US Food and Drug Administration (FDA) Commissioner Margaret Hamburg recently announced that her agency would soon end a long-standing policy of enforcement discretion toward a classification of diagnostic devices known as laboratory-developed tests (LDTS), but now at least one association has filed a Citizen Petition with the agency seeking to exempt LDTs from new guidance, new regulation or seemingly any regulation whatsoever.

Background

Under normal circumstances, medical devices can reach the market in one of two ways. Either they obtain FDA approval through the premarket approval (PMA) process-a difficult and expensive pathway that requires clinical data to support an application-or a premarket notification [510(k)] application that aims to show that a device is substantially equivalent to a predicate device, usually avoiding both the cost and clinical data required of PMAs.

There is, however, in practice a long-practiced exemption given to a subset of diagnostic devices. Whereas most in vitro diagnostic tests need to be approved or cleared by FDA, LDTs do not. That's because the devices were historically intended to be developed by and exclusively used within a laboratory, and regulators feared that subjecting the devices to regulatory review would stifle their development entirely.

"Initially, laboratories manufactured LDTs that were generally relatively simple, well-understood pathology tests or that diagnosed rare diseases and conditions that were intended to be used by physicians and pathologists within a single institution in which both were actively part of patient care," FDA explained in a 2010 meeting notice. "These tests were ordinarily either well-characterized, low-risk diagnostics or for rare diseases for which adequate validation would not be feasible and the tests were being used to serve the needs of the local patient population."

Increasing Complexity Leads to Breakdown of LDT Framework

But in recent years, FDA has noticed LDTs becoming increasingly complex and in some cases nearly indistinguishable from their FDA-cleared or -approved counterparts. Of particular concern to FDA is that many LDTs play critical roles in clinical decision-making in the context of personalized medicine (e.g. genetic testing), which it said raises the risk of incorrect or missed diagnoses, resulting in untimely or improper treatment.

The agency has long asserted its right to regulate the devices-and indeed maintained that LDTs are medical devices-and since 2011 has begun to move strongly toward a system of stricter regulation of LDTs, albeit not quite as strict as the current system for in vitro diagnostic devices. That's because FDA said it "recognizes that while the absence of FDA oversight may make it easier for laboratories to develop and offer tests on a rapid timeline, the absence of a level playing field creates a disincentive to innovation by other manufacturers whose tests are approved or cleared by the agency."

In a June 2013 speech before the American Society for Clinical Oncology, Hamburg reiterated this push toward an end to its enforcement discretion policy for LDTs, again noting the extraordinary complexity of some of the newest devices and their role in helping consumers to make medical decisions.

To that end, Hamburg said her agency will be "working to make sure that the accuracy and clinical validity of high-risk tests are established before they come to market" under a new risk-based framework that remains under development.

Petition: LDT's Are Devices, and FDA Can't Regulate Them

But according to a new Citizen Petition-a public petition requiring an official response from FDA regarding a statement of policy-released to the public on 4 June 2013, FDA should put this proposed risk framework on hold and refrain from regulating LDTs as medical devices entirely.

The petition from the American Clinical Laboratory Association (ACLA) notes that the 1967 Clinical Laboratories Improvement Act (CLIA) governs clinical laboratories, including the standards they use to "assure consistent performance… of valid and reliable laboratory examinations and other procedures." In other words, ACLA maintains that CLIA, and not the Federal Food, Drug and Cosmetic Act(FD&C Act), should cover the regulation of LDTs.

FDA's assertion, ACLA noted, has not yet been challenged in court since FDA has infrequently asserted its right to regulate the devices and has declined to do so (though it has acted to pressure some devices off the market).

ACLA's Citizen Petition goes on to state that it believes that FDA lacks the jurisdictional authority with which to regulate LDTs, and thus does not have the legal authority to change its enforcement policies to include new regulation or guidance.

At the core of ACLA's argument is that it considers LDTs not to be devices, but rather procedures for performing diagnostic testing using reagents and equipment. "They are essentially know-how, not articles," ACLA wrote. "Therefore, they are not subject to regulation under the FD&C Act." ACLA further cited the history of CLIA, arguing that Congress had never given FDA any explicit authority over LDTs.

In addition, ACLA said, because the devices do not leave the laboratories, they do not enter commercial distribution, and thus do not meet FDA standards for interstate commerce regulation.

General Harms: Less Availability

The Citizen Petition goes on to note some of the more general harms that it claims could come about if LDTs are regulated as devices, including reduced availability of testing for diseases for which there is an insufficient demand to bring an approved or cleared device to market, increased "lag time" for tests coming to market, and a general reduction in availability of LDTs.

But ACLA makes clear that its main gripes have to do with the legal problems associated with FDA regulation of LDTs. "To the extent that stakeholders have concerns about possible regulatory gaps under CLIA, the most logical and appropriate solution would be to amend CLIA and/or its regulations-not to impose an additional layer of regulation based on a different statute designed for products rather than laboratory testing," it concluded.

"FDA's contemplated new oversight will superimpose a new bureaucracy on an already highly-regulated industry that serves highly-trained physicians and professionals," it added.

FDA now has 180 days to respond to the petition, though it may delay further based on defined criteria as explained in its guidance document on Citizen Petitions.

ACLA's Citizen Petition

RAPS 2013: What is a Laboratory Developed Test versus an FDA Cleared Test?