This story has been updated from a previous version to include additional comments from TessArae.
The US Food and Drug Administration has granted emergency use authorization to TessArae for its RM-Fluchip, TessArae said this week.
An EUA allows clinicians to use an unapproved medical product during certain types of emergencies to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by biological, chemical, radiological, or nuclear agents.
The decision enables TessArae to sell its Resequencing Influenza A Microarray Detection Panel to help physicians detect the 2009 H1N1 influenza A virus until April 26, 2010, when the declaration of emergency expires, the company said. The EUA can be renewed, the firm added.
The test is a targeted sequencing assay intended for the in vitro qualitative detection of the 2009 H1N1 influenza A virus. The firm said the assay is aided by an algorithm that relies on seasonal A/H1N1 and seasonal A/H3N2 influenza virus results.
Manufactured by Affymetrix on its GeneChip platform and run on Affy instrumentation, the assay is performed on throat swabs taken from patients with symptoms of respiratory infection, TessArae said.
Potomac Falls, Va.-based TessArae becomes the first array firm to have received an EUA to sell chips for the monitoring and early diagnosis of the H1N1 flu. Other firms, such as Sunnyvale, Calif.-based Arrayit and Boulder, Colo.-based InDevr, have expressed an interest in pursuing an EUA for their respective flu chips in the past (see BAN 5/5/2009). Representatives for Arrayit and InDevr reaffirmed plans to seek an EUA in separate e-mails to BioArray News this week.
In addition, Mukilteo, Wash.-based CombiMatrix, Singapore-based Veredus Laboratories, and Hyderabad, India-based Ocimum Biosolutions have announced the ability of their flu chips to detect H1N1, though they have not been granted EUA status.
According to the FDA, as of Dec. 11, 12 devices have been authorized for emergency use to monitor and treat the virus, including those made by Roche, Diatherix, Focus Diagnostics, Prodesse, Elitech Molecular Diagnostics, and GeneStat. The majority of these are real-time PCR-based tests or those that use alternative forms of PCR technology.
TessArae CEO Klaus Schäfer said in a statement that the authorization demonstrated the "power of [TessArae's] technology to detect a ... pathogen using the appropriate targets."
He also said that the RM-Flu assay "harnesses both DNA sequencing technologies and large public DNA-sequence databases that are available today, and represents a new approach to sequencing-based diagnostics."
Matthew Lorence, vice president of marketing and sales at TessArae, said the authorization from the FDA could have wider implications for the company as "an up-and-coming molecular diagnostics company" both in the infectious disease testing market, as well as the genetic disease and disorder testing market. Though TessArae initially focused on infectious disease testing, it last month announced a deal with Gaithersburg, Md.-based GeneDx to develop array-based tests for Noonan Syndrome and Periodic Fevers Syndrome (see BAN 11/10/2009).
Lorence told BioArray News this week that TessArae also hopes that the authorization will facilitate FDA-clearance of the other pathogens that are detected by the firm's TessArray RPM-Flu test, which detects and differentially identifies more than 35 classes or types of viral and bacterial respiratory pathogens, but is not cleared for in vitro diagnostic use. According to Lorence, the content on the RM-Flu chip is essentially a subset of the content on the RPM-Flu test, which has been available for research use for several years.
While almost all other assays to receive an EUA for H1N1 testing are RT-PCR based, Lorence said that TessArae's array-based method has some advantages over those tests.
"The RM-Flu test results represent nucleotide sequences from multiple influenza virus genes from the three targeted strains — 2009 H1N1, seasonal A/H1N1, and seasonal A/H3N2 viruses — including the hemagglutinin, neuraminidase, matrix and non-structural genes," Lorence said. "A single RM-Flu test result is based upon hundreds to thousands of nucleotides of virus gene sequences for identification of a detected virus," he said. "This feature of RM-Flu is very different from RT-PCR assays that base detection and identification of the virus upon a quantitative measurement of fluorescent signal from a biomarker probe."
[ pagebreak ]
Lorence noted that when users run an RM-Flu test, the resulting sequences of detected virus are compared against TessArae's validated reference database to determine the most similar sequence records. "The influenza virus strains of the matching sequence records provide a definitive identification of the 2009 H1N1 virus if present in the specimen," he said.
He also said that the fact that the test runs on the Affy platform is not a hurdle, as the kinds of labs that would offer such testing are likely to have an Affy system in house. "Both the RM-Flu and the RT-PCR tests have been authorized by the FDA for use with specific instrument platforms at high complexity CLIA labs, so the requirement of the Affymetrix platform is not an obstacle, especially since there are numerous such labs with access to the Affymetrix GeneChip System," he said.
Obtaining an EUA
To receive emergency use authorization, TessArae had to meet certain performance testing and validation standards required by the FDA. Lorence said that the firm was asked to provide replicate serial dilution endpoint limit of detection studies to determine the analytical sensitivity of the assay.
Titered stocks for the three different influenza virus strains were used and the reproducibility of the assay was demonstrated using 20 replicate dilutions at limit of detection to provide positive results in 95 percent of the replicated, Lorence said.
TessArae then had to demonstrate accurate detection of 2009 H1N1 with specimens from patients that had been confirmed using an FDA-authorized assay, which at that time this study was conducted, was the assay developed by the US Centers for Disease Control.
"All of these studies required access to purified virus stocks of each of the three strains, which the FDA recommended we request from the CDC," Lorence said "We were never able to obtain the necessary virus stocks from the CDC, but the FDA did allow us to use comparable stocks that were prepared for us from isolates provided by a [US Department of Defense] military lab, all of which were from the 2008-2009 flu season, so current virus strains."