October 23, 2020
Entrepreneurs, scientists, and politicians all recognize the important role of testing for the Coronavirus Disease 2019 (COVID-19). Manufacturers and laboratories commenced the development of various types of tests almost as soon as COVID-19 was declared a public health emergency. Tests fall into one of three categories: diagnostic, serology/antibody, or tests for management of COVID-19 patients. This article briefly reviews the types of authorized tests and recent regulatory measures taken to enhance consumer confidence in them.
Diagnostic tests detect parts of the SARS-CoV-2 virus and can be used to diagnose infection with the virus. Tests within this category include molecular tests and antigen tests. Between March 15, 2020 and October 13, 2020, the Food and Drug Administration (FDA) issued 182 Emergency Use Authorizations (EUA) for individual molecular diagnostic tests. A complete list of the individual EUAs issued for molecular diagnostic tests is available here.
On March 31, 2020, the FDA issued an umbrella EUA for molecular laboratory developed tests (LDTs) for detection of SARS-CoV-2 that meet certain criteria for eligibility described in the EUA. Under this EUA, tests are authorized for use in the single laboratory that developed the authorized test and that is certified under Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a to perform high complexity tests. A manufacturer may request the addition of an eligible molecular-based LDT to Appendix A by submitting a request to CDRH-EUA-Templates@FDA.HHS.GOV. Between April 2, 2020 and September 22, 2020, the FDA issued 35 EUAs for molecular LDTs. A complete list is available here.
The FDA issued six EUAs for antigen diagnostic tests between July 17, 2020 and October 13, 2020. A complete list of the approved antigen diagnostic tests is available here.
The Department of Health and Human Services recently announced that the FDA will not require premarket review of LDTs in an effort to alleviate the regulatory burden upon laboratories developing these tests and expedite availability. Laboratories opting to use LDTs without FDA premarket review or authorization may do so with the understanding that they forsake PREP Act coverage eligibility without approval, clearance or authorization and remain subject to regulation by the Centers for Medicare & Medicaid Services (CMS) under CLIA, 42 U.S.C. § 263a, and its implementing regulations at 42 C.F.R. pt. 493. However, laboratories developing LDTs may voluntarily submit to the EUA review process. In order to make the best use of its resources, the FDA has prioritized its review of EUA requests for point of care (POC) tests, home collection tests, at-home tests, tests that reduce reliance on test supplies, and high-throughput, widely distributed tests, according to an October 7, 2020 updated Q&A.
Serology/antibody tests detect antibodies to the SARS-CoV-2 virus, including IgM and IgG. These tests should not be used to diagnose a current infection. On April 28, 2020, the FDA issued an umbrella EUA for SARS-CoV-2 Antibody tests (Lateral flow or Enzyme-linked immunosorbent assay [ELISA] tests) evaluated in an independent validation study performed at the National Institutes of Health’s (NIH) National Cancer Institute (NCI) or by another government agency designated by the FDA, and are confirmed by the FDA to meet the criteria set forth in the Scope of Authorization of the EUA. The FDA subsequently revoked that umbrella EUA on July 21, 2020. The FDA has issued 56 individual EUAs for SARS-CoV-2 serology/antibody assays between April 15, 2020 and October 9, 2020. Notably, the FDA revoked an EUA for a rapid test on August 6, 2020, following another revoked EUA for an antibodies test on June 16, 2020, due to concerns about detection effectiveness and public safety. The FDA’s revocation of these tests for antibodies should assure the public of its commitment to safety and transparency. For more information about the EUAs relating to serology and antibody tests, click here.
Tests for Management of COVID-19 Patients
Tests for Management of COVID-19 patients are tests that go beyond detection of the virus or antibodies, but have been authorized for use in the management of affected patients to detect other biomarkers, such as those related to inflammation. As of October 1, 2020, only two EUAs have been issued for the management of COVID-19 patients: one to Roche Diagnostics on June 2, 2020, and another to Beckman Coulter, Inc., on October 1, 2020. Details are available here.
Recent CMS Activity to Protect Integrity of COVID-19 Testing
On October 9, 2020, CMS announced measures taken to protect the integrity of COVID-19 testing by ensuring CLIA certifications are both accurate and current. In a review of records conducted since August 12, 2020, CMS issued 171 cease and desist letters to testing laboratories after determining deficiencies with their CLIA certification. Of those 171 letters, 66% were issued to facilities testing outside the scope of their CLIA certification. The remaining 34% were issued to facilities testing without a CLIA certificate at all. All of those entities were ordered to stop immediately and required to provide CMS an attestation certifying their cessation of COVID-19 testing.
CMS educated the non-certified laboratories with information about the CLIA certification process and encouraged the non-compliant certified CLIA labs to obtain appropriate certification. To make the CLIA certification process more user-friendly, CMS has developed and released a guide to assist labs with the application process. The quick start guide walks laboratories through the expedited application process.
States play an important role in the CLIA certification process as each state has one designated agency responsible for reviewing the CLIA application process. The South Carolina Department of Health and Environmental Control (SC DHEC) regulates CLIA certification for laboratories in the State of South Carolina. Questions or concerns regarding the application or compliance process may be directed to:
SOUTH CAROLINA DEPARTMENT OF HEALTH & ENVIRONMENTAL CONTROL
Bureau of Certification/Health Regulation
2600 Bull Street
Columbia, SC 29201
(803) 545-4291; FAX (803) 545-4563
Recent CDC Guidance for Point of Care Testing
On October 14, 2020, the Centers for Disease Control and Prevention (CDC) issued Guidance for SARS-CoV-2 Point of Care Testing. POC testing allows for rapid results and may occur in a variety of clinical settings. Common point of care clinical settings include physician practices, schools, nursing homes, urgent care clinics, and drive through clinics. The CDC’s Guidance reviews the five types of CLIA certificates, any one of which is appropriate for POC testing, and outlines the steps necessary to obtain a CLIA Certificate of Waiver. POC testing may be performed once the laboratory receives its CLIA certificate number. The CLIA lab must notify the local State Agency, such as SC DHEC referenced above, of any change in ownership, name, address or director within 30 days.
The CDC publication reiterates and redirects stakeholders to the CMS resources referenced herein regarding confirmation of COVID-19 testing integrity.
An understanding of the types of COVID-19 tests authorized by the FDA’s EUA program and coordination of appropriate CLIA application review by the state regulatory authority and recent CLIA laboratory records review by CMS should afford the consuming public with a higher degree of confidence in the integrity of laboratories conducting COVID-19 testing.