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MDCG releases rapid COVID antibody test guidance

Posted 16 March 2021 | By Kari Oakes 

MDCG releases rapid COVID antibody test guidance

Europe’s Medical Device Coordination Group (MDCG) has set out guidance for developers of rapid COVID-19 antibody tests, identifying minimum performance criteria and considerations for devices intended to detect antibodies against SARS-CoV-2.
In formulating the guidance, MDCG looked to other regulators’ considerations for antibody tests, including the World Health Organization (WHO). Additionally, the working group reviewed the instructions for use from 102 separate rapid COVID-19 antibody tests that, by September 2020, were being marketed in Europe.
From this analysis, MDCG drew up a framework for “state of the art” for these devices; the guidance clarifies that in this context, “state of the art does not refer to the best in class but rather to what is achievable by a majority of devices, and is therefore expected to be achieved by the devices on the market.”
Tests covered by the guidance may be qualitative or semi-quantitative and may be used along or in a “small series.” By design, they should give results quickly via a non-automated procedure.
In meeting requirements of Directive 98/79/EC on device performance, developers should keep in mind the intended purpose within the context of the pandemic. Some of these particulars include the window between infection and when antibodies can be detected; how the assay is designed, including which antigens are the targets and which antibodies will be detected; excluding antibody tests as first-line diagnostic tools; and whether the test is meant to track recovery, detect infection, or measure vaccination response.
“For biological analytes such as virus specific antibodies there is no reference procedure of higher order,” noted MDCG in the guidance. Therefore, developers should use a reference device that measures the same analyte as does the test device under development and conduct more assays or delve into patient history to clarify which is the “’true’ status, as far as possible,” according to MDCG.
Performance should ideally be evaluated for each clinical specimen type for which the test is intended, unless different types have been shown to be equivalent. Testing should include interference studies and cross-reactivity studies that include other coronaviruses and other viruses that cause respiratory infections, including influenza viruses. Cross-reactivity testing should be updated in the post-marketing stage as needed to stay abreast of circulating pathogens.
For diagnostic sensitivity, at least 200 positive samples – coming from individuals with a confirmed SARS-CoV-2 infection – should be used. The guidance adds that the timing between sampling and any symptom onset should be tracked.
“Considering that diagnostic sensitivity depends highly on the time interval between the contact with the virus and sample taking, diagnostic sensitivity studies should use samples at various stage and severity of disease and from putative infection,” wrote MDCG. Longitudinal samples that follow the course of infection in individuals over time are permissible.
If access to “well-defined panels reflecting the full diversity of potential antibody responses” is difficult, then the device being tested can be used in parallel with an established device in an environment where SARS-CoV-2 infection incidence is high.
For evaluating specificity, the panel of negative specimens should also be at least 200 samples in size. The samples could either be collected before November 2019, or from those who have tested negative for SARS-CoV-2 antibodies by other means. In any case, they should be broadly representative in terms of demographics and health and medication use status.
Although the diagnostic sensitivities in the devices MDCG studied in the run-up to the guidance were determined by heterogeneous means, the group noted that other performance criteria, including those published by WHO, “generally require at least 90% diagnostic sensitivity for each antibody type (IgM, IgG or total Ig).”
Specificity should be at least 98%, and when providing estimates for diagnostic sensitivity and specificity a 95% confidence interval is recommended.
MDCG guidance


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