Companies that think they’re developing a device might unwittingly find themselves facing a drug submission mandate they are unable to pursue. Greenleaf Health consultant and former FDA combination products chief Mark Kramer talks about how to avoid or at least prepare for the cross-labeling challenge and why more clarity is needed from FDA and Congress on the issue.
Welcome to Consultants Corner, where we check in with independent experts about questions they are answering or challenges they are solving for clients on the front lines of medtech regulatory, reimbursement, and market access.
Mark Kramer (firstname.lastname@example.org) is an Executive VP for Medical Devices and Combination Products at Greenleaf Health. He previously established FDA’s Office of Combination Products and served as its director for five years. He also has worked as a device reviewer and manager at CDRH and as a regulatory affairs executive at device companies. Prior to joining Greenleaf in 2022, he ran an independent consulting practice for about 13 years.
The Question: Is Your Device ... Not Just a Device?
Let’s say your company is developing a new twist on a catheter or an updated iontophoresis device. Your route to showing substantial equivalence to a predicate seems passable and you’re feeling optimistic.
But as you engage with FDA, the regulatory path takes a dramatic swerve. In the agency’s view, it turns out, the product is not a routine 510(k) device, but a device constituent part of a “cross-labeled combination product.” That means the drug center, not CDRH, will likely be assigned to lead the review and your company may be expected to submit a drug application that it is operationally or legally unable to pursue.
Mark Kramer, an executive VP at Greenleaf Health and the founding director of FDA’s Office of Combination Products, says this issue crops up more than many companies realize. He’s seen it with catheters, injectors, nebulizers, infusion pumps, and any other variety of drug delivery device.
“The conundrum of this cross-labeling issue has really been that some devices may have no pathway to get to market absent the cooperation of the drug sponsor.”
“It happens a fair amount,” Kramer said in an interview. “I'm going to say at least 10% or more of my work involves situations where this either is a real issue or can be. The company will explain what they have in mind for a particular product. And right away my mind will just go to, ‘Sounds like a cross-labeling issue to me.’”