Authored by Innovative Science Solutions, now part of Lumanity
US distributors and agents trying to import rapid antibody tests for coronavirus face a number of obstacles. The good news is that the US Food and Drug Administration (FDA) has opened up the Emergency Use Authorization (EUA) program to include SARS-CoV-2 (the virus) and COVID-19 (the disease), expediting time to market. However, applying for a COVID-19 EUA Letter from the FDA is not as easy as might be expected, despite the overwhelming need for diagnostic tests to address the SARS-CoV-2 pandemic. Not surprisingly, there are still no authorized rapid antibody tests at this time, creating an opportunity for distributors and agents to import these tests.
Despite a less rigorous regulatory pathway and the ability to market your product prior to receiving full marketing approval, the EUA process itself is unfamiliar to most and has been modified more than once since initiation. In the sections below, we outline four pitfalls or submission package deficiencies that can cause delays and/or rejection of the application.
- Inadequate information regarding testing procedures. Many EUA requests that we’ve seen for rapid antibody tests don’t include adequate information about the testing procedures. Some don’t even meet FDA’s requirements. For example, the matrix equivalency test requires that the test be studied in every matrix (type of blood) that it is intended for. The intended use of many rapid antibody tests is venipuncture whole blood, fingerstick whole blood, serum, or plasma. Nevertheless, only data with fingerstick samples are presented. If this is simply an omission it can be rectified by the manufacturer providing the complete test information. If the data are not available for all intended matrices, then an additional study will likely be required. The same holds true for cross-reactivity (i.e., inadequate number of samples for potentially cross-reactive pathogens) or failure to disclose sensitivity and specificity calculation methodology.
- Failure to provide study protocols. FDA is also looking for complete study protocols, including test site locations, number of individuals collecting the samples and conducting the tests, and whether samples are of actual patients or spiked negative samples. Many EUA requests only provide a topline synopsis of the study, which is not acceptable. FDA really wants to see exactly how studies are conducted. This is particularly important regarding the types of samples and how they are collected. While samples could be prospective clinical samples (blood drawn from patients with uncertain SARS-CoV-2 infection history), retrospective clinical samples (blood drawn from patients with known SARS-CoV-2 infection history), or spiked samples (known SARS-CoV-2 negative blood samples spiked with antibodies against coronavirus), the type of sample and collection needs to be specified. Along these lines, it is critical to provide detailed information about the method used to validate positive and negative samples, whether through a validated ELISA test or, preferably, a validated PCR test.
- Only topline data is presented. FDA would like to see subject line data for the clinical tests rather than only analyzed data. (Both should be shown.) Subject line data are the results for each sample tested by the rapid flow antibody test (IgG, IgM, or IgG and IgM, as applicable) and the validated control methodology (PCR or ELISA). Failure to include subject line data usually only causes delays, as it can easily be provided in response to an FDA query. However, due to the fact that the pandemic will end and EUA letters will be terminated at some point, securing an EUA letter sooner rather than later allows for more time on the market. Similarly, avoiding delays increases the benefits derived from first mover advantage, i.e., the first to market has a temporary monopoly and making that time period as long as possible yields better return on investment.
- Incomplete manufacturing data. It is important that the sponsor, distributor, or agent provide thorough manufacturing data. Examples of the type of data that is often missing from these applications includes the following: manufacturing site(s), manufacturing capacity, time to maximum capacity, source species for all antibodies in the test, manufacturer of labels and packaging, etc. This level of detail isn’t always provided in the applications we have reviewed and its omission will certainly cause delays, even though it is not a requirement that the manufacturer(s) are FDA-approved facilities at the time of EUA application.
Remember, the EUA regulatory pathway is not intended as a permanent solution, but rather as a temporary process to address a critical need. Once the EUA process for a particular category expires, all EUAs will become defunct and EUA products removed from the market unless applications have been submitted via the standard (i.e. long and laborious) regulatory pathways.
We have assisted with the submission of dozens of EUA packages, and not just for coronavirus-specific drugs, diagnostics, and devices. We’ve worked directly with the FDA on behalf of our clients (as authorized US agents) in order to address deficiencies or revise submissions based on evolving requirements. We know this process inside and out.
Read our free white paper “Applying for an FDA Coronavirus EUA Letter” or contact us today to discuss how we can help.