FDA clamps down on Covid-19 antibody tests

Tests from Ortho-Clinical Diagnostics and Becton Dickinson are in the danger zone as FDA moves to pull less accurate Covid-19 kits.

So far the US FDA has granted emergency use authorisation to 10 commercially developed blood tests that are intended to assess whether a person has developed antibodies to the novel coronavirus, and therefore might carry some level of immunity. But the evidence backing these disparate assays varies in quality, and some other groups are selling tests in the US, quite legally, without providing any accuracy data at all.
The FDA is finally doing something about this situation. On Monday it said developers would have to provide accuracy data within the next 10 days or risk their tests being pulled. Furthermore, the regulator has set out the exact standards it will require the tests to meet – and some of those on the market will not, on current evidence, make the cut.
The agency has previously not required accuracy data on a test to award an EUA – and companies do not have to obtain an EUA to sell their tests in the US anyway. Abbott, for example, obtained EUA for its antibody test on April 26, but had started selling it in the US on April 15. It is not known exactly how many antibody tests are on sale in the country, but the figure is believed to be in the hundreds.
This soft-touch approach is to change. Stating that “the careful balancing of risks and benefits has shifted from where it was in mid-March”, the agency has revised its policy and laid out the kind of evidence it needs to allow Covid-19 antibody tests to remain on sale.
Instead of sensitivity and specificity the FDA has used the terms positive and negative percent agreement (PPA and NPA). These values are calculated identically to sensitivity and specificity, but are used when the comparator test is recognised as being imperfect. In this case the best available comparator is PCR testing for coronavirus RNA, which is not currently recognised as a clinical reference standard.
Meeting the standards
In summary, the FDA states that the data backing Covid-19 antibody tests should demonstrate a minimum overall 90% PPA, equivalent to sensitivity, and overall 95% NPA, equivalent to specificity. For tests that report specifically IgM and IgG results, minimum PPAs of 70% and 90% are required for IgM and IgG respectively.
The guidance also states that clinical agreement data should be provided using at least 30 antibody-positive samples for each immunoglobulin claimed, and 75 antibody-negative samples.
The table below summarises the accuracy figures made for some of the tests known to be on sale in the US. An important caveat is that it relies on information the companies, and in some cases distributors or academic researchers, have released. The companies might well have better data that they have kept confidential – though why they would do this is unclear.

Accuracy figures for selected Covid-19 antibody tests sold in the US
Company	Test name	Date of US EUA	Sensitivity or PPA (%)	Specificity or NPA (%)	Meets FDA requirements?
Cellex	qSars-CoV-2 IgG/IgM cassette rapid test	Apr 1	93.8	95.6	Yes
Ortho-Clinical Diagnostics	Vitros anti-Sars-CoV-2 total reagent pack	Apr 14	83.3	100.0	No
Chembio Diagnostic System	DPP Covid-19 IgM/IgG system	Apr 14	93.5	90.2	No
Diasorin	Liaison Sars-CoV-2 S1/S2 IgG test	Apr 24	97.4	98.5	Yes
Ortho-Clinical Diagnostics	Vitros anti-Sars-CoV-2 IgG reagent pack	Apr 24	87.5	100.0	No
Autobio Diagnostics*	Anti-Sars-CoV-2 rapid test (IgM and IgG)	Apr 24	93.0	100.0	Yes
Abbott Laboratories	Abbott Sars-CoV-2 IgG test	Apr 26	100.0	99.5	Yes
Bio-Rad Laboratories	Platelia Sars-CoV-2 total Ab assay	Apr 29	98.0	99.0	Yes
Roche	Elecsys anti-Sars-CoV-2 antibody test	May 2	100.0	99.8	Yes
Euroimmun (Perkinelmer)*	Anti-Sars-CoV-2 Elisa (IgG)	May 4	65.0	96.0	No
Becton Dickinson/ Biomedomics	Covid-19 IgM/IgG rapid test	No EUA	88.7	90.6	No
Creative Diagnostics	Sars-CoV-2 antibody Elisa	No EUA	94.5	100.0	Yes
CTK Biotech	OnSite Covid-19 IgG/IgM Rapid Test	No EUA	96.9	99.4	Unknown
Epitope Diagnostics	EDI Novel Coronavirus Covid-19 IgG Elisa kit	No EUA	100.0	100.0	No
Epitope Diagnostics	EDI Novel Coronavirus Covid-19 IgM Elisa kit	No EUA	45.0	100.0	No
Intec Products	Rapid Sars-CoV-2 antibody (IgM/IgG)	No EUA	95.2	98.0	Unknown
Nirmidas Biotech	Covid-19 (Sars-CoV-2) IgM/IgG antibody detection kit	No EUA	81.4	94.4	No
SD Biosensor	Standard Q Covid-19 IgM/IgG Duo	No EUA	81.8	96.6	No
*Accuracy figures from this paper. All other accuracy claims made by companies or distributors. Includes only tests with FDA emergency use authorisation. Source: EvaluateMedTech & company websites.

Some of the tests fail to meet the FDA’s standards for sensitivity/PPA or specificity/NPA. One example is the test developed by Biomedomics, which is sold by Becton Dickinson. Others fail on the sample size on which the testing was conducted – Epitope Diagnostics’ IgG test was validated on too few samples, and CTK Biotech, for instance, claims sufficient accuracy for its test but has not provided the sample sizes.
There is also a separate plan for the FDA, in conjunction with the CDC and NIH, to double-check the accuracy of tests on sale in the US. This collaboration has looked at 13 tests so far, the FDA said, with the data still under review. The agency recently issued an umbrella EUA for antibody tests that complete this validation process, and will announce in future which tests have made the grade.
The question is whether the FDA will follow up on its promise to remove underperforming tests from sale in the US. If this is left as an idle threat, the agency risks being seen as toothless.
https://www.evaluate.com/vantage/articles/analysis/spotlight/fda-clamps-down-covid-19-antibody-tests