FDA Holds Workshop on Evaluation of Next-Generation Sequencing

On Nov. 12, 2015, FDA held a public workshop, Standards-Based Approach to Analytical Performance Evaluation of Next-Generation Sequencing In Vitro Diagnostic Tests, with the intention of receiving feedback on possible analytical standards and approaches the agency may use to develop and/or revise regulation of next-generation sequencing (NGS)-based in vitro diagnostic tests. FDA hopes to also use comments received from the workshop “to advance the further development of appropriate and relevant performance standards for evaluation of next generation sequencing in vitro diagnostic tests that produce results on variation in the human genome.” According to an FDA discussion paper, the workshop was developed as a way for FDA to consider ways of optimizing the regulation of NGS tests for human genomes and develop a “flexible, adaptive regulatory approach”.

A paper posted by the agency on Feb. 20, 2015 outlined FDA’s strategies for developing this approach, including identifying and implementing analytical standards to ensure NGS tests produce reliably accurate results and develop ways to use databases of genetic variants to guide clinical interpretation of NGS test results. Feedback from the publication of the February paper led FDA to further develop their strategies published in a companion paper, which was discussed at the November workshop.

FDA proposes two approaches to assure the development of analytically valid NGS tests. One approach establishes performance standards that include specific metrics and acceptance criteria that the test would have to satisfy. The other approach would develop design concept standards that would ensure, when complied with, that the manufacturer can achieve the proper design and validation of an NGS test.

The Performance Standards approach would establish the testing metrics and performance criteria and, possibly, prescribed validation studies for establishing the analytical and clinical performance of the test. FDA states that the standards could be developed by FDA or by a FDA-recognized third party. FDA states that the performance standards would not use a specific platform, chemistry, or software, and the developer “would be free to specify intended use, design, and other parameters, as long as the final test could achieve the defined performance metrics.”

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