CLN - Regulatory Roundup

Vela Diagnostics Gets FDA Authorization for NGS Test for HIV Drug Resistance

Regulatory Roundup: January/February 2020

The Food and Drug Administration (FDA) has granted de novo authorization to Vela Diagnostics USA for its Sentosa SQ HIV Genotyping assay, making this the first FDA-authorized test that detects HIV type-1 drug resistance mutations using next-generation sequencing (NGS). Traditionally, healthcare providers have used viral load tests to monitor the efficacy of HIV antiviral drugs, with increasing viral loads indicating that the virus might have mutated and that a patient’s current regimen is no longer effective at suppressing the virus. By identifying mutations in the HIV-1 virus that impact the efficacy of certain drugs, the Sentosa SQ assay is designed to provide additional information beyond viral load that could help healthcare providers better tailor drug treatment for patients who have developed resistance to HIV drugs, as well as for patients who are just beginning antiviral therapy.

The Sentosa SQ assay is performed with plasma or serum samples, and detects 342 drug resistance mutations, including Group M subtypes A through K as well as drug resistance mutations in the virus’s integrase, protease, and reverse transcriptase genes. Additionally, unlike traditional methods for HIV genotyping such as Sanger sequencing, this assay delivers results in days rather than weeks. To evaluate this test, FDA reviewed data from studies demonstrating that the test performs with a sensitivity and specificity greater than 95%.

FDA Emphasizes That Biotin Interferes With Troponin Test Results

The Food and Drug Administration (FDA) has updated its safety communication about biotin interference with laboratory tests to underscore the fact that biotin interference can cause falsely low results for troponin testing. Since FDA released its 2017 safety communication, some lab test manufacturers have successfully mitigated biotin interference with their assays, but others have not, according to FDA. FDA expresses concern over this in its updated communication, particularly because the agency continues to receive adverse event reports about falsely low troponin results caused by biotin interference. In an effort to make sure that lab professionals, healthcare providers, and the public are aware of this issue, the agency has published a list at of all the troponin diagnostic devices that are still subject to biotin interference. FDA also encourages lab professionals to inform healthcare providers if any tests used in their lab are subject to biotin interference, and to communicate with clinicians to identify patient samples that contain biotin.

T2 Biosystems Gets CE Mark for Direct-from-blood Antibiotic Resistance Test

The CE mark has been given to T2 Biosystems for the T2Resistance panel, which identifies 13 of the most serious antibiotic-resistance genes on the 2013 Centers for Disease Control and Prevention Urgent Threat list. These genes include the gram-negative markers KPC, OXA-48, NDM/VIM/IMP, CTX-M 14/15, and AmpC (CMY/DHA) and the gram-positive markers vanA/B and mecA/C, which indicate resistance to common empiric antibiotic therapies such as carbapenems, vancomycin, and penicillin. The test detects all of these resistance markers directly from whole blood in 3 to 5 hours, and features broad inclusivity of resistance variants, as well as ≤10 CFU/mL detection demonstrated for all targets. Studies have shown that the T2Resistance panel does not exhibit cross-reactivity with or inhibition due to common interfering substances. It was developed with funding from CARB-X, a global nonprofit partnership that works to accelerate technological development to combat the threat of drug-resistant bacteria.

FDA OKs NantHealth’s Sequencing Test for Overall Tumor Mutational Burden

NantHealth has earned Food and Drug Administration (FDA) clearance for the Omics Core, the first whole exome tumor-normal in vitro diagnostic that measures overall tumor mutational burden (TMB). The test is performed with formalin-fixed paraffin-embedded tumor tissue matched with normal specimens from patients with solid malignant neoplasms. It uses targeted next-generation sequencing to determine overall TMB by analyzing 19,396 protein-coding genes, as well as somatic alterations—such as point mutations and small insertions and deletions—in 468 cancer-relevant genes. TMB is then reported via two metrics: The first metric is the total number of somatic non-synonymous exonic variants within the protein-coding genes surveyed, and the second is an estimate of mutation rate calculated by counting all somatic, synonymous, and non-synonymous variants detected in gene coding regions and dividing by the approximate size of the whole exome. According to NantHealth, this information might be used to guide cancer treatment, as some studies have shown that patients with high TMB respond better to immunotherapy compared to those with low TMB (though at the moment FDA’s clearance for the test does not cover any therapeutic indications).

CE Mark Granted to Genedrive for Genetic Antibiotic-Induced Hearing Loss Test

The U.K.-based company Genedrive has received the CE mark for its rapid point-of-care test for antibiotic-induced hearing loss, the Genedrive MT-RNR1 ID kit. Performed with an inner cheek swab sample, the test screens infants in critical care settings for the m.1555A>G mutation in the MT-RNR1 gene, which makes individuals susceptible to lifelong deafness if they are given the frontline antibiotic gentamicin. The U.K.’s National Institute for Health and Care Excellence recommends that infants with suspected infection be treated with an antibiotic regimen including gentamicin within 1 hour of arrival in a neonatal intensive care unit. However, current genetic tests for the risk of gentamicin-associated hearing loss typically take 3-5 days to return results. To address this problem, Genedrive designed the MT-RNR1 ID kit to provide susceptibility results in less than 1 hour, so that infants with the m.1555A>G mutation can be prescribed a safer alternative to gentamicin.

Bioneer Earns CE Mark for HCV Test

The CE mark has been granted to the South Korea-based company Bioneer for its AccuPower HCV Quantitative RT-PCR kit, which quantifies hepatitis C virus (HCV) RNA in human samples such as serum and EDTA-plasma. The test detects HCV genotypes 1-6 through real-time reverse transcription polymerase chain reaction (RT-PCR) and runs on Bioneer’s semi-automated­ real-time quantitative PCR molecular diagnostic system ExiStation. The test also uses Bioneer’s proprietary AccuPower Dual-HotStart RT-PCR premix, which includes Dual-HotStart reverse transcriptase. This reverse transcriptase can achieve RT reaction in unusually high temperatures (up to 70°C), making it possible to adopt template RNAs even if they have a complex secondary structure. Additionally, the AccuPower HCV Quantitative RT-PCR kit is designed for use with ExiStation Manager software, which automatically analyzes the test results from this kit based upon the threshold cycle value.