Diagnostic testing has an important role in medical care. The CDC estimates approximately 70% of medical decisions rely on a laboratory test result. The validity of In vitro diagnostic products has a significant impact on the public health, e.g. a false positive can delay a diagnosis and treatment.
Laboratory Developed Test (LDTs) are in vitro diagnostic products intended for clinical use that are used in the collection, preparation, and examination of samples to measure or detect a wide variety of substances, analytes, or markers in human body. LDTs are designed, manufactured, and used within a single clinical laboratory. This clinical laboratory has to be certified under the Clinical Laboratory Improvement Amendments (CLIA) and meet the regulatory requirements to perform high-complexity testing under CLIA.
The FDA initially adopted a general enforcement discretion approach over most LDTs, under the Medical Device Amendments of 1976. At that time LDTs were considered low risk, manufactured in small volume by local laboratories and used to meet the needs of a local patient population. There were some well-characterized standardized tests, but variants were locally allowed.
LDTs are now more widely used for diverse populations with large laboratories accepting specimens from across the country. The evolution and proliferation of LDTs increased concerns about their safety and effectiveness. The FDA has been engaged in discussions with research and clinical communities, holding workshops in 2010 and proposing draft guidance documents in 2014 as well as asserting that medical providers using these tests need assurance that they are safe and effective in guiding good medical decisions.
Recent evidence raises serious questions about using LDT results for medical decisions. In 2015, FDA published a report with cases studies involving inaccurate, unsafe, ineffective, or poor quality LDTs that caused or may have caused patient harm.
In response, FDA proposed a rule for Laboratory Developed Test (LDTs) to amend the definition of “in vitro diagnostic“ (IVD) products in the FDA regulation to clarify that the IVDs are under the Federal Food, Drug, and Cosmetic Act, and include laboratory manufacturers. Additionally, the Act proposes a policy that grants oversight of LDTs through FDA’s general enforcement discretion approach. FDA recognizes that a sudden change to the regulatory landscape could have a negative effect on the healthcare community, that patients have been treated using these IVDs, and that coming into compliance will take time for the manufacturers of LDTs.
FDA is proposing a gradual approach, with a phase-out policy that grants a 4-year period during which LDTs on the market can come into compliance with applicable requirements. The policy has been structured to contain five key stages, during which the general enforcement discretion approach will change at the pace of approximately one stage each year:
- Stage 1: MDR requirements and correction and removal reporting requirements.
- Stage 2: Registration and listing requirements, labeling requirements, investigational use requirements.
- Stage 3: Quality System (QS) requirements. Some of the mandatory QS requirements are Design controls; purchasing controls; acceptance activities; corrective and preventative actions (CAPAs); and records requirements.
- Stage 4 : Premarket review requirements for high-risk IVDs. This stage is set to fall 3-5 years after the FDA publishes their final phaseout policy, but not before October 1, 2027.
- Stage 5: Premarket review requirements for moderate risk and low risk IVDs (that require premarket submissions). This stage is set to fall 4 years after the FDA publishes their final phaseout policy, but not before April 1, 2028.
Because of this proposed rule, current LDTs on the market and upcoming LDTs to the market must undergo the stages proposed by FDA to get approved as an In Vitro Diagnostic Device. RQMIS is here to help navigating the stakeholders on the path forward for their product and get FDA approvals. We will provide the necessary regulatory strategy to put your product either as a high-risk or moderate to low risk IVD and let you know the appropriate next steps.
Based on the FDA’s timeline on the final phase out stage for LDTs (i.e., April 2028), the FDA could publish a final phaseout policy anytime Q1 or early Q2 of 2024. Let’s get a regulatory strategy in place so your team is ready!
