FDA Draft Guidances Designed to Streamline Regulatory Oversight for Next-Generation Sequencing Tests

The FDA has published two draft guidances proposing methods to streamline oversight of Next Generation Sequencing (NGS)-based tests. These tests are capable of rapidly identifying or ‘sequencing’ large sections of a person’s genome and are important advances in the clinical applications of precision medicine. The new guidances provide adaptability and flexibility that test developers need to innovate in this dynamic field while still enabling the FDA to meet its mandate of ensuring that tests are safe and effective.

The FDA is a partner in President Obama’s Precision Medicine Initiative (PMI), which aims to take advantage of the progress made in genomic testing to accelerate the development of new treatments designed to meet patients’ individual characteristics. Targeting the right treatments to the right patients at the right time is the goal of the PMI. However, precision care will only be as good as the tests that guide diagnosis and treatment.

It is the FDA’s responsibility to ensure that doctors and patients can depend upon the accuracy and reliability of NGS-based tests. While current regulatory approaches are appropriate for conventional diagnostics that detect a single disease or condition (such as blood glucose or cholesterol levels), these new sequencing techniques contain the equivalent of millions of tests in one. That means that the FDA is adapting its regulatory approach to accommodate this rapidly-evolving technology. As these tests proliferate, they must produce results that are accurate, reliable, and understandable – providing actionable information about a person’s health, their future risk of disease, and/or treatments for conditions they may have or develop.

Working within its existing regulatory authority, and incorporating extensive insights from patient and provider groups, test developers, industry coalitions, professional societies, and leading academicians, the FDA has drafted guidances that would streamline submission and review of data supporting the clinical and analytical validity of NGS-based tests. They represent a significant step toward the FDA’s long-term goal of establishing a dynamic and flexible regulatory approach for genomic tests.

The first draft guidance, entitled “Use of Standards in FDA Regulatory Oversight of Next Generation Sequencing (NGS)-Based In Vitro Diagnostics (IVDs) Used for Diagnosing Germline Diseases,” provides recommendations for designing, developing and validating NGS-based tests for hereditary diseases, and addresses the potential for using FDA-recognized standards to demonstrate analytical validity.

The second draft guidance, entitled “Use of Public Human Genetic Variant Databases to Support Clinical Validity for Next Generation Sequencing (NGS)-Based In Vitro Diagnostics” proposes an approach for test developers to cite data and assertions from FDA-recognized public genome databases as valid scientific evidence to support clinical claims for their tests and help assure accurate clinical interpretation of genomic test results – an easier path for marketing clearance or approval.

The guidances explain how the FDA would consider, in the future, whether to exempt certain NGS-based tests from premarket review. This system would be efficient and flexible: as technology advances, standards can be updated to help ensure test accuracy. Similarly, as clinical evidence improves, new interpretations could be supported. This adaptive approach would ultimately foster innovation among test developers and improve patients’ access to these new technologies.