FDA Pulls Back the Reins on Makers of Unproven Coronavirus Serology Assays

The U.S. Food and Drug Administration continues to struggle in its quest for a regulatory policy to unlock the potential of blood-based COVID-19 serology testing while reining in fraudulent marketing and accuracy challenges. Here is a look at the latest developments. The Diagnostic Challenge As the curve flattens and society turns to the business of reopening, a new kind of coronavirus diagnostic testing is needed, one that is capable of not only detecting SARS-CoV-2 antibodies in a person’s system but also determining whether they are due to a current or previous COVID-19 infection. In addition to enabling governments, employers and other decision makers to figure out if a person is “safe” for public activity or needs to be in quarantine, such data is crucial to tracking COVID-19 among specific populations. Because serology testing offers that potential, the U.S. Food and Drug Administration (FDA), the agency that has maintained air-tight control over unproven laboratory developed tests for over a decade, has relaxed its regulatory standards to an unprecedented degree, allowing tests beset with accuracy problems to reach the market without regulatory review. At the same time, it created a more rigorous pathway requiring Emergency Use Authorization (EUA) for higher quality serology tests. Serology tests tend to be lacking in specificity resulting in false positives causing people who are still susceptible to COVID-19 into falsely believing they are immune; the other issue is lack of sensitivity resulting in false negatives. And in the COVID-19 planning context where sample sizes are limited, small errors in either direction have a disproportionate magnifying effect that can lead to dangerously wrong conclusions. However, the FDA decided to roll the dice. The good news is that more than 150 serology tests reached the market as a result of the strategy. The bad news is that only 11 of those tests used pathway requiring EUA clearance. SARS-CoV-2 Serology Tests with FDA EUA Clearance, as of May 18

Date	Manufacturer(s)	Serology Test Receiving EUA
April 2	Cellex	qSARS-CoV-2 IgG/IgM Rapid Test
April 15	Chembio Diagnostics	DPP COVID-19 point-of-care test and analyzer for IgM and IgG antibodies
April 16	Mount Sinai Laboratory	COVID-19 ELISA IgG Antibody Test
April 24	Autobio Diagnostics	Anti-SARS-CoV-2 Rapid Test immunoassay
April 24	Ortho Clinical Diagnostics	SARS-CoV-2 immunoassay
April 24	DiaSorin	Liaison SARS-CoV-2 S1/S2 IgG serology assay detecting IgG antibodies)
April 26	Abbott Laboratories	SARS-CoV-2 IgG antibody test
April 29	Bio-Rad Laboratories	Platelia Total Ab immunoassay for SARS-CoV-2
April 30	NY State Department of Health’s Wadsworth Center	New York SARS-CoV Microsphere Immunoassay for Antibody Detection
May 2	Roche	Elecsys Anti-SARS-CoV-2 antibody test
May 4	Euroimmun	Anti-SARS-CoV-2 ELISA test

  To make matters worse, companies that took the easy route misrepresented their tests as having FDA approval and made unsubstantiated claims about their products’ capabilities. Rather than take the enforcement action, FDA encouraged test makers to use the EUA pathway in the future and submit tests already on the market to independent validation. Predictably, the response was “thanks but no thanks.” FDA Creates New Umbrella Pathway After coming under enormous criticism, the FDA backed down. Well, sort of backed down. On April 29, the FDA announced creation of a new “umbrella” pathway requiring test makers to submit tests for independent evaluation. Under the new process, an interagency testing group at the National Cancer Institute would assess the approximate specificity, sensitivity and overall predictive value of submitted tests against a panel of samples confirmed positive for anti-SARS CoV-2 IgM and IgG antibodies. Tests would also be run against confirmed antibody negative samples or pre-COVID-19 samples, with 10 of these 80 negative samples being HIV positive. To receive clearance:

• Tests reporting on both IgM and IgG must perform with overall sensitivity of 90 percent and specificity of 95 percent;
• Tests reporting the immunoglobulins separately must have sensitivity of at least 70 percent for IgM and 90 percent for IgG; and
• Tests must show no cross-reactivity with HIV.

The first batch of tests to undergo evaluation were the assays that received EUA clearance. Takeaway The agency continues to walk back its previously ill-advised leniency with serology test makers. On May 22, the agency named 28 assays that it says should be taken off the market. Not surprisingly, all of those tests were products that came through the pathway not requiring EUA clearance, mostly manufactured overseas. The list also includes he list includes tests made by: 

• Beverly Hills, California-based Vita Testing;
• Diazyme Laboratories, a subsidiary of defense contracting giant General Atomics;
• Pharmatech, which was acquired by Caris Life Sciences last year; and
• BioMedomics, which developed a rapid fingerstick test formerly sold by Becton Dickinson.