By Ben Butkus
IQuum, a Boston-area company developing what it calls "lab-in-a-tube" technology for PCR-based molecular testing, said this week that it has been granted emergency use authorization from the US Food and Drug Administration for its influenza A/2009 H1N1 assay.
With the flu season coming to a close in the US and the FDA's EUA period set to expire on June 23, the authorization may not translate into immediate revenue opportunities for IQuum, which is currently scurrying to market the approved test.
However, the vote of confidence is a significant milestone for IQuum because it "demonstrates the maturity" of the company's testing platform, called the Liat Analyzer, Lingjun Chen, IQuum's vice president of operations and strategic planning, told PCR Insider this week.
It is also a stepping stone for the company to seek 510(k) approval for an H1N1 test on the Liat platform; to tackle the point-of-care diagnostic market; and to further develop additional Liat tests for seasonal influenza, HIV viral load testing, and cytomegalovirus, Chen said.
For now, the EUA covers an assay that is performed on the Liat and detects and differentiates 2009 H1N1 influenza viral RNA from collected nasopharyngeal swab samples.
The authorization allows the assay to be used in laboratories certified under the Clinical Laboratory Improvement Amendments to perform "moderate complexity" tests, enabling its use in hospital near-patient settings, IQuum said.
The EUA is the first regulatory approval of any kind for an assay performed using the Liat platform, which has been more than a decade in the making since the company was founded in 1998.
But over that time period, IQuum has developed a platform that can perform a full soup-to-nuts nucleic acid test in anywhere from 25 minutes to an hour; is small enough to be deployed in a point-of-care setting; and has sensitivity that is equivalent to a typical "high-complexity" laboratory-based PCR test performed on a much larger instrument platform, the company said.
"We took a couple of years developing the technology, and then focused on nucleic acid tests as the initial applications," Chen said. "To develop a product like this that is so small, yet so quick and easy to use, takes a long time."
IQuum describes Liat as a "lab-in-a-tube" system that is designed to enable "less-experienced personnel to perform more sophisticated biological sample testing," which includes collecting a raw biological sample such as whole blood, plasma, or swab into a Liat Tube; scanning the tube’s barcode; and inserting the tube into the analyzer.
From there, the Liat uses "established, proven, gold-standard assay chemistries" to perform a test in 25 minutes to 1 hour, depending on the initial biological sample.
"For sample prep we use silica magnetic bead-based extraction, which is the same chemistry you would find on the large automated systems that you would find in centralized labs," Chen said. "Likewise, for detection, we use real-time PCR. Those are very tried-and-true chemistries that everybody knows and have been proven over many years."
This is important, Chen said, because "once we enter the point-of-care arena, result comparability is a big deal. You want to have the POC device to have the same output as a laboratory device, and by using the same chemistry we can achieve that."
The Liat has a benchtop footprint of about four inches by seven inches, with a height of about seven inches; yet, despite its small size, it contains six optical detection channels for multiplex target detection and doesn't sacrifice the sample or reaction volumes typically used in larger testing instruments.
"Lab-on-a-chip devices usually have microliter sample or reaction volumes, and we are still in the range of hundreds of microliters to one milliliter," Chen said. "That's very important for sample representivity."
Likewise, he said, many microfluidic devices will use PCR reaction volumes in the 1 to 5 µL range. "We still use a 50-µL reaction volume similar to big lab instruments," Chen said. "We believe that has a big impact on the quality of the results."
About half the time of an assay performed on Liat is sample prep, with the other half amplification and detection, Chen said. Thus, for the H1N1 assay, which can be run in about 26 minutes, about 13 to 15 minutes are devoted to sample prep with a little over 10 minutes used for amplification and detection.
IQuum has also demonstrated in an internal study, which it conducted as part of its EUA application, that its H1N1 viral RNA assay had 100 percent positive and negative agreement with an undisclosed comparator EUA assay in 85 clinical samples tested, including 35 samples positive for H1N1 flu.
IQuum is the latest in a slew of companies to receive FDA EUA for PCR-based H1N1 testing. Others include Longhorn Vaccines & Diagnostics, IMDx, Qiagen, Cepheid, Diagnostic Hybrids, Diatherix, ELITech, Focus Diagnostics, DxNA, IMDx, Prodesse, Roche, TessArae, and ViraCor.
The Department of Health and Human Services' declaration of emergency justifying the H1N1 EUAs is set to expire in late June, but could be extended if certain criteria are met, according to the FDA's website.
As such, IQuum is not likely to see direct revenues from Liat H1N1 assays in the near term, although it could if H1N1 flu testing picks up or if another EUA period is declared. In the meantime, IQuum ultimately hopes to penetrate the POC testing market with Liat, and the EUA is a big step in that direction, according to Chen.
"There is still some testing for H1N1 ongoing, but with the flu season winding down, the volume is not high right now," Chen said. "But over the last couple of years people have been talking about [decentralizing] molecular diagnostics, and trying to get it out of just the centralized laboratory setting. This authorization shows the technology's potential to do that."
In addition to the H1N1 test, IQuum is developing a seasonal flu assay that uses all six optical detection channels to detect US seasonal strains, influenza B, and H5N; and contains an internal control.
It also has a test for HIV viral load testing in the pipeline, which is the most promising for POC applications, Chen said. That assay is quantitative, can be run from a plasma sample, and can be completed in under an hour, he said.
"This is especially important in countries where HIV is endemic, and they don't have the capability to guide treatment using a nucleic acid quantitative test," he said. "They're still using CD4 counts, which the research has shown has many disadvantages to nucleic acid testing.
"Our assay can allow them to do such testing without the laboratory infrastructure or trained personnel or heavy investment in capital equipment," Chen added. "In those types of environments, for lots of patients, follow up is a major issue. You can't really take a sample and ask them to come back in a week. Being able to give them the result in one hour to provide any changes in the treatment regimen is very significant."
Chen said that it is developing this test in collaboration with a number of undisclosed "institutional evaluators — hospitals, universities, testing labs, and other HIV field leaders."
IQuum is also working on a Liat test for cytomegalovirus, Chen said.