In yet another move toward precision medicine this week, the FDA is mapping out co-development pathways for companion diagnostic devices to accompany targeted therapies.
Underscoring the complexity of developing intertwined products, the FDA’s draft guidance released July 15 recommends that companies develop them in tandem because the agency supports simultaneous approval and because it could hasten approval. The agency recommends that sponsors of both the IVD and the therapeutic product meet with the appropriate FDA centers prior to launching a trial.
The guidance describes general principles to guide codevelopment of therapies and their companion diagnostics, regulatory requirements that sponsors should be aware of, and considerations for planning clinical trials.
The document — which is applicable to drugs, biologics and devices — notes that clinical trial design will be informed mainly by the device component, as it will point drugmakers to the adequate patient population, the document says.
Herceptin was the first targeted therapy to be approved with a companion diagnostic, the HercepTest, which measures expression of human epidermal growth factor receptor 2 (HER2) in breast cancer. The two products were approved in 1998, and there are now numerous examples of therapies approved with companion diagnostics, the guidance notes.
In vitro companion diagnostics (IVDs) may be used to:
When a device is not developed in tandem with the therapy, the agency provides strategies to prove that the clinical outcome is correlated to the device and therapy. Trials should support the claims for both the therapy and companion device.
The agency notes that errors with the devices could introduce bias in recruitment of patient populations. To guard against that bias, the guidance suggests gathering a second set of independent clinical samples and validating those against sample data that includes the device.
Risk Assessment and IDE Requirements
IVDs have generally been classified as high-risk, Class III devices, requiring premarket approval applications; however moderate-risk IVDs could be considered Class II devices, requiring 510(k) premarket notifications or de novo requests.
However, risk assessments applied to the use of an investigational IVD in the context of a clinical trial is likely to be different than the risk assessment for marketing purposes. The guidance highlights criteria for examining risk and whether IVDs would be considered exempt, significant risk or non-significant risk. It notes that significant risk would come into play when IVDs are used to make treatment decisions in a trial and an incorrect test result poses potential serious risk to the health, safety, or welfare of a patient.
The document recommends that companies design trials that assess specific markers in patients, because these will establish the clinical validity of the therapy and device. An alternative approach would be to use prospective-retrospective studies, which rely on a plan to collect specimens and then retrospectively analyze them.
When the accompanying device is used outside of its indication during the clinical trials, the agency warns that it should meet the requirements of the investigational device exemption.