FDA Recognition
What is an FDA-Recognized Human Variant Database?
In April 2018, the FDA announced the initiation of a Public Human Genetic Variant Database regulatory approach to support the agency’s precision medicine initiatives. "The goal of this effort is to help ensure patients receive accurate, reliable, and clinically meaningful test results, while promoting innovation in test development” (www.fda.gov/media/99200/download). Data and assertions within an FDA-recognized database are considered valid scientific evidence that can be used to streamline the test development and validation processes. FDA recognition also incentivizes human variant data-sharing by recognizing the importance of transparency and peer-review for accurate human variant interpretation and pathogenicity classification. Thus, all data in an FDA-recognized human variant database is expected to be publicly accessible, including the variant curation and interpretation processes as well as the curated evidence to support the final variant classifications.
What did the FDA recognition of OncoKB™ involve?
OncoKB began the process to seek FDA recognition in August 2018 and received partial recognition on October 7, 2021. FDA recognition of a human variant database involves the FDA’s detailed review of the database’s standard operating procedures (SOP) and policies, including processes and validation studies for variant evaluation and assertion, data integrity and security, and transparency of all evidence. The FDA also reviews the database administration policies for hiring, training and continuing the education of the personnel who curate, evaluate and approve the inclusion of variants into the database, as well as the processes for ensuring their conflicts of interest are minimized and transparent.
What is the scope of the FDA recognition of OncoKB™?
The FDA reviewed all OncoKB processes documented in the OncoKB SOP v2.0 which included the following:
OncoKB’s processes and validation studies for variant evaluation and assertion, data integrity and security, and transparency of all evidence.
OncoKB’s administration policies for hiring, training and continuing the education of its curators and Scientific Content Management Team who evaluate and approve the inclusion of variants into the database.
OncoKB’s policies of oversight and governance.
OncoKB’s processes for ensuring its members’ conflicts of interest are minimized and transparent.
Mapping of OncoKB levels of evidence to the FDA levels of evidence.
Part of the OncoKB annotated content: Annotation of variants curated in OncoKB with an FDA level of evidence. FDA recognized content is clearly marked on the website and a pop-up message will appear when the user exits an FDA recognized portion of the OncoKB website.
Who is the intended audience for annotation of variants curated in OncoKB™ with an FDA level of evidence (#6 above)?
OncoKB is a database that links cancer variants with their clinical implications in specific tumor types. While the intended audience for OncoKB is primarily clinical oncologists, molecular pathologists and cancer researchers, tumor profiling next-generation sequencing (NGS) test developers may also rely on OncoKB for variant information and variant annotation with an FDA level of evidence to support the clinical validity of their tests.
What is the significance of the FDA partial recognition of OncoKB™?
OncoKB is the first somatic human cancer variant database to receive this designation. FDA recognition credentials the robustness and transparency of OncoKB processes involved in variant evaluation and interpretation as described in the OncoKB SOP v2.0. OncoKB will continue to interact with the FDA toward more expansive recognition as FDA policies in this area evolve.
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