Regulatory
tests validated externally and is the FDA the regulatory body for the job? Bennett is doubtful, at least of the second question. “They have this list of bad LDTs, but when you push them on it and ask for examples, they have a really hard time articulating what those bad tests are,” he says. “We certainly see FDA cleared or approved test kits that have problems, so clearly FDA oversight isn’t a panacea to fix all lab-testing issues.”
One problem Bennett sees arising when it comes to the FDA creating guidance for labs is the way the agency determines a validated test. “A big point of contention is what constitutes clinical validity,” he says. “I would read a published journal article from a well-respected journal saying this analyte is associated with this disease and there’s my clinical validity. The FDA has been very clear that a single journal article is not sufficient.” Part of the difference in opinion comes down to the role that test plays. For the FDA, an inaccurate test creates patient risk, but Bennett argues the agency has a tendency to interpret test results independently of the care process and that’s very different to the supporting role that laboratory diagnostics play in patient care. “Test results are not interpreted in a vacuum,” he says. “There’s a physician who sees how the patient is presenting and orders additional supportive tests, so it’s unlikely that one test result is going to drive the entirety of the patient’s treatment.” Bennett and his peers have argued this point strongly throughout the negotiations, but until the FDA drafts the relevant guidance documents, the lab-testing sector won’t know what validity requirements will look like.
“There’s a physician who sees how the patient is presenting and orders [...] supportive tests, so it’s unlikely that one test result is going to drive the entirety of the patient’s treatment. ”
Time and money Beyond the issue of validity, there’s also the time frame and the cost of approval to consider, and Bennett says elevating both of those significantly could ultimately harm patients. “I’ve heard colleagues, even from large academic medical centres, say they develop 100 new tests a year and maybe they’ll only be able to do 20, and those other 80 they’ll either send out to a large commercial laboratory or they just won’t offer that test,” he says. “If the test can go to a local laboratory and you can get a result the next day, that’s really good for the patient. If you have
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to send it out to a reference laboratory and it takes a week to get that result, that could have some significant patient impact, especially when you think about cancer treatments.” Bennett adds that the FDA has made some concessions to labs in this area, with low-volume tests expected to be exempt from regulatory oversight, but he says the agency’s definition of low volume will have an impact on how many tests certain labs develop, especially in the area of rare diseases. “Right now it’s set at five,” he says. “Everyone agrees five is too low. If that number is 100 or 500 for instance, then a lot of those low incidence tests will be exempt from submission and that will help a lot.” Although critical aspects of the regulatory process that would result from the VALID Act have yet to be decided, one of which would be a laboratory diagnostics user fee agreement – LDUFA perhaps – Bennett says although negotiations with the FDA and other stakeholders have led to several changes in favour of laboratories, he still has concerns about the transition. Firstly, he wonders whether the five- year transition period specified in the current legislative document – three of which he believes it will take for the FDA to write the necessary guidance documents – might not be long enough. “That only leaves two years for labs to move into compliance, and going from being a CLIA-regulated laboratory to being an FDA-regulated laboratory is a huge, huge jump. I’m a little worried that’s not going to be sufficient time.” His second concern is with the FDA’s ability to set up the comprehensive test information system (CTIS) required to drive submissions and adverse event reporting, especially when it could be flooded with submissions right away due to the rules on grandfathered tests laid out in the VALID Act.
“The FDA is not an IT company,” he quips. “I’m a little bit nervous about their ability to get CTIS up and running. It’s estimated there’s something like 100,000 LDTs on the market right now. Granted most of them would be grandfathered, but if even a percentage of them start having test modifications that would need to be submitted, I’m afraid that FDA is going to get slammed and not be able to handle it.” Citing the volume of EUA submissions the FDA had to get through over the past few years of the pandemic, Bennett foresees such a situation occurring again but much worse.
“For Covid EUAs they got a couple of thousand and it brought the agency to their knees,” he says. “Now they’re going to get tens of thousands of submissions in fairly short order. It’s going to be rough for them.” ●
Medical Device Developments /
www.nsmedicaldevices.com
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