FDA Issues Proposed Rule for Laboratory Developed Tests; Proposes Four Year Phase Out Plan
On Friday, September 29., 2023 the U.S. Food and Drug Administration (FDA) issued a proposed rule targeting laboratory developed tests (LDTs). The FDA stated that the primary goal of this rule is to bolster the safety and effectiveness of these tests, which are increasingly utilized in healthcare decisions. LDTs have faced ongoing concerns due to the increasing complexity and potential risks associated with modern LDTs. The FDA stated that it is worried that some LDTs may provide inaccurate results or perform inadequately compared to FDA-authorized tests and others adhering to FDA requirements.
LDTs, known as in vitro diagnostic products (IVDs), are designed for clinical use within a single laboratory that adheres to specific requirements. These tests are commonly used in analyzing specimens taken from the human body, such as blood, saliva, or tissue, and can detect various substances, proteins, glucose, cholesterol, or DNA, providing crucial information for diagnosing, monitoring, and treating diseases.
The FDA has stated the proposed rule aims to amend FDA regulations by explicitly categorizing IVDs as devices under the Federal Food, Drug, and Cosmetic Act, even when laboratories serve as manufacturers. Alongside this amendment, the FDA is proposing a policy to intensify oversight of LDTs, replacing the general enforcement discretion approach it had historically employed. In the past, the FDA had typically exercised enforcement discretion over most LDTs, meaning it did not strictly enforce applicable requirements for these tests. However,
FDA Commissioner Robert M. Califf, M.D., highlighted the significance of accurate diagnostic tests in modern medical care, stating, “According to the Centers for Disease Control and Prevention, 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.”
Historically, LDTs were lower-risk, low-volume tests primarily used for local patient populations’ specialized needs during the 1970s and 1980s. However, with shifts in business practices and advancements in rapid specimen transport, modern LDTs are now widely used, serving diverse populations and relying on advanced technology and software. They are increasingly performed in high volumes and play a vital role in guiding critical healthcare decisions.
The FDA believes this proposal promotes responsible innovation for both laboratory and non-laboratory IVD manufacturers by enhancing the safety and efficacy of IVDs offered as LDTs. It also eliminates disincentives for non-laboratory manufacturers to develop novel tests. Currently, the competitive landscape can discourage in-vitro diagnostic equipment manufacturers from innovating, as they are required to adhere to FDA requirements, while laboratory manufacturers do not.
Key Regulatory Changes:
LDTs will face premarket submission requirements, similar to class II or class III medical devices. This means that laboratories developing LDTs will need to obtain FDA clearance or approval before marketing these tests. Laboratories will be expected to adhere to Quality System (QS) regulations, ensuring the consistency, reliability, and quality of their diagnostic tests. Requirements for medical device reporting will apply, obligating laboratories to report adverse events associated with their LDTs to the FDA. Laboratories offering LDTs will be required to register with the FDA and list their diagnostic tests, enhancing transparency.Laboratories developing LDTs will incur various medical device user fees, including annual registration fees, premarket application fees, and annual fees for periodic reporting for class III devices.
Phased Transition: The FDA proposes a phased transition from the current enforcement discretion approach to full regulatory compliance. This multi-stage transition spans four years and is structured according to risk categories of In Vitro Diagnostic Devices (IVDs).
- Stage 1 (One Year): The general enforcement discretion approach will cease concerning medical device reporting (MDR) and correction and removal reporting requirements.
- Stage 2 (Two Years): Enforcement discretion will end for requirements other than MDR, correction and removal reporting, and premarket review requirements.
- Stage 3 (Three Years): The enforcement discretion approach will terminate for QS requirements.
- Stage 4 (Three and a Half Years): High-risk IVDs will see an end to enforcement discretion regarding premarket review requirements.
- Stage 5 (Four Years): Enforcement discretion for moderate and low-risk IVDs requiring premarket submissions will conclude.
The FDA recognizes certain categories of LDTs that will continue to benefit from the existing enforcement discretion approach. These include 1976-Type LDTs, Human Leukocyte Antigen (HLA) tests, forensic purposes tests, and those exclusively used for public health surveillance activities.
The FDA has initiated a 60-day comment period to gather feedback on the proposed rule. Key areas of interest include the potential grandfathering of currently marketed LDTs, tailored enforcement discretion policies for specific public health scenarios, potential unintended consequences of the phaseout policy, and considerations for academic medical center laboratories (AMCs) operating under unique circumstances.
The FDA has issued draft guidance documents multiple times in the past but has balked at issuing final regulatory guidance for LDTs to date given significant push-back from the industry. Congress has also proposed legislation to regulate laboratory developed tests. The VALID (Verifying Accurate Leading-edge IVCT Development) Act, a piece of legislation aimed at providing the FDA with regulatory authority over Laboratory Developed Tests (LDTs), had been under development since 2018 and was formally introduced to the House in 2021. Its primary objective was to empower the FDA to oversee LDTs, addressing concerns surrounding their safety and effectiveness. In December 2022, the VALID Act was attached to a year-end omnibus spending package. However, despite its inclusion, provisions aimed at enhancing the regulation of diagnostics, which the VALID Act intended to address, were ultimately left out of the final version of the legislation.