Regulatory
requirements as IVD manufacturers before they could provide them to doctors and patients. Despite the medical world’s indignation over Theranos, the legislation failed to gain the required support until its second iteration in 2020, which – although it enjoyed bipartisan support – was shelved due to the Covid-19 pandemic. Introduced again in its third form in 2021, the Act got a boost from an October 2020 paper in The New England Journal of Medicine, in which Jeffrey Shuren and Timothy Stenzel of the FDA looked at 125 Emergency Use Authorization (EUA) requests from laboratories and found that 82 had design or validation problems, with several being denied authorisation. Although it was omitted from the recently passed Medical Device User Fee Agreement Bill (MDUFA V), many believe the VALID Act could hitch a ride on another legislative vehicle before the year is up.
Find a path to validation
Shannon Bennett has witnessed all these events during his 23 years working in clinical testing laboratories run by Mayo Clinic, before moving into his role as director of regulatory affairs for the company’s department of laboratory medicine and pathology. “About five years ago now, my role shifted more firmly into the regulatory affairs realm to coincide with VALID,” he says. “The position I’m in now was essentially created to help Mayo Clinic navigate FDA regulation of laboratory tests.”
“It’s not an even playing field, IVDs and lab- developed tests (LDTs) are not regulated in the same way. But, in lab, we would say that’s because the risk profile is very different.”
At the heart of the debate is the fact that in-vitro diagnostics (IVDs) and lab-developed tests (LDTs) broadly speaking perform the same duty of testing for analytes or biomarkers that can give an indication of health and can help diagnose diseases. In fact, all that’s required for an LDT to lose its regulatory discretion exemption and be reclassified as an IVD is for a single component in a test to be developed outside of the development laboratory. Given how easy it is to blur the lines between the two, it’s unsurprising that many of those within the IVD manufacturing space see the VALID Act as “a long-overdue modernisation of the law for all diagnostic tests”. Those were the words of Scott Whitaker, president and CEO of the Advanced Medical Technology Association (AdvaMed) – a major advocacy group for medical device and IVD manufacturers – when
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the act was reintroduced to the House and Senate in June 2021. Currently, laboratories are regulated by the Centers for Medicare and Medicaid Services (CMS) under the Clinical Laboratory Improvement Amendments (CLIA), and undergo an inspection every two years to maintain their CLIA certification, but don’t have to provide evidence of validity for their tests to any higher power.
Bennett acknowledges that LDTs have a privileged position as far as the diagnostic market goes, but argues there’s an important distinction to make that justifies it. “It’s not an even playing field,” he says. “IVDs and lab-developed tests (LDTs) are not regulated in the same way. But, in lab, we would say that’s because the risk profile is very different.” Indeed, in LDTs, the conditions for each lab remain the same; for an IVD manufacturer, devices must be developed to sell to hundreds of laboratories all over the world, with different climates, staff and equipment, all of which introduce variables that can add risk to the process of testing. “Running a test in humid Florida is different to very dry Minnesota in the wintertime,” Bennett explains as an example. That’s only the technical argument for why
LDTs shouldn’t be overseen with the same rigour as IVDs too. Bennett believes the application of LDTs creates another key distinction between them and IVDs. “What drives our test development is the doctor across the street calling me up and saying, ‘I have this biomarker that I need to test for to treat my cancer patients’, and then we’ll scramble to develop that test and validate it,” he says. “At Mayo Clinic, we have a reputation for developing a lot of highly esoteric tests, so a lot of rare disease testing. If we don’t develop a given test, no one probably will. It’s not cost-efficient for a large IVD manufacturer to make a test kit that they’ll only sell a couple hundred of.”
Manufacturing complications When it comes to the practical aspects of the FDA regulating LDTs, individual laboratories would have to seek approval for each test before they can run it, providing evidence for its efficacy, in essence forcing them to jump through the same hoops that IVD companies do. “Many laboratories today in the US don’t submit their test information to anybody,” says Bennett. “Going from that environment to the rigour of an FDA submission is a huge jump. If VALID passes, or it doesn’t and FDA starts regulating anyway, clinical laboratories are going to need a lot of education and, frankly, handholding.” There’s also the question of capability, as the theoretical questions posed by the VALID Act, are do labs need to have their
Medical Device Developments /
www.nsmedicaldevices.com
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