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FDA Watch: Why the New NGS Guidance May Be a Paper Tiger

by | May 28, 2018 | Essential, FDA-lir, Industry Buzz-lir, Laboratory Industry Report

From - Laboratory Industry Report Last month, the FDA finalized a pair of guidance documents designed to liberalize and speed up approval of new next-generation sequencing… . . . read more

Last month, the FDA finalized a pair of guidance documents designed to liberalize and speed up approval of new next-generation sequencing (NGS) in vitro diagnostic (IVD) tests and devices. (See LIR, May 2018, for the details.) The self-stated objective: “Help ensure patients receive accurate, reliable, and clinically meaningful test results, while promoting innovation in test development.” Predictably, FDA officials ran a post-guidance victory lap, with Jeffrey Shuren MD, director of the FDA’s Center for Devices and Radiological Health, predicting that the new final guidance on genetic variant databases “will change the paradigm” of NGS development. Regrettably, though, the new guidance is likely to fall far short of those heady expectations.

Too Limited in Scope
The first problem is that the guidances apply only to new NGS tests that are undergoing premarket review. But premarket review is not required to secure FDA approval of lab developed tests (LDTs). Accordingly, NGS test makers typically treat their NGS-based tests as LDTs to get around the need for premarket review. Result: The guidance will likely have minimal practical impact on LDTs development, at least for the near future.

Too Many Exclusions
Similarly, the scope of the guidances is drastically narrowed by the express exclusion of so many types of NGS-based tests, including:

  • Companion or complementary diagnostic testing;
  • Cell-free DNA testing;
  • Microbial infection diagnosis;
  • Microbial genome identification;
  • Detection of antimicrobial resistance and virulence markers;
  • Pre-implantation embryo testing; and
  • RNA sequencing.

The FoundationACT Breakthrough Designation
Meanwhile, on the positive side, the FDA made headlines by granting Breakthrough Device designation to the new liquid biopsy assay Foundation Medicine is developing as an expanded version of its FoundationACT assay. The Breakthrough Device program, an expansion of the Expedited Access Pathways program, enables test makers to work together with the FDA to cut development costs and approval lead time.

Foundation is developing the assay, an NGS-based IVD for detecting substitutions, indelss, copy number alterations and gene rearrangements in 70 genes as well as genome signatures in circulating cell-free DNA isolated from plasma, as a companion diagnostic to identify patients who may benefit from certain cancer therapies. According to the company, if the assay is ultimately approved, it would become the first FDA-approved liquid biopsy to incorporate multiple companion diagnostics and biomarkers to inform the use of targeted therapies, including immunotherapies. However, other firms, including Guardant Health, are developing similar products.

New FDA Approvals
Meanwhile, here’s a rundown of the key new FDA approvals announced from mid-April to mid-May:


Manufacturer(s) Product(s)
Foundation Medicine Breakthrough Device designation to new liquid biopsy assay which is an expanded version of its existing FoundationACT assay
Cepheid Expanded clearance for Xpert Carba-R test for use on perirectal swabs and pure colonies
Roche Approval of additional claim for Cobas Zika test for use on Cobas 6800 and 8800 systems enabling streamlined screening of multiple individual blood or plasma donations that have been pooled together
Roche Clearance for modification to previously-cleared CoaguChek XS Plus System for monitoring blood-clotting values with Roche’s CoaguChek XS PT test strips
Roche Clearance for modification to previously cleared CoaguChek XS Pro system used to quantitatively determine prothrombin time using capillary blood or whole blood from a vein
Siemens Healthineers 510(k) clearance for Atellica IM Folate Assay for quantitative detection of folate in serum or red blood cells using Atellica IM Analyzer
Siemens Healthineers 510(k) clearance for Sysmex UF-5000 Fully Automated Urine Particle Analyzer to analyze red blood cells, white blood cells, epithelial cells, cast and bacteria
BacterioScan 510(k) clearance for 216Dx urinary tract infection detection system
DiaSorin Clearance to market Liaison BRAHMS PCT II Gen assay for quantitative determination of procalcitonin
Infrared Laboratory Systems Clearance for Synermed Enzyme Immunoassay for qualitative and semi-quantitative detection of opiates in human urine at cutoff value of 300 ng/mL when calibrated against morphine
Immucor Clearance for Echo Lumena instrument for donor-patient blood matching
Hologic Clearance for Eviva Stereotactic Guided Breast Biopsy System to enable providing breast tissue samples for diagnostic breast abnormalities under stereotactic breast biopsy guidance
Hologic Premarket approval for ThinPrep Integrated Imager
Quotient Clearance for seven different blood-bank reagents, including four monoclonal antisera reagents and three anti-human globulin reagents
Bruker Clearance for use of MALDI Biotyper system to detect Candida auris
Qiagen Clearance for PartoSure test for assessing risk of spontaneous preterm birth in patients with preterm labor symptoms
Assure Tech Clearance for Panel Dip Tests and Quick Cup Tests competitive binding, lateral flow immunochromatographic urine drug testing assays

During the period, the following FDA CLIA waiver was announced:


Manufacturer(s) Product(s)
Cepheid CLIA waiver for Xpert Xpress Strep A test to detect Group A Strep infection

New CE Marks & Global Certifications
Notable European CE certifications:


Manufacturer(s) Product(s)
Beckman Coulter Diagnostics CE marking for Early Sepsis Indicator, a hematology test that alerts emergency department clinicians to sepsis risk of ED patients
Applied BioCode CE/IVD marking for BioCode MDx 3000 molecular testing platform
Applied BioCode CE marking for Gastrointestinal Pathogen Panel tests for nucleic acids of 18 common bacteria, viruses and parasites that cause infectious diarrhea
Genetic Signatures CE marking for EasyScreen ESBL & CPO Kit, a PCR-based superbug detection kit
Altona CE marking for AltoStar Molecular Diagnostic Workflow for detecting infectious diseases

During the period, the following FDA CLIA waiver was announced:


Manufacturer(s) Country(ies) Product(s)
Genetic Signatures to Australia Approval to market Extended Spectrum Beta-Lactamase and Carbapenemase Producing Organisms Detection Kit for detecting superbugs

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