New FDA Guidances Address NGS and Supporting Variant Databases

By Kelly Hardy Briganti, Editorial Director, G2 Intelligence

Promoting flexibility and efficiency, the U.S. Food and Drug Administration (FDA) issued two draft guidances last week addressing oversight of next generation sequencing-based tests and the databases that support clinical claims for these tests. Public comments on the drafts should be submitted within 90 days.

Acknowledging input from genomics experts, providers, patients and other industry stakeholders via public workshops and other efforts, Jeffrey Shuren, M.D., J.D., director of the FDA’s Center for Devices and Radiological Health said in a statement that the agency believes the guidance documents “will encourage innovation and advance the goal of precision medicine: to speed the right individualized treatments to patients sooner.”

Here is a snapshot of what the draft guidance documents, both issued July 8, address:

• “Use of Standards in FDA Regulatory Oversight of Next Generation Sequencing (NGS)-Based In Vitro Diagnostics (IVDs) Used for Diagnosing Germline Diseases”—provides the FDA’s proposed recommendations for “designing, developing, and validating NGS-based tests for germline diseases, and also discusses possible use of FDA-recognized standards for regulatory oversight of these tests.”

• “Use of Public Human Genetic Variant Databases to Support Clinical Validity for Next Generation Sequencing(NGS)-Based In Vitro Diagnostics”—details the FDA’s thinking on “how publicly accessible databases of human genetic variants can serve as sources of valid scientific evidence to support the clinical validity of genotype-phenotype relationships in FDA’s regulatory review of NGS-based tests.”

“While current regulatory approaches are appropriate for conventional diagnostics that measure a limited number of substances associated with a disease or condition, such as blood glucose or cholesterol levels, the new sequencing technologies can examine millions of DNA variants at a time, and thus require a flexible approach to oversight that is adapted to the novel nature of these tests,” the agency explained in its press release announcing the guidance. “When the guidances are finalized, adherence to them will offer appropriate flexible and adaptive regulatory oversight of these tests, while allowing for variations in development and validation and accommodating the rapid evolution of NGS technologies.”