On January 13, 2017, the U.S. Food and Drug Administration (FDA) issued a discussion paper1 in which the FDA announced that it would delay issuing final guidance on laboratory developed tests (LDTs).2 The FDA cited two reasons for the delay: i) to allow further public discussion on an appropriate oversight approach; and ii) to give Congress, via its oversight committees, the opportunity to develop a legislative solution to LDT oversight.
In lieu of issuing final guidance, the FDA synthesized a large number of previously received comments regarding LDT regulation, and offered a possible approach to regulating LDTs. The FDA notes that its synthesis and possible regulatory approach do not represent a final FDA position and that the proposal is not enforceable. Nevertheless, the possible regulatory approach is interesting because it shows the FDA’s current thinking on regulating LDTs, which has evolved since the FDA issued its 2014 draft guidances.
In the discussion paper, the FDA sets forth a framework for a possible approach to LDT regulation. The framework is prospective, and focuses on new and significantly modified high- and moderate-risk LDTs. Under the framework, previously marketed LDTs would not be expected to comply with most or all FDA regulatory requirements but would be grandfathered.3
Additionally, some new and significantly modified LDTs would be exempted from complying with premarket review, quality systems, and registration and listing requirements, unless necessary to protect the public health. These include: low risk LDTs; LDTs for rare diseases; traditional LDTs; LDTs intended solely for public health surveillance; LDTs used in CLIA-certified, high-complexity histocompatibility labs to perform allele typing, antibody screening and monitoring, or crossmatching in connection with organ, stem cell, and tissue transplantation; and LDTs intended solely for forensic use. The FDA would retain its ability to enforce various levels of regulation in certain situations, including if the LDT was determined to be analytically or clinically invalid, or if there was insufficient data to support the LDTs analytical and clinical validity.4
Similar to what was outlined in its 2014 guidances, the FDA proposes to phase in LDT regulation based on the level of test risk. The discussion paper framework differs from the 2014 guidances in that the FDA proposes to phase in regulation over a period of four years instead of nine months.5 The FDA notes that new tests could continue to be offered to the public during the period of premarket review,6 and that the LDTs would be given two additional years to meet Quality System requirements.7 Registration and listing would occur at the time an LDT receives marketing authorization.8
The FDA also commented on the evidence-based standards for LDTs, noting that the FDA evaluates whether there is a reasonable assurance of analytical and clinical validity for the test, whereas the Centers for Medicare and Medicaid Services (CMS) evaluates whether there is clinical utility for the specific test.9 Thus, the FDA asserts that its premarket review would be “complementary to, and not duplicative of, CMS’s postmarket oversight of laboratory operational processes as well as its determinations of clinical utility.”10 The FDA notes that clinical validity “can often be supported by literature, well-curated databases, or other appropriate sources that meet the valid scientific evidence standard.”11
Under the proposed approach, the FDA would expand its third-party premarket review program to include eligible LDTs.12 The FDA proposes leveraging existing programs, such as New York State’s Clinical Laboratory Evaluation Program and the programs run by organizations approved by the Clinical Laboratory Improvement Amendments (CLIA) to accredit laboratories.13
Other aspects of the FDA’s possible approach include: expanding a collaborative network to develop measurement and review standards for LDT analytical validity;14 transparency—making evidence of LDT analytical and clinical validity available to the public;15 flexibility—allowing test manufacturers to make modifications without creating an undue burden;16 leveraging CMS/CLIA when evaluating LDTs;17 and postmarket surveillance—where laboratories, in some instances, would initially be obligated to report serious adverse events to the FDA, with the future goal of decreasing or discontinuing such reporting efforts by leveraging data collected as a part of clinical practice.18
With the publication of the discussion paper, the FDA’s regulation of LDTs continues to be delayed. The discussion paper’s proposed regulatory framework, although not enforceable, is considerably more favorable to laboratories offering LDTs than the regulatory framework put forth in the FDA’s 2014 draft guidances. Laboratories offering—or planning to offer—LDTs should continue to monitor the evolving LDT regulatory landscape, and should submit comments to the FDA when appropriate.
For questions on LDTs or any other FDA regulatory matter, please contact David Hoffmeister or any member of the FDA or life sciences practices at Wilson Sonsini Goodrich & Rosati.
Compliments of Wilson Sonsini Goodrich & Rosati – a member of the EACCNY