Pharmacogenetic Tests: Recent FDA Authorization for One and Warnings about Others

On October 31, 2018, FDA announced that 23andMe could market its Personal Genome Service Pharmacogenetic Reports test (the “23andMe test”) as a direct-to-consumer test for providing information about genetic variants that may be associated with medication metabolism.  The 23andMe test was reviewed using the de novo premarket review pathway.  FDA authorized the 23andMe test to detect 33 variants for multiple genes after finding that the test is accurate and provides reproducible results, and that consumers can understand the test’s instructions and reports.

On November 1, 2018, just one day after authorizing the 23andMe test, FDA issued a safety communication warning patients and health care providers against the use of other genetic tests that claim to predict patient responses to medications.  The safety communication was accompanied by a joint statement from the directors of CDRH and CDER, Dr. Jeffrey Shuren, J.D. and Dr. Janet Woodcock.  FDA’s safety communication applies to tests offered through health care providers, as well as tests advertised directly to consumers.  The safety communication stated that “claims for many genetic tests to predict a patient’s response to specific medications have not been reviewed by FDA, and may not have the scientific or clinical evidence to support this use for most medications.”  FDA also warned genetic testing companies that the agency is looking into test developers who may be inappropriately selling genetic tests for unapproved uses and that the agency “will take compliance actions when appropriate.”

FDA’s safety communication focused on genetic tests that claim to provide information about a patient’s response to medications including predictions about which medication should be used, which medications may be less effective, and which medications may have an increased chance of side effects. FDA raised concerns that health care providers may make inappropriate changes to a patient’s medication based on the results from these genetic tests which may put patients at risk for potentially serious health consequences.  However, FDA also acknowledged that some genetic tests may provide information about patient responses to medication based on evidence that supports a correlation between a genetic variant and drug levels within the body.  FDA stated that medications’ labels may provide general information on how genetic variations may impact medication levels in patients or may describe how genetic information can be used in determining therapeutic treatment.  Drug labeling was the only data source referenced by FDA.

The FDA safety communication did not explicitly mention laboratory-developed tests (LDTs). However, reports generated by laboratories currently provide pharmacogenetic data beyond that which appears in the drug labeling.  FDA has long taken the position that it will exercise enforcement discretion with LDTs.  It is difficult to see any basis for departing from that practice here.

FDA’s statement focuses heavily on the information in drug labels. While that is one important source, it is hardly the only one; there is a significant and growing amount of scientific literature regarding pharmacogenetics.  It appears in the safety communication that FDA is establishing drug labeling as the only currently acceptable source of pharmacogenetic information.  Given the rate at which new pharmacogenetic data are being generated and the lag in updating drug labeling, this approach could lead to clinicians not being given the most current pharmacogenetic information.  It will also be important to watch this area further to see if FDA departs from its standard enforcement discretion approach towards LDTs.