FDA Issues Draft Guidance on NGS-based Tests for Infectious Diseases

The Food and Drug Administration (FDA) has issued draft guidance about how labs should establish performance characteristics of next-generation sequencing (NGS)-based tests for infectious diseases. NGS tests for infectious diseases are complicated systems due to the diversity of infectious disease agents, different specimen types, and the entire sequencing data pipeline. In light of their complexity, FDA proposes evaluating these devices as complete systems, with each individual step in the sequencing data pipeline as part of that system. This approach is similar to what the agency uses for other molecular-based diagnostics and also draws on methods from systems science.

As outlined by FDA, the testing steps that are considered part of the system include sample collection, specimen preparation for sequencing, sequencing/chemistry/data collection, data storage/data analysis, and the reporting of clinically actionable data. Databases and genome assembly, annotation, and finishing may also fall under regulatory oversight if they are used as part of the data analysis pipeline to generate the final diagnostic report.

FDA also recommends that NGS tests for infectious diseases be clinically evaluated using an alternative comparator that relies heavily on public databases populated with regulatory-grade target sequences. One such database that supplies a set of validated, regulatory-grade microbial genomic sequence entries is the FDA Database for Regulatory Grade Microbial Sequences, known as FDA-ARGOS.

FDA is accepting comments on the draft guidance through August 11. They can be submitted at www.regulations.gov.

Roche Collects Double Approval From FDA for PD-L1 Assay and CMV Test

The Food and Drug Administration (FDA) has approved Roche’s cobas TaqMan CMV test, a standardized real-time PCR-based assay for the diagnosis of cytomegalovirus (CMV) infection. In conjunction with the cobas AmpliPrep/TaqMan system, this nucleic acid amplification test quantitatively measures CMV DNA and is intended to aid in assessing the virological response to antiviral treatment. The test conforms to the World Health Organization International Standard, which enables labs worldwide to compare results when testing for CMV.

Additionally, Roche has received FDA approval for the Ventana PD-L1 assay as a complementary diagnostic for Tecentriq (atezolizumab) immunotherapy. The assay evaluates patient programmed death-ligand 1 (PD-L1) status using immune cell staining and scoring within the tumor microenvironment. According to Roche, this personalized cancer immunotherapy and complementary diagnostic serve as the first advancement in more than 30 years for the treatment of urothelial cancer. The PD-L1 assay is available on the BenchMark Ultra automated staining instrument, and uses the OptiView DAB IHC detection kit with OptiView amplification.

FDA Grants Emergency Use Authorization to Quest for Zika Test

Focus Diagnostics, a subsidiary of Quest Diagnostics, has received an emergency use authorization (EUA) from the Food and Drug Administration (FDA) for the Zika Virus RNA Qualitative Real-Time RT-PCR test, which is intended to detect RNA from the Zika virus in serum specimens from individuals who show symptoms or are at risk of Zika infection. This is the first Zika test from a commercial lab to be granted an EUA. Previously, Zika testing was only available through qualified laboratories designated by the Centers for Disease Control and Prevention (CDC). Quest promises that patients will receive results within 3 to 5 days after their samples are received at the Focus Diagnostics laboratory in San Juan Capistrano, California. Positive test results will subsequently be reported to CDC.

Despite the availability of a commercial test for the virus, timing and accuracy issues with Zika testing still linger. Recent research has revealed that testing urine for the Zika virus produces more accurate results than blood. Only CDC has FDA authorization to test for Zika in urine, however, and processing the results takes a minimum of 3 weeks.

Australia Approves Assay for Genotyping Hep C

Vela Diagnostics’ Sentosa-SQ HCV Genotyping assay has received approval from the Australian Therapeutic Goods Administration for viral genotyping in patients diagnosed with hepatitis C virus (HCV) infection in order to guide treatment selection. Using plasma or serum samples, the Sentosa assay covers clinically relevant regions of NS3, NS5A, and NS5B and detects genotypes 1–6, as well as subtypes 1a and 1b. The limit detection for genotypes 1–4 is 1000 IU/mL, and 2000 IU/mL for genotypes 5 and 6. Launched in June, the assay has demonstrated 100% clinical sensitivity, with 99.39% clinical genotyping correctness. Laboratories can use the assay in coordination with the Sentosa next-generation sequencing workflow, which enables automated RNA extraction, library construction, template preparation, sequencing, data analysis, and generation of pathology and quality control reports.This assay is also currently being reviewed for CE-IVD and Singapore Health Sciences Authority approval.

