As promised last year, this Monday FDA released the final rule formally eliminating the 30-year-old “enforcement discretion” for Lab Developed Tests (LDTs) by requiring all such tests to be formally regulated. The final rule contains critical timelines and clarifications and is accompanied by two new guidance documents. New LDTs will cease to exist immediately and those currently available have to start working on compliance activities on Day 1, which is 6 May 2024, this coming Monday.
Regulation of LDTs has been one of the most controversial regulatory issues for the last 20 years. FDA tried to regulate these tests numerous times but repeatedly failed owing to the strong resistance from patients and providers, and weak arguments from the Agency. For an Agency that prides itself on making decisions based on unambiguous data, most arguments presented by the FDA against the enforcement discretion for LDTs were based on anecdotal data and cherry-picking a few cases as examples while acknowledging that tens of thousands of LDTs existed with no obvious red flags. Depending on who you asked, the process for the regulation of LDTs divided the community like no other issue. On one hand, an argument could be made that it is important to have accountability for LDT providers through the FDA, the counter-argument was made that the enforcement discretion was sufficient for tests that are used by few patients under the supervision of physicians. To date, the FDA has acknowledged that it does not have a reliable count of existing LDTs and even in the final rule, made generic statements about the risk of LDTs. Previous attempts at passing a new law for LDTs or finding a compromise with the LDT industry groups failed, leading to the FDA hardline.
Despite thousands of comments to the proposed rule, the final rule is practically unchanged from the draft rule proposed last year with some critical timelines and clarifications. No new LDTs will be allowed from 6 May 2024, the day the final rule will be published. For the LDTs introduced before 6 May 2024, there would be a four-year “phase-out” period with increasing regulatory obligations each year with a goal of all LDTs to be compliant with traditional IVD requirements by the end of Year 4. All dates for compliance start this Monday, 6 May 2024. The “phase-out” period is a misnomer as several requirements start on Day 1. Within one year of Day 1 (by 6 May 2025), LDT manufacturers must be compliant with medical device reporting (MDR) requirements, correction and removal reporting requirements, and quality system (QS) requirements regarding complaint files. By the end of Year 2 (6 May 2026), LDTs must be compliant with registration and listing requirements, labeling requirements, and investigational use requirements. By the end of Year 3 (6 May 2027), all LDTs must be compliant with complete QS requirements not already completed by Year 1. FDA expects PMAs to be filed by 6 November 2028 (3 and half years from Day 1) and 510k applications by the end of Year 4 (6 May 2028).
The proposed timelines for enforcement by the FDA are ridiculously aggressive. First, there is the question of resources needed for these commitments. As we reported earlier, the FDA does not have the resources to review almost 100,000 LDTs currently available. Argumentatively, if the FDA was unable to apply its “enforcement discretion” appropriately due to the lack of resources, how can one expect it to review all these applications and make timely decisions? It would mean an unprecedented increase in hiring by the FDA when it has argued repeatedly that it is finding it tough to recruit and retain new talent. Just recently, the FDA was practically paralyzed by the increased IVDs for just one indication, Covid-19. How can one expect the FDA to handle tens of thousands of unique diagnostics? Second, this would create an unprecedented delay in new IVD reviews and approvals and create a backlog for other activities at the FDA. Again, taking the cue from Covid-19 days when the FDA delayed all non-Covid applications owing to the extra pandemic-related workload. Third, there is practically no time for the current LDTs to meet the requirements. As mentioned above, the compliance activities must begin on 6 May 2024 and must be completed, including the filing of 510k or Premarket Approval (PMA) by 6 May 2028, which is aggressive by any standards.
The industry groups had promised litigation to delay the new rule, and it might happen. But it is hard to imagine going back to the LDT days. LDTs are no more. Anyone in this space needs to move on into the new world where there is only one kind of diagnostic, that which is registered and formally approved by the FDA.
