What to Know: FDA Laboratory Developed Tests (LDT) Final Rule

Contributing Expert at Medrio: Tina Caruana, Director of eClinical Solutions

In May 2024, the FDA Laboratory Developed Tests (LDTs) final rule was released.  

According to the FDA, this new policy will help ensure the safety and efficacy of these tests, while assuring patient access and reliance. Meanwhile, many industry leaders oppose the new policy. 

In this article, you will learn: 

What is a Laboratory Developed Test (LDT)?

LDTs are a category of in vitro diagnostics (IVDs) developed by a specific laboratory for use within that laboratory. Until recently, they were exempt from FDA oversight. 

LDTs may be used to measure or detect substances or analytes in the body, such as proteins, glucose, cholesterol, or DNA. This information can be used to diagnose, monitor, or determine treatment for diseases and conditions. 

Examples of laboratory developed tests include:

  • Toxicology panels to identify drug exposure 
  • Toxicology panels to monitor treatment compliance
  • Newborn screening for early diagnosis of serious conditions
  • Panels to monitor organ rejection after transplant
  • DNA testing to detect cancer-associated mutations 
  • Diagnostic tests for rare diseases 

LDTs are often developed out of necessity because no test is commercially available. In some cases, available assays don’t meet the unique needs of a specific patient population. 

The FDA estimates that 80,000 LDTs are currently on the market, with nearly 8,000 new LDTs introduced each year

FDA LDT Regulation: Impact by the Numbers

Laboratory developed test (LDT) vs In vitro diagnostic (IVD)

Typically, IVDs are produced by device manufacturers. Some, however, are produced within a laboratory for use within that same laboratory. This specific type of IVD is called a laboratory developed test (LDT). 

Until now, LDTs were under the jurisdiction of the Centers for Medicare and Medicaid Services (CMS) and exempt from FDA review. IVDs developed by device manufacturers, however, were subject to FDA review. 

Since the final rule, LDTs will be held to the same review process by the FDA as all other IVDs.

Main Takeaways from the FDA LDT Regulation

Until now, the FDA has taken an enforcement discretion approach to LDTs. They are phasing out this hands-off approach. 

In the final rule, the FDA makes it clear that IVDs are devices under the Federal Food, Drug and Cosmetic Act, including when the IVD manufacturer is a laboratory. IVDs manufactured by laboratories will now fall under the same enforcement approach as other IVDs.

The final rule applies to LDTs:

  • Intended for clinical use.
  • Designed, manufactured, and used within a single laboratory.
  • Not yet on the market.

The FDA states that “the risks associated with most modern LDTs are much greater than the risks that were associated with LDTs used decades ago.” 

The agency expressed concern that some LDTs may not provide accurate test results. It also casts doubt on whether LDTs perform as well as FDA-authorized tests and others complying with FDA requirements.

The FDA cites data from the Centers for Disease Control and Prevention (CDC), stating that “70% of today’s medical decisions depend on laboratory test results. Given the role these tests play in modern medical care, their accuracy and validity have a significant impact on public health.”

There are a few exceptions to the final rule, including:

  • LDTs that are already on the market.
  • New LDTs designed to address unmet needs will remain under the former regulatory framework. 
  • LDTs approved by the New York State Department of Health’s Clinical Laboratory Evaluation Program are excluded from premarket review requirements. 
FDA Laboratory Developed Test (LDT) Final Rule and Exceptions

What does this mean for LDT manufacturers?

Under the FDA’s new policy, LDTs are now subject to a more rigorous premarket review process. Manufacturers must register new LDTs with the FDA and report adverse events to the agency.

LDTs will now fall under device requirements, including:

  • Adverse event reporting
  • Labeling requirements
  • Investigational use requirements
  • Quality system requirements
  • Premarket review

Phaseout policy enforcement: Laboratory Developed Tests regulation

Under the final rule, the FDA’s former approach to LDTs will be phased out over four years to address patient access and reliance. 

Stage 1: Beginning on May 6, 2025, the FDA expects compliance with medical device reporting (MDR) requirements, correction and removal reporting requirements, and quality system (QS) requirements regarding complaint files.

Stage 2: Beginning on May 6, 2026, the FDA expects compliance with requirements not covered during other stages of the phaseout policy, such as registration and listing requirements, labeling requirements, and investigational use requirements.

Stage 3: Beginning on May 6, 2027, the FDA expects compliance with QS requirements.

Stage 4: Beginning on November 6, 2027, the FDA expects compliance with premarket review requirements for high-risk IVDs offered as LDTs. If the FDA has already received a premarket submission by the beginning of this stage, then it will continue to exercise enforcement discretion during its review.

Stage 5: Beginning on May 6, 2028, the FDA expects compliance with premarket review requirements for moderate-risk and low-risk IVDs offered as LDTs that require premarket submissions. If the FDA has already received a premarket submission by the beginning of this stage, it will continue to exercise enforcement discretion during its review.

Following this phaseout, the FDA expects LDT makers to meet all requirements. An exception will be made if laboratories can leverage certain requirements under the Clinical Laboratory Improvement Amendments (CLIA).

Phaseout Policy Enforcement: LDT Regulation

Industry Reaction to the Final Rule

Overall, the final rule has not been well-received by the industry. Some experts have raised concerns that the new regulations are problematic. 

Industry concerns include: 

  • Delays or prevention of patient access to innovative diagnostics
  • Reduced patient access to testing
  • Barriers to rare disease testing
  • Slowed testing response to health crises 
  • Prohibitive costs incurred by LDT manufacturers to meet FDA approval

In May 2024, the American Clinical Laboratory Association (ACLA) sued the FDA in an effort to stop the FDA’s new LDT rule. 

The ACLA argues that LDTs are services carried out by laboratory professionals. They argue that the FDA does not have the authority to enforce stricter standards on LDTs, nor regulate them as medical devices, and accuses the agency of regulatory overreach. The ACLA insists that LDTs are federally regulated by CMS under CLIA. 

The Future of LDT Testing

While the phasing in of enforcement is spread across four years, labs making LDTs need to start preparing now to meet these requirements. 

The FDA promises to hold educational webinars, publish guidance documents, provide templates, and participate in conferences to help labs navigate the transition. Any IVD manufacturer can also use the FDA’s question submission process for answers to specific questions.

FAQs About the FDA’s Final Rule for LDTs

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