NEW YORK – A US District Court's recent decision vacating the US Food and Drug Administration's final rule on laboratory-developed tests (LDTs) made clear that the agency does not have the legal authority to regulate these tests, settling, at least for the moment, a decades-long dispute between the FDA and industry.
But while the court's decision ends the rollout of the agency's final rule, several observers suggested that the FDA still has a number of routes through which it could exert authority over LDTs if it chooses.
Given the agency's strong push for LDT regulation in recent years, it's unlikely it will entirely abandon its efforts to exercise oversight of these tests, said Michael Ryan, a partner with law firm McDermott Will & Emery. He noted several steps the FDA might take in the wake of the court's decision, including increasing its scrutiny of the use of research-use-only (RUO) or investigational-use-only (IUO) reagents, kits, and equipment by clinical labs and more tightly regulating specimen collection kits used with different LDTs.
On the RUO/IUO front, Ryan noted that the agency has previously clashed with clinical labs over proposed rules policing the use of these materials. In 2011, the FDA issued a draft guidance clarifying that products labeled as RUO or IUO should be confined to research applications and not used in clinical testing. The agency also noted in this guidance that manufacturers of RUO and IUO products should not support or advise customers they believe are using these products for clinical purposes or sell them to laboratories they know use the products in clinical testing.
The lab industry pushed back on this guidance and, in particular, Ryan said, on the notion that manufacturers were expected to police how their customers were using their products. However, he noted, the FDA's final guidance, which the agency released in 2013, makes clear that RUO and IUO products are not approved for clinical use.
"I think that is an area where FDA could consider taking a closer look at what some RUO [product] developers are saying about their products and how that fits within that [guidance]," Ryan said.
Last year, the FDA sent a warning letter to Agena Bioscience regarding RUO materials and its iPLEX HS Colon Panel, which is intended for the detection of genetic variants in colorectal cancer specimens. The panel is labeled as being RUO, but the FDA wrote in its letter that "on numerous occasions your iPLEX HS Colon Panel … [was] not being shipped or delivered for an investigation. And these devices were not for use in the laboratory research phase of development but rather were represented as effective IVDs."
The letter raised concerns among some industry observers that the FDA was planning to tighten enforcement of its rules around RUO/IUO labeling, which Sheila Walcoff, founder and CEO of regulatory consulting firm Goldbug Strategies, noted at the time could have "tremendous" implications "in terms of laboratory supply."
James Boiani, an IVD, drug, and medical device life sciences attorney at Epstein, Becker & Green in Washington, D.C., likewise said he is watching for an uptick in warning letters from the FDA regarding the use of RUO and IUO materials in clinical assays.
"I'm wondering if [FDA] will take an approach of, 'We can't get the labs, but we can get the suppliers,' and try to crack down more in that way," he said.
Boiani also suggested the FDA might move to exert authority over LDTs via their specimen collection devices. He noted that while the court ruled that LDTs themselves are services, developed and deployed in a single lab, and are not subject to FDA regulation, specimen collection kits are FDA regulated.
"The argument FDA could put forward is, OK, you can do whatever you want in the lab, but as soon as you distribute this [specimen collection] product for use with [a particular LDT], you need [FDA] clearance for this product to be used with [that] LDT," Boiani said.
Benjamin Zegarelli, an attorney with law firm Mintz, focused on medical device compliance and also highlighted specimen collection devices as a route by which the FDA might try to continue to exercise oversight of LDTs.
A specimen collection itself "is a medical device," Zegarelli said. "These are physical devices that are distributed in commerce, and FDA's regulations are clear that in vitro diagnostic products include devices that are intended for obtaining samples. The [LDT decision] changes nothing in that regard."
Zegarelli cited as an example, dried blood spot cards, which he noted are used for sample collection for a variety of LDTs but which have only been cleared by the FDA for use in newborn screening applications. He said the agency has in the past occasionally issued warnings to labs about the use of unapproved collection devices — especially in the case of tests using at-home sampling — but that these warnings have generally been "few and far between."
In one instance, last year the agency sent HIV testing outfit Blackfly Investments a warning letter informing it that sales of its dried blood spot self-collection kits for HIV serology testing violated the Federal Food, Drug, and Cosmetic Act (FD&C Act).
Boiani suggested that the FDA could require clinical studies demonstrating that an LDT performs as intended with a given sample collection kit.
The agency could say "We don't have assurances that this [collection kit] can be used with this test unless we see data showing that the test is going to provide accurate results with this sample collection kit," he said. "They could back into making labs do [studies] that way."
Software could also be an area where the agency tries to exert authority, Ryan said, observing that the FDA has long regulated software as a medical device. He noted, however, that the court decision vacating the LDT rule could be seen as calling into question the FDA's authority to regulate software.
"Some intrepid plaintiff's council later on might take that up if they wanted to challenge FDA's authority to regulate software," he said. "But I think for the time being, the court case doesn't directly impact FDA's ability to regulate software, so that could be something FDA looks at."
Whether under the current administration the FDA has any interest in pursuing any of these strategies is another question. Zegarelli suggested that if the administration does wish to continue pushing FDA oversight of LDTs, it can simply appeal the recent court ruling rather than attempt to regulate these tests via indirect approaches like cracking down on RUO reagents or specimen collection kits. While the Trump administration did continue to argue the FDA's case in court after coming into office, it is generally seen as unsympathetic to FDA claims of authority over LDTs.
The strategies will be available to the FDA under future administrations, though, Boiani said, both as a means of overseeing LDTs as well as potentially putting pressure on Congress to come up with a legislative resolution to the matter.
Lale White, executive chairman and CEO of lab data and revenue management firm Xifin, suggested that despite the recent court decision, the LDT question is not going away.
White strongly opposed the FDA rule on LDTs, but, she said, the increasing complexity of lab tests as well as their increasingly important roles in patient management and care call for updates to the rules and regulations governing their development and use.
"There is a role for oversight here that needs to be addressed one way or another," White said, adding that she believes modernization of CLIA would be the best route to achieve this.
"I think everybody recognizes that labs have a role in making sure their quality assurance and quality control mechanisms are keeping up with innovation," she said. "I think from that perspective it would be good for the lab industry to really start looking seriously at how to do that."