August 30, 2022 | The pros and cons of the Verifying Accurate Leading-edge IVCT Development (VALID) Act, various iterations of which have been circulating since 2018, was the topic of a lively panel discussion during last week’s Next Generation Dx Summit in Washington, D.C. Those supporting the legislation, intended to modernize regulatory processes for in vitro diagnostics (IVDs) and laboratory-developed-test (LDTs), point to several promising provisions added over the past few months—including grandfathering of LDTs already on the market and creation of a moderate-risk tier—as well as the importance of leveling the playing field so all test developers are held to the same evidentiary standard.
Cynthia Bens, senior vice president of public policy at the 220-member Personalized Medicine Coalition, moderated the discussion. LDTs are a critical component of personalized medicine, she notes, and up to now have been overseen by the Centers for Medicare and Medicaid Services (CMS) under the Clinical Laboratory Improvement Amendments (CLIA) of 1988. The VALID Act would clarify the authority of the Food and Drug Administration (FDA) to regulate LDTs and better align their pathway to market with FDA-cleared or -approved tests.
The VALID Act seeks to address longstanding concerns about the discrepancies, and has been introduced multiple times as standalone bill, says Bens. Most recently, the Senate released an updated version of the VALID Act attached to a larger legislative package that would reauthorize the Medical Device User Fee Amendments (MDUFA), which expires at the end of September 2022.
The legislation would establish a new, risk-based framework for in vitro clinical tests (IVCTs), and allows for a five-year transition period, she explains. High-risk tests (e.g., novel assays) would be required to go through premarket review, low-risk tests would be exempt, and moderate-risk tests could be brought to market through a “technology certification” program requiring companies to demonstrate that they have appropriate internal test validation processes.
Panelists weighing in on the matter were Sarah Thibault-Sennett, director of public policy and advocacy for the Association for Molecular Pathology (AMP); Susan Van Meter, president of the American Clinical Laboratory Association (ACLA); Jeff Allen, president and CEO of Friends of Cancer Research; Lauren Silvis, senior vice president of external affairs at Tempus (which operates clinical labs specializing in cancer); and Zach Rothstein, executive director for AdvaMedDx.
Friends of Cancer Research has had prolonged interest in the VALID Act, says Allen, given the significance of accurate, high-performing tests in guiding the treatment decisions of patients. The goal of the nonprofit think tank is to ensure consistently high-quality diagnostics for diseases treated on a more molecular basis.
AdvaMedDx, which represents IVD manufacturers, is in favor of the VALID Act being part of MDUFA, says Rothstein. It advocates strongly for regulations that are “reasonable” as well as predictable and scientifically based and holds that IVCTs should all come under FDA review with demonstrated safety and effectiveness.
It is no one’s first choice for the FDA to have “informed discretion,” which the VALID Act is seeking to redress, says Silvis, who has a law degree and formerly worked for the agency. Unless regulations are modernized, one way or the other, it will continue to be “hard to find the lines.”
AMP, representing 2,600 molecular professionals, has been engaged in conversations about regulatory oversight of LDTs for many years, says Thibault-Sennett. It is concerned that the VALID Act conflicts with existing regulations and creating legal uncertainties.
It is questionable whether the FDA even has the authority to regulate LDTs, she adds. AMP believes congressional action is needed to update CLIA regulations, as outlined in its 2015 modernization proposal.
Other CLIA-centric legislative options AMP supports include the Verified Innovative Testing in American Laboratories (VITAL) Act of 2021, introduced by U.S. Senator Rand Paul, which would strip the FDA of any oversight of LDTs and instead give the Department of Health and Human Services (of which CMS is a part) sole jurisdiction to regulate such tests.
The challenge for clinical labs is the “uncertain regulatory landscape,” says Van Meter, who has been involved with reform efforts and engaged both sides of the aisle on Capitol Hill. She previously represented IVD manufacturers through AdvaMedDx and has hospital and health system experience. Top concerns of the ACLA are assuring the VALID Act describes a comprehensive, risk-based framework that applies to all IVDs and has an appropriate transition period.
