NEW YORK – One silver lining in the ongoing SARS-CoV-2 pandemic is that it has accelerated development and production of innovative diagnostics technologies. After pivoting its handheld PCR system to SARS-CoV-2 test development, Visby Medical has begun to turn its focus back to its sexually transmitted infection assay and can now use expanded manufacturing capacities to make both tests.
With 510(k) clearance and CLIA waiver of the PCR test to detect three sexually transmitted infections simultaneously announced this week, Visby Medical is now preparing to scale up test manufacturing and marketing.
When the SARS-CoV-2 pandemic began, Visby had just completed its clinical trials for its Visby Medical Sexual Health Test — a 30-minute handheld PCR assay device that detects and distinguishes chlamydia, gonorrhea, and trichomoniasis.
Gary Schoolnik, Visby's chief medical officer, said in an interview this week that when the COVID-19 pandemic hit, the firm fully pivoted from its STI path to address the crisis, developing an Emergency Use Authorized SARS-CoV-2 test in 100 days.
Visby's subsequent expansion was dramatic. The firm scaled from 60 employees to 600 over four months, enabled in part by $9.6 million in support from the National Institutes of Health's Rapid Acceleration of Diagnostics, or RADx program, and $12.3 million from the US Department of Health and Human Services' Biomedical Advanced Research and Development Authority.
This included hiring staff for clinical trials and quality control, but also manufacturing expansion.
"We went from pilot manufacturing to a full scale of three shifts per day, involving hundreds of operators," Schoolnik said, which enabled the firm to go from producing approximately 100 devices per week to 9,000 per week, he added.
The RADx program has aimed to accelerate POC testing for SARS-CoV-2, and its contract with Visby specifies production numbers for the most recent iteration of the Visby COVID test, Schoolnik said, noting that this version was developed to make it easier to manufacture.
Although test demand had declined earlier this year, since April the firm has been selling more of its COVID tests — due to the spread of the Delta variant — to the point that, "now, we are getting more orders than we can produce," Schoolnik said.
Some modifications were required to adapt the firm's chemistries to detecting the SARS-CoV-2 RNA virus, as compared to DNA of bacteria and protozoa in the STI test, but the basic device was the same.
Now, Visby will be able to adapt the manufacturing facilities it built to support COVID test production to quickly manufacture high volumes of its STI assays, Schoolnik said.
Visby Medical has also been pivoting from manual device assembly to automated, robotic assembly of its tests, a process Schoolnik said will be fully installed in the next four to six months. This will scale Visby's production capacity by more than tenfold, he said.
In the past month, however, the convergence of the Delta variant and back-to-school testing requirements has led Visby to experience high demand for SARS-CoV-2 tests that is currently exceeding its manufacturing capabilities.
While the precise product mix going forward remains to be determined, Schoolnik said the STI product is "very unique in the market" and will likely be something many clinics will want to adopt.
Cases of sexually transmitted diseases had risen to an all-time high before the pandemic, according to the CDC, and the pandemic has since exacerbated systemic problems for STD control.
K.C. McGrath, director of business development at Visby Medical, noted in an email that the improved quality of care may "reduce community spread and flatten the STI curve," thereby minimizing the burden on healthcare costs.
Visby has a growing direct sales force and continues to explore multiple sales and marketing channels to ensure its platform will be available to the most patients, McGrath said.
"The COVID-19 pandemic accelerated the growth of our commercial team including sales, marketing, and customer support to meet the emerging need for our [EUA] test," he said, adding that the firm continues to scale its commercial team to support the STI test launch as well as the COVID-19 test customers.
How it works
According to the instructions for use for the Visby Medical Sexual Health test, the assay requires patients to self-collect a vaginal specimen with a swab, then elute the sample in collection media.
A test operator then transfers the media to a sample port using a fixed-volume pipette. This rehydrates lyophilized reagents, and the sample flows into a lysis module for heat and chemical treatment.
Extracted DNA moves to a mixing chamber where it rehydrates lyophilized PCR reagents, and the device then performs thermal cycling.
