NEW YORK – BioMérieux is targeting the point-of-care diagnostics space with a new rapid syndromic testing system, the BioFire SpotFire, while also planning future menu for the system that may have distinct competitive advantages in reaching sites such as urgent care centers, family medicine practices, and pediatric clinics.
The SpotFire was granted 510(k) clearance and CLIA waiver last week through the US Food and Drug Administration's dual pathway. The instrument, which can perform multiplex PCR in less than 20 minutes, was cleared along with a syndromic respiratory assay called the SpotFire R Panel, which simultaneously detects 15 common viral and bacterial respiratory pathogens.
BioMérieux also disclosed that it is developing a five-target respiratory virus mini-panel for the SpotFire. Called the SpotFire R Panel Mini the panel could potentially boost uptake in outpatient and ambulatory clinics and be differentiated from competing combination tests through the inclusion of a target for the common cold.
"We were motivated to develop SpotFire to expand our reach into the outpatient and ambulatory care market, to be able to bring PCR syndromic testing even closer to patients," said Jennifer Zinn, BioMérieux's president of clinical operations for North America who is heading up the rollout of SpotFire.
Although the SpotFire instrument has the footprint of a standard sheet of paper, Zinn said it is not just a smaller version of the firm's legacy BioFire FilmArray system.
BioMérieux began developing SpotFire in late 2016, she said, a time when there was a flurry of regulatory clearances and waivers for point-of-care molecular systems.
"It utilizes much of the same technology as FilmArray, but includes enhanced chemistry, optimized sample prep, and improved thermal cycling," Zinn said. These enhancements give it the run time of 15 minutes, compared to 45 minutes with FilmArray.
Zinn joined BioMérieux five months ago after senior positions at Siemens Healthineers and Ortho Clinical Diagnostics. She also served as Roche's senior VP of point-of-care when that firm was first introducing the Liat system.
While BioMérieux had expected to launch the SpotFire in 2021, the pandemic crimped that timeline somewhat, Zinn said, particularly because conducting clinical trials had been more challenging. Still, the pandemic was also a master class in the benefits of rapid diagnostics.
"Especially now, given what we've all lived through, we really see the power of this opportunity," she said.
The core technology
According to BioMérieux, the SpotFire core technology is based on methods that were patented in 2021 by Carl Wittwer and Jared Farrar of the University of Utah. Wittwer cofounded Idaho Technology, the firm that developed the FilmArray system and syndromic respiratory panel, which was eventually rebranded as BioFire Diagnostics and acquired by BioMérieux in 2014 for approximately $486 million.
At U Utah, Wittwer and Farrar had performed exhaustive studies of PCR conditions and discovered that reactions can be sped up through various tweaks, including the use of higher concentrations of reagents.
Incorporating methods such as these enables the SpotFire system to provide results in 15 minutes. And, while a single SpotFire module can perform one test at a time, modules can be linked together in stacks of up to four instruments.
Although SpotFire has the same LIS capabilities as the FilmArray, it also has additional IT capabilities like POCT1-A software for use in decentralized settings, Zinn said. Because it was always intended to be installed and used by customers in CLIA-waived spaces, it is also overall easier to use than FilmArray, Zinn said.
The respiratory panel detects 11 respiratory viruses and four bacterial targets. Specifically, it detects adenovirus, SARS-CoV-2, seasonal coronavirus, human metapneumovirus, human rhinovirus/enterovirus, influenza A as well as flu A subtypes H1-2009 and H3, influenza B, parainfluenza virus, and respiratory syncytial virus.
The bacterial targets are Bordetella parapertussis, Bordetella pertussis, Chlamydia pneumoniae, and Mycoplasma pneumoniae.
In picking the targets, the firm referenced its own pathogen surveillance data gleaned from connected FilmArray systems, consulted with key opinion leaders, and looked at what else was happening in the market.
The final choice of the targets "was a balance between the highest level of diagnostic yield — or the highest chance of getting a positive result with one test — and what we were able to get CLIA waived," Zinn said.
BioMérieux also chose to go directly to 510(k) rather than pursue Emergency Use Authorization, in part so that it could add future menu without any hindrance.
A full commercial launch of SpotFire and the 15-target panel is expected in April. In terms of marketing, Zinn said the point-of-care market is different enough from the end users of the FilmArray and CLIA-waived FilmArray systems to warrant new approaches.
BioMérieux revealed SpotFire at AACC in 2022, and presented at IDWeek, but Zinn said the firm is looking to markets such as urgent care centers, family medicine, and pediatrics.
"We are thinking more broadly than just the lab-based community, and really talking about the role of testing in clinical practice," she said.
And, while the CLIA-waived FilmArray and SpotFire might seem to compete with each other for users, Zinn said the SpotFire and 15-target panel will build upon the legacy system's success, while the mini panel "will capture the frontline testing that FilmArray is currently missing."
