Going Solo: Combo Products With Device But No Drug Sponsor To Get Hearing
Executive Summary
US FDA seeking input on proposed approach to allow device sponsors to seek marketing authorization for a device labeled for use with a drug – even if the drug sponsor does not want to cooperate on the new use.
The US FDA is holding a public hearing on “Devices Referencing Drugs” (DRD) Nov. 16 to discuss a potential combination product approach to allow device sponsors to seek marketing authorization for a device labeled for use with an already-marketed drug – even when the drug sponsor does not want to pursue the new use.
The combo product approach would most likely affect drugs administered through inhalers or injectors, but could also apply to digital health sponsors who are interested in adding a tech component to an approved drug.
FDA says DRDs may be proposed to enhance the safety or effectiveness of the marketed drug for its already approved indication; for use with the approved drug for an indication for which the drug is not approved; or to provide some other benefit, such as increasing user comfort or convenience. “Such new uses have generally also involved a change in how the drug is used or administered, such as a change in dose, route, or rate of administration,” the Federal Registernotice states.
FDA wants input on its “Devices Referencing Drugs” proposal at the November meeting. FDA has been grappling with the larger issue of “cross-labeled” or “two-way labeled” combination products for years and held a similar meeting over a decade ago in 2005.
Office of Combination Products Deputy Director John Barlow Weiner highlighted cross-labeled combination products among priority issues for FDA and industry during the DIA Combination Products Conference Oct. 25-26. He used his presentation to encourage sponsors to attend the upcoming meeting and to submit comments on the proposal.
Creating Clarity For Post-Market Safety
DRD cases are not the “dominant category” when it comes to the number of products that OCP sees, Weiner said, but “they do dominate some time because it’s a complicated thing when they do come up.”
Clarity on cross-labeling may be most important for the purposes of post-market safety reporting. “Where the constituent parts are marketed by different sponsors, so there’s two different sponsors for the combo, they have duties to share information with each other, if they hear about an adverse event, they’re supposed to tell each other about it,” he said. “So, it’s nice to know when you have such a product so you know you have such a duty.” FDA’s current stance is, “it’s good to coordinate in general” and “we’re just trying to codify that a bit.”
FDA “strongly recommends” collaboration between sponsors on “new combined uses of their medical products” and is prepared to work with sponsors to facilitate partnering, per the Federal Register notice announcing the DRD meeting.
But FDA is also proposing an approach for cases when collaboration isn’t feasible or one sponsor simply doesn’t want to work on a particular program.
FDA outlines five factors that could allow for a DRD to be reviewed and approved via a device PMA without approval of conforming labeling changes for the approved, marketed drug through an NDA or sNDA. The five factors are:
- Safety and effectiveness of the new use of the drug,
- User confusion and medication error/use error,
- Postmarket change management,
- Postmarket safety, and
- Data reliance.
Under the proposal, staff in the Center for Drug Evaluation & Research and Center for Devices & Radiological Health would collaborate on the review for the DRD, and a PMA would generally be the appropriate application.
FDA is seeking public comment on other issues it should consider, and is asking specifically whether the approach should be limited to situations where there is an unmet medical need.
At the DIA meeting, Weiner included DRDs in a list of areas of where there are “ripple effects” that relate to combo products. DRDs “could be a drug referencing a device too, but more often than not, it’s going the other direction,” he noted. Typically, a company wants to have their device used with a drug in a way that’s not on the drug label “so it’s getting ahead of the drug label.”
“Is this a good idea? Are there ways to make this work? Does it matter what kind of use you’re talking about?” Weiner asked.
FDA has not specified if a similar approach could be applied to drugs or biologics that reference devices for a new intended use, though that issue is likely to arise in comments to the proposal.
Devices that are intended to have a whole new use for the drug and “essentially changing the drug labeling” represent an area of interest for FDA, according to Weiner, “because the drug company doesn’t want to cooperate.”
“We’ve had this come up as a practical matter from time to time with sponsors getting very frustrated if they have a great idea, they have really good data, and they can’t find a partner – so what do they do?” Weiner said.
The hearing is meant to help FDA answer that question via discussion of a potential set of factors for analyzing whether a DRD scenario could work. “If you or your companies see this as a topic of interest to you, either because you’re worried about someone messing with your drug or because you have a great idea for someone else’s drug, or both, please come.”
From the editors of the RPM Report