FDA Watch: New NGS Data Guidance May Ease Antiviral Drugs & Companion Test Approvals

A new FDA Technical Specifications document (Tech Doc) lists recommendations for sponsors on use of next generation sequencing data to secure approval of new antiviral drugs and related diagnostic tests providing crucial guidance on six key issues.

1. Acceptable NGS Platforms: The Tech Doc says the agency will accept nucleotide sequencing data generated from most standard NGS platforms as long as the sponsor submits:

• The appropriate details for the sequencing platform;
• The protocols used for sample preparation;
• The raw NGS data in fastq format; and
• The methods used to analyze the data.

2. Information about NGS Protocol: Sponsors should submit a detailed NGS protocol that includes six design elements:

• A description of the subjects, study time points and sample matrices to be analyzed;
• A description of the NGS platform and all associated performance characteristics;
• Target gene region name(s) and size(s) to be analyzed;
• A description of the general analysis strategy;
• The coverage level to be attempted; and
• A description of the approach used to identify, filter or process sequencing errors.

3. Frequency Tables: Sponsors should provide a frequency table reporting all amino acid substitutions that differ from baseline at frequencies greater than or equal to 1%.

4. Sample Preparation Information: The Tech Doc calls on sponsors to list their methods for:

• Extracting nucleic acids from samples;
• Purifying viral sequences from contaminating background nucleic acids;
• Concentrating viral nucleic acids, including the estimated target copy number input for reverse transcription polymerase chain reaction (RT-PCR) (viral RNA) or PCR (viral DNA) reactions for each sample;
• Denaturing secondary structure;
• Generating double stranded DNA (dsDNA), including a description of the primers;
• Purifying dsDNA for sequencing;
• NGS library preparation; and
• Adding barcodes for multiplexing (if applicable).

5. Information about Data Analysis & Reporting Results: Submissions of sequence data must include a thorough description of the analysis pipeline used to analyze the sequencing dataset and the raw sequence information, including:

• Summary statistics for each sequence run, including total number of reads sequenced per sequence run, quality scores and average length of reads;
• A description of how sequence barcodes were processed;
• Contig and mapping reports—the Tech Doc recommends two data analysis approaches and establishes standards for each: i. mapping of short reads to a reference sequence; or ii. de novo assembly of short reads to assemble contigs.

6. Acceptable Data File Types: The Tech Doc calls on sponsors to provide all raw NGS data from each sequence run in the fastq format, which may also include an assembled read mapping in .fas, .ace, .sam, or .bam formats along with the appropriate reference sequences and accession numbers used for any reference mappings.

New FDA Approvals

Here’s a look at other new product approvals announced from late August through late September:

NEW FDA APPROVALS

New CE Marks & Global Certifications

Notable European CE certifications announced during the period:

NEW CE MARKINGS IN EUROPE

Other international clearances announced during the period: