The End* of a Long and Winding Road: FDA Publishes Final LDT Rule (*Or Is It?)

On April 29, 2024, FDA announced its finalization of the laboratory developed test (LDT) rule.  The final rule will be published in the Federal Register on Monday May 6, 2024 (here).  The final rule marks another milestone in the more than three decades long battle over LDTs.  FDA notes that it received over 6,500 comments on the proposed rule.  Showing how motivated FDA was to quickly finalize the rule, the Agency claims to have reviewed and addressed all major issues they raised in less than 5 months.

As regular readers of the blog know, we have written about LDTs many times before.  In this post, we focus on the final rule.

Overview of the Rule

In short, the Final Rule makes explicit that LDTs are, in FDA’s view in vitro diagnostic devices subject to FDA regulatory oversight, and always have been.  With the Final Rule’s publication on Monday, May 6, 2024, it will start the countdown to a four-year, 5-phase transition away from what FDA deems to have been its exercise of enforcement discretion for LDTs.  (The rule’s effective date is 60 days after publication.)  Below we provide a brief summary table of the phases and timeline.  These did not materially change from before.

Table 1: Phase-Out Policy Stages, Timeline, and Requirements

Not all LDTs will be required to comply with all aspects of the phases above.  One of the most interesting aspects of the final rule is the exemptions that FDA established.    FDA has created a number of categories of tests for which FDA intends to exercise enforcement discretion.  These largely did not appear in the proposed rule.  In the table below, we summarize the types of devices for which FDA intends to exercise varying levels of enforcement discretion.

¹ In addition to standard registration and listing information, FDA is requiring the submission of labeling pursuant to 21 C.F.R. § 807.26(e) to obtain “information on test performance and a summary of the supporting validation, among other things.”  Public Inspection version p. 47, 58, 59.

² While required, FDA explains that compliance with NYS CLEP clinical laboratory standards could satisfy the required portions of the QS Regulation with the exception of the design control requirements in 21 C.F.R. § 820.30.

³ This exemption is limited to the portions of the QS Regulation other than the Records requirements in 21 C.F.R. Part 820, subpart M.

Things People Aren’t Talking About But Should Be

While significant focus on the nuts and bolts of the final rule has been paid by the press and others, including the phase out periods and enforcement discretion carve outs, there is a lot more in this final rule, which comes in at 528 pages (in the Public Inspection version).  Below we discuss some of the notable points from the rule.  Note: there are no shortage of interesting points in this Final Rule and these are just a select few.

Revisionist History.  FDA claims that it has exercised enforcement discretion since 1976 over LDTs.  That would be rather shocking considering that the concept was only first introduced publicly by the Agency in 1992 (see earlier post here).  (Back then, LDTs were called “home brews.”  While FDA repeatedly disparages LDTs as unsafe, it has at least dropped this disparaging term.)  This revisionist history appears to be part of the Agency’s attempt to claim jurisdiction over LDTs dating back to the enactment of the Medical Device Amendments.  (This is roughly analogous to the statement that “Oceania had always been at war with Eurasia” in 1984.)

LDTs are Illegal.  Almost as disturbing as FDA’s revised history is its bald statements that LDTs are, and always have been, illegal.  FDA states, “Although FDA is phasing out its current general enforcement discretion approach over a period of years, the phaseout policy does not in any way alter the fact that it is illegal to offer IVDs without complying with applicable requirements.”  Of course, the natural consequence of saying that LDTs are allowed only on sufferance through FDA’s exercise of discretion means that every LDT is illegal, but FDA here is blunter in its language.

FDA’s Claims Regarding NY State Experience.  FDA notes as evidence of LDTs lacking appropriate analytical and clinical validity that New York State Department of Health Clinical Laboratory Evaluation Program (NYS CLEP) couldn’t approve more than half of initial applications because of deficiencies such as, including inadequate validation data.  Only needing to ask questions regarding deficiencies in approximately half of submissions actually sounds like the lab industry submitting to NYS CLEP is doing quite well in these authors’ opinion.  By FDA’s logic, the entire medical device industry must be in total shambles because in the last 10 fiscal years (FY14-24) in the first cycle review, between 63 and 78% of 510(k) submissions receive a request for additional information meaning that it could not be initially cleared without addressing various deficiencies. See page 107 of FDA’s 1^st Quarter FY2024 MDUVA V Report (here).  The real issue is how many tests were ultimately approved, not how many raised questions in the initial submission.

FDA’s Stance on Collection Devices.  While some of the enforcement discretion carve outs may be modestly helpful, even labs that enjoy certain enforcement discretion may not be free from regulatory oversight.  Footnote 21 states, “We note that “IVDs offered as LDTs” does not include IVDs manufactured or used outside of a laboratory, including collection devices.”  In recent years, we have seen FDA challenging use of common collection device materials in LDTs.  Thus, labs will need to ensure that the collection materials they employ are being used for their on-label purpose.  If not, FDA may claim that the lab needs to seek clearance/approval for the collection device.  FDA’s attacks on collection devices can provide a backdoor route to challenge LDTs that enjoy continuing enforcement discretion.

FDA Collection and Review of Labeling.  As noted above in Table 2, FDA is requiring that certain LDTs submit, as part of its device listing process, copies of a to‑be‑listed LDT’s labeling. FDA notes that it views the labeling requirements of 21 C.F.R. Parts 801 and 809 as potentially being “encompassed in more than one document, such as the test protocol, test report template, and test menu.”  See response to Comment 176.  Thus, affected labs will be required to submit to FDA significant amounts of information as part of the device listing.  What will FDA do with this information?  The Final Rule states, “This labeling will facilitate FDA surveillance for potentially poor performing LDTs that should otherwise be addressed.”  Public Inspection version p. 58.  What is a “poor performing LDT?”  How will FDA assess performance?  Will FDA give a lab the opportunity to address any claims of poor performance or will such tests be required to exist the market?  Bottom line – while these tests are “exempt” from the premarket approval/clearance process, FDA appears to still be reviewing them and perhaps with less transparency than would otherwise occur in the ordinary course.

What Happens Next

The Final Rule will become effective in 60 days, on Friday July 5, 2024.  In a sort of reverse Independence Day for labs, all labs offering LDTs will be on a ticking clock to begin efforts to comply with the various stages of the phase out plan, as applicable.  One looming question for many in this space is – what happens to new tests?  While the preamble to the rule is not expressly clear, it appears that new LDTs can continue to enter the market so long as they comply with the requirements at the time (i.e., per the Phase Out Policy Stages, see Table 1 above).  Of course, as time goes by, some labs will not be able to meet these timelines, and so some tests will not be introduced or their introduction will be delayed.

While there will almost certainly be a legal challenge to the final rule, how such a challenge could affect the timeline for implementation is not clear.  It took 32 years from the first challenge to FDA regulation of LDTs to today.  If there is litigation, this next phase will be resolved far faster.