oversight

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By John T. Aquino

Sept. 29 — The FDA's plan to expand oversight of laboratory-developed tests (LDTs) will drive many labs out of business, an oncologist insisted during a combative webinar on Sept. 29, but an FDA official countered that the agency's plan is measured and needed.

The Food and Drug Administration's LDT framework has been controversial from the moment the agency issued it. Formal comments to the proposed plan have ranged from those submitted by diagnostic device industry group AdvaMedDx, part of the Advanced Medical Technology Association, which supports the FDA's plan, to the American Medical Association, which urged the FDA to withdraw the proposal.

Roger Klein, medical director for molecular oncology for the Cleveland Clinic, said during the webinar, “FDA is proposing applying pre-existing medical device regulations on LDTs, making laboratory scientists into medical device manufacturers and supplanting the current system where the CMS [Centers for Medicare & Medicaid Services] regulates the tests and the FDA regulates diagnostic tests only if they are developed and sold by device manufacturers as diagnostic kits. Most labs can't afford the hundreds of thousands of dollars FDA submissions cost.”

Alberto Gutierrez, director of the FDA's Center for Devices and Radiological Health's Office of In Vitro Diagnostics, said, “I thought we were going to have a reasonable discussion of the issues and not get into policy agendas.”

Andrew Fish, founding executive director of AdvaMedDx, was also on the panel and supported the FDA's proposed framework.

The FDA says LDTs are often made by big companies with components and instruments that aren't legally marketed for clinical use. Others say labs can't handle the costs of FDA submissions for approval.

Moderator Lakshman Ramamurthy, vice president at Avalere Health who used to work for Gutierrez at the FDA, said the webinar's tone clearly demonstrated how strongly stakeholders feel about their positions, especially because the tests affect the health of patients.

The panel was sponsored by Avalere.

FDA's Oversight Risk-Based, Phased-In

The FDA has long held that in vitro diagnostics (IVDs), which include LDTs, meet the definition of medical devices, thus giving it the authority to regulate them under the 1976 Medical Device Amendments (MDA) to the Federal Food, Drug, and Cosmetic Act. The FDA has asserted that it decided to exercise “enforcement discretion” over LDTs because in 1976, LDTs were manufactured in small volumes by local laboratories and were similar to well-characterized, standard diagnostic devices.

The FDA said in its fall 2014 proposal to increase its oversight of LDTs that the landscape has changed dramatically since 1976, with LDTs frequently being manufactured by large corporations with components and instruments that aren't legally marketed for clinical use. LDTs today also rely more heavily on complex, high-tech instrumentation and software to generate results and clinical interpretations, the FDA said.

The agency characterized the regulatory framework in its guidance as risk-based and phased-in. Under the framework, the FDA will continue to exercise enforcement discretion for some LDTs, such as traditional LDTs, LDTs for rare diseases or unmet needs and when the LDT is used only for forensic purposes.

Is There a Problem to Fix?

Klein said, “FDA has presented no history or examples of problems with lab tests, and yet they propose sweeping changes that will greatly affect patients, physicians and laboratories. There have been great advances in LDTs, and they have presented little evidence of harm.”

Gutierrez responded that the agency has seen situations where tests that haven't been clinically validated have led to, if not deaths, at least serious injury.

Ramamurthy said to Klein, “You say there is no systemic problem. The reason for that may be that there is no system to track these problems. And that is what the FDA wants to provide.”

“What we have proposed is that we regulate LDTs by risks imposed on the patient by the test,” Gutierrez said. “In the first five years under the framework, we will be concentrating on high-risk tests. After that, we could bring in other tests for review.”

Can Small Labs Afford FDA Submission Costs?

Picking up Klein's issue of cost, Ramamurthy said to Gutierrez that executives at highly regarded laboratories have told him that if the framework goes through, even if it initially only applies to high-risk tests, once they have to establish mechanisms to comply with FDA regulations, they are afraid that their labs will grind to a halt.

“The last thing I heard Myriad Genetics isn't out of business,” Gutierrez said. “And they have a PMA [pre-market approval under the MDA] approved.”

Klein said, “You're mentioning Myriad shows why it's absolutely the wrong thing for the FDA to expand its oversight of LDTs. Myriad is a huge commercial company that does a few tests in large volumes. Most labs do many, many different tests, and they know that FDA submissions for approval can cost hundreds of thousands of dollars. Even if it's only $50,000, multiplied by the number of tests, it's unbearable.”

AdvaMedDx's Fish said that the discussion prompted the question of what the business models are for bringing an LDT to market and how that model stands up under FDA regulations.

One Framework, One Agency

“AdvaMedDx's essential policy position is that all diagnostics pose the same risk to patients and that they should be regulated by a single agency under a single framework,” Fish said. “Over the last few years, all of the counter-proposals to the FDA's on LDT oversight have conceded that additional data on LDTs is needed. The FDA has the resources and the authority to obtain the data.”

“What has been lost in all this debate,” Fish added, “is that the FDA will be flexible. It will continue to exercise enforcement discretion in some areas.”

To contact the reporter on this story: John T. Aquino in Washington at jaquino@bna.com

To contact the editor responsible for this story: Randy Kubetin at rkubetin@bna.com