In the view of AdvaMedDx, the VALID Act and CLIA complement one another, says Rothstein, noting that the FDA has decades of experience reviewing diagnostic tests. An “important innovation” introduced with the VALID Act is the technology certification provision that allows for the development of tests within the same scope of a representative test’s approval without going back through FDA review each time. The FDA expects to eventually use the same approach with medical devices beyond IVD, he adds.
Predictability and flexibility are important attributes of legislation that Friends of Cancer Research would support, says Allen, pointing out that the tech cert provision would “cure the blind spot” when it comes to low-risk tests that currently require notification to the agency rather than premarket review. This should ensure that those labs are regularly testing those assays themselves, and that higher-risk tests (including some IVCTs) consistently perform as intended in the real world.
Tech cert is “like an update to IVD regulations,” says Thibault-Sennett. “The problem is that it brings LDTs into the same pathway [as other IVDs].” AMP is proposing different pathways to achieve the same end—a transparent process for ensuring tests all perform at the same level.
Should the VALID Act fail to pass, modernization efforts would nonetheless need to continue, says Silvis. The development of next-generation cancer treatments requires working with the FDA and, in many cases, companion diagnostics. But “not everything needs to come through the [agency].”
The technology certification provision has promise, says Van Meter. “We [ACLA] want to ensure the tests we rely on continue to be valuable.” She highlights the high cost of implementing the VALID Act should it become law, as well as the ACLA’s support of the Saving Access to Laboratory Services Act requiring CMS to use a statistically representative sample of rates from the laboratory market to stop artificially deflating reimbursement rates.
AMP represents small labs that could be harmed by the VALID Act, says Thibault-Sennett. These include many labs situated at academic medical centers, “the training grounds of molecular professionals” where workforce issues might be exacerbated. While sponsors of the VALID Act say it has no common ground with CLIA, AMP members see “substantial sections of overlap” that need addressing. Legislation with greater flexibility will be required for labs to help deal with the next pandemic, she stresses.
Over the past six months, the VALID Act has seen many changes for the better, says Rothstein, including “a lighter touch regulatory process” inclusive of a middle risk tier like the FDA’s De Novo marketing pathway. Implementation also now better aligns with the five-year cycle of the MDUFA process that has just wrapped up.
Recent experience with the FDA’s Emergency Use Authorization (EUA) process demonstrates the importance of being well resourced and having achievable goals and dates, says Silvis. The agency, despite its best efforts, became quickly “overwhelmed” with EUA requests. Avoiding a slowdown in implementing the VALID Act would require plenty of time, setting clear expectations, and planning on the industry side regarding requirements and available templates.
Added responsibilities and resources come with any new regulation and is “no excuse not to pursue this,” says Allen. “It needs to be driven by science independent of where a test is developed [and] not just supported by user fees... [but also a commitment] of public monies.”
The need to submit an EUA application to launch testing for COVID-19 after it was declared a public health emergency is a “case study of how FDA doesn’t have the bandwidth,” says Thibault-Sennett, noting that hundreds of those requests were for LDTs. Even with plenty of monetary resources, she adds, the agency might well have trouble finding the number of people needed to review LDTs in a timely manner. She also questions why the latest iteration of the bill, unlike earlier versions, requires registration and listing of tests even if they are exempt from premarket review.
Van Meter brings up the allowance for a “more robust” third-party review process in the bill, as well as the five-year ramp-up time on IVCT certification. Entities like the New York State Department of Health’s Wadsworth Center are already being used to augment FDA resources in reviewing submissions through the 510(k) premarket pathway, she says.
The understanding reached between the FDA and industry in negotiating user fees is that the agency will boost hiring twofold to increase bandwidth across all divisions, says Rothstein. Those new hires could be seated in the division reviewing IVCTs. But what the regulatory landscape looks like over the longer haul may well depend on results of the mid-term elections this November, he adds.