Long-Awaited Draft Guidances on Next Generation Sequencing Diagnostic Tests Released Today

July 7, 2016

By Allyson B. Mullen, Jeff N. Gibbs, McKenzie E. Cato* –

Technological advances have resulted in Next Generation Sequencing (NGS) being used more and more frequently by diagnostic laboratories.  NGS in vitro diagnostics (IVDs) present a new set of regulatory and technical challenges for FDA and the lab community because, unlike traditional IVDs which are generally focused on a small number of specific analytes, NGS can produce volumes of data regarding millions of base pairs.  Moreover, the significance of the resulting data may not be immediately known (e.g., the clinical value of a mutation may not be known for years). 

For years, FDA and the lab community have been contemplating how best to regulate NGS-based IVDs.  In November 2013, FDA cleared the first NGS instrument platform through the de novo process (K123989) signaling the formal entry of NGS into the world of clinical diagnostics.  FDA’s registration and listing database shows that since this original clearance, only two other companies have listed NGS instruments.

FDA has also held three public meetings (September 2014, February 2015, and November 2015) regarding regulation of and standards relating to NGS IVDs.  As part of the most recent meeting, in November 2015, FDA published a discussion paper entitled “Use of Databases for Establishing the Clinical Relevance of Human Genetic Variants.”  The combined efforts of FDA and the lab community through these meetings led to FDA’s issuance of two draft guidances relating to NGS IVDs.  The first, “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 IVDs and discusses use of standards as part of the regulatory controls.  The second, “Use of Public Human Genetic Variant Databases to Support Clinical Validity for Next Generation Sequencing (NGS)-Based In Vitro Diagnostics,” describes how publicly available databases can be used as a source of valid scientific evidence to support the clinical validity of an NGS IVD.  Both aspects are important to a clear regulatory pathway for NGS IVDs.

We will be posting a detailed analysis of these draft guidances next week.  These draft guidances currently only apply to IVDs subject to regulatory oversight by FDA.  Should FDA’s efforts to regulate laboratory developed tests (LDTs) come to bear, these draft guidances would also apply to the numerous NGS-based LDTs. FDA will be accepting comments on the draft guidances through October 5, 2016.

*Summer Associate

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