By Monica Heger
While it is still early days for the clinical use of next-generation sequencing, the recent availability of desktop sequencers opens the door for the technology to be used in a regulated clinical diagnostic setting, according to Siemens Healthcare Diagnostics.
Trevor Hawkins, vice president of strategy and business development at Siemens Healthcare Diagnostics, told Clinical Sequencing News that the current "maturity, performance characteristics, and price point" of next-gen sequencing technology means that "now is the time to start asking the key question — can you use this research instrument in clinical diagnostics?"
Hawkins spoke to CSN after the company announced last week that it is partnering with Illumina to transition its Trugene HIV genotyping assay to the MiSeq platform (CSN 11/2/2011). The companies said they will eventually adapt all of Siemens' HIV tests for the MiSeq, as well as other infectious disease assays.
As it moves the HIV assay to the MiSeq, Hawkins said that Siemens would also initiate discussions with the US Food and Drug Administration about gaining regulatory clearance for the test.
"The whole diagnostics community is asking questions about how the FDA will view next-gen sequencing," said Hawkins. "We wanted to become part of that conversation."
While the deal with Illumina is Siemens' first partnership in the next-gen sequencing arena, Hawkins said that the company is open to any sequencing technology, and that its agreement with Illumina does not preclude it from developing other diagnostic tests on different platforms if appropriate.
Hawkins added that the company has access to "all the major next-gen sequencing platforms that are available today," and that it is particularly interested in the desktop sequencing instruments like the MiSeq and Ion Torrent's PGM.
'A Good Test Bed'
Hawkins said the company chose its Trugene HIV assay as the first to move to the MiSeq because it was approved by the FDA 10 years ago and the company "updates the technology every six months with the FDA," based on new research.
"We have a massive amount of understanding with how clinicians are using the sequence data, what they expect, what reporting should be like," said Hawkins. "It will be a really good test bed."
The first step is to compare the results of the current assay with results from runs on the MiSeq. Company researchers will have to determine how much depth of coverage is needed, optimum read lengths, and the necessary Q scores in order to achieve the same sensitivity and specificity as the current test, said Hawkins.
The next challenge will be determining how to analyze and interpret the data. "How can we seamlessly integrate the production of data and the output of a report that clinicians can use to make treatment decisions?" said Hawkins. "That's a big step."
A next-gen sequencing test will have to give clinicians a report that they can understand, at a level of quality they are familiar with, and will have to have a workflow that is cheaper, easier, and faster than the current test, said Hawkins.
Hawkins said the company does not have a timeline or a predicted cost for a next-gen sequencing-based Trugene assay. Additionally, he said it was too early to say whether the company would eventually convert its entire fleet of Sanger-based diagnostic tests to next-gen.
However, "if the next-gen systems live up to the promise … the whole clinical diagnostics community will be moving to next-gen sequencing for the vast majority of assays that are performed today," he predicted.
As Siemens converts the test to the MiSeq, it will still offer the FDA-approved Sanger-based HIV test. Hawkins said it was too early to say how the FDA would view the assay on the MiSeq and whether it would grant 510(k) clearance for the test or whether the company would have to file a pre-market approval application.
Hawkins predicted that these questions would be resolved in 2012 "as everyone gets a better understanding of what these new [desktop] machines can do."
Both Illumina and Life Technologies are trying to figure out how the FDA will view diagnostics that run on next-gen sequencing platforms, and Siemens thought it was important to become part of that conversation early enough to have an impact, he added.
Siemens has experience "taking products into the healthcare marketplace and through regulatory bodies," which could be beneficial in figuring out how diagnostics based on next-gen would be regulated, he said.
Illumina has said that it plans to seek 510(k) clearance for its MiSeq platform in 2012 (CSN 8/3/2011). Greg Heath, the company's senior vice president and general manager of diagnostics, told CSN this week that Illumina will pursue FDA clearance with one of its own internally developed assays, not Siemens' Trugene assay, though he declined to disclose further details.
Siemens' experience in developing FDA-approved diagnostics could be beneficial as Illumina moves for FDA clearance of the MiSeq, but Heath said that the company is not relying on Siemens' experience and is expanding its diagnostic capabilities internally.
He noted that as part of this strategy, the company recently created a new position, chief medical officer, and tapped Daniel Grosu to fill that role. Prior to joining Illumina, Grosu worked at Ortho-Clinical Diagnostics, Bayer Healthcare Pharmaceuticals, and Siemens Medical Solutions.
The partnership with Siemens does help expand Illumina's expertise into the infectious disease area, said Heath, adding that he could foresee similar partnerships in areas where the company does not have in-house expertise. Internally, Illumina has been doing clinical sequencing in the fields of genetic disease and cancer, but does not have in-house expertise in infectious disease, he said.
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