Monday, April 29, 2024

FDA Publishes Final Rule for LDT Regulation

On Monday, April 29, 2024, the FDA released the final rule for its regulation of LDTs.   The rule had been released in proposed form for public comment last fall.

FDA continues to plan an enforcement deadline of 3.5 years from now for high risk LDTs and 4 years from now for moderate risk LDTs.  However, as FDA had proposed, submitting a PMA (or  510k and de novo) application will "stay the clock" for the duration of its review.  

In thinking about 510K's and PMA's, remember #1 the FDA has promised to downclassify many PMA tests to 510k and #2 has early plans to completely revamp and speed the 510K process.  Consider also wider use of predetermined change plans.

FDA reserves the right to march in faster on "problematic" tests (the word problematic appears 46 times in the final rule, 6 in the draft rule).   

FDA creates several new flexibilities for itself:

  • NYS CLEP: Rule does not generally apply to NYS CLEP approved tests;
    • The term CLEP appears 145 times in the final rule, 1 time in the proposed rule.
    • See ChatGPT Sidebar here.
  • WITHIN SYSTEM: Generally not applying to LDTs "by a laboratory within a healthcare system to meet an unmet need of patients receiving care in the same healthcare system."   
    • (This is similar to a pathway in the new European IVDR system).
    • The term "same healthcare system" occurs 42 times in the final rule, 0 times in the proposed rule. 
    • See ChatGPT Sidebar here
  • GRANDFATHER: Generally enforcement discretion for LDTs marketed prior to the rule, and not altered.
  • VA-DOD: Rule does not apply to V.A. or DOD;
All of the above points are not part of the regulation; they are part of the free-flowing and shape-shifting "discretion" that FDA may use or revisit as leadership changes, without returning to rule-making.  For example, the regulatory change (several words long) says it is "effective" 60 days after publication; that follows a federal law for regulations.  But FDA says that its grandfather date is THE DAY of publication, and chooses that at is own fancy.

See ACLA comment here. ARUP here.  Congr. Rodgers (R) here.  Sen. Cassidy (R) here. AdvaMed here (wait for VALID!). Biopharma Dive here and here.  Endpoints here.  Deep dive day 2 article at Genomeweb here.  See a listing of more articles from FDA GROUP here.  Kevin Nichols here.   Deep dive from Hogan Lovells here.

Massive Down-Shift in Expected Costs

In the Fall 2023 projection, FDA predicted costs to industry to be $40-50B dollars in the first five years (reflecting a impossible workload in man-years).   

In the Spring 2024 final project, FDA expects costs no higher than $500M over the first 3 years, and then onward costs of $1.5B per year.   That works out to about $5B not $50B in the first five years.  Using my own ballpark figure of $200,000 per regulatory professional (fully loaded overhead), that is still 25,000 man-years of regulatory time in the first five years (down from 250,000 man-years in the proposal).

click to enlarge (shows fall table 35, spring table 40, regulatory impact document)

Benefits are still calculated in value per statistical life year (VSLY) (new regulatory impact, page 68ff).  That is, costs continue to be real costs like professional labor and benefits continue to be  projected life-years added or projected deaths delayed by IVDs.

Final Rule Six Times Bigger

The inspection (typescript) copy of the proposed rule was 83 pages; the inspection copy of the final rule is 528 pages, or 6X.  The 528 pages add up to 175,000 words.  


Regulatory Change Tiny; Satellite Rules All FDA Discretion

Most of the important stuff is still "FDA discretion," the actual rule change is only a few words long.   Everything else (like pivotal proposals like grandfathering) relates to FDA internal plans and/or FDA discretion as time goes by.  (E.g. FDA remarks on its ability to change the rules by guidance, p 42.) 



See the FDA webpage for the rule's release here:

See the Fed Reg location for the final rule here. The typeset rule will appear May 6.

See the typescript or pre-publication version of the actual final rule here--528 pages.

See the webpage for regulatory impact analysis here:

See the 178-page final impact analysis here:


See a new guidance document for "public health response" issues absent an actual declared emergency:

See a new guidance document for declared public health emergencies:

More About NYS CLEP

The final rule mentions CLEP 145 times, vs. just once or twice in the proposal.  In my white paper on the proposed rule, I suggested that we should just require CLEP-like reviews - not 510(k) reviews by NYS CLEP, but the CLEP review itself.   ("I think the [FDA"s] accuracy concern could be met by less drastic measures, such as having something roughly the equivalent of New York State review of LDTs.")

FDA notes (FN29) that certain tests exempted from NYS CLEP review are NOT exempted from this FDA rule.

FDA discusses CLEP processes at p.43 ff.   Tests approved under CLEP are still subject to various listing and reporting rules, just like 510K/PMA tests  (p. 47), including labeling requirements [claims].  

AMCs are discussed at page 50ff.  See ChatGPT Sidebar here.

CLEP is discussed again, in the context of response to comments, at p.302ff.

FDA discusses phaseout policy at section V ("5") (p30ff), V.B.2 including CLEP (p. 41ff).

See a Chat GPT sidebar about the FDA's CLEP pages, here.