FDA News: Precision Medicine, Next Gen Sequencing Guidances – Drug and Device Digest

FDA BRIEF: Week of   July 4, 2016 

FDA advances Precision Medicine Initiative by issuing draft guidances on next generation sequencing-based tests

In support of the President’s Precision Medicine

Two draft guidances for next generation sequencing (NGS)

• New technology to scan a person’s DNA to detect genomic variations for risk of disease
• Conventional diagnostics provide limited  measure of disease/conditions
• NGS can examine millions of DNA variants at a time

Regulatory Perspective

• Encourage innovation while assuring NGS-based tests are accurate and useful
• Adherence will offer flexible and adaptive regulatory oversight
• Ensure Precision Care –  is only as good as the tests that guide diagnosis and treatment
• Draft guidances  important step in the development of NGS-based tests
• Encouraging public comments during the 90-day comment period.

Scope: Content and standards in providing oversight for whole exome human DNA sequencing (WES) or targeted human DNA sequencing NGS-based tests

Recommendations: Designing, developing, and validating NGS-based tests for germline diseases

Classification: Class II and potentially exempting them premarket notification;  longer-term goal to establish special controls for 510(k)

Key Elements:

Test Design Considerations .

• Indications for Use Statement(s) of the Test
• Specific User Needs for the Test
• Specimen Type
• Interrogated Regions of the Genome
• Performance Needs
•  Components and Methods

Test Performance Characteristics

• Accuracy
• Precision (Reproducibility and Repeatability) .
• Limit of Detection (LoD)
• Analytical Specificity

Test Run Quality Metrics

• Coverage (Read Depth and Completeness)
• Test Run Metrics and Performance Thresholds

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Scope:

• Whether a genetic variant database could support NGS-based test validity in  premarket submission
• Using curated databases using expert human interpretation for test developers to rely on clinical evidence from FDA-recognized public genome databases to support clinical claims

Recommendations: Recognition of Publicly Accessible Genetic Variant Databases

• Database Procedures and Operations .
• Data Quality
• Curation, Variant Interpretation and Assertions
• Professional Training and Conflicts of Interest

Process: Genetic Variant Database Recognition

•  Submission for Recognition
• FDA Review
• Maintenance of FDA Recognition
• Use of Third Parties
•  Use of Data and Assertions from Recognized Genetic Variant Databases

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