On August 19, 2020, the U.S. Department of Health and Human Services (HHS) announced the rescission of guidances and other Food and Drug Administration (FDA) issuances concerning premarket review of Laboratory Developed Tests (LDTs). HHS said FDA will not require premarket review of LDTs “absent notice-and-comment rulemaking, as opposed to through guidance documents, compliance manuals, website statements, or other informal issuances.” HHS added that those clinical laboratories seeking approval, clearance, or an emergency use authorization (EUA) for an LDT may still submit a premarket approval application/premarket notification/EUA request, but they are not required to do so.
Although we expect FDA may continue to assert authority over LDTs – primarily through its authority to regulate device components used to make LDTs – this HHS announcement immediately upends more than 30 years of established FDA policy and constructively ends the agency’s authority over a wide variety of LDTs (including a large number of COVID-19 LDT diagnostic tests with already-issued EUAs) unless and until FDA completes a notice-and-comment rulemaking, or Congress changes the law. In any event, no matter what steps are taken by FDA or Congress in the future, the HHS notice will likely have additional, significant, and immediate implications, stirring debate in the months – and possibly years – to come.
FDA history of asserting authority over LDTs
Historically, FDA has asserted authority over LDTs, but generally limited enforcement to LDTs for high risk applications (e.g., cancer screening, prenatal screening, etc.), companion diagnostic uses, direct to consumer applications, tests developed by multiple parties, or LDTs used during emergencies and certain health crises. During the current COVID-19 public health emergency, FDA had been requiring notification and EUA (or state laboratory review) for LDTs used to detect SARS-CoV-2 genetic material, antigens, or patient antibodies. The HHS policy change announced this week now asserts that FDA may not require clinical laboratories to submit any premarket application or EUA submission for an LDT irrespective of what they detect and the risk of the disease for which they are used. For such LDTs used in emergency use contexts, the policy clarifies that those entities developing LDTs in their laboratories without FDA premarket review or authorization will not be eligible for PREP Act coverage.
Whether FDA has authority to regulate these LDTs or not has been a long-debated topic, addressed by multiple stakeholders in many contexts for at least the last 25 years, with the agency asserting that they are medical devices subject to review (but permitted under enforcement discretion unless certain higher risk factors were present). Arguments to the contrary have been made by multiple stakeholders, with all parties generally settling in late 2016 into a status quo that legislative clarity would be needed, but that continued enforcement discretion for most LDTs and specific premarket review for the highest risk LDTs would continue.
HHS’s announcement is a sea change in that status quo, and demonstrates the Department’s current thinking that FDA does not have the authority to regulate LDTs. HHS’s policy change is also not limited in duration to the current pandemic, suggesting that LDTs broadly will not require FDA premarket review unless and until there is a specific regulation promulgated under notice-and-comment rulemaking or new legislative action. Whether or how FDA will seek to counter these arguments will involve reading tea leaves in enforcement actions as we move forward.
FDA will likely continue to assert authority over LDT or LDT parts
In spite of this new HHS policy statement that rulemaking will be needed, we expect FDA will look for ways to assert that it does have authority over some aspects of LDT development and commercialization. It would be feasible, for example, for FDA to try to assert greater control over the parts used to make LDTs, based on the regulations issued relating to these items. These parts include analyte specific reagents (ASRs), general purpose reagents (GPRs), sample collection devices, In Vitro Diagnostic (IVD) products labeled “for research use only” (RUOs), and general purpose instruments.
FDA may also seek to limit the relevance of HHS’s announcement by arguing that the ASR regulations and the preamble to those existing final rules provide a basis for regulating LDTs that are combined with any of these components as “jointly manufactured, regulated systems,” which would thus not be LDTs covered under HHS’s announcement. Similarly, FDA potentially may renew prior enforcement efforts focused on limiting the definition of LDTS to allow enforcement authority over tests that were not developed and validated for use in a single laboratory. Previous FDA policies regarding excluding direct-to-consumer tests from the definition of LDTs subject to enforcement discretion may also be revisited. However, it must be remembered that whatever actions FDA may wish to take to limit the scope or effect of the HHS policy change will be subject to further HHS review and, one must expect, approval. Unless there is a change in administrations in January 2021, it is likely that HHS will carefully scrutinize any further actions by FDA in connection with the regulation of LDTs.
FDA authority over CDx LDTs now moot
In October 2014, FDA issued a draft guidance, never finalized, which provided a risk-based framework for addressing the regulatory oversight of clinical laboratories that manufacture LDTs. This guidance provided the basis for FDA’s authority over companion diagnostic (CDx) LDTs based on risk. With HHS’s recent announcement upending the relevance of FDA guidance documents as a means to establish authority over LDTs, FDA’s premarket review requirements for CDx LDTs now appears to be moot unless FDA asserts that these products do not fall within the accepted definition of LDTs for some reason other than their level of risk. In the weeks to come, we anticipate significant debate over whether FDA may nevertheless be able to retain regulatory authority over CDx LDTs.
States, Congress, and CMS retain authority to regulate labs & lab testing
Clinical laboratories are regulated at the federal level through the Clinical Laboratory Improvement Amendments (“CLIA”), and the HHS announcement regarding FDA regulation of LDTs doesn’t affect those regulations. Labs are regulated under CLIA based on the complexity of tests being performed in the lab, and LDTs can only be performed in labs certified to perform high complexity tests. In addition to the federal CLIA regulatory authority, individual states also have, and will retain, separate authority to regulate labs and lab testing conducted in the state or on specimens from the state. In the context of the COVID-19 pandemic, some states have notified FDA that they are authorizing labs in their state to develop and validate COVID-19 tests separate from the FDA EUA process, and FDA has not objected to that exercise of state authority.
A number of states license and regulate clinical labs separate from the CLIA regulations, and New York state already requires that LDTs (or any test that isn’t FDA-cleared or -approved) be submitted for review and approval by the NY Clinical Laboratory Evaluation Program before it is performed on a specimen from New York. Other states could enact similar rules, or impose other requirements on labs providing LDTs, if they perceive that the rescission of FDA premarket review requirements for LDTs removes safeguards necessary to ensure the safety of LDTs.
Last, it is worth noting that as the coronavirus pandemic continues, Congress has a strong incentive to act on LDT-related legislation, such as S. 3512, the Verified Innovative Testing in American Laboratories (VITAL) Act of 2020, which would place laboratory developed testing procedures within the CLIA process and assess the availability and utilization of laboratory developed testing procedures during the COVID-19 response, and S. 3404, the Verifying Accurate Leading-edge IVCT Development (VALID) Act of 2020, which would establish a regulatory framework to place LDTs in a new product category called in vitro clinical tests (IVCTs).
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