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New Rules for LDTs

FDA finalized their ruling on LDTs on May 6, 2024. The final rule clarifies that Laboratory Developed Tests (LDTs) are in vitro diagnostics (IVDs) and are considered devices under the Federal Food, Drug, and Cosmetic Act, even if they are manufactured by laboratories. Under the new ruling, laboratories will be required to register their LDTs and undergo the FDA’s premarket review process for medical devices. As part of the new ruling, the FDA is implementing a 4 years phase out policy to phase out its general enforcement discretion approach so that LDTs will generally fall under the same enforcement as other IVDs¹.

The FDA defines Laboratory Developed Tests (LDTs) as in vitro diagnostic products (IVDs) that are intended for clinical use and are designed, manufactured, and used within a single clinical laboratory which meets certain laboratory requirements¹. IVDs are medical devices, medical tests, or examinations that are performed in samples such as blood, urine, or tissue outside the body. They assist doctors in diagnosing diseases or conditions, monitoring health, and guiding treatment decisions.

Previous Regulations

Under the previous regulation, clinical laboratories that develop LDTs were required to be certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) and comply with CLIA regulatory requirements. CLIA ensured that laboratories performing tests on human specimens demonstrated how well they perform using performance characteristics such as analysis of accuracy, precision, analytical sensitivity, analytical specificity, reportable range, and reference interval. CLIA categorized laboratories based on the complexity of the tests they performed, with higher complexity tests subject to more stringent requirements. While CLIA and FDA can be seen as complimentary to each other, CLIA is focused on a specific test in a specific lab with specific staff.

CLIA provided a framework to ensure that the tests performed by labs met certain quality standards, helping to ensure the accuracy and reliability of test results for patient care. CLIA prohibited any test results from an LDT not subject to FDA clearance or approval to be released prior to the laboratory establishing performance specificalities related to analytical validity for use of that test system in the laboratory’s own environment (see 42 CFR 493.1253(b)(2)). Analytical validity was established and reviewed by CLIA, but CLIA did not require the laboratories to establish the clinical validity of the LDT.

FDA cleared or approved devices must establish analytical and clinical validity. The FDA requirements for analytical validity are more extensive which will expand beyond the testing characteristics seen in one laboratory. Historically, the FDA has generally exercised enforcement discretion over most LDTs, meaning that the agency has generally not applied unique requirements to these tests as they were governed under CLIA.

FDA Concerns and Impetus for Change

Over the past few decades, the LDT market has expanded significantly. Initially LDTs were developed in small volume and were performed in specific laboratories. LDTs were considered lower risk. With advancements in technology and increased demand for personalized healthcare, more labs have begun to develop their own tests. Hence, LDTs are being used more frequently to help guide critical healthcare decisions.

Due to the increased use, a debate was sparked on increasing regulatory requirements and oversight on LDTs. The FDA has been concerned about the risks associated with LDTs and has raised concerns about the accuracy, reliability, and safety of LDTs due to the tests becoming increasingly complex and widely used². Errors or inaccuracies in test results can have serious consequences for patient care and outcomes.

Impact on Industry

As a result of FDA’s new ruling on regulating LDTs, companies performing testing will be subject to additional attention and oversight from regulatory authorities. Increased regulation could disrupt the availability of certain tests, potentially causing delays in patient care and diagnostic procedures. Additionally, laboratories, especially those with fewer resources and less experience navigating FDA regulations, may face challenges in process development, validation, compilation of a Design History File (DHF), and many other potential challenges. Applying for FDA premarket review can be challenging for teams who have not navigated this process before. Seeking help from an experienced device development and regulatory team will help you undertake the tasks with a methodical approach.

Global Impact

LDT regulations are also becoming more stringent globally, including in the European Union (EU). The European Commission (EC) released new regulations for In Vitro Diagnostic Medical Devices in 2022, inclusive of LDTs which are also referred to as “In-House IVDs”. More rigorous requirements include having a risk-based classification system, criteria for oversight of notified bodies, rulings on clinical and performance, and stricter controls for high-risk devices. The impact of increasing LDT global regulations, classification and rules are rapidly evolving. Having a thorough understanding of Global regulations is crucial, particularly for companies aiming to launch their products worldwide.

Why Choose Innovenn for your LDT Regulatory Needs?

Our team comprises experts with decades of collective experience in the medical device industry. With a diverse portfolio of projects, we possess an in-depth understanding of product development and regulatory standards. Having successfully navigated numerous premarket review applications, including, CLIA regulation, certifications, 510(k), De Novo, and PMA, we’ve provided comprehensive guidance to our clients throughout the submission process.

Innovenn’s experienced device development and regulatory teams are poised to help you navigate the FDA regulations, evolve your Quality Management System, develop Standard Operating Procedures (SOPs), prepare for audits, respond to audits, file the premarket review applications to enable your company to successfully maintain distribution of your test, while maintaining focus on the patients you care for. By partnering with us, we will work with you to identify risk mitigations associated with regulatory compliance, particularly considering changes resulting from the finalization of the LDT ruling by the FDA.

To learn more about Innovenn’s LDT Regulatory Consulting, contact us to discuss your specific needs.

The LDT (Laboratory Developed Test) Regulatory Landscape