Target DNA hybridizes to probes located on a flow channel, with a separate dot for detection of each target via a colorimetric readout.
The most recent STI guidelines from the US Centers for Disease Control and Prevention have embraced molecular testing for CT, NG, and TV, and point-of-care testing, in particular, has been advocated for by a recent National Academies of Sciences, Engineering, and Medicine publication on STIs.
For point-of-care or decentralized molecular testing, however, one obstacle to uptake historically has been concerns among laboratorians about test accuracy.
Specifically, highly sensitive cartridge- and instrument-based assay systems could potentially yield false positive results if they become contaminated when they are used outside of a lab by operators who aren't experts in lab techniques.
In a number of cases previously reported — such as at Geisinger Health, Henry Ford Health System in Michigan, and in some pediatric hospitals — decentralized MDx systems have been adopted but were run by designated trained users, housed in special containment boxes, or only used in the laboratory for stat testing.
But, the COVID-19 pandemic continues to challenge the status quo of how diagnostics are developed and used.
Schoolnik, who is also an infectious disease specialist at Stanford University and has taken care of approximately 150 COVID patients to date, said Visby hasn't experienced much resistance to POC MDx.
Indeed, the experts Visby works with — including clinicians and clinical microbiologists on its scientific advisory board — are open to point-of-care disposable PCR in particular, he said.
"We have a single-use device, so the problem of contamination is much lower," Schoolnik said, noting that the Visby test is essentially both a cartridge and an instrument in one, unlike other systems.
Visby is addressing potential environmental concerns about single-use tests, as well. Its system comes with a reusable power cord that plugs into the wall, rather than using batteries. The firm is currently also working on a program to have users return devices in order to reuse some of their components.
Cost has also been a factor in POC MDx uptake, as previously reported.
Schoolnik said that Visby Medical expects to commercialize its STI test "for less than the reimbursable amount" from the Centers for Medicare and Medicaid Services, about $100, according to Visby's website.
Utility of POC STI testing
The Visby STI test clinical trial results were published in May in The Lancet Infectious Diseases.
The trial showed sensitivity for the CT, NG, and TV targets of 97.6 percent, 97.4 percent, and 99.2 percent, respectively, compared to lab-based PCR tests. The specificity was 98.3 percent, 99.4 percent, and 96.9 percent for CT, NG, and TV respectively.
Charlotte Gaydos, an STI expert at Johns Hopkins University and lead of the JHU site of the Point of Care Technologies Research Network, or POCTRN, was a coauthor on the trial publication, but she had been providing more casual consultation to Visby for years.
The FDA clearance is "momentous," and the CLIA waiver in particular is "a game changer," Gaydos said in an email. "This is the first POC STI assay that is highly accurate, does not require a platform machine to run it, and tests for three STIs at the same time."
The biggest advantage of testing for these three common STIs is that they are all highly prevalent, and it is possible to have more than one at a time, Gaydos said.
The 30-minute time to result is also important, as work by Gaydos and others has shown this is the window of time that people are willing to wait for results, and getting test results during the initial visit improves patient outcomes and reduces the spread of infection.
Rapid, in-office testing can also reduce the likelihood of a patient being given a prescription they don't actually need, which contributes to antibiotic stewardship, Gaydos said.
While there are a growing number of in-development and FDA-cleared point-of-care tests for CT and NG — like Binx Health's Binx io or Novel Microdevices' Novel Dx — there are fewer options for rapid TV testing.
A method called a "wet mount" essentially involves putting a patient sample on a slide and watching for moving protozoa. But the organism does not survive well in the external environment, and this type of test, while rapid, has a low sensitivity.
There is an FDA-cleared TV test from Quidel, but it is not CLIA waived, so must be run in a lab, Gaydos said. A test from Sekisui Diagnostics called the OSOM test, however, is waived and has high sensitivity and specificity, she said.
Going forward, Gaydos said adapting the Visby STI test for male samples, especially self-collected penile swabs, would be beneficial.
Visby also won a $19 million prize from the National Institutes of Health last year to develop the NG test to also detect antimicrobial resistance markers.