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Lab Group Submits Citizen Petition against FDA Regulation of Lab Developed Tests

NEW YORK (GenomeWeb News) – A group representing US clinical laboratory service providers has submitted a petition asking the US Food and Drug Administration to not regulate lab-developed tests, charging that the agency lacks the legal authority to do so.

Instead, the American Clinical Laboratory Association recommends that if stakeholders have concerns about gaps in the existing regulation of LDTs under the Centers for Medicare & Medicaid Services Clinical Laboratory Improvement Amendments, then "the most appropriate solution would be to amend CLIA and … not to impose an additional layer of regulation based on a different statute designed for products rather than laboratory testing."

In its Citizen Petition, dated June 4, ACLA maintains that LDTs are not medical devices and as such do not fall under the agency's oversight as laid out under the Federal Food, Drug, and Cosmetic Act. ACLA has asked the agency to respond to its petition by confirming that LDTs are not devices as defined by the law.

In short, according to ACLA, the FDCA defines devices as articles, such as an instrument, machine, or in vitro reagent that is used to diagnose disease. Although these devices can make up the components of a laboratory's testing service, "the LDT ... represents a laboratory's proprietary procedure for performing the test – essentially it's knowledge or know-how," ACLA wrote in the Citizen Petition signed by President Alan Mertz.

"The fact that laboratory testing entails the use of tangible articles does not change this conclusion," according to ACLA. "Congress did not intend that FDA would regulate every clinical service as a medical device simply because the service involves the use of tangible articles" that are subject to FDA regulation.

The petition comes a few days after FDA Commissioner Margaret Hamburg spoke at the American Society of Clinical Oncology's annual meeting about the agency's intent to regulate LDTs, reviving a contentious issue over which the FDA has repeatedly clashed with the laboratory industry in recent years.

Hamburg said at ASCO that the FDA is in the process of developing a risk-based regulatory framework for LDTs. "The agency is working to make sure that the accuracy and clinical validity of high-risk tests are established before they come to the market," she said. "The risk-based framework that we have under development will ensure that diagnostics used in cancer treatment will provide medical professionals with a critical baseline for confidence in the tests they order for their patients. Our intent in considering what to do about LDTs is to provide for safe and effective diagnostics while promoting innovation and patient access."

The FDA has repeatedly expressed its intent to issue guidance on LDT regulation, but hasn't yet done so likely due to significant industry pushback and the difficult political climate in Washington, DC. The US Congress enacted the Food and Drug Administration Safety and Innovation Act last year, which includes a provision restricting the FDA from issuing guidance on LDTs under the FDCA without 60 days notice to two congressional committees and without releasing the details of its regulatory plan.

In its Citizen Petition ACLA hinted that the lab community might take legal action against the agency if it does attempt to regulate LDTs by issuing guidelines. "Because the agency has not acted to regulate LDTs, the clinical laboratory industry has not challenged FDA's assertion of jurisdiction in court," ACLA wrote.

Historically, the FDA has exercised enforcement discretion over LDTs, tests developed by laboratories for use at that particular facility. However, as these tests became more complex technologically and companies began marketing them more broadly, the FDA expressed its desire to regulate LDTs as medical devices and has taken action against a number of labs that in the agency's opinion are manufacturing LDTs as medical devices.

ACLA also takes issue with FDA's assertion that laboratories "market" LDTs. "LDTs are not distributed, delivered, or placed on into the market," the lab group wrote in the petition. "Although the reagents, components, and specimens used in performing LDTs, may meet this criteria, the LDTs themselves do not."

In contrast to ACLA's position, many drug and device manufactures that support FDA regulation of LDTs believe that CLIA doesn't have sufficient measures in place to ensure the clinical validity of tests, and they have pushed for all diagnostics to be overseen under one regulatory pathway. Genentech submitted a Citizen Petition in 2008, saying as much.

AdvaMedDx, a group representing the interests of diagnostics developers, has released a statement urging the FDA to issue risk-based regulation of advanced molecular tests. The group believes the agency should focus its "limited resources" on tests that pose the highest risk to patients; speed access to lower-risk tests and exempt well-established tests; and oversee higher-risk tests developed by labs.

ACLA contends, however, that FDA regulation of LDTs will harm the public's access to critical tests for rare conditions. As the molecular diagnostics industry moves toward next-generation sequencing technology platforms, the lack of flexibility in current FDA regulations is a particular point of concern for many lab industry players. CLIA is a more appropriate regulatory pathway, ACLA maintains, since it allows labs in charge of running specific tests to quickly adjust proprietary procedures to ensure the quality of the tests and stay up to date with scientific advances.

In its petition, ACLA also highlighted the ability of labs under CLIA to quickly make available critical tests of public health importance before the FDA can approve such tests. For example, HIV viral load testing was available as an LDT in 1990, six years before the FDA approved a kit to gauge disease progression. More recently, KRAS genetic tests to determine which patients will respond to colorectal cancer treatments were available as LDTs, several years before the FDA approved a companion test kit.

"FDA's regulation of LDTs as devices would adversely affect patient care in the US," ACLA wrote in the petition. "If FDA were to regulate LDTs as devices, its workload would increase exponentially. … This immense workload would slow an already protracted premarket review process."


For more on Hamburg's comments regarding LDTs at ASCO, please see this article in Pharmacogenomics Reporter.