For the first time, FDA formally recognized a public database containing information about genes, genetic variants, and their relationship to disease. FDA announced its formal recognition of the genetic variant information in Clinical Genomic Resource (ClinGen) consortium’s ClinGen Expert Curated Human Genetic Data, a database funded by the National Institutes of Health, on December 4.
This formal recognition is the result of a process outlined in FDA’s guidance document, Use of Public Human Genetic Variant Databases to Support Clinical Validity for Genetic and Genomic-Based In Vitro Diagnostics (Guidance). See our posts on the draft version of the Guidance, here, and final version, here.
By formally recognizing public genetic information databases, FDA permits sponsors to use information from a recognized database as a source of valid scientific evidence to support the clinical validity of genetic and genomic-based in vitro diagnostic. The key benefit is that sponsors should have confidence that FDA has already vetted the database, and sponsors do not have to expend resources to collect the same data on their own.
FDA’s announcement explains that FDA’s review of ClinGen included a review of its standard operating procedures (SOPs) and policies. This review included “processes and validation studies for variant evaluation, data integrity and security, and transparency of all evidence.” Additionally, FDA reviewed how ClinGen “qualifies and approves researchers and clinicians to evaluate variants, including conflict of interest and disclosure policies.”
FDA also issued a lengthy decision summary, detailing the basis for its recognition of the ClinGen database. The decision summary describes in detail all information FDA reviewed in deciding to recognize the database.
Notably, the decision summary includes a section titled “Scope of Recognition.” This section states that the recognition is for the use of the ClinGen database “for germline variants for hereditary disease where there is a high likelihood that the disease or condition will materialize given a deleterious variant (i.e., high penetrance).” FDA’s Guidance did not specify that the scope of FDA recognition would be limited to certain applications, and doing so can limit the usefulness of FDA recognition. It remains to be seen how strictly FDA will apply the limited scope of recognition when a sponsor relies on data from a recognized database in a premarket submission.
FDA plans to review FDA-recognized databases annually to verify that they continue to follow their SOPs and data collection practices. As noted in our post on the draft version of the Guidance, it is unclear whether undergoing regular FDA scrutiny will be appealing to database administrators. This formal recognition is perhaps not only a test case for how sponsors may use database information in supporting a premarket submission, but also how well database administrators will tolerate regular FDA review in order to maintain recognized status.