In the middle of April, FDA finalized two guidance documents intended to support the development and validation of next-generation sequencing (NGS)-based tests, which are gradually making their way toward routine application in clinical laboratories.
“As disease detection technologies rapidly evolve, so too must FDA’s approach to reviewing these new innovations,” said FDA Commissioner Scott Gottlieb, MD. “The new policies issued today provide a modern and flexible framework to generate data needed to support FDA’s review of NGS-based tests, and give developers new tools to support the efficient development and validation of these technologies.”
The first guidance, Use of Public Human Genetic Variant Databases to Support Clinical Validity for Genetic and Genomic-Based In Vitro Diagnostics, describes how test developers can use clinical evidence from FDA-recognized public databases to support clinical claims for their tests, and to help provide assurance of the accurate clinical evaluation of genomic test results.1 The guidance describes how product developers can use the databases to support the clinical validation of NGS tests they are developing.
“The rapid adoption of NGS technologies in research and clinical settings is helping to identify countless new genetic variants. However, information about genetic variants is generally stored in a manner that is not publicly accessible,” said Jeffrey Shuren, MD, JD, director of FDA’s Center for Devices and Radiological Health. “Today’s release of FDA’s final guidance on genetic variant databases will help change this paradigm by encouraging data sharing and the accumulation in public databases of evidence supporting the clinical validity of genomic tests, to help provide an even more efficient path to market.”
The second guidance, Considerations for Design, Development, and Analytical Validation of Next-Generation Sequencing (NGS)–Based In Vitro Diagnostics (IVDs) Intended to Aid in the Diagnosis of Suspected Germline Diseases, provides recommendations for designing, developing, and validating NGS-based tests used to diagnose individuals with suspected genetic diseases.2 It describes what FDA would look for in premarket submissions to determine a test’s analytical validity, including how well the test detects the presence or absence of a particular genomic change.
Also in April, FDA’s Oncology Center of Excellence gave a boost to companies that are conducting research in the emerging field of immunooncology, where novel diagnostics are playing vital roles in developing new therapeutics and qualifying the patients who will benefit from them. A draft guidance issued by the center promises to provide a streamlined process for determining the risk profile of an IVD being codeveloped with an oncology investigational drug, potentially simplifying the administrative burden related to FDA review of the diagnostic.3
While the areas of application for these new guidances are quite narrow, it’s clear that they represent solid progress toward the development of novel diagnostics that will be needed in the coming era of personalized medicine.
- Considerations for Design, Development, and Analytical Validation of Next-Generation Sequencing (NGS)-Based In Vitro Diagnostics (IVDs) Intended to Aid in the Diagnosis of Suspected Germline Diseases: Guidance for Stakeholder and Food and Drug Administration Staff.Silver Spring, Md: Center for Devices and Radiological Health, FDA, 2018. Available at: www.fda.gov/ucm/groups/fdagov-public/@fdagov-meddev-gen/documents/document/ucm509838.pdf. Accessed April 13, 2018.
- Use of Public Human Genetic Variant Databases to Support Clinical Validity for Genetic and Genomic-Based In Vitro Diagnostics: Guidance for Stakeholders and Food and Drug Administration Staff.Silver Spring, Md: Center for Devices and Radiological Health, FDA, 2018. Available at: www.fda.gov/ucm/groups/fdagov-public/@fdagov-meddev-gen/documents/document/ucm509837.pdf. Accessed April 13, 2018.
- Investigational In Vitro Diagnostics in Oncology Trials: Streamlined Submission Process for Study Risk Determination: Guidance for Industry [draft guidance]. Silver Spring, Md: Center for Devices and Radiological Health, FDA, 2018. Available at: www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm604441.pdf. Accessed April 13, 2018.
Chief Editor, CLP