FDA Revisits Unsubstantiated Claims Surrounding Pharmacogenetic Testing

Pharmacogenetic Testing and the FDA’s 2018 Warning

The advent of direct-to-consumer genetic testing has yielded an explosion in the development of various types of genetic tests for clinical treatment and diagnostic purposes. These tests include pharmacogenetic tests, which are used to better understand the role genetics play in an individual patient’s reaction to certain drugs or therapies. Some types of pharmacogenetic tests have been approved by the FDA, such as those tests that assess a patient’s sensitivity to blood thinners or tests that assess a patient’s ability to readily metabolize certain medications.

However, just as each patient has unique attributes, so do pharmacogenetic tests; and not all tests are created equal. In late 2018, the FDA issued a stern warning (“2018 Warning”) that some pharmacogenetic tests marketed to consumers made unsubstantiated claims, including predicting how a patient would respond to certain medications. At the same time, the Agency clarified that many of those tests have not been evaluated by the FDA and may not be supported by adequate scientific evidence. Further, the FDA noted that use of these unsubstantiated tests could lead to potentially serious adverse health consequences for patients, particularly if the test result(s) led a consumer or prescriber to change medication dosages or to elect or forego additional therapies, tests, medications or procedures that could treat a given disease or condition.

Need for an Updated Approach to Pharmacogenetic Testing

The 2018 Warning was apparently insufficient to stem the tide of unsubstantiated pharmacogenetic tests. On February 20, 2020, the FDA published a statement (“2020 Statement”) noting its continued concern with unsubstantiated pharmacogenetic tests and new steps it will take to address those concerns consistent with its mission to protect and promote public health.[4] As noted by FDA, “[u]nfortunately, in the time since our safety communication was issued, some manufacturers of pharmacogenetic tests with claims not adequately supported by sound science have continued marketing their tests, including some for medications to treat seizures, mental illness and pain, including opioids.”

That begs the question: how did the use of unsubstantiated pharmacogenetic tests continue to proliferate without adequate scientific basis? According to the 2020 Statement, “[m]any pharmacogenetic tests are being offered as laboratory-developed tests (“LDTs”).” The 2020 Statement also clarifies that LDTs are technically subject to the same regulatory requirements as in vitro diagnostic products, including the requirements for premarket review, but the agency stated that it has “generally not enforced applicable regulatory requirements for LDTs.” This discretionary approach is at least partially due to the fact that the enforcement framework for LDTs was developed decades ago when the field of LDTs was, “much different, and often relied on simpler technologies in local settings.” With ever-evolving innovation regarding pharmacogenetic testing showing no signs of slowing down, the FDA has committed to a more robust approach for oversight of these products.

FDA’s Updated Approach to Pharmacogenetic Testing

Amidst this scene of unfettered pharmacogenetic testing evolution and growth, FDA has adopted new strategies that will accomplish three primary goals: (1) support the burgeoning field of pharmacogenetic tests; (2) enhance the scientific evidence surrounding pharmacogenetic testing; and (3) provide regulatory oversight over unsubstantiated pharmacogenetic tests. On balance, FDA has established a promising platform to support each goal:

Support for the Development of Scientifically Supported and Beneficial Pharmacogenetic Tests

To support beneficial uses of pharmacogenetic testing, FDA published a Table of Pharmacogenetic Associations (“Table”) simultaneously with the 2020 Statement as a tool for health care providers to use in evaluating whether pharmacogenetic tests may be appropriate for use in their prescribing practices. The Table is the product of a collaboration between the FDA’s Center for Devices and Radiological Health and Center for Drug Evaluation and Research and is “intended to provide the agency’s view of the state of the current science in pharmacogenetics.”

Currently, the Table lists three (3) categories of pharmacogenetic associations for which the data:

Support therapeutic management recommendations;
Indicate a potential impact on safety or response; or
Demonstrate a potential impact on pharmacokinetic properties only and the impact of these genetic variants or genetic variant inferred phenotypes on the safety or response of the corresponding drug has not been established.

Note that the Table is not merely a compendium of FDA-approved gene-drug interactions, but rather a reference that includes a broader array of gene-drug interactions that are “consistent with the current FDA labeling and for which there is sufficient scientific evidence based on published literature.” Additionally, the FDA recognizes that the Table is only one tool that health care providers will use when making prescribing decisions and is not intended to substitute other FDA-approved product labeling or regulations.

Development of Scientific Evidence Surrounding Pharmacogenetic Testing

To further develop the scientific evidence surrounding pharmacogenetic testing, FDA has opened a docket for public comment to solicit feedback on specific pharmacogenetic associations that should or should not be included in the Table and has proposed a community-based collaborative approach to evaluate the scientific evidence related to this field.

Regulatory Oversight of Unsubstantiated Pharmacogenetic Testing

The Agency’s approach to address scientifically unsubstantiated pharmacogenetic testing is less clear, though nonetheless mentioned in the 2020 Statement. Specifically, FDA notes that it is, “committed to continuing to work with Congress on a broader legislative solution . . . which would modernize our regulation of these tests.” It also notes that “while the landscape of LDTs has changed, the agency’s oversight framework has remained the same,” which signals that FDA may start to leverage its existing regulatory authority to provide comprehensive oversight of LDTs and pharmacogenetic tests directly, essentially reversing the Agency’s prior discretionary approach.

Practical Takeaways

The Agency has clearly indicated that unsubstantiated pharmacogenetic tests have been prioritized for enforcement efforts. Additionally, the FDA indicates that it is working to modernize its regulatory approach to pharmacogenetic tests and other LDTs in a way that may represent a paradigm shift from the prior enforcement regime. While FDA’s exact enforcement strategy is not outlined in its 2020 Statement, manufacturers of LDTs should be aware that a marked change may be on the horizon.

To prepare for potential regulatory or enforcement changes, manufacturers should closely review the Table published by the FDA for alignment on findings related to their specific tests, monitor ongoing FDA activity in this area and consult with counsel as to how best to ensure that their products are in compliance with all applicable requirements applicable to in vitro diagnostics.

Health care providers, industry stakeholders and researchers with insight into specific pharmacogenetic tests should consider commenting on FDA’s public docket or participating in a community-based collaboration effort in consultation with counsel.

Hall Render attorneys regularly monitor FDA activity related to medical devices, including pharmacogenetic testing and in vitro diagnostics. To receive updates on this topic, you can sign up for Hall Render articles related to this topic here. If you have any questions about this or other related topics you can contact: