FDA Holds Public Workshops to Discuss Regulatory Strategies for Next Generation Sequencing Diagnostics, Part 1

As we discussed in a previous FDA News article, the Agency is in the midst of developing “novel ways to optimize its regulation of Next Generation Sequencing (NGS) tests.” The Agency’s ultimate goal is to develop a flexible and adaptive “regulatory approach that ensures that patients receive accurate and meaningful results, while accommodating innovation in test development.”

In December 2014, FDA published a paper which outlined a number of possible strategies to accomplish its goal. Earlier this month, FDA held two, back-to-back public workshops, where both of these strategies were discussed along with plans for the regulation of NGS diagnostics.

On November 12, 2015, FDA discussed the first strategy. Details and highlights from the workshop include:

Strategy 1: “Identifying and implementing analytical standards that would ensure that NGS tests produce accurate and reliable results.”

Last week, FDA held a workshop entitled, “Standards Based Approach to Analytical Performance Evaluation of Next Generation Sequencing In Vitro Diagnostic Tests,” to address the standards for evaluating the analytical performance of NGS.

During this workshop, FDA Deputy Commissioner for the Office of Medical Products and Tobacco, Dr. Robert Califf, stated that although these tests have a lot of potential, there is still a tremendous amount of uncertainty surrounding them; and, according to him, it all comes down to accuracy – or “how accurate [and] how useful can we make the predictions that come from these tests.” Dr. Califf also said that any regulation addressing NGS testing must be flexible and able to adapt with the technology as advances are made.

The development of a regulatory framework for NGS diagnostics has been in the works since 2014 (as a part of President Obama’s Precision Medicine Initiative (PMI)). In September of this year, FDA published a paper which presented and described two approaches that “might be used to assure the development of NGS tests that are analytically valid.” These approaches represent opposite ends of a spectrum, and involve:

1. Performance Standards:

“…would establish the metrics and performance criteria that are necessary for the developer to address and the test to meet, and could also include prescribed validation studies that a developer would be expected to carry out in establishing the analytical and clinical performance of the test. These standards could be developed by FDA, or by one or more third parties and recognized by FDA.”

FDA’s perspective: This approach would validate NGS diagnostics by defining “individual performance evaluation studies that must be conducted and specific performance criteria that must be met.”

2. Design Concept Standards:

“A set of defined activities and goals that are documented, and when complied with, are expected to yield a product that has the intended characteristics and consistently delivers results within the established acceptance criteria.”

FDA’s Perspective: This approach is the more flexible of the two, and “would rely on the established ability of the developer to implement well-described principles of test design and validation, and thus consistently generate tests that meet user needs, with performance characteristics that allow correct clinical interpretation.”

During the workshop, the Agency asked the public for feedback on which approach (or a combination of the two approaches) it feels “would best provide assurances that all NGS tests can provide accurate and reliable analytical results.” The panelists at the meeting appeared to favor a combination of the two approaches.

FDA will be accepting comments on both workshops until next Wednesday, November 25, 2015, and will also be holding two additional workshops on the subject of NGS diagnostics next year (February and March).

For more information and details of the discussion, view the webcast of the public workshop here.

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