The fate of U.S. Food and Drug Administration (FDA) regulation of laboratory-developed tests (LDTs) seems to be in limbo after a previous announcement from the Department of Health and Human Services (HHS) that stated that the agency does not have the authority to regulate LDTs was removed from the HHS website.
In August 2020, HHS had announced that the FDA does not have the authority to require premarket review of LDTs unless the agency goes through a lengthy rulemaking process. This meant that makers of any new LDTs no longer needed FDA review to demonstrate the accuracy of their products. Until the HHS announcement, the FDA had maintained that it had enforcement discretion over LDTs, although it rarely exercised that discretion. While the FDA’s initial announcement referenced LDTs to test for SARS-CoV-2, the virus that causes COVID-19, HHS later clarified that the decision applied to all LDTs. This announcement drew mixed reactions.
Groups representing clinical laboratories praised the decision, saying they appreciate that HHS recognizes the importance of flexibility for laboratories to innovate. But groups representing cancer treatment providers expressed concern about the decision, saying it puts Americans at risk and that oversight of LDTs should be updated, not dismantled.
“FDA has been judicious in its interventions with LDTs, providing a largely hands-off approach while addressing dangerous tests and bad actors,” said Lisa Lacasse, president of the American Cancer Society Cancer Action Network (ACS CAN), in an August 21, 2020, press release. “Preventing FDA from exercising oversight over LDTs, especially during a pandemic, creates an environment where consumers may receive inaccurate test results, or worse, be subjects of fraudulent testing, potentially diminishing faith in the diagnostic testing ecosystem.”
Removal of the announcement from HHS’s website could indicate that the Biden Administration has different ideas about how LDTs should be regulated; however, the administration has not yet made its views known publicly.
In a January 11, 2021, issue brief on clinical laboratory testing, The PEW Charitable Trusts seems to support ACS CAN’s position, pointing out that LDTs now number in the tens of thousands and in some cases have become more complex and widely used, increasing the potential risk to public health.
PEW notes that the FDA has approved more than 30 companion diagnostics, which are intended to guide the safe, effective use of a particular therapy. Once companion diagnostics are approved by the FDA, clinical laboratories often develop their own tests to identify the same mutations. “Because individual labs may have different approaches to analyzing samples—particularly for newer, more complex tests—the same patient may get different results depending on the LDT used,” said the brief. “Though some variability in test results is normal, FDA review would set baseline requirements for test performance and validity, which would ensure greater consistency across testing sites and reduce the likelihood of incorrect results being reported back to patients.”
Some LDT developers also claim to test for additional mutations that have not been adequately reviewed to predict drug response, said the brief, arguing that the use of unapproved companion diagnostics can present significant risk to patients, who may receive ineffective therapies for a condition or miss out on more beneficial ones.
PEW believes the solution is for Congress to pass legislation that establishes a unified, risk-based FDA regulatory system for diagnostics, including LDTs. Specifically, PEW supports passage of the Verifying Accurate and Leading-Edge IVCT Development (VALID) Act, which would set out a regulatory framework for in vitro clinical tests (IVCTs) covering an array of tests, including LDTs and in vitro diagnostics. Groups representing clinical laboratories largely oppose the VALID Act, saying that it would give the FDA new, expansive powers to regulate LDTs and would decrease patient access to essential tests. The VALID Act, introduced in spring 2020, failed to pass last year, but likely will be reintroduced this year.
In comments on the VALID Act submitted to lawmakers last fall, the American Clinical Laboratory Association (ACLA) said that any new statutory framework should balance government oversight with the need for flexibility, innovation, and timely responses to emerging public health threats. ACLA also urged the boundaries of jurisdiction be clearly defined between the Centers for Medicare and Medicaid Services (CMS) and the FDA, and that the new regulatory framework not be redundant, conflicting, or superfluous to the existing framework under the Clinical Laboratory Improvement Amendments (CLIA).
“Laboratories serve a critical function in the health care system and need clarity and certainty about how these life-saving services are regulated,” said Thomas Sparkman, ACLA’s senior vice president of government affairs and policy, in an email to Clinical Lab Manager. “Over the past several years, ACLA and our members have been actively working with stakeholders to advance comprehensive statutory reform for clinical laboratory diagnostics. It’s critical that any modernized framework ensure sustained innovation for patients and provider, and support continued access to the laboratory tools necessary for diagnosis, monitoring, and treatment of disease.”
Michael Ryan, JD, a partner with McDermott Will and Emery (Washington, DC), says there are still some major areas of disagreement on the VALID Act that would need to be worked out before the bill is approved, including classifications of risk, eligibility for technology certification, and FDA oversight of test modifications.
“I think there is a fair amount of substantive work to be done on the bill itself,” he says. “Ultimate support will depend a lot on the details.”
Whether an agreement on the bill can be reached this year is unclear, adds Ryan, who notes that there may be a greater chance of passage in 2022 when the Medical Device User Fee Amendments (MDUFA) come up for reauthorization. Because laws reauthorizing user fee programs are so critical, they are considered must-pass legislation. Lawmakers often use these must-pass bills as an opportunity to pursue “riders,” legislative provisions that are not part of the agreement negotiated between the FDA and industry but that are related to some aspect of FDA regulation and oversight.
“If stakeholders can reach agreement, MDUFA seems a logical vehicle to address some of these issues concerning FDA oversight,” says Ryan.