By Ben Butkus
Clinical diagnostic test maker Iquum this week received US Food and Drug Administration clearance for its Liat Influenza A/B assay and fully automated and integrated Liat Analyzer.
Iguum said the real-time PCR-based test — its first 510(k) win — is designed to enable clinical labs to detect and differentiate influenza A and B in about 20 minutes, or about as fast as currently used immunoassays, but with the increased sensitivity afforded by nucleic acid testing.
As the privately held company prepares to market the assay and instrument for the upcoming flu season, it said it hopes to use this week's regulatory clearance as a springboard to bring to market several other molecular assays and laboratory tools based on the same core technology. These include a higher-throughput molecular testing workstation and assays for HIV viral load monitoring, influenza subtyping, and cytomegalovirus, company officials said.
The clearance "validates the technology and demonstrates the potential of the Liat system to deliver molecular diagnostics to decentralized locations and provide the type of immediate and accurate results that can provide better patient outcomes," Lingjun Chen, vice president of operations and strategic planning, told PCR Insider this week.
The ability to offer even one commercial product has been a long time coming for Iquum, which was founded in 1998. The Marlborough, Mass.-based company has spent the better part of the last decade developing its flagship Liat Analzyer to run a full sample-to-answer, point-of-care molecular assay in less than an hour with minimal user intervention.
Last May, FDA granted Iquum Emergency Use Authorization for its first test for the Liat analyzer, an assay to detect the influenza A/2009 H1N1 virus (PCR Insider, 5/13/10). Though Iquum received the near the end of flu season, thus minimizing revenue opportunities, Iquum said it saw the EUA as a general vote of confidence for its platform.
Since that time, Iquum put the finishing touches on the Influenza A/B assay, and Chen said this week that the company made a few improvements to the platform's performance.
"The platform has largely stayed the same, except we've made some significant improvements to time to result," he said. "The 2009 H1N1 assay took 26 minutes, which, other than this test, is still the fastest nucleic acid [flu] test. For this influenza A/B assay, we've reduced the time to 20 minutes."
Chen said the Liat Analyzer achieves this speed primarily through a proprietary PCR procedure called flow cycling.
Most traditional PCR machines consist of a large heating block that houses one or more reaction tubes containing reaction mixtures. The temperature of the block is then ramped up and down repeatedly to the target denaturing and annealing and extension temperatures.
Although manufacturers have devised many ways to reduce the amount of time this takes, the entire process still typically requires between 30 minutes and several hours to complete.
The Liat, however, combines two innovations to hasten the procedure: a flexible reaction vessel and a modular sample processor, which compresses various segments of the reaction vessel to heat and cool them much faster, Chen said.
"Combining those for PCR, we place the reaction mixture in the flexible tube, and then we set one modular processor at a high denaturing temperature, and set another processor at a low annealing/extension temperature," he said. "And then basically those processors alternatively squeeze this flexible reaction vessel to move the liquid from one segment to another. This allows us to cycle only the fluid … and do PCR very quickly, on the order of 10 to 15 minutes."
The Liat also integrates silica magnetic bead-based extraction for sample prep, which is commonly used in larger automated molecular testing systems; and has six optical detection channels for multiplexing. These features are housed in a benchtop instrument less than one square foot in size.
According to Chen, the upshot is that the Liat Analyzer can run assays that are "much more sensitive than immunoassays in about the same amount of time and with the same ease of use."
With the 510(k) approval in hand, Iquum is now "focused on launching this product for the upcoming flu season" for use in CLIA moderate-complexity labs in hospitals and some group practices, Chen said.
In addition to hospitals, "in many cases physicians' group practices [also] have moderate-complexity labs on site," he said. "Right now these sites in many cases are frustrated by rapid immunoassays that have very low sensitivity. Often they have to do a test, and even when it comes up negative, there is a limitation as to how they can use that result. In many cases it needs to be confirmed."
Next in the pipeline for Iquum is an HIV viral load assay, which will also be designed to run on the Liat Analzyer. Iquum said it believes the assay may be particularly useful in resource-poor areas of the world where central lab testing is either limited or nonexistent.
Chen said that in the past year research groups at the University of North Carolina at Chapel Hill and the University of Washington have validated the assay and presented data from these studies at various scientific meetings.
Results thus far have shown "excellent correlation" with existing FDA-approved HIV viral-load tests, including Roche's Cobas HIV-1 test for the Roche Amplicor platform and the Abbott Real-Time HIV-1 assay, which runs on the Abbott m2000. Both platforms are much larger and offer higher throughput than Iquum's Liat.
"The performance of our test is really good when considering that the test itself takes 15 minutes compared to several hours for the Roche and Abbott tests," Chen said. "And also, considering the sample volume we use, which is 200 microliters, versus 0.6 to one milliliter for the Roche and Abbott tests."
Chen said that Iquum is "working on" submitting a regulatory approval package to both US and European regulatory authorities, and that the company expects to be able to launch the assay in 2012.
Iquum is also developing a cytomegalovirus test; an influenza sub-typing test; and an assay for dengue fever. None of these — except perhaps the influenza sub-typing test — takes full advantage of the Liat's six-channel multiplexing capabilities. Chen noted that the company is currently exploring other applications in microbiology, genetic testing, and pharmacogenomics that might more fully leverage this feature.
Lastly, the company is also developing a higher-throughput testing instrument called the Liat Workstation, which is essentially eight standard Liat analyzer modules strung together to test up to eight samples simultaneously, a capability some of the company's customers have asked for, Chen said.
"Many labs have a certain level of throughput they'd like to achieve," he said. "In some cases, because the Liat Analyzer is so fast, many labs say they can achieve almost 24 tests per eight-hour day, and that's sufficient for them. For other labs, they have sufficient sample flow that they need higher throughput. The Liat Workstation was designed for that."
Iquum unveiled a prototype of the product last month at the American Association of Clinical Chemistry meeting in Atlanta. The company has been testing it internally, but has not yet signed on early users. Chen declined to provide a commercialization timeline for the instrument.
As it begins selling its Influenza A/B assay and fleshing out its development pipeline, Iquum is, for the time being, financially sound.
"We have generated cash from private investors, as well as grants to this point," CFO Daniel Sutherby told PCR Insider. "We do have cash to take us to and through commercialization [of the flu A/B test]. Of course that will generate revenue for us, which is exciting. But we're also open to strategic partnerships or other collaborations as part of our commercialization plan."
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