FDA Finalizes Guidances to Accelerate Development of Next-Generation Sequencing Tests

The FDA has finalized 2 guidances to accelerate the development of reliable, beneficial next-generation sequencing (NGS)—based tests, the agency announced Thursday. Both guidances aim to provide a flexible and adaptive regulatory approach to the oversight of NGS-based tests.

Playing a large role in the advancement of precision medicine, NGS works by examining a person’s DNA to pinpoint genetic variations that may determine whether a person has, or is at risk for developing, a genetic disease and can help inform treatment decisions. Rather than detecting chemical changes associated with a condition, NGS scans millions of DNA changes in a single test to determine the cause of a person’s disease or condition.

The first guidance, “Use of Public Human Genetic Variant Databases to Support Clinical Validity for Genetic and Genomic-Based In Vitro Diagnostics (IVD)," describes how publicly accessible databases of human genetic variants can aid test developers by serving as sources of reliable scientific evidence to support clinical claims for their tests, as well as help offer assurance of the accurate clinical evaluation of genomic test results.

The guidance also provides product developers direction on how to use these databases to support the clinical validation of the NGS tests they are developing, which will provide them with an efficient path for marketing clearance for approval of a new test, according to the release.

The second guidance, “Considerations for Design, Development, and Analytical Validation of NGS-Based IVD Intended to Aid in the Diagnosis of Suspected Germline Diseases,” outlines key considerations for designing, developing, and validating NGS-based tests used to diagnose individuals with suspected genetic diseases. It also describes what the FDA would look for in premarket submissions to determine the test’s analytical validity, including how well the test detects the presence or absence of a particular genomic change.

“As disease detection technologies rapidly evolve, so too must the FDA’s approach to reviewing these new innovations,” said FDA Commissioner Scott Gottlieb, MD, in a statement. “The new policies issued today provide a modern and flexible framework to generate data needed to support the FDA’s review of NGS-based tests and give developers new tools to support the efficient development and validation of these technologies.”

Gottlieb also announced the release of these guidances during his address at the 2018 Community Oncology Conference.

Last month, CMS finalized a National Coverage Determination (NCD) to cover diagnostic laboratory tests that use NGS for patients with advanced cancer. When the tests are used as a companion diagnostic to identify patients with certain genetic mutations who can potentially benefit from an FDA-approved therapy, they can assist patients and their physicians in making more informed treatment decisions. If there is no available therapy, the results can help determine a patient’s candidacy for a clinical trial.

The NCD followed the FDA’s approval of the first-of-its-kind comprehensive companion diagnostic test for solid tumors, FoundationOne CDx. The test searches for genetic mutations in 324 genes known to drive cancer growth and is a companion test for 15 available targeted therapies.