Laboratory developed tests (LDTs) are in vitro diagnostic devices (IVDs) for use in clinical settings and play a vital role in the health industry. LDTs are still regulated by the federal government, via the Department of Health and Human Services (HHS) and the Food and Drug Administration (FDA) under the Public Health Service Act. Laboratories manufacturing LDTs must not only meet regulatory requirements but also maintain certification under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). As the term suggests, these tests are developed and are to be used in one specific laboratory for the gathering of human health information through the detection and measurement of substances and body markers (proteins, cholesterol, etc.), which will also assist in the diagnosis and treatment of certain conditions. LDTs, which until now have not been classified as medical devices, have not been required to undergo a premarket review by the FDA and as such, there is a lack of understanding of their safety and effectiveness. LDTs were once developed for low-risk indications, but as more complex processes and higher risk indications have been used, there are concerns over the validity and accuracy of the tests and potentially negative effects on healthcare decisions leading to a need to readjust the thinking behind the FDA’s oversight and control. The call is now for LDTs to be considered as medical devices and to require FDA review, similar to how diagnostics are managed. Without this, information as to the number of LDTs in existence or the identification of which labs have used them is unknown and, to make matters worse, there is no traceable data as to the test results and/or problems with the test themselves.
This has now been addressed. On October 3, 2023, the FDA’s proposed a rule to amend its regulations to make explicit that in vitro diagnostic products (IVDs) are devices under the Federal Food, Drug, and Cosmetic Act (FD&C Act) including when the manufacturer of the IVD is a laboratory (Federal Register :: Medical Devices; Laboratory Developed Tests). As stated in the notice of proposed rulemaking, the standard 60-day comment period is in effect. It is advised that comments on the proposed rule must be submitted to the docket by December 4, 2023, in accordance with the procedures described in the notice.
The FDA plans to phase out the 1970s enforcement discretion of LDTs in such a way as to avoid disruptions in the market. This five-phase approach is being proposed to be completed over a five-year period. Beginning (stage 1) with the requirement that LDT manufacturers, like all IVD manufacturers, will need to comply with medical device requirements for corrections and removals, as well as medical device reporting. This first phase will be mandatory within the year following the finalization of the proposed rule. Moving forward within the next 3.5 years and by phase four (but no later than Oct. 1, 2027), high-risk LDT manufacturers will need to follow the QMSRs and comply with premarket review requirements. In phase five, the timeline expands to April 1, 2028 allowing for four years for low and medium-risk manufacturers to meet these same requirements. It should be noted that the rule would not apply to all LDTs currently on the market.
It should be noted that the rule would not apply to all LDTs currently on the market and if finalized in its current state, finalized as written, enforcement discretion for certain LDTs (e.g., for blood or tissue screening, emergency use, and forensics) would continue. FDA has shown itself to be flexible in consideration of alternate methods of enforcement. Take for instance LDTs made in academic medical centers which have provided the strongest opposition to the ending of the enforcement discretion due to added burdens.
What are some benefits? While hard to quantify, benefits would be realized in circumventing health losses that may have occurred due to problems with IVDs that were marketed as LDTs. Additionally, reductions in costs in the healthcare systems and potential legal actions would also be favorable. Currently, an IVD manufacturer would probably not consider developing tests because of the competition they would face with laboratories that are manufacturing unregulated tests, but regulating LDTs would solve this issue.
As with many governmental actions, this could take a significant amount of time, given the amount of public comment that will need to be reviewed and considered prior to a final rule and subsequent implementation. In that time, Congress could pass the Verifying Accurate, Leading-edge IVCT Development (VALID) Act, making IVDs diagnostic devices, and rendering the LDT rule a non-issue.
