Background

The use of Laboratory Developed Tests (LDTs) has grown significantly over the years as they can be used to screen for and diagnose a variety of medical conditions – from manageable chronic conditions and genetic disorders to life-threatening diseases like cancers. Healthcare providers rely on their results to make clinically sound decisions for patients’ treatment plans, so it is paramount these tests are accurate.

The FDA has historically exercised enforcement discretion, choosing not to enforce relevant regulations for most LDTs, or In Vitro Diagnostics (IVDs) developed for clinical use in a single CLIA-certified laboratory. This approach was adopted several decades ago, when LDTs were primarily used to test for specific conditions in smaller populations, making them low-risk. However, on April 29, 2024 the FDA announced its Final Rule on the matter, imposing more stringent regulations on these essential diagnostics as a result of their growing popularity and widespread safety and reliability concerns.

So what does this mean for developers and manufacturers exactly?

LDTs are now designated as devices subject to the more stringent regulation under the Federal Food, Drug, and Cosmetic (FD&C) Act

The large-scale use of LDTs for the testing of larger, more diverse populations from across the country has prompted public health concerns pertaining to their accuracy (i.e. they aren’t as accurate as FDA-regulated tests). Additionally, many rely on instruments and software of high complexity in order to produce results for clinical decision-making, or have been developed from instruments and components that have not been approved for clinical utility.

According to the FDA’s announcement, increased oversight will have the potential to impact health equity by promoting representation of the populations who will benefit from these tests and transparency surrounding unknown performance for certain populations.The Final Rule makes it explicit that IVDs are devices, and must be regulated as such. Laboratories will need to adhere to requirements for premarket review, quality systems, adverse event reporting, device designation, labeling, and more when developing their novel diagnostics. 

While the FDA insists that the Final Rule will result in reduced healthcare spend from eliminating inaccurate and unreliable IVDs offered as LDTs, there are growing concerns over the upfront costs associated with conducting studies to bring existing LDTs up to par with the FDA’s new mandate. Laboratories are limited in the financial support they are able to receive, so they may need to fundraise to execute this research alone or seek relevant collaboration opportunities. Pharmaceutical companies may also need to aid in footing the bill of this research to ensure adequate availability and development of the diagnostics they rely on to validate clinical findings in their own trials.

The FDA will phase out the general enforcement discretion of LDTs over a four-year period

This phaseout period consisting of five stages aims to give manufacturers of LDTs ample time to comply with new requirements without disrupting established patient care. This phase plan was created taking into account over 6,500 comments from the public. 

After four years following the issuance of the Final Rule, LDTs will need to be developed in accordance with the below criteria in order to be continue to performed:

• Stage 1: Adherence to guidelines for medical device reporting (MDR), reporting corrections and removals, and quality systems (QS) pertaining to complaint files by May 6, 2025
• Stage 2: Adherence to labeling, investigational use, registration and listing, and all other requirements not captured in other stages by May 6, 2026
• Stage 3: Adherence to all other quality systems requirements by May 6, 2027
• Stage 4: Adherence to premarket review criteria for high-risk IVDs offered as LDTs by November 6, 2027
• Stage 5: Adherence to premarket review criteria for moderate-risk and low-risk IVDs offered as LDTs by May 6, 2028

There are few exceptions to the Final Rule

Even the Final Rule has its exceptions. The FDA plans to selectively apply enforcement discretion in varying capacities for premarket review and many quality system requirements across specific types of IVDs. The announcement cites just a few examples, including:

• LDTs that entered the market prior to May 6, 2024, including that won’t see significant modification following the issuance of the Final Rule
• LDTs approved by the New York State’s Clinical Laboratory Evaluation Program
• LDTs targeting unmet needs

Currently marketed IVDs offered as LDTs fall under the umbrella of devices operating under the enforcement discretion policy to avoid running the risk of patients losing access to effective and reliable tests as a result of full conformity to the Final Rule. In addition, manufacturers of LDTs that serve “unmet needs” (i.e. testing for rare diseases, utilization of an approved test in an indication/population in which it is not currently approved when no other approved option is available, etc.) will not need to take further action at this time to ensure compliance with the Final Rule.

Conclusion

The FDA stands firm on its decision to regulate LDTs as devices in efforts to mitigate the safety, reliability, and financial concerns of existing and potential problematic diagnostics. This greatly impacts laboratories, IVD manufacturers, and diagnostic sponsors who have not previously sought FDA authorization for their products, as more rigorous testing and analysis will now be required for clinical utility. 

However, the conversation doesn’t stop there, as the FDA has plans to host several webinars over the course of the next few months to provide further clarification and guidance on the matter. The first will be held May 14, 2024.

With an extensive resume in running medical device and diagnostic clinical trials, Lindus Health’s world-class clinical operations team is prepared to assist sponsors in the development of diagnostics that meet the FDA’s new requirements. Learn more about our full offering to diagnostics pioneers here, or contact us to discuss your research.