NEW YORK—Illumina has received premarket clearance from the U.S. Food and Drug Administration for its MiSeqDx system, two cystic fibrosis assays and a library prep kit that enables laboratories to develop their own diagnostic tests. The designation marks the first time a next-generation sequencing (NGS) system has received FDA premarket clearance.
“NGS is changing the way we look at genomics,” said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics and Radiological Health in FDA’s Center for Devices and Radiological Health. “Before NGS, sequencing genes associated with a particular disease was a long and costly process. Today, we have the capability to read and interpret large segments of DNA very quickly in a single test and this information-rich technology is becoming more accessible for use by physicians in the care of their patients.”
"With the FDA clearance of the MiSeqDx, Illumina is providing clinicians and clinical laboratories with the tools needed to obtain comprehensive and reliable results from a DNA sequencing analyzer and enabling them to create and deploy NGS-based molecular diagnostic tests for cystic fibrosis and a wide range of other applications," says Greg Heath, senior vice president and general manager of Illumina's diagnostics business.
The two cystic fibrosis assays include the MiSeqDx Cystic Fibrosis 139-Variant Assay, which detects 139 clinically relevant mutations and variants within the cystic fibrosis transmembrane conductance regulator (CFTR) gene. It includes all the variants recommended for carrier screening by the American College of Medical Genetics and Genomics (ACMG) and the American College of Obstetricians and Gynecologists (ACOG).
More than 10 million Americans are CF carriers and approximately 30,000 children and adults in the U.S. are affected by the disease. Most children with CF are diagnosed by age 2 and the average life span for people with CF who live to adulthood is approximately 37 years.
In addition to the Illumina MiSeqDx Cystic Fibrosis 139-Variant Assay, the cleared devices include: Illumina MiSeqDx Cystic Fibrosis Clinical Sequencing Assay, which sequences a large portion of the CFTR gene to detect any difference in the CFTR gene compared to a reference CFTR gene, including the protein coding regions and intron/exon boundaries of the entire CFTR gene. Illumina also received premarket clearance for its MiSeqDx Universal Kit, which includes library preparation reagents, sample index primers, and sequencing consumables that laboratories can use to develop their own assays on the cleared MiSeqDx system.
Francis Collins, director of the National Institutes of Health, called the decision a "landmark move that will help realize the promise of personalized medicine." He added that he commends the FDA for both the immediate impact of the decision, as well as "the pathway it has created for the clearance of future devices that may incorporate further improvements in sequencing technology and cost effectiveness."
Data submitted by Illumina for their cystic fibrosis tests included comparisons of the sequence results to Human Genome Build 19, a reference representation of the human genome. In addition, Illumina evaluated the performance of its instrument and reagent systems against a publically available quality-weighted human reference genome that was created through collaboration between the FDA and the National Institutes of Standards and Technology (NIST).
The FDA also granted de novo petitions for the Illumina MiSeqDx instrument platform and the Illumina Universal Kit reagents, two devices that make up the first FDA-regulated test system that allows laboratories to develop and validate sequencing of any part of a patient’s genome. The Universal Kit reagents isolate and create copies of genes of interest obtained from patient blood samples, and the MiSeqDx platform analyzes the genes. The software compares the patient’s genomic sequence to a reference sequence and reports back any differences between the patient and the reference.
“The FDA’s review of the MiSeqDx and sequencer and Universal Kit reagents provides clinical laboratories with information about the expected performance of the device and the quality of the results,” said Dr. Gutierrez. “This information was not previously available for next generation sequencers, and, with this platform, labs can develop tests for clinical use with greater confidence because they use FDA authorized devices.”
The FDA reviewed the Illumina MiSeqDx instrument platform and the Illumina Universal Kit reagents through its de novo classification process, a regulatory pathway for some novel low-to-moderate risk medical devices that are not substantially equivalent to an already legally marketed device.
