Diagnostics & Imaging Week

Tm Bioscience (Toronto) and the FDA reported earlier this week that Tm Bioscience's Tag-It Cystic Fibrosis Kit is the first FDA-approved DNA-based blood test to assist in detecting cystic fibrosis (CF). It was approved as the first multiplexed human disease genotyping test and as an in vitro device for diagnostic use.

Greg Hines, president and CEO of Tm Bioscience, said that approval of the test has unusually broad significance.

It is not only the first FDA-approved genetic test for CF, he told Diagnostics & Imaging Week, but the first such test approved for a specific disease. This compares to other approved genetic tests that look at biomarkers for bacteria, viruses and enzymes, he said which are indicators of, but not assays for, specific diseases. Thus, he noted that the FDA calls the Tag-It Cystic Fibrosis Kit, specifically, a "predicate device."

Hines told D&IW that he was "on cloud nine" as a result of the news.

The FDA said that the Tag-It Cystic Fibrosis Kit directly analyzes human DNA to find genetic variations indicative of the disease. The test will be used to help diagnose cystic fibrosis in children and to identify adults who are carriers of the gene variations.

Daniel Schultz, MD, director of the FDA's Center for Devices and Radiological Health, said in a statement that the test "represents a significant advance in the application of genetic technology and paves the way for similar genetic diagnostic tests to be developed in the future."

The company said the test is used to simultaneously detect and identify mutations and variants in the cystic fibrosis transmembrane conductance (CFTR) gene in human blood specimens in order to determine CF carrier status in adults, as an aid in newborn screening and in confirmatory diagnostic testing in newborns and children.

The test which Hines told D&IW "has been run probably about 50,000 times" has proven that it operates with 100% accuracy and greater than 99.9% reproducibility and precision.

"This whole industry of genetic testing for the most part [has] been done with home-brew tests," he said. "Companies such as ours have been supplying laboratories with certain reagents and chemicals [that allowed] labs to build their own home-brew tests."

With the clearance of Tm Bioscience's test, however, Hines said it "really simplifies the process for the lab."

"The lab no longer has to take on the risk of developing an assay that might not meet the accuracy criteria [and] the legal liability issues that they would involve in building their own [tests]," he said.

The CF diagnostic test is "very complicated," Hines said; the Tag-It kit runs about 86 chemical reactions in one tube at one time.

Tm Bioscience provided estimates that cystic fibrosis affects about one out of every 3,200 live births. It has also been said that in as many as 80% of births with CF, there was no family history of the disease.

The Tm Bioscience kit simultaneously screens for the 23 cystic fibrosis transmembrane conductance regulator gene mutations and four variants, as recommended by the American College of Medical Genetics (ACMG; Bethesda, Maryland) and the American College of Obstetricians and Gynecologists (ACOG; Washington) in 2004. In addition, the kit screens for 16 additional mutations prevalent in North America or the world.

But the FDA said that because the Tag-It Kit "detects a limited number of the more than 1,300 genetic variations identified in the CFTR gene," the test should not be used alone to diagnose CF.

"Physicians should interpret tests results in the context of the patient's clinical condition, ethnicity and family history," the agency said.

The test will be priced to labs at "about $40 to $50," Hines said, but the product won't be available on the market for another two months or so. The cost to the payer will be higher, he said, because of the associated costs of testing, which includes providing a report to the physician with genetic counseling information.

Currently, about 1.5 million of CF tests performed annually in the U.S. either for diagnosis in children or in family planning, Hines said. That market has grown from about 300,000 to 400,000 tests in 2003, and it is anticipated that the number of tests performed may reach as high as 2 million to 3 million a year, depending on the birth rate.

Perhaps the real beauty of FDA approval of the Tag-It Cystic Fibrosis Kit is, more broadly, an approval of Tm Bioscience's platform technology, according to Hines.

"We can put any biomarkers on it; we can put the biomarkers for asthma, for diabetes, for cancer, for whatever disease you want," he said. "They all run exactly the same way."