The FDA has provided details on how it plans to regulate diagnostics that detect infectious disease organisms, antimicrobial resistance and virulence markers.
The agency spells out the data it expects to see in a submission for infectious disease next-generation sequencing (NGS) diagnostic devices, in draft guidance released May 13.
Tagged as Class II devices, the FDA will regulate infectious disease NGS Dx devices based on a “one system” approach, similar to the way it regulates molecular-based diagnostic devices. The guidance notes that in contrast to human sequencing diagnostics, infectious disease sequencing diagnostics generally require rapid and actionable results, “as delayed or incorrect diagnoses can result in fatalities.”
The broad range of specimen types and the diversity of infectious disease agents in a sample don’t allow for straight-forward pre-analytical testing, the FDA said.
The guidance was drawn from stakeholder input during an April 13, 2015 meeting that stressed the need for more advanced testing to better detect and identify infectious disease organisms. Stakeholders stressed that next-generation sequencing can replace previous methods with a single approach.
“Documentation of the locked-down bioinformatics pipeline, including all required steps, from handling the ‘raw’ sequencing data to producing the diagnostic output, should be provided and should demonstrate robustness for clinical microbiology use,” the guidance says.
The sequencing system is made up of the following steps:
The guidance proposes the use of an alternative comparator to validate NGS-based tests for infectious diseases. To that end, the agency developed the FDA-ARGOS [FDA dAtabase for Regulatory Grade microbial Sequences] database to supply validated regulatory-grade microbial genomic sequence entries collected from public databases.
To qualify as a regulatory-grade genomic sequence entry, the microbial organism or resistance and virulence marker has to be explicitly identified prior to sequencing.
The guidance outlines requirements for:
Benefit-risk analysis: Premarket submission should include a discussion of potential benefits and risks associated with the device, as well as risks of device failure.
Device description: Manufacturers need to demonstrate precise intended use for targeted and agnostic sequencing approaches and conditions, including test methodology, ancillary reagents, controls and interpreting test results and reports.
Device validation: The FDA recommends seeking advice before undertaking any clinical or analytical validation studies to discuss whether additional recommendations are available due to new advancements in this fast moving field. Manufacturers should include documentation in the form of diagrams and pictures displaying the flow of information on analytical performance, instrumentation and software and clinical evaluation.
Device modification: Submissions should also include a detailed procedure for acceptance criteria, risk analysis, database updates and validation testing.
The guidance does not apply to products intended to screen for communicable disease, which are classified as high-risk Class III devices.