In support of the President’s Precision Medicine Initiative, the US Food and Drug Administration (FDA) has issued two draft guidances that, when finalized, will provide a flexible and streamlined approach to the oversight of tests that detect medically important differences in a person’s genomic makeup.

The powerful new technology, known as next generation sequencing (NGS), can scan a person’s DNA to detect genomic variations that may determine whether a person has or is at risk of disease or may help to inform treatment decisions. 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.

“Targeting the right treatments to the right patients at the right time is the goal of the President’s Precision Medicine Initiative,” said FDA Commissioner Robert Califf, M.D. “Soon, patients will have a much more complete picture of their health than in the past, informed by their genetic and genomic makeup. The FDA is preparing for this exciting approach at multiple levels.”

The field of genetic and genomic testing is dynamic, and the agency understands that there is a need to encourage innovation while assuring that NGS-based tests provide accurate and useful results. 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.

“The FDA values the input we received from genomics experts, industry, health care providers and patients from four public workshops and other outreach opportunities. Based on this input, we crafted draft recommendations that we believe will encourage innovation and advance the goal of precision medicine: to speed the right individualized treatments to patients sooner,” said Jeffrey Shuren, M.D., J.D., director of the FDA’s Center for Devices and Radiological Health. “Precision care is only as good as the tests that guide diagnosis and treatment. 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.”

The first draft guidance, titled "Use of Standards in FDA’s 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 rare hereditary diseases, and addresses the potential for using FDA-recognized standards to demonstrate analytical validity, which is how well a test predicts the presence or absence of a particular genomic change.

The second draft guidance, titled "Use of Public Human Genetic Variant Databases to Support Clinical Validity for Next Generation Sequencing (NGS)-Based In Vitro Diagnostics" describes an approach wherein test developers may rely on clinical evidence from FDA-recognized public genome databases to support clinical claims for their tests and provide assurance of accurate clinical interpretation of genomic test results – an easier path for marketing clearance or approval.

“The draft guidances are an important step in the development of NGS-based tests,” said Francis Collins, M.D., Ph.D., director of the National Institutes of Health (NIH). “NIH sees great value in these guidances and encourages test developers to adopt the best practices outlined in the guidances so that high quality tests can become available to the patients who need them.”

This adaptive approach to regulating NGS-based tests is part of the FDA’s engagement in the Precision Medicine Initiative (PMI). The PMI, launched by the White House in early 2015, is an innovative approach to developing a new kind of health care that takes into account individual differences in people’s genes, environments and lifestyles. The FDA’s role in the PMI is foundational: to create regulatory processes that encourage advances in genomic testing while assuring that NGS-based tests are safe and effective. The FDA has been working with experts in the genomics community to conceptualize this flexible approach that strikes the important balance between safeguarding public health and promoting innovation.

The FDA encourages public comments on the draft guidances during the 90-day comment period.