This article has been updated from a previous version to clarify information regarding the targets included in the FilmArray Respiratory Panel.
By Ben Butkus
The US Food and Drug Administration recently awarded 510(k) clearance to Idaho Technology's FilmArray Respiratory Panel, but the company has chosen not to commercialize the product, PCR Insider has learned.
Instead, Idaho Tech has applied for FDA clearance for a follow-on version of the panel containing two additional targets not included in the approved version, and hopes to receive approval within a week, a company official said this week.
FilmArray is a multiplex PCR-based assay panel that tests a nasopharyngeal sample for the presence of 15 viral, including adenovirus, bocavirus, coronavirus subtypes, enterovirus, influenza subtypes, respiratory syncytial virus, and rhinovirus.
According to the company's website, the panel can also detect three bacterial pathogens: Bordetella pertussis, Chlamydophila pneumoniae, and Mycoplasma pneumonia. However, these targets have not been cleared by the FDA for inclusion in the FilmArray test.
The FilmArray instrument integrates sample preparation, amplification, detection, and analysis, and is designed to provide results in less than one hour with about two minutes of hands-on time, according to Idaho Tech's website.
Last January, the company initiated clinical trials for the panel at University of Texas Southwestern Medical Center, Detroit Medical Center, and the Medical University of South Carolina (PCR Insider, 1/28/2010).
In November, Idaho Tech filed with the FDA for 510(k) clearance to market the panel as an in vitro diagnostic product for patients with symptoms of upper respiratory tract infection (PCR Insider, 11/4/2010).
According to the FDA website, Idaho Tech received clearance for the product in February of this year. However, the clearance flew under the radar as the company made the decision not to commercialize that product due to the absence of two particular respiratory targets, parainfluenza 1 and 2, Wade Stevenson, diagnostics product manager at Idaho Tech, told PCR Insider this week.
"The panel that got cleared is missing a couple of really important targets," Stevenson said. "Hospital labs right now can [test for parainfluenza 1 and 2] with [direct fluorescence antibody] testing; and those two targets are also available on other FDA-cleared respiratory PCR assays.
"All of the potential customers that we've talked to, when they hear about the targets that are missing, are not at all interested," he added. "So we think it would be rather foolish of us to try and commercialize the panel [without those targets]."
Stevenson said that the company omitted parainfluenza 1 and 2 from the initial submission "because in the respiratory season in which we conducted this trial, these were just low-incidence targets. There just wasn't a lot of this in circulation last year, and consequently we didn't detect enough" to satisfy FDA standards.
Nevertheless, Idaho Tech felt that all other data regarding FilmArray would support an approval, and as such the company applied for 510(k) clearance without the targets in the hopes of expediting approval once data on parainfluenza 1 and 2 were added.
"We knew we had a lot of great data we wanted to submit, and the first submission was much bigger, because the FDA has to review the instrument, the software, a lot of the labeling, plus all of the data on the assays," Stevenson said. "We wanted to get working on that right away with the idea that once we had additional data for the parainfluenza viruses, we could add them a lot quicker, which in fact has been the case."
According to Stevenson the company has now worked with FDA to add data from new prospective and retrospective studies, and the agency now seems "very comfortable" with the data.
"We have submitted data to the FDA that they said looks great to get the additional targets cleared, and we expect that clearance potentially within a week," Stevenson said, noting that he could not accurately predict the timing of FDA action on the panel.
Once cleared, FilmArray may set the standard among multiplexed respiratory molecular tests in terms of the number of pathogens detected, with more than 20. Other examples either on the market or in development include panels from Luminex, Nanosphere, GenMark, and Celera.
In addition, many other real-time PCR-based tests exist for qualitatively and quantitatively detecting various important respiratory viruses; however, multiplexing has been challenging for these types of assays.
While FilmArray performs PCR to initially amplify nucleic acids from target pathogens, its multiplexed detection capabilities are primarily enabled by high-resolution melt curve analysis.
In a talk this week at Select Biosciences' Advances in qPCR conference in Boston, Carl Wittwer, a co-founder of Idaho Tech and a professor of pathology at the University of Utah, said that detection based on melt curve analysis can "qualitatively pick up PCR products for diagnostic purposes that qPCR can't."
FilmArray, he said, first performs a single, massively multiplex PCR reaction followed by individual singleplex PCR reactions to generate PCR products for each target pathogen. Then, the platform's software uses endpoint melting curve data to generate a result for each target.
Wittwer noted that potential customers are often surprised that FilmArray's detection is based on melt curve analysis rather than qPCR; and said that almost all commercial qPCR machines can perform melt curve analysis.
"Temperature and fluorescence" are the only two variables in HRM, he said, adding that the technique depends on instrument precision, choice of dye, and software – all of which are optimized for HRM on the FilmArray platform.
"HRM is a process, not a product offered by companies," Wittwer said. "A lot of companies want to say that they offer high resolution melt curve analysis."
When pressed by a conference attendee as to what specific elements make an instrument capable of performing HRM, Wittwer responded that there is "no defined cut-off. The easiest way to improve resolution is to do it slower, but that's at odds with the rapid PCR cycling that so many people are used to."
In general, he added, "it's not so much about fluorescence as it is control and measurement of temperature."
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