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Technical Specifications for Next Generation Sequencing Data in Antiviral Drug Development

This guidance provides technical specifications for submitting next generation sequencing (NGS) data to FDA's Division of Antiviral Products for resistance assessments in antiviral drug development. It focuses on data submission requirements, protocols, and analysis methods to ensure proper characterization of viral resistance.

  1. Consult with FDA Division early in the process before submitting sequencing data
  2. Submit a mock NGS dataset to validate data formats and processes
  3. Prepare detailed NGS protocol documenting sample processing and analysis procedures
  4. Implement proper file naming conventions and organization
  5. Generate required frequency and summary tables
  6. Document all analysis methods, algorithms and parameters thoroughly
  7. Ensure target coverage levels are met and documented
  8. Validate PCR amplification steps if used
  9. Prepare secured portable hard drive for raw data submission
  10. Set up proper data analysis pipeline with error assessment and quality control
  11. Implement contamination detection procedures
  12. Create coverage graphs and statistics for all samples

Key Considerations

Non-clinical testing

  • Target coverage should be greater than 5,000 reads
  • Samples not reaching target coverage should be identified
  • Evidence needed that PCR amplification steps are representative of target population
  • Methods for extracting, purifying and concentrating viral nucleic acids must be described

Software

  • Description of analysis pipeline and algorithms used required
  • Parameters and settings for mapping reads and variant calling must be documented
  • Programs used for de novo assembly and annotation must be specified

Cybersecurity

  • Secured portable hard drive required for raw NGS data submission
  • Password protection procedures if used must be coordinated with CDER

Labelling

  • Specific file naming conventions required for fastq files
  • Files must be labeled with unique subject identifier and timepoint
  • Resequenced samples must be distinctly labeled

Other considerations


Original guidance

  • Technical Specifications for Next Generation Sequencing Data in Antiviral Drug Development
  • HTML / PDF
  • Issue date: 2019-07-18
  • Last changed date: 2020-05-05
  • Status: FINAL
  • Official FDA topics: Medical Devices, Clinical - Antimicrobial, Drugs, Biologics
  • ReguVirta summary file ID: 815d8a289f6cb09cb939c413cf59effc
This post is licensed under CC BY 4.0 by the author.