With the deadline for the reauthorization of the Medical Device User Fee Amendments (MDUFA) looming in September, many observers expect that the push for reform in the regulation of in vitro diagnostic (IVD) tests may soon be coming to a head on Capitol Hill.

At its core, the debate boils down to whether regulatory oversight of laboratory developed tests (LDTs) should fall under the purview of the Food and Drug Administration (FDA) or remain under the jurisdiction of the Centers for Medicare & Medicaid Services (CMS), through Clinical Laboratory Improvement Amendments (CLIA).

The discussion can be more broadly understood through the differences between the bicameral/bipartisan Verifying Leading-edge IVCT Development (VALID) Act, introduced on June 24, 2021, by U.S. Reps. Diana DeGette (D-CO) and Larry Bucshon (R-IN) and U.S. Sens. Michael Bennet (D-CO) and Richard Burr (R-NC) and the Verified Innovative Testing in American Laboratories (VITAL) Act sponsored by Sen. Rand Paul (R-KT).

How we got here

While both sides of the conversation have been quick to update their talking points with examples from the nation’s pandemic experience, the debate over which federal agency should exercise regulatory control over IVD tests is longstanding. The pandemic has only served to fuel the argument over whether the industry and public could be better served by a system in which the FDA exercises authority over all IVD tests or whether CMS should maintain regulatory oversight over LDTs.

The legislative and regulatory language of the 1970s and 1980s, which established the current jurisdictional divide, did not—and reasonably could not—anticipate the advances in medical technology or changes in business models since their adoption.

The Medical Device Amendments of 1976 to the Food, Drug and Cosmetic Act (FD&C Act) gave the FDA authority to regulate medical devices sold in the United States and intended for use in humans. The agency exercises this authority through the Center for Devices and Radiological Health (CDRH), which categorizes medical devices across three broad classifications depending upon their potential for patient harm and the associated need for government regulation. Class I devices present the least potential for patient harm and have the shortest pathway to market, while Class III devices have the greatest potential for harm and are consequently the most strictly regulated.

CLIA (42 U.S.C. 263a) provides the U.S. Department of Health and Human Services Secretary (and by delegation, CMS) with the authority to exercise oversight of laboratories, including those which develop LDTs. Approximately 260,000 laboratory entities currently fall under CLIA regulations. Their compliance with CLIA standards is assured through surveys conducted by CLIA “partner” accrediting organizations and/or laboratory programs in the individual states.

The distinction between the authority of the FDA and CMS in the context of emerging technologies has given rise to an especially gray area when it comes to LDTs, and the FDA has been eager to claim the disputed jurisdiction as its own.

In draft guidance released in 2014, the FDA noted that the definition of medical device under Section 201(h) of the FD&C Act, includes “an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is… intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals.”

The FDA argued that it had previously exercised “enforcement discretion” in not asserting authority over LDTs. It contended that while CLIA’s process of biennial certification of laboratories includes assessment of analytical validation—in essence, how well does a test measure what it is intended to measure—it does not pursue clinical validation, i.e., confirming the relevance of the test to a clinical condition.

For the FDA, this means that CLIA review is not sufficient to ensure that LDTs are both safe and effective. The FDA further argued that CLIA does not assess the manufacture of LDTs, require reporting of adverse events, provide for post-marketing review of tests, or include a protocol for the removal of defective tests or devices. CLIA, the FDA contends, is not protecting public safety.

VALID Act

The roots of the VALID Act can be traced to the Diagnostic Accuracy and Innovation Act (DAIA) which was introduced in the House of Representatives as a discussion draft by Rep. Larry Bucshon and Rep. Diana DeGette in March of 2017.

DAIA incorporated input from the Diagnostic Test Working Group (DTWG), an independent coalition of diagnostic manufacturers and clinical laboratories that included such organizations as Roche and LabCorp. The FDA submitted 59 pages of comments as technical assistance to the proposal in August of 2018, including the outline of a pathway for precertification of certain in vitro clinical tests and direct-to-consumer in vitro clinical tests.

Shaped with industry input and sharpened with FDA advice, the principles of DAIA reappeared on Capitol Hill as a discussion draft of the VALID Act in December of 2018. It was introduced as a bill in March of 2020 and again last year.

The VALID Act would give the FDA sole authority over a newly defined category of products: in vitro clinical tests or IVCTs. This category would include both in vitro diagnostic products and LDTs. Along with the elimination of a distinction between LDTs and distributed products would come codification of the regulatory authority the FDA has long asserted it already has.

