2016 ACMG: Risk Assessment and Quality Plans for Next-Generation Sequencing (NGS) assays in the context of evolving regulatory frameworks

Next generation sequencing (NGS) technologies enable high-throughput sequencing and play an essential role in the operational implementation of personalized or precision medicine approaches. NGS-based assays are generally developed and offered by clinical laboratories as Laboratory Developed Test (LDTs). LDT testing services and procedures are central to public health and to support medical decision-making. Clinical laboratories offering LDTs operate under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations, which require a laboratory to have quality control (QC) procedures to monitor the accuracy and precision of the complete testing process. Modernization of the CLIA oversight framework in relation to high complexity LDT services is currently under discussion and the U.S. Food and Drug Administration (FDA) is re-evaluating its enforcement discretion approach to LDTs. The Centers for Medicare & Medicaid Services (CMS), the College American of Pathologist (CAP), the American College of Medical Genetics (ACMG), the American Medical Association (AMA), the Association for Molecular Pathology (AMP) and other organizations are key stakeholders in this complex process of changing regulatory frameworks.