Initial studies
BioMérieux scientists and their collaborators at five hospital lab sites presented two posters at IDWeek in October. The collaborators included teams at Indiana University School of Medicine, University Health Truman Medical Center and Children's Mercy Hospital in Kansas City, Missouri, Nationwide Children's Hospital in Columbus, Ohio, and University College London.
The group showed that for 1,131 nasopharyngeal samples prospectively collected at the five locations, the 15-target panel had a positive predictive agreement (PPA) of 98.4 percent and a negative predictive agreement (NPA) of 99.1 percent compared to an FDA-cleared multiplex PCR assay. The team found similar results — 98.9 percent PPA and 99.3 percent NPA — using archived samples containing less prevalent organisms.
In the prospective studies, the team also found that nearly 70 percent of samples had at least one organism detected. The majority were positive for the rhinovirus/enterovirus target in the 15-target panel, which detects but does not distinguish between the two viruses.
The team also showed the system had a success rate of 97.3 percent for obtaining valid results on an initial specimen test.
The same group also evaluated the ease of use of the SpotFire system based on a total of 2,002 runs performed over eight months at the five sites.
Based on anonymous questionnaires completed by 35 end users at the sites, 97 percent found the system and panel were easy to use and the training materials were sufficient to allow the user to perform the testing.
The team also showed that the 97 percent success rate of obtaining valid results on the initial run was similar to the rates seen when trained laboratory personnel used the system, and that the reproducibility between operators at the point of care and lab personnel had an overall positive percent agreement of 99 percent.
Possible competitive advantages of the mini panel
The next menu item for the SpotFire will be the R Panel Mini, which will simultaneously detect SARS-CoV-2, influenza A and B, respiratory syncytial virus, and rhinovirus.
BioMérieux completed the clinical trials at 14 locations for the R Panel Mini in 2022, Zinn said, and it will be submitted to the FDA this quarter for potential marketing clearance.
Regarding the rhinovirus target, "we think it will definitely differentiate this mini-panel," Zinn said.
There are other syndromic respiratory panels that are lab-based and run in the 45-minute to two-hour time frame which also include rhinovirus targets. These include the Qiagen QiaStat-Dx Respiratory SARS-CoV-2 Panel, Seegene Allplex RV Master Assay, Applied BioCode Respiratory Pathogen Panel, and GenMark ePlex Respiratory Pathogen Panel 2, for example.
At the point-of-care, however, although firms like QuantuMDx and Cepheid have commercialized rapid molecular tests for influenza, COVID, and RSV, rapid multiplex assays including targets for the common cold do not seem to be commercially available at this time.
The BioFire FilmArray Respiratory Panel EZ detects rhinovirus/enterovirus and is CLIA waived but has a 45-minute run time. A 25-minute syndromic respiratory panel on the QuidelOrtho Savanna rapid molecular instrument called RVP11 is slated to have a rhinovirus target, but that panel has not yet entered clinical trials. Imperial College spinout, ProtonDx, obtained the CE mark on its 30-minute Dragonfly system and a syndromic panel that includes a rhinovirus target in July but it is unclear if it is commercially available.
Still, rhinovirus is by far the most common respiratory viral pathogen, and the rhinovirus target also increases the diagnostic yield for the small panel.
"We want to be able to equip clinicians to be able to run tests that can allow them to say with confidence to their patients, 'You have a cold,'" Zinn said.
Small panels may also be a key to reimbursement, which in turn is a key to outpatient and ambulatory spaces.
In 2018, Palmetto finalized a local coverage determination that determined the use of five or fewer targets in multiplex panels could be justified for the reimbursement of syndromic respiratory panels, citing a lack of outcomes data on the benefits of larger panels.
Nevertheless, "over the past few years we've seen a higher level of guidance from payors," Zinn said. Specifically, large syndromic panels are sometimes supported as covered benefits for patients with preexisting conditions or comorbidities as well as those in some hospital settings.
That said, BioMérieux's decision to develop the five-target mini-panel was based on a desire to expand patient access to this technology, Zinn said, with broader coverage and reimbursement in mind.
And, although there is clearly more favorable coverage for panels of five targets or fewer, BioMérieux is still confident in the value of the 15-target panel at the point of care.
Going forward, "we are going to continue to lobby and drive efforts that will support coverage and reimbursement so that patients have access to this innovation," Zinn said.
The firm also anticipates that the system is going to help clinicians "make the right decisions at the right time for the right patient," Zinn said, to help improve antimicrobial stewardship and combat the looming crisis in antimicrobial resistance.
Past debates over the feasibility of point-of-care testing seem less relevant now that people are routinely using diagnostics on their kitchen counters, Zinn said, and the COVID-19 pandemic has clearly highlighted the importance of bringing testing closer to patients.
"This day is here, and I think we have to rise to the occasion," she said.