For over a year, makers of laboratory developed tests (LDTs) have been free of the yoke of US Food and Drug Administration (FDA) premarket review requirements. But on November, the Department of Health and Human Services (HHS) restored order by announcing that the agency will resume premarket review and emergency use authorization (EUA) of new lab tests. Adding to the effect, HHS has also imposed new limitations on which COVID-19 tests will be allowed to reach the market via the EUA pathway. Here’s a rundown of the latest twist in the story of FDA regulation of LDTs during the public health emergency.
How FDA Regulates LDTs
The COVID-19 public health emergency laid bare a truth that the lab industry has been pointing out for decades: the FDA’s makeshift and improvised regulation of LDTs via the premarket pathway is ineffective and blocks badly needed innovative tests from reaching the market. Put into the context of a global pandemic, the need to address this perennial problem assumed a new urgency.
The FDA responded in March 2020 by unveiling a new policy allowing labs to develop and utilize their own tests, provided that they notify the agency that they were shipping products. In May, when it had become clear that the new policy had gone too far in the other direction by allowing unproven tests of dubious value to reach the market, the FDA changed course by requiring EUA for diagnostic tests.
In August 2020, HHS took matters into its own hands by ordering FDA not to require premarket review for LDTs. This latest surprise policy reversal was heavily criticized as another overreaction, one that threatened to undermine the agency’s ability to provide critical advice to test developers and crack down on bad tests.
New Policy Restores Premarket Review of LDTs
With supplies of COVID-19 tests stabilizing and high-profile Class I recalls threatening public confidence in test reliability, HHS has made still another 180⁰ turn by retracting the August 2020 policy of allowing makers of LDTs to bypass the 510(k) premarket review clearance and EUA processes. From now on, LDTs will once more be subject to the historic review rules and won’t receive separate treatment.
Consequences: Test makers currently offering tests launched without submission of an EUA request will have to submit an EUA request. In addition, the agency will review pending EUA request submissions for LDTs. If the agency doesn’t subsequently approve the EUA request, it will notify the test maker who will then have to stop marketing the product within 15 calendar days.
New Limits on Access to EUA Process
But the November 15 new/old policy does more than simply restore the pre-August status quo; it also sets new limits on which SARS-CoV-2 tests will be able to use the EUA pathway. Specifically, FDA will now concentrate on high throughput tests that can be manufactured in large volumes, including at-home and POC tests for use on a prescription and OTC basis. Also receiving priority will be SARS-CoV-2 assays and diagnostics that offer the potential to expand testing capacity, including:
- Tests that can be performed on using specimen pooling methods;
- High-volume, laboratory-based molecular diagnostic tests in which specimens are collected at home and shipped to a laboratory;
- Tests designed for screening asymptomatic populations; and
- Multianalyte and other tests that are capable of detecting multiple different types of respiratory viruses at once.
Access to the EUA pathway will also remain open to laboratory-based and POC high-volume antibody tests that measure the amount of antibodies in a patient’s system, such as fully quantitative antibody tests that measure neutralizing antibodies.
Finally, FDA will also afford priority to tests for which request for EUA clearance comes from a US government entity, such as the Biomedical Advanced Research and Development Authority (BARDA) or the US National Institutes of Health’s Rapid Acceleration of Diagnostics (RADx) initiative.
Here are some of the key new FDA EUAs and clearances announced in November 2021:
New FDA Emergency Use Authorizations (EUAs) & Approvals (NEW)
| Manufacturer(s) |
Product |
| InBios International |
EUA for SCoV-2 Ag Detect Rapid Self-Test, over-the-counter SARS-CoV-2 home antigen test |
| Meridian Bioscience |
EUA for Revogene SARS-CoV-2 molecular test run on firm’s Revogene instrument |
| Talis Biomedical |
EUA for Talis One COVID-19 point-of-care test |
| iHealth |
EUA for COVID-19 Antigen Rapid Test lateral flow assay |
| LumiraDx |
Expanded EUA for use of COVID-19 antigen test to test the asymptomatic |
| BloodHub |
510(k) clearance for version v1.1.0 of BloodRelay blood establishment inventory management software |
| Clever Culture Systems |
510(k) clearance for APAS Independence platform for bacterial culture analysis for use with methicillin-resistant Staphylococcus aureus samples |
| Detect |
EUA for over-the-counter, at-home Detect SARS-CoV-2 Test |
| Ortho Clinical Diagnostics |
510(k) clearance for Vitros Immunodiagnostic Products NT-proBNP II Reagent Pack to measure N-terminal pro brain natriuretic peptide |
| Siemens Healthineers |
510(k) clearance for N Latex FLC Kappa and Lambda IVD reagents to detect kappa and lambda free light chains in serum |
| Roche |
510(k) clearance for Cobas Cdiff real-time PCR nucleic acid test run on firm’s Cobas Liat point-of-care system |
New CE Marks & Global Certifications
Notable European CE certifications announced during the period:
NEW CE MARKINGS IN EUROPE
| Manufacturer(s) |
Product(s) |
| NGeneBio |
HLAaccuTest, NGS-based human leukocyte antigen (HLA) typing assay |
| DiaSorin + MeMed |
Liaison MeMed BV high-throughput, immune-response assay |
| Roche |
New Cobas 5800 molecular instrument |
| BforCure |
Bfast SARS-CoV-2 RT-PCT kit |
| Genetron Health |
Onco PanScan genomic profiling test for cancer |
| Qiagen |
QiaStat-Dx Respiratory 4 Plex Flu A-B/RSV/SARS-CoV-2 test to distinguish seasonal respiratory infection from SARS-CoV-2 |
| Scope Fluidics |
BacterOmic system to diagnose the antimicrobial susceptibility of bacteria causing respiratory, blood, urinary tract and skin infections |
| Agilent Technologies |
Expanded use of PD-L1 IHC 22C3 pharmDx CDx to identify patients with triple-negative breast cancer |
Other international clearances announced during the period:
| Manufacturer(s) |
Country(ies) |
Product(s) |
| Co-Diagnostics |
England |
Logix Smart SARS-CoV-2 DS test |
| Berry Genomics |
China |
Version of Sequel II instrument |
