A genetic variant database contains information about genetic differences (also called genetic variants). Researchers submit data to these databases, which collect, organize, and publicly document the evidence supporting links between a human genetic variant and a disease or condition. These databases may make assertions about genetic variants, which are informed assessments of the correlation (or lack thereof) between a disease or condition and a genetic variant based on the current state of knowledge. Better understanding the relationships between genotypes (the genetic code of an organism) and diseases or conditions can aid in the diagnosis and treatment of individuals with genetic conditions.
The FDA’s April 2018 final guidance “Use of Public Human Genetic Variant Databases to Support Clinical Validity for Genetic and Genomic-Based In Vitro Diagnostics” provides a mechanism for test developers to leverage publicly accessible databases of human genetic variants to support the FDA’s regulatory review of genetic and genomic tests. The FDA hopes that this program will encourage database administrators to submit genetic variant information to publicly accessible databases, which could help reduce regulatory burdens on test developers and spur advancements in the evaluation and implementation of precision medicine.
FDA recognition of a database indicates that the FDA believes the data and assertions contained in the database can be considered valid scientific evidence. This program will allow sponsors to use the assertions within FDA-recognized databases to support the clinical validity of their tests.
Database administrators who wish to seek recognition for their databases should follow the recommendations outlined in the final guidance.
Participation in the FDA database recognition process is voluntary and participation does not subject the database to FDA oversight, beyond what is needed to retain the recognition. There are no user fees associated with the FDA Database Recognition program.
A request for recognition can be for the entire genetic variant database or for a subset of the database as decided by the database administrator. Submissions should demonstrate that the recommendations in the final guidance have been followed, or should explain why an alternative approach was taken.
1. Prior to submitting an application for database recognition, database administrators should contact FDA staff at OIRPMGroup@fda.hhs.gov to determine how to address their recognition request. Database administrators should then submit an application as an eCopy. The eCopy should be in the form of a DVD, CD, or flash drive and should be sent to the Document Mail Center at the following address:
U.S. Food and Drug Administration
Center for Devices and Radiological Health
Document Mail Center – WO66-G609
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
The eCopy should meet the technical standards outlined in Attachment 1 of the FDA guidance “eCopy Program for Medical Device Submissions.”
2. The cover letter of this application should identify the appropriate division that will undertake the review of the application (this information is obtained by contacting FDA staff prior to submission at OIRPMGroup@fda.hhs.gov). The application should be submitted as an “informational meeting” Q-submission based on the FDA guidance document “Requests for Feedback on Medical Device Submissions: The Pre-Submission Program and Meetings with Food and Drug Administration Staff.” The following types of documents, which show that the recommendations in the final guidance have been met, should be submitted as part of an application for recognition:
- Standard Operating Procedures (SOPs), policies or other documents related to the recommendations in the final guidance, such as:
- General operation of the genetic variant database
- Personally identifiable information and protected health information confidentiality and privacy
- Data integrity and security
- Curation, variant evaluation, and reevaluation
- Training for curation, evaluation, privacy and security, and other relevant activities
- Validation studies for evaluation SOPs
- Documentation of the qualifications of the individuals evaluating variants and policies for approving those individuals
- Data preservation plan
- Conflict of interest policies and disclosures of conflicts of interest
- A commitment to make all recommended documents publicly accessible via weblinks
3. Applications should be accompanied by a cover letter, which should include the following information:
- Identification of the submission as an “Informational Meeting” Q-Submission
- Identification of the submission as a request for Database Recognition
- Statement of the types of variants the genetic variant database assertions address (e.g., germline)
- Scope or portion of the database for which recognition is being sought
- Point of contact
- Entity name
- Statement that the submitter believes, to the best of his or her knowledge, that all information submitted are truthful and accurate and that no material fact has been omitted
If you have any questions, please contact us at OIRPMGroup@fda.hhs.gov
|Database||Database Recognition Decision Summary||Scope of Recognition (if applicable)||Date Recognized|
|Decision Summary||Tumor mutations of Level 2 (evidence of clinical significance) and Level 3 (potential clinical significance) biomarkers
|Clinical Genome Resource (ClinGen)||Decision Summary||Germline variants for hereditary disease where there is a high likelihood that the disease or condition will materialize given a deleterious variant (such as high penetrance)||12/4/2018|
- Webinar - Final Guidances on Next Generation Sequencing-based Tests - May 24, 2018
- Final Guidance: “Use of Public Human Genetic Variant Databases to Support Clinical Validity for Genetic and Genomic-Based In Vitro Diagnostics” (PDF - 444KB)
- FDA finalizes guidances to accelerate the development of reliable, beneficial next generation sequencing-based tests