The FDA's Experience with Emerging Genomics Technologies-Past, Present, and Future.

Area of Science:

• Genomics
• Regulatory Science
• Bioinformatics

Background:

• Advancing genomics technologies necessitate robust validation for regulatory applications.
• The U.S. Food and Drug Administration (FDA) established the Voluntary Genomics Data Submission (VGDS) program.
• The FDA led the MicroArray Quality Control Consortium (MAQC) for 10 years to address genomics data quality.

Purpose of the Study:

• To establish reliability and robustness standards for genomics technologies in regulatory settings.
• To assess gene expression microarrays, whole genome genotyping arrays, and whole transcriptome sequencing (RNA-seq).
• To provide solutions for the fit-for-purpose application of genomics data in regulatory environments.

Main Methods:

• The MAQC consortium conducted projects assessing reproducibility, precision, specificity/sensitivity, and data interpretation.
• The SEquencing Quality Control (SEQC) project focused on next-generation sequencing using reference samples with built-in controls.
• Comparative analysis of RNA-seq and microarrays in clinical settings and safety assessments.

Main Results:

• MAQC projects have yielded peer-reviewed publications with basic parameters for genomics data in regulatory environments.
• SEQC studies demonstrated accurate and reliable relative gene expression measurement across laboratories and RNA-seq platforms.
• RNA-seq exhibits comparable prediction performance to microarrays, with enhanced sensitivity for low expression and novel transcriptomic feature discovery.

Conclusions:

• Established quality control measures ensure the reliability of genomics technologies for regulatory decision-making.
• RNA-seq is a reliable and sensitive tool for safety and efficacy assessments, offering advantages over microarrays.
• Future MAQC efforts will focus on quality control for whole genome and targeted sequencing.