NEW YORK – Most testing for SARS-CoV-2 has so far relied on patients having to go to a provider in order to find out whether they may be infected with the coronavirus. And while interest is high in at-home diagnostic tests that make it easier for consumers to determine their coronavirus status, questions abound about their sensitivity, dependability, and overall clinical utility.
But one company, OraSure Technologies – the only company to have ever obtained US Food and Drug Administration clearance for a home-use infectious disease diagnostic test – is progressing on its at-home COVID-19 test and in the next six months, it anticipates receiving US Food and Drug Administration Emergency Use Authorization for such an assay.
The test in development will encompass two other innovations beyond home-use indication. It will test for active infection by detecting viral antigens, and it will use OraSure's oral fluid sample collection technology.
The project won funding from the US Department of Health and Human Services' Biomedical Advanced Research and Development Authority, which was announced Monday, totaling $710,000. Director of BARDA Rick Bright emphasized in a statement that "rapid at-home coronavirus testing would be a game-changer."
Stephen Tang, CEO of OraSure, said in an interview this week that the company expects to fully develop the test and get it on the market in the next four to six months. The funding will be used for prototype development, clinical studies, and technology transfer into manufacturing.
"Those funds are matched with a significant amount of our own funds, to get us to Emergency Use Authorization for the product," Tang said.
Viral antigen tests, which use antibodies embedded in lateral flow strips to capture protein antigens expressed on the outer surface of the virus, could be particularly beneficial, as it solves some of the problems faced by other methods.
Unlike molecular tests, antigen tests don't require extraction steps or wait times for amplification. Antigen tests also detect active infections, not host antibodies to the virus like serological tests do. The window of time that antigen tests would be most sensitive in is thus shifted closer to the onset of disease, reducing the likelihood of false-negative results seen in serology tests used before a sufficient antibody response has been mounted.
However, antigen tests are not without their own challenges. They do not involve amplification of viral materials, so they need to be exquisitely sensitive to pick up the lower levels of viral particles in early infection. They also tend to have issues with cross-reactivity to similar proteins expressed by other viruses.
The OraSure test will detect a pan-SARS-coronavirus antigen, although the other SARS species that caused the severe acute respiratory syndrome outbreak in 2003 is not known to be circulating any longer.
Tang, however, noted that the firm's viral antigen Ebola test, as well as its HIV tests, have specificities and sensitivities in the upper 90 percent range.
FDA has been evolving its stance toward related rapid serological tests, in part due to concerns about test sensitivity. "Serological tests have gotten a bad name … but I think we have a track record of really being the gold standard," Tang said.
There is at least one other company developing a viral antigen test to detect SARS-CoV-2. Startup E25Bio has announced it is pursuing EUA for a 15-minute paper-based test that detects viral antigen in nasal swabs. The firm raised $2 million in financing from VC firm Khosla Ventures last month for development of its coronavirus test. Its technology has been demonstrated to distinguish the four dengue serotypes from Zika virus, and it has partnered with lateral flow assay developer DCN Dx to develop a test for detecting dengue, chikungunya, and Zika viruses in a single device.
OraSure also has experience in developing tests for emerging infectious diseases. The firm's Ebola test, which was recently authorized by FDA under the de novo premarket review pathway, is the first rapid diagnostic for Ebola that the FDA has allowed to be marketed, and was granted breakthrough device designation by the agency. It is intended for use with oral fluid from deceased persons, to determine infection and the safest burial practices.
For the Ebola test, OraSure worked closely with the US Centers for Disease Control and Prevention and the FDA to obtain high-quality samples, and Tang said the firm expects to do the same for COVID-19, particularly with the new support from BARDA.
In addition to the uniqueness of the antigen tests, OraSure's oral fluid testing is also uncommon among commercial assays.
Although it is sometimes called a spit test, OraSure's oral fluid testing is not exactly saliva, according to Tang.
"Oral fluid is really using the saliva as well as the tissue along the gum line, so you have an enrichment of plasma components – it's a proxy for blood," he said, noting that there is evidence in human and non-human primate studies that SARS-CoV-2 can be present in the mouth.
The firm's line of HIV tests also relies on oral fluid. "It is a technology and platform we understand extremely well," Tang said.
