The Basics of the FDA’s Proposed Rules for Laboratory Developed Tests

David G. Grenache, PhD, D(ABCC) and Melissa M. Budelier, PhD, D(ABCC)
March 1, 2024


David G. Grenache, PhD D(ABCC), TriCore’s Chief Scientific Officer, and Melissa M. Budelier, PhD D(ABCC), TriCore’s Medical Director of Clinical Chemistry and Toxicology, were interviewed for this article.

On September 29, 2023, the Federal Drug Administration (FDA) proposed rules to regulate laboratory developed tests (LDT). These rules could significantly affect patient care and labs nationwide. During the comment period, which ended December 4, 2023, TriCore provided comments to the FDA listing the potential consequences of these proposed rules.

On January 18, 2024, the FDA and the Centers for Medicare & Medicaid Services issued its own joint statement, reiterating their reasons for the proposed rules.

The purpose of this article is to educate the public on the potential consequences of these proposed rules.

What Are Lab Developed Tests?

Most lab tests are commercial tests, which are regulated by the FDA, are manufactured by companies, and globally marketed to laboratories. In contrast, LDTs are created, validated, and used within a single laboratory and are not sold as test kits to other laboratories or healthcare facilities. LDTs are already regulated under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) and can be performed by laboratories certified by CLIA to perform high complexity testing.

“Lab-developed tests are designed to fill gaps not addressed by commercial tests and to meet specific, local needs. Commercial tests, in contrast, typically are designed to diagnose major conditions found in large populations.” Therefore, Melissa Budelier says, “The idea of FDA regulation for LDTs is concerning, because LDTs and commercial tests serve two different purposes.”

G2 INTELLIGENCE: LAB INDUSTRY ADVISOR, FDA Proposal for LDTs Risks Serious Consequences November 2023.

What Are the FDA’s Proposed Rules and Their Possible Consequences?

The FDA’s proposed rules seek to regulate LDTs in the same way as commercial tests, which require more stringent regulations. The proposed rules could compromise patient care and labs across the country. Here are a few of the consequences:

  • They would cause a dramatic shift in how LDTs are regulated, forcing laboratories to make difficult decisions about which LDTs they can continue to offer, which in turn would disrupt patient access to much needed diagnostic tests.
  • The cost of compliance for submitting an LDT for FDA review and approval can take years and can cost hundreds of thousands of dollars, an expense many laboratories could not afford.
  • They would stifle innovations and hinder the ability of laboratories to develop tests needed to address emerging needs such as tests to detect novel drugs of abuse.

Approximately 20 percent of TriCore’s test menu would be classified as LDTs under the current definition. Examples of LDTs TriCore currently performs are:

  • Tacrolimus, an immunosuppressive drug, is used for post-transplant organ rejection prophylaxis. Therapeutic drug monitoring (TDM) of immunosuppressants is essential for ensuring optimal care with transplant patients. The predominant methods for TDM include immunoassays and liquid chromatography-mass spectrometry tests.
  • Thiopurines, which possess immunosuppressive properties, are used to treat certain cancers and autoimmune disorders. However, they can cause elevated toxicity levels. Genetic testing for TMPT and NUDT15 genes play a vital role in individualized dosing of thiopurines, enabling reduced toxicity without compromising efficacy.

What Is the Industry’s Response to the Proposed Rules?

When the FDA announced the proposed rules, pushback was immediate. Thousands of organizations and laboratory trade associations issued submission letters during the comment period, which ended December 4, 2023. The American Clinical Laboratory Association (ACLA) is at the forefront of the resistance, submitting a 107-page document that outlines “grave concerns” and urges the FDA to withdraw the proposal. A 26-page analysis by a George Washington University professor of public policy and public administration was submitted. Hospitals and healthcare provider groups, like the American Hospital Association (AHA), also oppose the FDA’s proposal.

Tricore has also responded:

  • Grenache and Budelier have been interviewed by various healthcare publications on the potential consequences of proposed rules.
  • TriCore has engaged New Mexico U.S. Senators Ben Ray Lujan and Martin Heinrich about the concerns with the proposed rules.

What Happens Next?

The FDA plans to finalize its controversial rule seeking to assert regulatory authority over LDTs by April 2024. This action would avoid a lookback period for so called “midnight rules” under the Congressional Review Act and avoid Congressional scrutiny.

“The last time I looked, there were at least 2,500 submissions, so it’s going to take them some time to read all of that,” said Dr. Grenache. “I’m putting on my future goggles and say the FDA will probably make some modifications to their rules based upon what was shared, but I doubt they’re going to do a U-turn and say ‘oh, forget it, we’re not going to pursue this anymore.’”