It’s rare when a milestone in medical technology attracts much attention among the nation’s top healthcare brass. But last week, several paused to acknowledge FDA’s clearance of the first high-throughput gene sequencer for clinical lab use. In press releases and articles, FDA and NIH officials noted the novelty of the occasion and hinted that a new era in healthcare will soon follow.

At the center of the celebration was the MySeqDx Platform by Illumina Inc. (San Diego), a platform for next-generation sequencing (NGS) that received market clearance and Class II designation via FDA’s de novo 510(k) process on 19 November. The agency also cleared the company’s reagent kit and two assays for sequencing regions of the cystic fibrosis conductance regulator (CFTR) gene, where DNA changes can result in the onset of cystic fibrosis.

In a press release announcing the Illumina clearances, FDA looked beyond the initial tests to the broader implications of such a system for future healthcare. “These instruments, reagents, and test systems allow labs to sequence a patient’s DNA,” noted the agency. “The new technology also gives physicians the ability to take a broader look at their patients’ genetic makeup, and can help in diagnosing disease or identifying the cause of symptoms.”

“NGS is changing the way we look at genomics,” said Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health at FDA’s Center for Devices and Radiological Health. “Before NGS, sequencing genes associated with a particular disease was a long and costly process. Today, we have the capability to read and interpret large segments of DNA very quickly in a single test, and this information-rich technology is becoming more accessible for use by physicians in the care of their patients.”

In an FDA Voice post on the day following the announcement, CDRH Director Jeffrey E. Shuren, MD, JD, emphasized the Illumina clearance as an example of FDA’s progress in the realm of regulatory science. “Knowing the potential of next-generation sequencing to advance personalized medicine, “ Shuren wrote, “FDA researched next-generation sequencers to understand how they work and their likely limitations.” By the time Illumina walked in the door, he added, “FDA had the expertise and tools needed to timely review the submissions for the next-generation sequencers.”

“We are working on many fronts to achieve the promise of personalized medicine, so that patients can get medical treatments that are right for them,” Shuren observed. “Clearing the marketing of these four devices moves us closer to that goal.”

The significance of the event was similarly marked by National Institutes of Health Director Francis S. Collins, MD, PhD, and FDA Commissioner Margaret A Hamburg, MD, who jointly authored a special online Perspective item for the New England Journal of Medicine on the day of the clearances. Amid examples of the potential utility of NGS for making personalized medicine a reality in clinical practice, the authors also acknowledged that “even the most promising technologies cannot fully realize their potential if the relevant policy, legal, and regulatory issues are not adequately addressed.”

Collins and Hamburg cited the June 2013 Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics as “a breakthrough for access to individual genetic tests” as well as for the integration of genome sequencing into clinical care. “Before the Myriad decision, there were substantial concerns that in order to offer whole genome sequencing, clinical laboratories would have to pay royalties to a long list of gene patent holders,” they wrote. “The decision has opened the creative doors to an as yet unimaginable set of products that may benefit the public health.”


But labs seeking to develop such tests may find themselves facing a whole new set of obstacles. Foreshadowing the coming era of greater FDA regulation of clinical labs, the authors noted that the Illumina clearance of a non–disease-specific platform “will allow any lab to test any sequence for any purpose. Thus, putting in place an appropriate risk-based regulatory framework is now critical to ensure the validation and quality of tests (called laboratory-developed tests, or LDTs) developed in-house by clinical laboratories.”


The still more troublesome issue of how to establish an equitable payment regime for NGS testing made a cameo appearance in the authors’ short article, but not until the penultimate paragraph, when they acknowledged that ”reimbursement issues need to be resolved to assure that patients have access to the best tests and that manufacturers have incentives to develop them.”


With such top-level recognition, Illumina’s first-mover advantage will be significant—but it may not be long-lived. In a [removed]statement[/removed] about the Illumina clearance, competitor RainDance Technologies (Billerica, MA) commented: “Sequencing-based testing is the future of healthcare, and RainDance is committed to advancing this technology further by providing tools that enable our customers to target specific, actionable regions of the genome, more cost-effectively, accurately, and at higher throughput using any next-generation sequencer.”


First-mover or otherwise, NGS companies and their clients will be challenged to meet the high expectations of the nation’s top health experts while also dealing with a host of ongoing policy, legal, and regulatory issues. If adequate reimbursement remains mostly an afterthought, building on NGS to achieve the full potential of personalized medicine could prove to be just one challenge too many.