OraSure has a lot of experience in home-use tests, too. Its oral fluid HIV assay was cleared by the FDA in 2012 and remains the only infectious disease diagnostic to attain home-use approval. The process was quite rigorous, as previously reported.
"The fact that we've done it before is extremely important," Tang said. "Any other company that would try to [pursue home-use authorization] would find out that there is a learning curve to it, which we invested in back in 2011-2012 to get FDA approval for our [over-the-counter] product," he said.
The firm's Ebola test, meanwhile, was originally authorized through an EUA process, and then subsequently obtained full FDA clearance, so the firm is in a unique position to contrast the FDA home-use test authorization process and the EUA process.
"We are pioneers in both," Tang said. "We are counting on close collaboration with FDA in order to expedite review and make sure that we get samples and specimens to be able to do the necessary work, to show good clinical efficacy for our product," he said.
The highest hurdle will be for home use, but the COVID-19 test may also be authorized for professional use. The FDA has recently clarified that non-EUA tests for the point of care can only be used in CLIA-certified high-complexity labs.
The firm's HIV test is an antibody test, but it has had years of experience in home use and also use in the clinic.
Marketed as OraQuick In-Home HIV Test in the US, the test was recently used in a self-test screening program for at-risk populations and showed an ability to impact HIV testing rates. The test is also likely to become a part of the increased push for diagnostics in a new US initiative to end HIV.
A similar test, called OraQuick HIV Self-Test, is distributed internationally by the firm. It received prequalification status from the World Health Organization, and the firm participated in the Self-testing Africa (STAR) initiative that was supported by global nonprofit Unitaid and the Bill & Melinda Gates Foundation, as previously reported.
And, while the HIV assays from OraSure detect antibodies to the virus, the firm's Ebola test detects viral antigen, as does it's QuickFlu rapid influenza test, so the firm has experience with commercializing antigen-based testing as well.
The FDA has recently signaled it is interested in saliva-based testing. Tim Stenzel, director of FDA's Office of In Vitro Diagnostics and Radiological Health, said in a town hall earlier this month that while tongue swabs had low sensitivity, it is possible saliva samples would be better, if only due to higher sample volumes. Stenzel also noted that antibody and molecular test developers have contacted the agency regarding an interest in using saliva samples.
Indeed, testing lab MicroGen Dx recently described a molecular SARS-CoV-2 test it is offering that uses sputum as a sample type, but said it is also validating saliva testing and has seen comparable results so far.
The FDA is also interested in home tests. "We are very open to a home-based serology test," Stenzel said in a town hall this week. "The important factors are, how easy is it for an untrained patient to perform the testing, how easy is it to then read the test results, and how easy is it for them to interpret those results." He added that there are questions for each of these three aspects in typical rapid serology tests, and the agency is also concerned about safety of the device and reagents in the home.
One of the hurdles for OraSure in getting home-use authorization early on was setting up the support system for patients to help them interpret their test results and connect them to care when needed.
Whether such a system will be required for COVID-19 testing remains to be seen. Tang noted that for HIV testing, a positive result requires a molecular confirmation test and then triage into treatment. "For COVID-19, there is no approved therapy, so the main consideration is not necessarily care, but isolation."
Conversely, since the OraSure viral antigen test should be able to detect acute infection, it might be used to determine if someone is not infected, and perhaps allow them more latitude to resume a more normal life.
However, COVID-19 infection also needs to be reported to public health, and this has been a hurdle mentioned by FDA when discussing home-use tests. Tang said this could be accomplished in a number of ways, such as having public health agencies administer the test or having people self-report to employers, who could then report to public health before employees return to work.
OraSure is also pursuing at least two other COVID-related projects. The firm's DNA Genotek subsidiary received FDA clearance in January for a sample collection device that stabilizes DNA in saliva. These are separately being evaluated as an alternative to nasopharyngeal and oropharyngeal samples, Tang said, which would be used for lab-based molecular testing.
The firm is also pursuing an ELISA antibody test using oral fluid for laboratory testing.
"It is very satisfying that we can actually apply what we know and our capabilities to help solve some of these thorny issues in sample collection and testing," Tang said.