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Idaho Tech Demos Clinical Utility of FilmArray Respiratory Dx; Plans to Add Blood, GI Panels

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By Molika Ashford

Researchers from Idaho Technology and various academic labs have recently completed several research studies detailing the development and potential clinical utility of the company's FilmArray multiplex PCR system and first diagnostic test, a respiratory virus panel approved earlier this year by the US Food and Drug Administration.

Demand for the respiratory panel has exceeded the company's "high expectations," according to Wade Stevenson, diagnostic product manager at Idaho Tech. In addition, the company is currently developing two additional diagnostic panels for the FilmArray system, one to test positive bacterial blood cultures, and the other to identify pathogens in gastrointestinal infections, Stevenson said.

Idaho Tech's FilmArray platform integrates sample preparation, PCR amplification, detection, and analysis into a single system that the company said can detect more than 100 targets per sample in under an hour. Its multiplex detection capabilities are primarily enabled by melt curve analysis.

In May, the company received 510(k) clearance from the FDA for the instrument and its first assay, the FilmArray Respiratory Panel, a multiplex nucleic acid test designed to simultaneously detect 15 respiratory viruses (PCR Insider, 5/5/2011).

In a paper published last month in PLoS One, Idaho Tech scientists provided a detailed description of the FilmArray system, particularly its ability to perform melt curve analysis. The company hopes the paper will be of interest to current and potential customers interested in a "look under the hood" of the system, Stevenson and colleague Mark Poritz, director of biochemistry at Idaho Tech and corresponding author on the paper, told PCR Insider last week.

"One of the great things about the FilmArray is that it's so highly automated," Stevenson said. "It's only two minutes of hands-on time [for] something that right now in a lab [would take] hours and hours of hands-on labor."

One drawback to the automation, however, "is that it essentially means our system is a little bit of a black box, he said. "That can be an obstacle to overcome with a technically driven customer who wants to understand the details and this paper really lets them do that."

At a talk earlier this year 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 customers are often surprised that FilmArray relies on melt curve analysis-based detection rather than qPCR (PCR Insider, 4/28/2011).

Poritz said that the authors of the PLoS One paper made a "big point" of demonstrating how using melt curve analysis enabled pathogen identification.

"I think many of our customers are not used to that idea," he said. "So what we are showing [in the study] is that the melt curves, they're not technically high-resolution melt curves, but they give you an awful lot of information about the target."

"What we are saying is, you don’t need sequence. You can determine a lot about the molecule by the temperature [at which] the DNA falls apart," he said.

Portiz described the process that takes place in the FilmArray system from an initial multiplex PCR reaction; to individual singleplex PCR reactions that generate PCR products for each target pathogen; to the endpoint melting curve analysis that generates a result for each target.

"The shape of that curve, the way it melts, is characteristic of the sequence. What we've developed over many years and other people [are working on] as well is using a fluorescent dye that binds the double-stranded DNA, and fluoresces. This way, as you heat up the solution, the DNA melts, and the dye falls off and stops fluorescing. There is a characteristic drop [in fluorescence] at some temperature, say [75° F], and that [corresponds to] a particular molecule," he said.

One of the other main points of the paper, according to Poritz, was to detail the system's pouch design, which eliminates the risk of contamination; and to demonstrate that nesting and multiplexing are "a particularly good combination."

"We demonstrated that you can do a first PCR and have lots of competition and then reach into it and do individual second PCRs. You can have a high copy of one molecule and it won't affect the presence of the others. It can detect both."

"You can see a little bit of rhinovirus in the presence of a lot of flu and know that both viruses are present. I think a bunch of different technologies are working toward that but this turns out to be a pretty robust way to do it," he said.

Head to Head

Idaho Tech and collaborators have also recently completed several studies putting the respiratory virus panel to the test against competing technologies, Stevenson said.

In one of these studies, published in July in the Journal of Clinical Microbiology, University of Florida researchers compared the FlimArray Respiratory Panel to Luminex's xTAG RV panel. The authors reported that both systems detected 40 percent to 50 percent more viruses than traditional methods, but that the FilmArray panel "detected significantly more total viruses either alone or as part of mixed infections than the xTAG RVP, as well as an additional 21.6 percent more respiratory syncytial viruses."

According to the authors, the xTAG RVP requires five to six hours with two and a half to three hours of hands-on time, while the FilmArray RP takes about an hour with three to five minutes of hands-on time, making it much easier to perform.

Stevenson said two additional papers will soon be published comparing the FilmArray panel to other tests.

One, performed at the University of Texas Medical Branch, Galveston, compares the FilmArray respiratory panel to a group of Gen-Probe Prodesse real-time PCR assays, and was published ahead of print in the Journal of Clinical Microbiology in October.

The authors concluded that the pre-market version of the FilmArray RP had "generally comparable diagnostic performance as the FDA-cleared panel of Prodesse real-time PCR assays, for viruses detectable by both platforms." They wrote that the FilmArray RP may be less sensitive for detection of adenovirus, and that the system's low throughput "is a significant factor that laboratories must consider."

Another study comparing the FilmArray RP with Qiagen's ResPlex system has been submitted for publication, Stevenson said. In a poster describing results from this study on Idaho Tech's website, the authors, from St. Jude's Children's Hospital, reported that 80 percent of positive results were concordant between the two systems. ResPlex failed to detect 20 percent of FilmArray positives, and FilmArray failed to detect 4.4 percent of ResPlex positives, they wrote.

The company also has a study in the works comparing its panel to the GenMark respiratory viral panel for the XT-8 system, which is designed to detect 21 different upper respiratory viruses, Stevenson said. That system has not yet received FDA approval.

When Idaho Tech's respiratory panel was approved in May, Stevenson said that the company hoped to include several bacterial targets in a future version (PCR Insider, 5/05/2011). He told PCR Insider last week that the company is "very confident" it will have "at least two bacterial targets and some additional viral targets added to the panel in time for the 2012/2013 flu season."

According to Stevenson, the respiratory virus panel has been the vehicle through which most of the development of the FilmArray system has taken place. Now Idaho Tech is planning to expand the platform to other diagnostic applications, he said.

The next application will be a positive blood culture identification panel. "When one gets a positive blood culture, it’s a really strong indication that you have a very, very sick patient that needs to be treated really aggressively," Stevenson said. "Sadly, using current methods, it takes 24 to 48 additional hours, sometimes longer, to identify the organism."

A FilmArray-based panel for positive blood culture material "will allow for better more appropriate, faster treatment," he said.

Stevenson said the company has just finished a first round of beta testing with this panel, and that the product performed "really well."

"We found a few things we need to tweak and are making those changes now, but we anticipate starting a second round of beta testing in January of next year … and clinical trials seeking FDA clearance [are] slated to start in May of next year. If all goes well, we could launch [the panel] as early as early 2013," he said.

Another application, further down the pipeline, is a gastrointestinal panel to identify pathogens causing acute cases of diarrhea.

"We are in the middle of developing a panel that will simultaneously test for a host of bacteria, viruses and protozoa that will really be incredibly labor- and time-saving compared to the work labs have to do right now to identify pathogens in stool," Stevenson said.


Have topics you'd like to see covered in PCR Insider? Contact the editor at mashford [at] genomeweb [.] com.

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