Need to know:
- The VALID Act would create a new risk-based framework for regulating lab-developed tests including a new category called “in vitro clinical tests.”
- Traction in the US House and Senate sees plans to attach the bill to the Medical Device User Fee Amendments which is set to expire in September 2022.
The VALID act, a bipartisan bill that could close the legal loophole within the FDA’s medical device regulations that allowed disgraced startup Theranos to market and sell fraudulent tests, could finally be headed towards a resolution.
At a Senate Health pandemic preparedness hearing earlier this month, US Senator Patty Murray said the Verifying Accurate, Leading-edge IVCT Development (VALID) Act – which would close the gaps in diagnostic test oversight – is headed toward committee consideration later this spring. This would be a major development, given the years of negotiation that preceded the bill.
“Senator [Richard] Burr and I are working on a bipartisan policy to try and improve the regulation of laboratory-developed tests. I really welcome members’ input on that policy, which we are actually working to include in the FDA user fee reauthorization package that we will do later this spring,” said Murray.
Similarly, Reps. Larry Bucshon, R-Ind and Diana DeGette, D-Colo., members of the House Energy & Commerce Committee, said that they hope to attach the VALID Act to other must-pass legislation this year.
As it stands, the FDA has little control over lab-developed tests (LDTs). If a test is designed and used in a single lab, that lab can market the tests without the US authority’s approval, regardless of its risk.
This is thanks to an ‘enforcement discretion’ that was set in 1976 when the US Congress gave the FDA the authority to regulate medical devices, including in vitro diagnostic tests (IVDs). At that time, this was a risk-based decision given the state of technology: LDTs were far simpler, often localised and meant for small patient populations such as in the case of rare diseases.
However, “right now, there is an unknown but significant number of IVDs that have never been reviewed for validity by the FDA, even if they are high-risk tests,” explains Liz Richardson, who directs the healthcare products project at The PEW Charitable Trusts, a non-profit calling for Congress and the FDA to close this loophole.
“That creates real issues for patient safety. Tests should be regulated according to their risk to patients and if it works, not based on where they are developed and used. ”
As Richardson goes on to outline, the current regulatory system means that even high-risk tests do not have any external review for clinical validity and there is no requirement to report adverse events that may occur as a result of inaccurate results.
In addition, there is no central registration to track how many are out there and what they’re being used for. LDTs range widely in complexity and can measure or detect a large variety of analytes/substances such as proteins; chemical compounds like glucose or cholesterol; or DNA.
The VALID act
At a high level, the VALID Act would create a new category of products that would be regulated by the FDA.
Currently, IVDs are regulated under the medical device framework. VALID would create a new category called “in vitro clinical tests,” which will apply to both commercial test kits that are manufactured by pharma, as well as LDTs.
By creating a risk-based framework, the act will require high-risk tests, like novel assays, to go through premarket review, while lower-risk tests, like cholesterol tests, could go to market after passing “technological certification.” This would be a significant change to the way IVDs are regulated right now. The law will grandfather in LDTs currently in use.
The bill also states certain categories of tests will be able to come to market directly if they meet certain criteria. For example, these would be for relatively rare diseases, tests that are custom or used five times a year or less, and tests for public health surveillance that aren’t used for clinical decision making but rather to track diseases over time across populations.
Technology certification review is a new approach that will allow IVD developers to submit a single representative test for FDA approval. If the FDA approves the developer’s design and clinical validity and the test gets to market, the developer would be able to make test tweaks and develop new ones that rely on the same underlying technology.
“The goal is to allow for flexibility,” says Richardson. If a high-quality developer has already demonstrated to the FDA that it can meet those standards, then technology certification allows continued innovation and test development to meet patient need without having to return to the agency for review, she adds.
“This has been proposed because diagnostics have a much more rapid cycle of innovation and modification compared to other devices,” says Richardson. “It allows a developer to adjust a test or develop a new test based on emerging research.”
Something PEW is working to change within the VALID Act, is that high and low-risk tests are more concretely defined and tests viewed as moderate risk, which also may be able to come to market without FDA review, have a far more solid postmarket review framework.
