NEW YORK – PCR testing is the gold standard for molecular tests and continues to be a major focus for test developers during the ongoing COVID-19 pandemic, but the lack of portability and a complicated workflow are major drawbacks often cited as hindrances to the technology.
Diagnostic startup Visby Medical, however, has a PCR technology to overcome those barriers and has had its tech acknowledged by the National Institutes of Health – to the tune of $19 million.
The San Jose, California-based infectious disease diagnostic company won the agency's Antimicrobial Resistance Challenge last month with its gonorrhea test, which runs on its Patient-side, Disposable, Molecular PCR Diagnostic Device, a single-use PCR machine the size of a cassette. Founder Adam de la Zerda called the device the "first and only" single-use PCR instrument up to now and emphasized that everything about the instrument "has been for single-use."
The palm-sized machine looks at individual point mutations and provides results in less than 30 minutes from sample to answer, de la Zerda said. It runs 40 cycles of thermocycling and the company focused very specifically on heat control, doing "an enormous amount of work" to ensure temperatures would be stable, de la Zerda said.
He emphasized that the device could enable new kinds of use cases because anyone can run it any time in any setting. With standard PCR, instrument availability usually determines the number of tests that can be run at any time, but by integrating the cartridge and test into one test, Visby's technology removes "the dependence on instruments" and allows many tests to be run in parallel. The hands-on time for loading the sample into the test is incredibly short – it takes only seconds, de la Zerda said. When developing the device, Visby's team started from scratch and considered what they would do differently to make PCR easier to use, working with a "radically different design constraint" to put their ideas in motion, he added.
"We just found a way to take a regular PCR machine and shrink it down to something that's a little bit bigger than a deck of cards," de la Zerda said.
Currently, the company, which was formerly called Click Diagnostics, is working on three different infectious disease tests. Its first multiplex panel for sexual health detects chlamydia, gonorrhea, and trichomoniasis, and the Phase III clinical trials for the test funded by grants from NIH are complete. Visby submitted the test to the US Food and Drug Administration for 510(k) clearance and CLIA-waiver in March, although de la Zerda declined to comment on what the timeline for clearance might look like. The firm noted that the CLIA waiver is important because it would allow "minimally trained operators to run this test."
The firm's other sexual health test, currently in development, detects Neisseria gonnorrhoeae and drug resistance markers. NIH awarded its $19 million prize in August to Visby specifically for the test, and in a statement, NIH Director Francis Collins said that it "could help reduce the unnecessary use of antibiotics, a major driver of antimicrobial resistance."
Jeffrey Klausner, a professor of medicine and public health at UCLA and an NIH investigator on Visby's trial for data submitted to the FDA, said the public health field has been waiting "for decades for a rapid test." In the clinical trial, researchers said untrained healthcare workers who used the machine found it easy to use.
The main benefit of Visby's device is that it addresses overtreatment by providing clinicians with a same-day, specific diagnosis allowing them to treat for the exact disease the patient has, instead of treating empirically with a more intensive antibiotic, Klausner said. It reduces the excess use of antibiotics, which has become a more serious problem as antibiotic resistance continues to grow across the world. It also has a public health benefit, Klausner added, since appropriate treatment can be provided more quickly to stop disease spread.
"The device could free up and increase access to STD testing," Klausner said. "There are currently fewer places for STD testing."
Sexual health is Visby's "founding" focus, but the COVID-19 pandemic has led many companies to shift their attention to SARS-CoV-2 the virus that causes COVID-19. Visby was no exception. De la Zerda said in an email the firm has submitted its moderate-complexity test, which uses nasopharyngeal and mid-turbinate samples, to the FDA for Emergency Use Authorization and is waiting to hear back from the agency.
The firm has been working steadily for almost eight years on two major fronts, de la Zerda noted. One has been the development of the technology and its test menu, while the other has been working to scale up production capacity and investing in manufacturing.
The Patient-side, Disposable, Molecular PCR Diagnostic Device doesn't include a service component, which de la Zerda highlighted as a benefit. If the device breaks down, instead of having to wait for a technician to come and fix it, as in the case of a standard PCR machine, the user can just throw it away. "The customer is liberated from the PCR instrument," de la Zerda said.
However, one question with any single-use test is that of sustainability and resource allocation. De la Zerda noted the firm can reuse some of the components of the device once a test has been run and said they're working on a program to allow users to recycle parts of the used device, although it is still in the preliminary stages of development.
Visby's instrument can be used in both high- and low-throughput facilities because it has a similar use model as a pregnancy test and volumes can be adjusted based on demand. Clinicians could keep a supply of the devices on hand for use when necessary, and De la Zerda said the firm plans to sell the devices in packs to ensure facilities have enough to meet demand. Pricing hasn't been determined yet, but he emphasized it would be affordable and competitively priced.
Klausner noted that it potentially could be used in a CLIA-waived setting, which would make it "one step away from an at-home test." As the winter months near and flu season coincides with the continuing COVID-19 pandemic, using the device as a home test could be a solution to COVID-19 testing demand if the firm's test receives EUA. "Everything needed to run the test is already inside," de la Zerda said, and the only addition needed is the sample collection.
Klausner also emphasized that the device and its tests can be applied to areas with limited testing capacity, such as rural regions. "It can be nimble," he said. "Large manufacturers aren't as nimble."