As the COVID-19 crisis continues to unfold, there is an immediate need for rapid diagnostic testing to identify and track people infected by or exposed to coronavirus.
While the urgency of the situation has presented a challenge, it has also spurred collaboration and innovation between medical device and diagnostic sponsors, biopharmaceutical companies, diagnostic labs, and nonprofit organizations on an unprecedented scale.
Regulatory authorities are doing their part to accelerate the approval of diagnostic tests through expedited pathways such as the FDA’s Emergency Use Authorization (EUA). This guidance relaxes parameters for approval such as the minimum number of patient samples used for validation. It also allows manufacturers to develop and distribute COVID-19 diagnostic tests after validating and posting their performance characteristics and notifying the FDA, as long as the manufacturer submits an EUA within 15 days. As of April 8, 2020, there are 30 COVID-19 diagnostic tests that have been cleared by the FDA through this pathway.
In this blog, we discuss the different types of diagnostics that have been authorized through this expedited pathway, their advantages and disadvantages, and how a strategic partnership can help diagnostic developers navigate regulatory considerations during this unprecedented time.
Innovating rapid diagnostics
Historically, the gold standard method for infectious disease diagnostics used by testing labs has been reverse transcription of the virus’ RNA followed by PCR amplification (RT-PCR). While RT-PCR is both sensitive and specific, it can take several hours to process and run patient samples.
To improve speed and accessibility, a number of rapid tests can be administered in a point-of-care setting. The first wave of these tests rely on the same underlying RT-PCR method, with various modifications to shorten the run time and reduce dependence on specialized lab equipment. For instance, the Cepheid Xpert® Xpress SARS-CoV-2 test, Mesa Biotech’s Accula SARS-CoV-2 test, as well as the Biomerieux BioFire COVID-19 test can all be run in less than an hour on smaller machines that are available at many hospitals.
Another variation on traditional RT-PCR-based diagnostics are tests that use isothermal amplification. These tests bypass the need for temperature cycling altogether, and in a point-of-care setting, can provide the fastest test result. For example, Abbott’s ID NOW COVID-19 test detects a positive result in 5 minutes and detects a negative result in 9 minutes.
Detecting antibodies with immunoassays
Immunoassays for SARS-CoV-2 have lagged behind other testing modalities due to the lack of disease-specific antibody targets. However, the widespread adoption of antibody testing is essential to determine whether an individual is immune to COVID-19 and can safely resume normal activities.
As of the time of writing, the Cellex qSARS-CoV-2 IgG/IgM Rapid Test is the only test that has been cleared under EUA. This is a lateral flow immunoassay, often referred to as a dipstick test, which can be used to detect antibodies indicating immunity to the virus in serum, plasma or whole blood in a laboratory setting. Seven additional COVID-19 immunoassays have been approved for diagnostic use outside the U.S., though none have received a EUA yet.
COVID-19 clinical operations
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Adapting operations to changing conditions
ICON has adapted its services to support sponsors during this time; offering remote monitoring where on-site visits were not permitted, providing additional support to get IMP to patients and pre-recording investigator meetings because of travel restrictions.
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Sequencing the whole virome
Next-generation sequencing of the SARS-CoV-2 virome is another approach that – while slower than PCR-based tests – can provide valuable insights into the epidemiology of the COVID-19 pandemic. A recent study of samples from the outbreak in Italy used Thermo Fisher Scientific’s AmpliSeq SARS-CoV-2 Research Panel for Ion Torrent sequencers to show that the novel coronavirus is slow-mutating. These findings suggest that a vaccine could be effective at preventing infection for many years.
The first few waves of expedited approvals have been based on established technologies that are backed by decades of data. However, a number of tests based on newer technologies are also in the pipeline, including the first CRISPR-based diagnostic tests. Both Sherlock Biosciences and Mammoth Biosciences are developing diagnostic tests using a variant of the CRISPR system that emits a visible signal in the presence of a SARS-CoV-2 specific RNA sequence. Moreover, these tests can be commercialized for the point-of-care setting with simple temperature control equipment, and with further research, for at-home use in the future.
The path forward for diagnostics manufacturers
The COVID-19 pandemic continues to drive collaboration and innovation in the diagnostics industry. ICON has quickly mobilised its laboratory and medical device and diagnostics experts to assist both government and commercial clients in addressing the COVID-19 global threat by providing diagnostic testing, clinical monitoring, program oversight, and strategy and safety oversight on numerous coronavirus trials. Contact us to speak with our experts today.
Infectious diseases and vaccines insights
ICON's Infectious Diseases and Vaccines teams contribute regularly to media and industry conversations in addition to the production of thought leadership content in the form of whitepapers and blogs.Read more