• FDA Proposes Regulatory Framework for Next Generation Sequencing-Based Tests
  • August 11, 2016 | Authors: Edgar Asebey; Maureen Bennett; Christian B. Fulda; Colleen M. Heisey; Cristiana Spontoni
  • Law Firms: Jones Day - Miami Office ; Jones Day - Boston Office ; Jones Day - Munich Office ; Jones Day - Washington Office ; Jones Day - Brussels Office
  • FDA recently released, as a part of President Obama's Precision Medicine Initiative, two draft guidance documents proposing what the Agency is calling a "flexible and streamlined approach" for regulating next generation sequencing ("NGS")-based tests. The first guidance document, "Use of Standards in FDA Regulatory Oversight of Next Generation Sequencing (NGS)-Based In Vitro Diagnostics (IVDs) Used for Diagnosing Germline Diseases," proposes, in part, that certain NGS-based tests (those for germline, e.g., hereditary, diseases) may be suitable for de novo classification and, if FDA makes a class II determination, potentially appropriate for exemption from premarket notification requirements.

    In evaluating whether a 510(k) is needed to provide reasonable assurance of the safety and effectiveness of an NGS-based test for germline diseases, FDA will consider, among other things, assurances of analytical and clinical validity. These assurances are consistent with the parameters that are assessed as part of most IVD premarket reviews-analytical performance and clinical performance. (For more on IVD premarket reviews, see the Overview of IVD Regulation page on FDA's website.)

    To provide assurance of analytical validity for an NGS-based test for germline diseases, FDA proposes that NGS-based test developers can follow the recommendations outlined in Section VI of the guidance document referenced above. (The section provides "Recommendations for Design, Development and Validation of NGS-based Tests for Germline Diseases," which "FDA believes can help demonstrate a reasonable assurance that an NGS-based test for germline diseases is analytically valid.") In the future, FDA suggests it may recognize standards consistent with those recommendations, and conformance with those standards could support or provide reasonable assurance of a test's analytical validity. FDA also suggests that its analytical validity-related recommendations could also form the basis for special controls or conditions for 510(k) exemption in the future.

    To provide assurance of clinical validity for any NGS-based test (i.e., not limited to those for germline diseases), FDA proposes that NGS-based test developers may utilize assertions of genotype-phenotype correlations and underlying data from FDA-recognized public genetic variant databases, as outlined in and consistent with FDA's second guidance document, "Use of Public Human Genetic Variant Databases to Support Clinical Validity for Next Generation Sequencing (NGS)-Based In Vitro Diagnostics." In some instances, FDA suggests that NGS-based test developers may not need to submit additional clinical data beyond what is provided from the recognized genetic variant database. Comments on both draft guidances are due October 6, 2016.