FDA Issues Guidelines on NGS-Based Tests

The U.S. Food and Drug Administration (FDA) has issued two sets of draft guidelines for next-generation sequencing (NGS). The guidance documents will likely be finalized later this year or in early 2017.

The reaction to the draft guidance, which total just 40 pages combined and were issued last month, has been mixed but seems to lack some of the teeth gnashing labs and the FDA have had over other regulatory issues.

One set of draft guidelines pertains to the use of NGS in in-vitro diagnostics for diagnosing germline diseases. The other set pertains to the use of genetic databases to support the clinical validity of NGSbased tests.

The FDA made clear that it considers NGS-based tests as a new form of class III medical device and should come under its scrutiny. However, it also put forth provisions for labs to obtain regulatory approval through the highly streamlined de novo process, which would also give many tests an exemption.

The proposed oversight of databases is broader. The FDA essentially has asked that the databases ensure patient confidentiality, do not contain redundant information that can lead to diagnostic errors, and that their managers are not engaged in professional conflicts of interest, among other recommendations.

“The FDA’s job is to ensure that doctors and patients can depend upon the accuracy, reliability and clinical validity of these tests. It’s our hope that this approach will achieve just that,” said Jeffrey Shuren, M.D., director of the FDA’s Center for Devices and Radiological Health.

The draft guidances underscore the uneasy relationship the FDA and the laboratory sector have had in recent years. The agency’s current regulatory authority extends to point-of-care tests, which still remain a small sliver of the entire clinical testing business. But the sector and the FDA have butted heads repeatedly in recent years over the agency’s attempt to more closely regulate laboratory-developed tests (LDTs). The lab sector has claimed that such regulation would be overly intrusive.

But despite NGS-based tests being highly sophisticated themselves— representing a growing market worth billions of dollars a year in the United States alone—the lab sector is taking a fairly reserved position regarding the draft guidance documents.

The American Clinical Laboratory Association, perhaps the most powerful of the sector’s lobbying groups, has suggested that the drafts are in the same category as the agency’s desire to govern LDTs.

“ACLA continues to assert that laboratory developed tests (LDTs) are not medical devices, including those LDTs that utilize NGS technology,” said ACLA President Alan Mertz. “While we recognize the FDA is looking for innovative solutions, these proposals show the inherent difficulty of attempting to shoehorn LDTs into medical device standards.”

But Francis DeSouza, chief executive officer of Illumina, the San Diego-based laboratory and testing platform manufacturer, welcomed the moves by the agency,

“We support the proactive actions the FDA is taking to recognize the benefits of next generation sequencing and provide appropriately flexible and adaptive regulatory oversight of these tests, while accommodating the rapid evolution of NGS technologies,” he said.

Takeaway: The laboratory sector, which has locked horns in recent years with the U.S. Food and Drug Administration, appears to be taking a more moderate, wait-and-see approach over its draft guidance for next-generation sequencing tests.