The FDA has begun to develop their program to evaluate sequencing based diagnostics. At a recent meeting, the Association for Molecular Pathology (AMP) advised FDA officials on many important considerations for evaluating the analytical validity of next-generation sequencing:
The analytical validation requirements for NGS will vary based on the clinical application at issue, such as a mutation panel for a Mendelian disease versus transcriptome analysis.
Performance of, and coverage needs for, a given platform are likely to differ depending on:
- the nucleic acid analyzed
- the characteristics of the DNA regions and the type of variations interrogated
- the relative allele proportions of particular variants
- whether quantitative or qualitative results are desired
Flexibility and individualization is necessary in the development of validation protocols, guidelines, and controls on an application-by-application basis.
The test system, the analytical validity of the instrument and the performance of the bioinformatics software should be evaluated both independently and as a complete system.