FDA Regulatory Oversight is Shifting for LDTs

Laboratory-developed tests, or LDTs, are in vitro diagnostic (IVD) tests designed and conducted in a single laboratory and ordered by a licensed practitioner. By definition, LDTs are not commercially manufactured, marketed, or sold in volume. They are essential to patient care, helping with diagnosis, monitoring, and treatment plans for various conditions. 

The history of LDTs & FDA oversight

LDTs are more complex now than when they were first defined. Initially, they were simple medical tests conducted on a small number of patients processed in the same lab that developed them. Compared to commercial tests, their purpose and scope were limited and low-risk.

In the late 1970s, the U.S. Food and Drug Administration (FDA) started regulating medical devices, including all IVDs. The FDA developed a framework to ensure the safety and effectiveness of commercial clinical laboratory tests. However, given the small scale and low risk of LDTs, the FDA decided to exercise general enforcement discretion for these in-house lab tests. Instead, LDTs are regulated by The Centers for Medicare and Medicaid Services (CMS) through the Clinical Laboratory Improvement Amendments (CLIA). 

Here’s how it works. CLIA certifies clinical labs, ensuring they meet specific laboratory standards and requirements. While the FDA authorizes specific commercial tests, CLIA regulates the lab itself. The lab is then responsible for performing validation studies for its tests and (as a CLIA-certified lab) operating in a professional and high-quality way. According to the FDA, LDTs must be designed and processed in a CLIA-certified lab. 

Over the years, the lack of strict regulatory enforcement over LDTs has allowed many new health-related tests to enter the market (without test-specific scrutiny) under the LDT umbrella. As LDTs expand in complexity and scope, the FDA is reconsidering its role in regulating them. 

This isn’t new. The FDA has been revisiting its oversight of LDTs since 2010; they have held workshops and meetings with stakeholders, drafted guidances, withdrawn draft guidances, issued a discussion paper on the draft guidances, and encouraged further stakeholder discussion. The FDA’s path to oversight of LDTs has drawn substantial and heated debate.

In September 2023, to a mixed and passionate response, the FDA announced a proposed rule regarding LDTs, stating that it intends to phase out its current approach and impose greater regulatory oversight over LDTs. 

LDTs are everywhere

LDTs are vital to everyday healthcare. Today, they include everything from basic routine bloodwork to diagnostic and preventive genetic tests to biomarkers for therapeutic monitoring.

Here are some common examples of LDTs: 

• Routine Screening: Regular health check-ups, such as complete blood counts or cholesterol levels, to monitor general health and detect early signs of disease. 
• Disease Diagnosis: Identification of specific illnesses or conditions, from infections like HIV to chronic diseases like diabetes. 
• Genetic Testing: DNA testing to identify genetic disorders, assess risk factors for inherited conditions, or guide cancer treatment strategies. 
• Therapeutic Monitoring: Tracking the effectiveness of treatments and making necessary adjustments based on test results. 
• Personalized Medicine: Tailoring treatment plans to individual genetic profiles, enhancing the efficacy and safety of medical interventions. 

Over the years, their complexity, impact on medical care, and role in the ever-growing field of personalized medicine have evolved. LDTs have grown in scope, as now a single lab can develop a test and accept samples from large and diverse populations across the country. 

Opposing Viewpoints

The FDA’s move to regulate LDTs in September 2023 triggered a dramatic response from everyone involved: those in favor and those opposed. The FDA received an unprecedented 6000 comments on the proposed rule.  

The FDA’s job is to ensure medical tests in the US are safe and effective for patients. They are haunted by bad actors like Elizabeth Holmes of Theranos, who successfully brought a medical device to market with false claims and fake test results as an LDT (process in a CLIA-certified lab). 

The FDA is concerned about LDTs that provide inaccurate results and LDTs with accurate analytics but invalid test claims about their relationship to disease. An FDA pre-market review evaluates a laboratory test’s analytical validity, clinical validity, clinical utility, test claims, and labeling. 

However, the FDA premarket review process is long, expensive, and, frankly, onerous. Stakeholders who oppose FDA oversight are worried that stringent regulation of LDTs will restrict patient access to essential medical care. 

Hospital-based labs, especially those in rural and underserved areas, won’t have the resources to meet compliance requirements for their LDTs. They will need to consolidate test menus and eliminate local testing options. LDTs developed for rare diseases that don’t serve a broad population and are not commercially viable will be discontinued as investing in an FDA’s submission won’t make sense. This means patients may no longer be able to get the tests they need.   

Stakeholders also worry that introducing FDA oversight of LDTs may stifle innovation and slow meaningful progress in clinical test development–which could negatively impact human health outcomes.

A delicate balance

LDTs are rapidly evolving. The integration of next-generation sequencing and digital health technologies has expanded their capabilities, offering deeper insights into complex diseases and patient-specific treatment options. However, to positively and meaningfully impact health outcomes, LDTs must be accurate, reliable, clinically useful, and easy to understand and act on. 

To ensure this, the regulatory landscape for LDTs is changing. 

The FDA says its approach will balance patient protection with continued access and innovation. Its LDT oversight framework will be prospective and focus on new and highly modified moderate- and high-risk LDTs. The next step, due this month (April 2024), is for the FDA to announce the details of their finalized LDT rule. Finding an approach that satisfies all stakeholders will be a challenge.  

LDTs are at the forefront of biomedical innovation and profoundly impact patient care. As the FDA moves to regulate LDTs, it’s important to consider fostering innovation and advances in lab medicine, ensuring patient access to critical medical tests, providing valid testing options to providers, and protecting patient safety.