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Siemens to Release RUO Zika Test While Seeking Emergency Use Authorization

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NEW YORK (GenomeWeb) – Siemens Healthcare Diagnostics has developed a real-time PCR assay for Zika virus and intends to apply for Emergency Use Authorization for the test in the US.

The test, which is currently for research use only, is designed to run on Siemens' Versant kPCR molecular diagnostic platform, but can also be performed on other qPCR platforms. However, Siemens also plans this month to launch the sample prep module of the Versant platform in the US as a registered Class I device which can be paired with the Zika test.

"It's a nice fit, customers can use our Versant sample prep and the Zika kit together," Joern Mosner, head of research and development for molecular diagnostics at Siemens, told GenomeWeb this week.

Last week the Secretary of Health and Human Services declared that circumstances exist justifying the authorization of the emergency use of in vitro diagnostic tests for detection of Zika virus or diagnosis of Zika virus infection.

The US Food and Drug Administration then granted EUA to the first test, an immunoassay from the US Centers for Disease Control and Prevention called the CDC Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay, or Zika MAC-ELISA.

"We have now seen this Emergency Use Authorization path in the US [open up], so we are going after that as well," said Mosner.

The Zika test was developed quite rapidly. "It took us pretty much overnight to design the assay," Mosner said. BLAST analysis to ensure specific primers and probes took 36 hours.

It then took about three weeks to do the analytical and performance studies. The firm used cultured Zika virus for sensitivity testing, and demonstrated the assay was specific by comparing it to other infectious diseases such as chikungunya, dengue, and West Nile viruses.

The assay requires purified, extracted RNA and a real-time PCR platform, and Siemens validated it using various extraction technologies and PCR systems. For example, the firm validated it on its own Versant kPCR Sample Prep system, but in parallel it evaluated sample prep from Qiagen. For detection, the firm validated the test on its Versant PCR module, but also tested a system from Bio-Rad, an Applied Biosystems (Thermo Fisher Scientific) thermal cycler, the Abbott m2000, and the Thermo Fisher QuantStudio 5, Mosner said. Siemens' Versant kPCR platform has had CE marking in Europe since 2008, but the system is not currently authorized for diagnostic use in the US.

Fernando Beils, project leader on the Zika assay and head of global molecular diagnostics at Siemens, said the firm will now offer the test globally as an RUO product, with a particular focus on Brazil, following Siemens' distribution network's determination of the exact locations in Latin America where an RUO test can be sold.

However, "Siemens Healthcare is represented in so many countries in the world, and we want to give access to anyone who would need this assay for research to make sure that they can use this test for patients," Beils added.

Wherever there is an emergency, the firm "would be able to help out," Beils further added, and the platform-agnostic approach of the Zika test development was intended to quickly make it available to as many people as possible.

Siemens' molecular business began in 2007 when it acquired the laboratory diagnostics business of Bayer Healthcare, which had in turn purchased the molecular diagnostics business established by Chiron in the 1980's. A core signal amplification technology is its branched DNA, or bDNA, method Beils said.

As previously noted, the firm launched the Versant kPCR system in Europe in 2008, including the sample prep system and detection unit.

In 2010, the firm agreed to a management buyout of the molecular oncology business, creating Sividon Diagnostics, and allowing it to focus on infectious disease. It formed a molecular diagnostics and microbiology business unit in 2011, then recently sold its clinical microbiology division to Danaher, with that firm intending to fold the micro piece into its Beckman Coulter business.

"We at Siemens want to focus on molecular diagnostics because we believe that this is the place where the market growth will be, and where you can enable healthcare providers worldwide," Beils said.

The Versant system has a menu of the "blockbuster" infectious disease assays, including viral load tests for HIV, hepatitis C, and B viruses, as well as a Chlamydia trachomatis and Neisseria gonorrhoeae test, covering "most of the molecular applications in the field," said Mosner.

The system is automated and multiplex, and each run takes about five hours. It divides individual sample eluate into six wells, so that testing is fully customizable by customers. This is advantageous in the transplant monitoring market, for example, in cases where local regulations or have different reimbursement and treatment guidelines, Beils said.

The firm also has an automated tissue prep system for formalin-fixed tissue samples which is available globally and currently used in the US, including in oncology labs at John Hopkins and Mayo Clinic, Mosner said.

"To grow the menu, we also work with third parties to bring their assays on our platform," Mosner said. This "open channel capability" makes the system "quite unique," he said.

In total, Siemens offers up to 29 different tests on the Versant kPCR system. It has also licensed the bDNA technology to other developers, such as Affymetrix.

Siemens intends to ultimately bring the entire Versant kPCR system to the US Food and Drug Administration, but is not yet ready to provide a timeline or details on which tests will be included. The firm envisions the Versant offering covering the mid-size hospital and smaller reference lab market.

"We see our core strength in this segment, where you have customers with a significant volume of testing, but where a [low-throughput] system doesn't work and a [high-throughput system] would be overkill," Beils said.

"We can be perceived as a late entrant for PCR assays in the US, and the major assays, like HIV, hepatitis, chylamydia, are already taken," he also said. "We'll really be looking for what is the best value that Siemens can bring to the customer when it comes to multiplexing and enabling them to run molecular assays."

Mosner added that "Siemens would like to be a respected, key player in the molecular field globally, so you will see this."