CE Mark Granted to Philips for Point-of-Care cTnI Test

Royal Philips has received the CE mark for a new handheld blood test, the Minicare I-20 system, for rapid diagnosis of a heart attack at the point-of-care. The Minicare I-20 system measures the level of cardiac troponin I in a drop of blood and delivers test results in less than 10 minutes compared to laboratory testing. Its performance was evaluated in acute care settings within the European Lab2Go project, a consortium of European hospitals. In addition to a handheld analyzer, the system consists of dedicated software and a single-use, disposable cartridge containing an application-specific test based on Philips’ proprietary biosensor technology. Initially, the test will be introduced in selected countries in Europe, including the U.K., Germany, the Netherlands, and Belgium.

Illumina Receives Product Approval Certificate in South Korea

Illumina’s MiSeqDx system, which includes the MiSeqDx Instrument and MiSeqDx Universal Kit, may soon be adopted into clinical use in South Korea following the company’s receipt of a product approval certificate from the Ministry of Food and Safety. This next-generation sequencing (NGS) system gives clinical laboratories the ability to analyze genomic DNA using sequencing by synthesis (SBS) chemistry. To target specific genomic regions of interest with SBS on the MiSeqDx system, labs can design and develop assays using oligonucleotide probes. These variant-specific probes hybridize to targeted sections of unfragmented genomic DNA, where extension and ligation occur between them. After indices and sequencing primers are added through PCR, the tagged library is then ready for cluster generation and sequencing. This could potentially enable labs in South Korea to develop new NGS-based diagnostic tests.

In the U.S., Illumina’s MiSeqDx system is cleared by the Food and Drug Administration for cystic fibrosis testing.

4Kscore Obtains Draft Medicare Local Coverage Determination

Novitas Solutions, a Medicare administrative contractor that covers jurisdictions L and H, issued draft local coverage determination for OPKO Health’s 4Kscore test, which identifies patient risk for high-grade, aggressive prostate cancer. In the past year, the blood test was included as a standard of care in the 2015 National Comprehensive Cancer Network Guidelines and in the 2016 European Association of Urology Prostate Cancer Guidelines for Prostate Cancer. The 4Kscore test calculates the risk of finding a Gleason Score 7 or higher grade of prostate cancer by combining information from the blood levels of four prostate-derived kallikrein proteins (total prostate specific antigen (PSA), free PSA, intact PSA, and human-kallikrein-2) with the patient’s age and other clinically relevant data. Novitas’ proposal, which is posted to the Medicare Coverage Database on the Centers for Medicare and Medicaid Services website, proposes establishing reimbursement coverage for patients with PSA levels >3 ng/mL who have not yet had a biopsy, or higher risk patients with PSA levels >3 ng/mL who have had at least one prior negative biopsy.

First CE Marked Assays for Diagnosing Systemic Sclerosis Now Available

In Germany, autoimmune diagnostic company Protagen AG launched two new enzyme-linked immunosorbent assays (ELISAs) to aid in the diagnosis of systemic sclerosis, representing the first CE-marked tests designed to combat this highly fatal orphan disease. The two ELISAs, known as the Multilisa CENP-B and Multilisa Scl-70, provide semi-quantitative determination of IgG antibodies specific for proteins CENP-B and Scl-70, respectively. Analysis of these autoantibodies is part of the guidelines for the diagnosis and treatment of systemic sclerosis. Their presence in the serum of patients is almost mutually exclusive and each antibody defines specific sub-forms of the condition, while also indicating patterns of organ involvement and disease outcome. Detection of these autoantibodies aids in the diagnosis of around 70% of systemic sclerosis patients, according to Protagen, as well as in the clinical management of the disease.

FDA Releases Draft Guidance on Genomic Samples and Data

In response to the increasing technological advances of genomics, the Food and Drug Administration (FDA) has issued draft guidance providing recommendations for genomic sampling and the management of genomic data in clinical studies. FDA worked with the International Council for Harmonization on the draft guidance. It examines the general principles of collecting, processing, transporting, storing, and disposing of genomic samples or data, and discusses the technical aspects of genomic sampling and research. The draft guidance also provides suggestions on how variations between the technical requirements of different regulatory agencies could be reduced.

FDA is accepting comments on the draft guidance through August 2. They can be submitted at www.regulations.gov.