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Use of Genetic Variant Databases as Sources of Valid Scientific Evidence for Clinical Validity of Genetic Tests

This guidance describes FDA's considerations for determining whether a genetic variant database can be a source of valid scientific evidence to support clinical validity of genetic and genomic-based tests in premarket submissions, regardless of technology type. It outlines the process for database administrators to voluntarily apply for FDA recognition and how FDA would assess such applications. The guidance only covers databases making assertions about human genetic variants, excluding databases directing therapies or used for microbial genome identification.

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By ReguVirta
3 min read

What You Need to Know? 👇

What is the FDA’s recognition process for genetic variant databases?

The FDA has established a voluntary three-step recognition process: (1) submission of detailed database information, (2) FDA review of policies and procedures, and (3) ongoing maintenance of recognition through annual reviews and transparency requirements.

How can genetic variant databases support clinical validity in premarket submissions?

FDA-recognized genetic variant databases can provide valid scientific evidence for genotype-phenotype relationships, potentially reducing the need for additional clinical data in premarket submissions for genetic and genomic-based tests.

What are the key requirements for database transparency and public accessibility?

Databases must make publicly available their data sources, standard operating procedures for variant evaluation, nomenclature used, and evidence supporting variant assertions to enable informed medical decisions by patients and healthcare providers.

What professional qualifications are needed for variant evaluation in databases?

Variant evaluation should be performed by at least two qualified and trained genetics professionals (genetic counselors, Ph.D. scientists, physicians) with adequate training and methodologies to maintain high quality standards over time.

How does FDA ensure data quality in recognized genetic variant databases?

FDA requires robust metadata documentation, validated evaluation protocols, version control of SOPs, data uniqueness verification, and regular auditing of data sources to ensure high-quality variant assertions.

What happens if an FDA-recognized database fails to maintain standards?

FDA may withdraw recognition if databases don’t maintain their specifications, making their assertions unlikely to constitute valid scientific evidence, and FDA would assess appropriate regulatory actions for dependent IVDs.

What You Need to Do 👇

  1. Develop comprehensive SOPs for database operations, data quality, variant evaluation
  2. Implement security and privacy protection measures compliant with regulations
  3. Establish professional training program for variant evaluators
  4. Create conflict of interest policies and disclosure processes
  5. Document validation protocols for variant evaluation
  6. Set up data backup and preservation plans
  7. Implement version control for SOPs and assertions
  8. Make policies and procedures publicly accessible
  9. Establish process for receiving and handling user feedback
  10. Create plan for regular review and updates of procedures
  11. Prepare documentation package for FDA recognition submission
  12. Set up process for maintaining FDA recognition through annual reviews

Key Considerations

Software

  • Database must have processes for assessing stability and architecture
  • Must maintain proper data linkages
  • Regular database backups required
  • Plan needed for data preservation if operations cease
  • Must use commonly accepted data formats and nomenclature

Cybersecurity

  • Must comply with all applicable federal laws regarding data security
  • Must implement adequate security measures to protect personally identifiable information
  • Staff training on security required

Labelling

  • Assertions must be truthful and not misleading
  • Must use clear and understandable language
  • Should not include clinical treatment or diagnosis recommendations
  • Should use descriptive language about variants (pathogenic, benign, etc.)

Safety

  • Must protect patient privacy and comply with applicable privacy laws (HIPAA, GINA, etc.)
  • Must have processes for protecting personal health information
  • Must comply with human subject protection requirements

Other considerations

  • Must have standard operating procedures (SOPs) that are documented and versioned
  • Must have at least two qualified professionals evaluate each variant
  • Must have processes for resolving evaluation differences
  • Must include metadata about variants and evidence sources
  • Must have conflict of interest policies and disclosures
  • Must make policies and procedures publicly available
  • Must maintain professional training standards for evaluators

Relevant Guidances 🔗

Related references and norms 📂

  • CLIA: Clinical Laboratory Improvement Amendments of 1988

Original guidance

  • Use of Genetic Variant Databases as Sources of Valid Scientific Evidence for Clinical Validity of Genetic Tests
  • HTML / PDF
  • Issue date: 2018-04-13
  • Last changed date: 2019-04-09
  • Status: FINAL
  • Official FDA topics: Medical Devices, Laboratory Tests, Premarket, IVDs (In Vitro Diagnostic Devices), Molecular and Clinical Genetics
  • ReguVirta ID: 9a24eb9eb6de753534f8fc0b75308c23
FDA guidance, Final
Medical Devices Laboratory Tests Premarket IVDs (In Vitro Diagnostic Devices) Molecular and Clinical Genetics
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