Use of Standards in FDA Regulatory Oversight of Next Generation Sequencing (NGS)-Based In Vitro Diagnostics (IVDs) Used for Diagnosing Germline Diseases

Many advances in precision medicine will depend on the safe and effective use of next generation sequencing (NGS) technology. As part of the Precision Medicine Initiative (PMI),  FDA has been focused on optimizing FDA’s regulatory oversight for NGS in vitro diagnostic (IVD) tests to help accelerate research and the clinical adoption of precision medicine while assuring the safety and effectiveness of these tests. As part of the PMI effort, this draft guidance document provides FDA’s proposed approach on the content and possible use of standards in providing oversight for whole exome human DNA sequencing (WES) or targeted human DNA sequencing NGS-based tests intended to aid in the diagnosis of individuals with suspected germline1 diseases or other conditions (hereinafter referred to as “NGS-based tests for germline diseases” or “NGS-based tests”). 

This document provides recommendations for designing, developing, and validating NGS-based tests for germline diseases, and also discusses possible use of FDA-recognized standards for regulatory oversight of these tests. These recommendations are based on FDA’s understanding o the tools and processes needed to run an NGS-based test and the design and analytical validation considerations appropriate for such tests.