FDA Proposes New Approach for the Regulation of NGS-Based Genetic Testing

Posted by Johannes Gross on Apr 3, 2015 9:30:00 AM

DNA_SequencingIn February of 2015, the US Food and Drug Administration (FDA) released a nine-page paper entitled “Optimizing FDA’s Regulatory Oversight of Next Generation Sequencing Diagnostic Tests—Preliminary Discussion Paper” that, among other ideas, proposed allowing the use of curated third-party databases to support submissions for FDA approval, rather than requiring new studies and the support of existing literature.

This represents a noteworthy change in the way diagnostic tests may be developed: the evidence supporting the clinical relevance of results will come from the community, not from the test developer!

The paper states that the FDA “is considering new regulatory approaches only for NGS tests because this technology allows broad and indication-blind testing and is capable of generating vast amounts of data, both of which present issues that traditional regulatory approaches are not well-suited to address.” The FDA plans to stick to the more traditional regulatory approaches for tests targeted to pre-defined genetic variations (i.e., PCR and SNP arrays).

Note that in granting approval to these tests, the basic questions have not changed, i.e., “does test accurately read the targeted set of base pairs, and are these base pairs clinically relevant?” However, NGS tests generate an overwhelming amount of data that can reveal rare and/ or previously unobserved variants as well as incidental findings and co-occurring conditions. Given the billions of nucleotides in the human genome, the traditional regulatory requirements for submitting a complete data set supporting a proposed genetic test can represent a tremendous burden.

“Regulatory-Grade” Database?

With this paper, the FDA has introduced the concept of a “Regulatory-Grade Database” that can provide evidence supporting the associations between genetic variants and clinical outcomes. The precedent was set with the FDA’s 2013 approval of the Illumina's MiSeqDx sequencing platform in diagnosing cystic fibrosis, which rested on a curated database of mutations generated by the research community. And according to the Preliminary Discussion Paper, the FDA hopes to expand this model for approval of NGS tests in general.

In fact, the FDA is already working with the NIH to determine whether the data in the publicly available ClinGen database can be leveraged as evidence to support the clinical significance of NGS testing. ClinGen is a NIH-funded clinical genome resource focused on examining the relationships between data from clinical genetic test results and other research results. Within the ClinGen program is an accessible database of reports on the relationships between genetic variations and phenotypes (ClinVar) as well as a portal that allows patients to share information, and other resources. ClinVar and ClinGen are publically accessible, curated, and continually updated—critical criteria for use of a database for FDA approval purposes.

However, there are many other databases—and biobanks containing DNA samples—that could be affected by, and feel, the profound influence of this new model of regulation, especially with regard to the concept of a Regulatory-Grade Database. For example, consider:

  • The Crohn’s and Colitis Foundation of America (CCFA). This non-profit, dedicated to curing Crohn’s Disease and ulcerative colitis, launched their Microbiome Initiative nearly six years ago and a Genetics Initiative in 2012, and has an active internet-based patient registry with more than 13,000 participants. The organization is pioneering a path toward precision medicine in its approach to combining clinical, patient, and molecular data.
  • The appearance of such entities as the “PatientsLikeMe” patient data-sharing platform, personal genotyping businesses such as 23andMe, and many other crowd-sourced research resources that could potentially add to community-contributed data.

Properly curated, this wealth of information may someday support FDA submissions and dramatically shrink the interval between the generation of genomic data and the availability of information that allows patients and physicians to make meaningful treatment decisions.

Dr. Francis Collins, Head of the NIH, has recently noted that scientific progress alone will not bring about the promised benefits of precision medicine. He noted that a change in the regulatory framework is also needed. The needed changes may be beginning, and it is noteworthy that it is occurring at the level of genomic sequencing.

What does this mean for researchers engaged in biospecimen-based research?

The Discussion Paper can be accessed at: The FDA collected comments on the paper through March 20th.    

To learn more about how cutting edge technologies and innovations are being used in conjunction with regulation, download our eBook Next Generation Cohort Studies and Biobanking: How Cloud Technology is Accelerating Translational Research.


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