In recent weeks the US Food and Drug Administration (FDA) has undertaken major steps meant to bring lab-developed tests (LDTs)—devices developed, tested and used within a single laboratory—under stricter regulatory controls. But now new questions are being raised about whether the agency is using the correct methods to enact those changes.
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-used 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 single 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."
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, but 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."
New Effort at Regulation
On 1 August 2014, FDA released a new draft guidance document, Framework for Regulatory Oversight of LDTs, that proposes regulating LDTs more or less like IVDs.
Under FDA's proposed regulatory framework, moderate-risk LDTs will be required to be registered and listed with FDA, meet adverse event reporting standards and undergo premarket preview starting five years after the guidance is implemented.
High-risk LDTs will need to meet all those requirements listed above, but will instead be required to submit to a premarket approval process within one year of the guidance document's implementation.
Some LDTs will be subject to far fewer requirements. Low-risk devices and LDTs intended to treat rare diseases will only be subject to registration, device listing and adverse event reporting requirements. Devices used solely for forensic purposes and devices intended to facilitate organ transplants in CLIA settings will also be exempt, FDA said.
For more, please see our 1 August 2014 story on FDA's LDT guidance document.
Legal Analysis: FDA Regulating the Wrong Way
But now at least one lawyer says the agency may be approaching the rollout of its LDT policy in the wrong way.
In a post on the Washington Legal Foundation's (WLF) website this week, Sidley Austin LLP attorney Gail Javitt said FDA's use of a guidance document to enact the policy was potentially problematic.
"Whatever one’s view of the substantive merits of FDA’s proposed framework, there is an important procedural point that must not be overlooked, namely, that FDA may not lawfully initiate regulation of LDTs through the use of guidance documents," she wrote.
The problem, she explained, is that guidance documents are intended to be non-binding documents expressing FDA's preference for a particular outcome—not a requirement.
"In a nutshell, according to longstanding principles of agency law and administrative procedure, FDA may not lawfully issue guidance that contravenes agency regulation," Javitt wrote. "In the case of clinical laboratories specifically, FDA may not lawfully, through guidance, require clinical laboratories to register as medical device establishments, since FDA by regulation exempted clinical laboratories from registration and listing almost 40 years ago."
FDA, Javitt explained, tries to avoid this by renaming "registration" as "notification"—a "newly-coined term."
"The agency then presents clinical laboratories with a Hobson’s choice—'notify' the agency or face enforcement for failure to register and list," she wrote. "Furthermore, laboratories that do 'voluntarily' notify FDA will, down the road, still be required to register and list at the time they submit an application for premarket review, and to pay device establishment user fees at that time."
Guidance or Regulation?
All this, Javitt says, runs counter to the spirit, if not the letter, of the rulemaking process.
"FDA’s attempted rulemaking circumvention only serves to underscore the importance of notice and comment rulemaking. FDA has exempted clinical laboratories from regulation for 37 years. Regardless of the asserted public health rationale, implementing a new regulatory scheme can be expected to cause significant disruption, at least in the short term, and not-insignificant new costs. Furthermore, the agency’s legal authority to regulate LDTs, which are used to provide a medical service and are not distributed in interstate commerce as freestanding products, remains a subject of debate."
The rulemaking process, though "cumbersome," would better serve both the agency and the LDTs industry by allowing for public comment and for the agency to develop better policies, Javitt argues.
And, she concludes, creating new requirements through a guidance document "creates grounds for a legal challenge," which might ultimately delay the implementation of any policy FDA creates.
WLF Posting on LDTs