FDA Considering How to Tailor its Oversight for Next Generation Sequencing

By: Margaret A. Hamburg, M.D.

FDA is weighing the appropriate regulatory approach to advances in technology that allow physicians to obtain information on large segments of a patient’s genetic makeup very quickly.

Margaret Hamburg, M.D.This technology is known as next generation sequencing, where a single test potentially can be employed to identify thousands—even millions—of genetic variants carried by a single individual. The results of such tests could be used to diagnose or predict a person’s risk of developing many different conditions or diseases and potentially help physicians and patients determine what course of treatment should be used to treat specific individuals.

Reliable and accurate NGS technologies promise to accelerate “personalized” or “precision” medicine, the tailoring of medical treatment to the individual characteristics of each patient. But they also pose some novel issues for FDA in carrying out our mission of protecting and promoting public health.

Most diagnostic tests follow a one test—one disease paradigm that readily fits FDA’s current device review approaches for evaluating a test’s analytical and clinical performance. Next generation sequencing produces a massive amount of data that may be better handled using a new approach.

Last year we took steps to adapt our oversight approach to this new technology with the marketing authorization of the first NGS sequencing instrument, Illumina’s MiSeqDx Instrument and its two tests for cystic fibrosis (CF) mutations. We applied practical regulation to these products: we looked at how accurately the instrument sequenced a representative set of genetic variants across the genome rather than requiring data on every possible variant. Doing so avoided years of data gathering and unnecessary delay in the public’s access to the benefits of this technology while still assuring its accuracy and reliability.

Similar flexibility was employed in assessing the two CF tests. FDA allowed Illumina to leverage a well-curated, shared database of CF mutations to demonstrate the clinical value of its tests, rather than requiring them to independently generate data to support each mutation’s association with the disease.

In the future, next generation sequencing tests may be available to rapidly address new medical knowledge that can be applied in treating patients. Medical knowledge itself can be strengthened through creating databases of research and clinical information tied to particular genetic variants. FDA intends to develop a practical and nimble approach that will allow medical advances to be implemented as soon as possible, using its regulatory flexibility and the power of the information placed into high-quality databases.

This week President Obama unveiled his Precision Medicine Initiative. As part of that effort, FDA has been reviewing the current regulatory landscape involving next generation sequencing as the technology moves rapidly from research to clinical practice. To get the dialogue started, FDA published a preliminary discussion paper in late December that posed a series of questions about how to best assure that tests are not only accurate and reliable, but are available for patients as soon as possible. Public comment is essential, so FDA has opened a public docket and will be holding a public meeting on NGS technology on February 20.

NGS technology is clearly integral to the future of personalized medicine. Whatever approach FDA ultimately adopts must be selected with care to ensure continued innovation in the advancement of medical care and public health for this still evolving technology.

Margaret A. Hamburg, M.D., is Commissioner of the Food and Drug Administration

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