Regulatory Roundup

As the range of the Zika virus continues to expand, the Food and Drug Administration (FDA) has issued emergency use authorizations (EUA) for two Zika tests, while also taking enforcement action against unapproved tests for the virus. The two tests designated for emergency use are the Centers for Disease Control and Prevention’s (CDC) Zika Immunoglobulin M (IgM) Antibody Capture ELISA (MAC-ELISA) and Trioplex Real-Time RT-PCR assay. The Zika MAC-ELISA detects Zika virus-specific IgM in human sera or cerebrospinal fluid (CSF), while the Trioplex assay detects and differentiates RNA from Zika, dengue, and chikungunya in human sera or CSF, and also detects Zika virus RNA in urine and amniotic fluid.

At the same time, FDA has sent a letter to Texas Children’s Hospital and Houston Methodist Hospital requesting more information on the Zika test they recently began offering to their patients. The two hospitals have developed the first rapid assay for the virus, known as the Zika direct test, which detects genetic material from Zika in blood, amniotic fluid, urine, or CSF and provides results in a few hours. In its letter, FDA states that, due to the current public health emergency, it believes that it is appropriate for the agency to review information related to this test’s design, validation, and performance characteristics. In an article in Regulatory Focus, FDA spokesperson Eric Pahon clarified that this means the agency is requesting that all tests for Zika go through the expedited EUA regulatory process. Some members of the healthcare community see this action as a reflection of FDA’s broader goal of bringing laboratory-developed tests under its oversight.

The agency’s letter also states that CDC and the Centers for Medicare and Medicaid Services asked FDA to evaluate the science behind the Zika direct test. FDA sent similar requests for information to First Diagnostics and MD Biosciences regarding Zika tests these companies have developed.

FDA Clears BioFire’s Multiplex PCR System for Use With Respiratory Panel

The Food and Drug Administration has granted bioMérieux’s molecular biology affiliate, BioFire Diagnostics, special 510(k) clearance to market the FilmArray Torch for use with the FilmArray Respiratory Panel (RP). The FilmArray Torch is a fully integrated, random, and continuous access multiplex PCR2 system that provides up to six times more sample throughput compared to the company’s existing system. It requires 2 minutes of hands-on time and has a total run time of about an hour. The FilmArray RP is a panel of 20 respiratory viruses and bacteria that is performed directly on nasopharyngeal swab-associated viral transport media. BioFire has also submitted special 510(k) applications for the FilmArray Torch’s use with other panels, including blood culture identification, gastrointestinal, and meningitis/encephalitis panels.

Bio-Rad Droplet Digital PCR System Becomes First to Earn CE IVD Mark

Bio-Rad Laboratories has received CE IVD marking for its QX200 Droplet Digital PCR (ddPCR) system, making this the first digital PCR system in the European Union that can be used for clinical applications. ddPCR had been available since 2011 for research use only. The technology partitions a DNA or RNA sample into 20,000 droplets and amplifies targeted sequences within each droplet, enabling laboratories to detect and quantify low concentrations of target DNA and RNA sequences. It has a range of genomic applications, including cancer mutation detection, gene copy number determination, viral load monitoring, and gene edit detection. In particular, the QX200 system is intended to aid in clinical decision-making for diseases ranging from cancer to transplant rejection and viral infection. According to Bio-Rad, it might also be an effective tool for liquid biopsy, and prospective trials are currently underway to evaluate the utility of combined ddPCR and next-generation sequencing in analyzing genomic alterations in circulating cell-free DNA.

Roche Gets Approval for HPV and HCV Tests

Roche has received regulatory authorization for two tests: the China Food and Drug Administration has approved the CINtec Plus Cytology test and the U.S. Food and Drug Administration (FDA) has approved the expanded use of Roche’s cobas AmpliPrep/cobas TaqMan HCV test, v2.0.

The CINtec Plus Cytology test is intended to improve the detection of and early intervention in pre-cancerous cervical disease. Virtually all cervical cancer is caused by the human papillomavirus (HPV), but only women with persistent HPV infections who have also developed high-grade pre-cancerous cervical disease should be treated. The CINtec Plus was designed to detect two biomarkers associated with persistent HPV infections that may lead to cancer, distinguishing them from infections that are likely to resolve on their own.

The cobas AmpliPrep/cobas TaqMan HCV test, v2.0 is a quantitative test for hepatitis C virus (HCV) RNA that is intended for use as an aid in the diagnosis of HCV infection for certain patient populations. With this expanded FDA approval, results from this test can now be used to confirm an active HCV infection, in addition to providing an accurate measurement of how much virus is in a patient’s blood. This is the first quantitative HCV RNA test that FDA has approved for this purpose.

FDA Clears Vermillion’s Ovarian Cancer Risk Test

Vermillion has obtained 510(k) clearance from the Food and Drug Administration (FDA) for Overa, the successor to Vermillion’s Ova1 test for determining ovarian cancer risk in conjunction with independent clinical and imaging assessment prior to planned surgery for a woman with a pelvic mass. Overa retains three of Oval's five biomarkers, while replacing two with human epididymis protein 4 and follicle stimulating hormone. The aim of this change is to improve specificity and reduce the need for physicians to determine menopausal status when interpreting the test. While other ovarian cancer tests such as CA 125, Risk of Ovarian Malignancy Algorithm, and Ova1 require patient reported or physician determination of menopausal status, Overa uses a single cutoff of 5, irrespective of menopause. This is intended to simplify  both interpretation of the result and patient counseling. The test is run on a single Roche cobas 6000 platform, and like Ova1, stratifies patients into low- or high-risk of malignancy on a scale of zero to 10.