This means the FDA should be able to demand and inspect clinical validation data and adverse event reporting must be thorough.
Solving a decades-long issue
The lack of FDA oversight of LDTs has been a cause of contention for some time, but some recent events have certainly helped bring the issue to the fore.
One being the Theranos saga, and another, the Covid-19 pandemic and the need for reliable testing.
The issue was also recently raised in a New York Times feature around the questionable quality of certain noninvasive prenatal testing products. The article outlined that as often as 83%-91%of the time prenatal genetic screening tests provide incorrect results in detecting various rare and serious genetic disorders.
One study found that four out of every 1000 tested pregnancies end in abortion because of a “detected fetal anomaly.”
The NYT article prompted almost 100 congressional Republicans to pen a letter to the FDA to ask what the authority was doing to regulate and reign in these tests, many of which were LDTs.
“That got some attention, for obvious reasons,” says Richardson. “It made clear what some of the consequences can be when you have a whole market of tests that are not subject to FDA review.”
One of the issues with prenatal testing, Richardson says, is that people get confused viewing the tests as a diagnostic when they are for screening.
The VALID Act would mean that the FDA would have authority to ensure these tests are safe but also to have control over how they are marketed and the language companies use to advertise their products.
User fee amendments: a vehicle for VALID?
The VALID Act has been in progress for more than six years.
Bucshon and DeGette first released a draft of the Act in December 2018, which was a revision of a previous bill, the Diagnostic Accuracy and Innovation Act (DAIA) following substantial input from the diagnostics and laboratory industry.
They first introduced the bill in Congress in March 2020.
At the same time a duplicate bill was introduced in the Senate sponsored by Sens. Michael Bennet, D-Colo., and Burr. Bennet and Burr also reintroduced the act in the Senate last June.
Recently, these House and Senate members have identified another opportunity to get the bill passed. In September this year, the Medical Device User Fee Amendments (MDUFA) – which since 1992 requires all companies putting a product through FDA review to pay a user fee – will expire. These user fees make up almost half of the FDA’s annual budget.
Bucshon has stated that he will try to attach the VALID act to MDUFA reauthorization. “It can be difficult as a standalone [bill] to get the attention of Congress, honestly,” said Buschon as reported in 360DX. “There’s an opportunity, because [MDUFA] is related to laboratory testing and devices that we might be able to get the VALID Act included.”
Bucshon has said that he has high hopes that the bill will have enough votes to pass if it is bought up this year, noting this version of VALID is broadly bipartisan in both the House and the Senate and has stakeholder support, “for the most part.”
Divided interests have slowed the bill’s progress
However, there is still controversy in regard to the VALID Act. “In general, there is no group that is wholly supportive of the current [bill] version and everyone has been weighing in to suggest things that they would like to see change,” says Richardson.
“In general, everybody agrees that the VALID Act needs some changes to get that balance right, but we disagree on what needs to change to get there.” But ultimately, at a high level, everyone’s goals are the same,” she adds.
Some lower resource labs and academic medical centres seem to be concerned about a potential increased burden of paperwork that the bill may usher in.
“You want a framework that appropriately balances the need for innovation, with the need to protect public health,” says Richardson. “That’s the fundamental tension.”
In November 2021, the American Association for Clinical Chemistry (AACC) president, Stephen Master, expressed concerns, including VALID’s proposal to grandfather in existing LDTs. He said this step could deter labs from making needed updates to tests at later stages if it means them going through the new regulatory process.
Throughout the years, since the concerns around LDTs were first raised in the ‘90s, the industry has been divided around how the FDA should regulate the tests (or if the agency should regulate them at all). Thus the VALID Act has been revised many times to include stakeholder input and suggestions.
When the agency published two Guidance Documents proposing a framework for the regulation of LDTs in 2014 also detailing the end of the enforcement discretion, Richardson says there was significant industry pushback leading the FDA to temporarily back off.
Broadly, organisations deeply involved in the business of LDTs were in opposition while those invested in IVDs broadly favoured the agency’s proposals. Notably, back in 2014, the American Clinical Laboratory Association (ACLA) considered suing the FDA in a bid to keep regulation of LDTs out of the agency’s hands.