The FDA has announced plans to ease the development of genetic and genomic-based tests and introduced guidelines designed to accelerate the submission process for investigational cancer drugs and biological products.
The agency said in a statement that it had finalized guidances intended to spur “efficient development of a novel technology that scans a person’s DNA to diagnose genetic diseases and guide medical treatments.”1
The first, titled Use of Public Human Genetic Variant Databases to Support Clinical Validity for Genetic and Genomic-Based In Vitro Diagnostics, allows test developers to rely on clinical evidence from FDA-recognized public databases to support clinical claims for their tests and help provide assurance of the accurate clinical evaluation of genomic test results.
The agency said that using FDA-recognized databases will provide test developers with an efficient path for marketing clearance or approval of a new test.
“As disease detection technologies rapidly evolve, so too must the FDA’s approach to reviewing these new innovations,” FDA Commissioner Scott Gottlieb, MD, said in a statement. “The new policies issued today provide a modern and flexible framework to generate data needed to support the FDA’s review of NGS-based tests, and give developers new tools to support the efficient development and validation of these technologies.”
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 the NGS-based tests used to diagnose individuals with suspected genetic diseases. It explains what data the FDA are looking 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.2
The agency also issued draft guidance titled Investigational In Vitro Diagnostics in Oncology Trials: Streamlined Submission Process for Study Risk Determination. It describes how oncology trial sponsors can use an optional streamlined submission process to determine whether use of an investigational IVD in a trial of investigational cancer drug or biological products presents a significant risk, a nonsignificant risk, or is exempt from further premarket review.
Many cancer treatments target a specific biomarker and so require a companion diagnostic, a type of IVD, to ensure the safe and effective use of the corresponding therapy. IVDs are commonly used with cancer therapies to identify which patients have certain biomarkers and are therefore more likely to respond to treatment. Investigational IVDs and investigational drugs and biological products have different regulatory requirements, and the process for determining whether an investigational IVD poses a significant or nonsignificant risk to patients requires extensive coordination across different FDA product centers.
The agency hopes to reduce the administrative burden on sponsors and FDA staff by outlining circumstances under which sponsors may be able to include information about an investigational IVD in the Investigational New Drug (IND) application submission to either the Center for Drug Evaluation and Research (CDER) or Center for Biologics Evaluation and Research (CBER). This would allow the premarket information related to the investigational drug and the investigational IVD to be contained in a single IND application.
Consolidating the information about both the investigational drug and device into the same application means a more efficient review and help better establish the scientific relationship between the drug and the diagnostic being used to select patients for treatment. CDER or CBER would then coordinate with the FDA’s Center for Devices and Radiological Health to determine whether use of the investigational IVD in the trial is considered significant risk, nonsignificant risk, or exempt.
Gottlieb said in a statement that the agency acknowledges that modern cancer treatment increasingly targets specific genetic features of disease, and that IVDs are necessary to match patients with the appropriate treatment. As a result, the FDA is streamlining the agency’s review of cancer diagnostics developed in conjunction with drug trials.
“This cross-center approach to streamlining the process for determining the review requirements for diagnostics used in drug trials is an example of the Oncology Center of Excellence’s ongoing efforts to expedite the availability of safe and effective cancer treatments for patients,” he said.
- FDA finalizes guidances to accelerate the development of reliable, beneficial next generation sequencing-based tests. Accessed April 12, 2018. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm604462.htm.
- FDA In Brief: FDA advances policy to make co-development of drugs and diagnostics in cancer trials more efficient. Accessed April 12, 2018. www.fda.gov/NewsEvents/Newsroom/FDAInBrief/ucm604469.htm.