NEW YORK – While the US Food and Drug Administration's recent proposed rule on regulation of laboratory-developed tests (LDTs) doesn't address in vitro diagnostics (IVDs) directly, it is nonetheless likely to impact this space.
Most straightforwardly, the rule, were it to go into effect, would bring LDTs and IVDs under the same regulatory regime, leveling what some on the IVD side have said is an uneven playing field.
At the same time, the increased workload the FDA would take on in overseeing LDTs raises concerns about backlogs that could delay the evaluation of IVD submissions.
Perhaps most significant to the IVD industry, however, is what some in the space see as a missed opportunity to use legislation to create a diagnostics-specific regulatory pathway that could be easier to navigate than the medical device framework the FDA currently uses to regulate IVDs.
IVD industry organizations like AdvaMed were among the proponents of the Verifying Accurate Leading-edge IVCT Development (VALID) Act, in large part because they saw the bill as providing a regulatory framework better tailored to diagnostics, with features like the bill's technological certification pathway, which would have offered more flexibility than the FDA's existing rules on IVDs.
The FDA decided to once again take up LDT regulation following Congress' failure last year to pass VALID, but Zach Rothstein, executive director for AdvaMedDx, said the organization is still hoping LDTs can be addressed through legislation like VALID.
"A lot of the main things in VALID that we liked, like technological certification and how the risk-based approach works, would require an act of Congress," he said. "So, our focus is still on VALID, and, if anything, the hope from our end is that this rule spurs a new round of conversations about whether VALID does make sense to work, as a community, on."
Ron Freeze, global head of medical technology at healthcare consulting firm ProPharma, was divisional VP of regulatory affairs at Abbott Diagnostics as VALID was being formulated in Congress. Like Rothstein, he said he and his colleagues in the IVD business saw the bill as not just a matter of upregulating LDTs but also a chance to implement a new regulatory process tailored to diagnostics.
"You could say, yes, it's a lost opportunity for the IVD space," he said.
Donna Hochberg, a partner with healthcare consulting firm Health Advances, similarly suggested that VALID's regulatory framework would have benefited the IVD world.
"Fundamentally, the considerations for data development and classification of products and tests [are] totally different for [diagnostics] than [medical devices]," she said, adding that it would be "more fair and accurate" to have a diagnostics-specific regulatory framework.
Such a framework would also seem to be the FDA's preference, even as the agency has decided to attempt to regulate LDTs under its rulemaking authority. For instance, when earlier this year Elizabeth Hillebrenner, associate director at the FDA's Center for Devices and Radiological Health, discussed the agency's decision to once again take up the issue of LDT oversight, she noted that it stood "ready to continue supporting Congress on the diagnostic reform legislation, VALID or otherwise."
There are also concerns that the increased workload involved in regulating LDTs could impact IVD firms by delaying processing of their test submissions.
"The backlog issue is very real," Hochberg said, adding that "the full impact will depend on how FDA applies [regulations] and over what timeline."
"Labs have thousands of assays on their test menus, many of which are LDTs," she said. "Plus, anything that is the same assay on a new sample type is technically an LDT. If all of these have to be submitted for FDA review and if many of these have to be submitted by the performing lab — with multiple labs submitting the same test because there is no kit — the sheer volume of submissions will be overwhelming."
Freeze said that a possible route to dealing with this issue might be to implement a sampling-based approach similar to that used by the European Union's In Vitro Diagnostic Medical Device Regulation (IVDR), which has had to contend with insufficient resources among the notified bodies responsible for certifying that moderate- and high-risk tests meet regulatory requirements.
IVDR "put[s] a lot of the onus on the manufacturers to elevate their quality systems, their documentation, the [medical device reporting] … and then the notified bodies use a sampling plan," he said. Under these plans, notified bodies do not inspect documentation for every device but instead look at a smaller number of devices meant to be representative of larger device groups.
"Stepping back to look at what would be reasonable, I think that is where the discussion could go, to not just FDA reviewing every product like they are today," Freeze said.
Rothstein said that while the concern that increased oversight of LDTs could tax the FDA and delay evaluation of IVD submissions was a fair one, he believed the proposed four-year transition period would give the agency and test makers time to prepare. He added that the FDA is in the process of hiring more reviewers as provided for in the Medical Device User Fee Amendments V (MDUFA V) bill signed into law last year. Additionally, he noted that the next medical device user fee package, MDUFA VI, would coincide with the proposed implementation of the FDA's rule on LDTs, giving the agency the opportunity to negotiate more funding to ensure it is adequately staffed to handle the increased workload.
FDA oversight of LDTs would, in theory, remove a competitive advantage these tests have enjoyed, but Rothstein said that while this competitive issue is there, it "is not the focus" of the companies AdvaMed represents.
He said that existing LDTs have made IVD vendors reluctant to move into some test areas but noted that competition from LDTs "has never been a driving factor for our businesses in terms of why we would want VALID."
Jonathan Romanowsky, cofounder and chief business officer at San Carlos, California-based diagnostics firm Inflammatix, said that increased FDA oversight of LDTs "may level the playing field" between LDT and IVD makers "from a cost-structure standpoint" as LDT vendors will likely need to invest more to conduct additional studies or provide additional evidence requested by the FDA.
He said that particularly in the case of commonly ordered tests available from a variety of providers, FDA regulation might provide "a slight tilt toward IVD manufacturers."
Romanowsky, who has experience in the LDT world having formerly worked in management at CardioDx and Veracyte, said that in the case of Inflammatix, which is developing IVDs for rapid infectious disease testing, increased LDT regulation will have little competitive impact as its products "will not compete at all with a test that has to be sent out to a lab."