Thus far, the FDA has approved only two NGS-based diagnostics for use in the clinic: Illumina's MiSeqDx Cystic Fibrosis 139-Variant Assay and its MiSeqDx Cystic Fibrosis Clinical Sequencing Assay (Nat. Biotechnol. 32, 111–112, 2014). Other NGS-based tests are developed in-house and offered by laboratories accredited under the Clinical Laboratory Improvement Amendments (CLIA) program. NGS-based diagnostic tests used to identify or predict disease differ from traditional genetic tests in their ability to assess large segments of the genome and to detect variants in an untargeted way. The variants that can be detected include single-nucleotide polymorphisms, insertions or deletions, and copy number changes. The methods used are diverse, from short-read and long-read to nanopore sequencing, a broad spectrum of genetic information that makes it difficult to find a single set of evaluation metrics applicable to all tests.
For now, the FDA aims to answer practical regulatory science questions. These are set out in the Perspective co-authored by agency researchers; representatives from the Center of Excellence in Regulatory Science and Innovation (CERSI) at Stanford University in California, and the University of California San Francisco (UCSF); the National Institute of Standards and Technology (NIST); and the bioinformatics company DNAnexus, a Mountain View, California–based bioinformatics company. The next step will be to set up a regulatory framework for NGS diagnostics. Plans to release a draft guideline for NGS diagnostics approval are slated for the end of the year.
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