The US Food and Drug Administration (FDA) on Thursday issued new draft guidance meant to establish the necessary performance characteristics for genetic sequencing tests used to diagnose infectious diseases.
Due to the complexity of these tests, FDA is proposing to regulate them as complete systems that encompass all processes from specimen collection through obtaining clinical results.
NGS Tests for Infectious Disease
In recent years, FDA has been working to develop its regulatory approach to so called next-generation sequencing (NGS) tests, which have the potential to revolutionize diagnostic testing.
Unlike traditional diagnostics that look for the presence of one, or several, biomarkers or genes, NGS-based tests can scan an entire genome for numerous variations or mutations that can identify specific strains of a disease or help guide treatment.
NGS-based tests for infectious diseases also differ from tests that sequence a patient's own genome, as they are used to detect pathogens infecting a patient.
"Next generation sequencing has the capability to replace previous methods with a single approach to accomplish what might have required several different tests in the past," FDA writes. "In contrast to human sequencing diagnostics, infectious disease sequencing diagnostics generally require rapid and actionable results, sometimes within hours, as delayed or incorrect initial diagnoses can result in fatalities."
These tests also differ from other diagnostics due to the variety of specimens they can be used for, such as blood, stool or urine, as well as an array of diseases they can detect. According to FDA, these factors make it impossible to conduct "straightforward pre-analytical, biochemical, or bioinformatics processes" when characterizing NGS-based tests for infectious disease.
"Each unique specimen type may require a different nucleic acid extraction procedure, a different library preparation protocol, and even a different bioinformatics algorithm to generate the final clinical result," FDA writes.
FDA says it plans to regulate NGS-based tests for infectious diseases as Class II devices using a "one system" approach.
The system is comprised of five or six steps, depending on whether the tests rely on databases or genome assembly, annotation or finishing to produce test results. The steps FDA plans to include as part of the system are:
- Specimen collection
- Specimen preparation for sequencing
- Sequencing/chemistry/data collection
- Data storage/data analysis
- May fall under regulatory oversight:
- Genome Assembly, Genome Annotation, Genome Finishing
In order to validate NGS-based tests for infectious diseases, FDA says sponsors should use an "alternative comparator" sourced from public databases of microbial genetic sequences.
FDA says it has already developed one such database, called FDA-ARGOS (FDA dAtabase for Regulatory Grade microbial Sequences) to provide sponsors with "a set of validated regulatory-grade microbial genomic sequence entries."
Additionally, the agency asks that sponsors contact it for feedback before conducting any clinical or analytical validation studies "to discuss whether additional recommendations are available due to new advances in this fast moving field."