FDA Releases Proposal to Exempt Carrier Tests From the 510(k) Clearance Process

The Food and Drug Administration (FDA) has formally announced its intent to exempt carrier screening tests from premarket authorization and has laid out the special controls they will have to meet as an alternative. With certain limitations, this exemption will apply to molecular diagnostic systems used for autosomal recessive disease carrier screening in adults of reproductive age and that are intended for either prescription or over-the-counter use.

The agency decided to exempt carrier screening tests from 510(k) clearance requirements after completing in February 2015 a review of a de novo request for classification of the 23andMe Personal Genome Service (PGS) Carrier Screening Test for Bloom Syndrome. FDA classified 23andMe’s Bloom Syndrome test and substantially equivalent devices into class II (special controls) and determined that premarket notification is not necessary to assure the safety and effectiveness of this type of test. Carrier screening is only intended to detect heterozygotes, so false positive or negative results would only suggest that a person is or is not a carrier of a mutation, and would not lead to conclusions of disease for the tested person or his or her future children. The agency therefore believes that the risks posed by these tests are relatively low, and sufficiently mitigated by the applicable special controls.

The special controls for carrier tests require rigorous analytical performance metrics and parameters to be met, and for this information to be posted on the manufacturer’s public website. The controls also require warnings in the labeling to ensure that users and individuals undergoing testing are able to understand the test in full, including its limitations, the probability of test failure, and scenarios in which failure might occur.

The full details about the proposed exemption and special controls are available at federalregister.gov/a/2015-27198.

CE Mark Granted to First NGS Test for Familial Hypercholesterolemia

Progenika Biopharma, a Grifols company, has been granted the CE mark for Seqpro Lipo Is, an assay for the genetic diagnosis of familial hypercholesterolemia (FH). This is the first approved kit for the diagnosis of this disease using next-generation sequencing. FH is characterized by high levels of low-density lipoprotein cholesterol and affects one in 300 people, making it the most common genetic cause of premature cardiovascular disease. The Seqpro Lipo Is assay is intended to improve the efficiency of FH diagnosis by enabling the sequencing of all six known genes associated with this condition: LDLR, APOB, PCSK9, APOE, STAP1, and LDLRAP1. Using the Illumina MiSeq sequencer, Seqpro Lipo Is can analyze these six genes in 96 patient samples simultaneously.

Enzo Biochem Receives NY State Approval for HCV Test

The New York State Department of Health has granted approval of Enzo Clinical Labs’ AmpiProbe-HCV assay for the quantitative detection of hepatitis C virus. This clears the way for Enzo to begin offering this assay on a national basis. AmpiProbe-HCV covers all the relevant genotypes of the virus, as well as the major subtypes seen globally, and is based on the proprietary nucleic acid amplification and detection technology platform developed by the Enzo Life Sciences team. Enzo validated the test in a study including nearly 400 specimens, with more than 50% of them positive. The study shows that the test detects as low as 5.5 IU/mL of serum with a positive rate greater than 95%, while the limit of quantification was observed to be 10 IU/mL. The assay also uses less input samples than current HCV tests, enabling additional testing to be conducted on the original sample.

FDA Scrutinizes DTC Genetic Test Providers

The Food and Drug Adminis­tra­tion (FDA) has sent letters requesting more information to three firms selling direct-to-consumer (DTC) genetic tests: DNA4Life, DNA-CardioCheck, and Interleukin Genetics. DNA4Life offers the Pharmacogenetic Report, a test that is intended to predict how patients will respond to more than 120 of the most commonly prescribed medications. DNA-CardioCheck markets a test for genetic markers linked to thrombophia, deep-vein thrombosis, cardiovascular disease, and stroke. Lastly, Interleukin offers three different DTC tests, the PerioPredict Genetic Test, Osteoarthritis Genetic Test, and Weight Management Genetic Test, which aim to identify individuals with a genetic predisposition for increased risk of diabetes and heart attack, osteoarthritis associated conditions, and obesity, respectively.

In the letters, FDA implies that these tests are not authorized to be marketed, stating that each one appears to meet the definition of a medical device, but that the agency does not have a clearance number for any of them. FDA goes on to ask the companies to provide either clearance numbers for their tests or a basis for why they believe they are exempt from FDA clearance. On previous occasions, DNA4Life and Interleukin have publicly stated that they consider their tests laboratory developed tests, which do not require FDA authorization. These claims come in the midst of a debate over whether FDA should regulate laboratory developed tests, in part to prevent companies from exploiting DTC testing as a way to circumvent the agency’s authority.

Roche Gets FDA Approval for Lung Cancer Co-Diagnostic, Hepatitis Tests

Roche has received Food and Drug Administration (FDA) approval for a new companion diagnostic, as well as for two hepatitis viral load tests. The companion diagnostic, known as cobas EGFR Mutation Test v2, is the first test to detect the type of drug resistance mutation targeted by AstraZeneca’s newly approved lung cancer treatment, Tagrisso (osimertinib). Tagrisso treats patients with advanced non-small cell lung cancer whose tumors have the epidermal growth factor receptor (EGFR) mutation T790M and whose disease has gotten worse after treatment with other EGFR-blocking therapy. The updated version of the cobas EGFR Mutation Test adds the T790M mutation to the clinically relevant mutations detected by the original cobas EGFR Mutation Test (v1).

The viral load tests that Roche earned approval for are the cobas HBV and cobas HCV, which are intended to help clinicians manage the treatment of patients chronically infected with hepatitis B (HBV) or hepatitis C virus (HCV). These are also the first tests approved by FDA for use on the cobas 6800 and cobas 8800 systems.