Key provisions of the VALID Act would:

• Establish a two-tiered framework for the pre-market approval of IVCTs under which high-risk tests would undergo reviews to verify both analytical and clinical validity
• Exempt IVCTs marketed before its enactment, low-risk tests, and tests under emergency use authorizations, while granting the FDA the authority to request information on such IVCTs under defined circumstances
• Establish a process for “technology certification” under which the FDA’s approval of a representative test can be carried forward to its subsequent iterations
• Outline what types of modifications could be made to a test without necessitating subsequent approval
• Establish a “breakthrough” category to incentivize and expedite the development of IVCTs for unmet medical needs
• Establish a system for the reporting of adverse events
• Specify FDA authority to conduct post-market studies
• Provide for the FDA’s establishment or designation of advisory committees specific to the IVCT approval process.

VITAL Act

While the over 245-page VALID Act offers a wealth of specificity, the VITAL Act, at seven pages, reflects a libertarian sensitivity to government regulation. Sen. Paul, the bill’s sponsor, described the VITAL Act as preventing government from “piling counter-productive bureaucratic hurdles in the way of our medical professionals.”

In making his argument for the VITAL Act, Paul pointed to delays in the availability of COVID tests in the United States after the FDA issued an emergency use authorization (EUA) to the U.S. Centers for Disease Control and Prevention (CDC) for a flawed COVID test kit in February 2020. The VITAL Act, according to Paul, would prevent similar delays in the future by making testing resources “quickly and widely available in health emergencies by removing unnecessary government barriers.”

The VITAL Act would:

• Establish CMS’s sole authority over the regulation of laboratory-developed testing procedures, specifying that “no aspects of laboratory-developed testing procedures shall be regulated under the Federal Food, Drug, and Cosmetic Act… including during a public health emergency.”
• Require CMS to hold a public meeting for the purpose of soliciting recommendations on updating existing regulations
• Require CMS to provide a report to Congress including solicited recommendations and an assessment of the availability and use of laboratory-developed testing procedures during the COVID-19 response, including “recommendations to ensure that during future infectious disease outbreaks, the public health system and clinical laboratories do not encounter delays to testing.”

In the public arena

Given that VALID stems from DAIA, which was developed with industry input, it is not surprising that VALID has been supported by most manufacturers of IVD test kits that want to see all IVD tests regulated in the same manner. As Jim Scott, CEO of Applied Policy notes, “VALID is a rare case of industry actually endorsing more regulatory oversight.”

The College of American Pathologists, the Infectious Disease Society of America, and the PEW Research Center have previously expressed for support for the VALID Act.

The VITAL Act is actively supported by the American Association for Clinical Chemistry, the Association for Molecular Pathology, and the Association of Pathology Chairs.

Advocates for both sides have taken to the opinion pages of medical journals to leverage the experiences of the pandemic to their advantage. Writing in the New England Journal of Medicine’s Perspective, Jeffrey Shuren, M.D., J.D., and Timothy Stenzel, M.D., Ph.D., of the FDA argued, “Our experience with COVID-19 highlights the need for a common legislative framework to ensure that all clinical tests are accurate and reliable.”

Meanwhile, in the Journal of the American Medical Association, Eric Q. Konnick, M.D., Jordan Laser, M.D., and Karen E. Weck, MD argued that “flexibility in no way means lax regulatory oversight” and called for “updating existing CLIA regulations to account for the technological and medical advances that have occurred in the decades since the law was written, rather than imposing duplicative regulatory schemes.”

In testimony at a CDRH hearing on MDUFA in Oct 2020, Jeff Allen of the Friends of Cancer Research noted that the current system “does leave open the possibility of variability between different tests that are being used across similar patient populations.”

The time may be now

 The current five-year authorization for MDUFA will expire on September 30 and Congress has begun hearings on its reauthorization. The FDA missed a deadline of January 15 to share a MDUFA commitment letter with Congress, but last week, Politico reported that the FDA and the medical device industry had reached an “an agreement in principle on a framework for MDUFA V.”

Many observers expect that discussions of this “must pass” legislation with a potential financial impact of $1.9 billion, could provide the context, timing, and impetus for the resolving the question of jurisdiction in the realm of laboratory developed tests. Applied Policy will be watching closely and sharing updates with our readers.