The Food and Drug Administration (FDA) may be closing in on solving one of its perennial regulatory problems, namely, the absence of a workable regulatory pathway for devices that seek to use older, mainly generic drugs in innovative ways. Under the current system, where a device sponsor proposes to label its device for use with a drug in a manner that may go beyond the existing drug labeling, FDA typically requires the submission of a new drug application (NDA). An NDA or supplemental NDA is often called for to modify the drug labeling to reflect the proposed use by the device. This puts the device sponsor in a regulatory box: (1) collaborate with the drug sponsor to seek the labeling change, (2) become a drug sponsor itself and file the NDA directly; (3) seek more general device labeling; or (4) abandon the program (at least in the U.S.). Where the drug is already available in generic form, device sponsors have found it nearly impossible to find a willing drug sponsor interested in developing new labeling for the drug. Further, device companies often reject the idea of becoming a drug sponsor where their device can be used with existing and already approved drug. All too often, we have seen device innovators choose the third and fourth options, leaving patients in the U.S. without access to potentially novel uses of well-established drugs. We call this the “cross-labeling problem” and we may now be heading toward a solution.

On September 26, 2017, FDA issued a notice in the Federal Register seeking comments on its proposal for a new regulatory category, known as Devices Referencing Drugs or DRDs. DRDs would be devices that (1) propose a new use for an approved, marketed drug, where (2) the new use is not included in the drug’s labeling, and the drug sponsor is not likely to seek to change the labeling.

Importantly, approval of a DRD would not result in a labeling change to the drug. Instead, the approval would be granted solely to that medical device that is intended to be used with a drug. In FDA’s proposal, clinical studies of the DRD could be conducted under either an approved Investigational Device Exemption (IDE) or an Investigational New Drug (IND) application. However, the resulting data would be submitted solely under a device application for review by the Center for Devices and Radiological Health (CDRH), with the Center for Drug Evaluation and Research (CDER) playing a collaborative role in the review. The new use of the drug would be supported by as much or as little data as needed to account for the use of the drug with the device, but the device sponsor would be able to submit all of the data within the four corners of a device marketing application. There would be no need for the device sponsor to make a dedicated drug for use with the device, or to gain approval of a new set of drug labeling under an NDA, particularly where the device does not require use with a singular, individually-specified drug product. In this way, the device sponsor avoids the combination product regime, and can proceed as a device-only sponsor for application and review purposes. For devices that can put older, substitutable generics to new use – particularly generic injectable drugs – the DRD category has the potential to lower the regulatory hurdles for some truly innovative programs.

During a hearing on the proposed DRD pathway held on FDA’s campus on November 16, 2017, FDA strongly encouraged industry to submit comments on the proposed regulatory framework and requested feedback on the specific questions raised in the Notice. FDA requests comments in 12 specific topic areas including whether to impose restrictions to the program, submission considerations, postmarket mechanisms to ensure ongoing safety and effectiveness of the combined use of the drug and device products, and interactions between the drug and device manufacturers in both the pre-approval and postmarket settings, among others.

FDA recently announced that it will be extending the comment period by another 30 days. Comments must be submitted to FDA by mid-February 2018 (precise date to be announced).