The regulatory status of drug/device combination products is a frequent source of dust-ups with the FDA. Companies prefer that their candidate be regulated under the less demanding device (as opposed to drug) pathway, but the FDA doesn't always come to the same conclusion under the so-called device exclusionary clause of the Food, Drug, and Cosmetic Act.
As the law firm Faegre Baker Daniels points out, the user fee for a 510(k) application was $5,018 in fiscal year 2015, compared to $2.34 million for a new drug application. And that's before factoring in the increased cost and difficulty of meeting the NDA requirements.
Classic examples of combination products include drug-eluting stents (which are classified and regulated as a device). Products that blur the line between drugs and devices, thereby posing a regulatory challenge, include skin washes and wound dressings.
Sens. Johnny Isakson (R-GA) and Robert Casey (D-PA) have introduced the Combination Product Regulatory Fairness Act of 2015 to tip the balance in favor of device product classifications, but attorneys from Hyman, Phelps & McNamara say it doesn't address the fundamental problems in their FDA Law Blog.
The main provisions of the bill would require the FDA's Office of Combination Products to provide a scientific rationale for its classification decision on whether to regulate product candidates as a drug or device. According to a brief from law firm Covington & Burling, "A sponsor would then be able to propose a study to establish the significance, if any, of the product's chemical action in achieving its primary intended purpose and FDA would be required to collaborate with the sponsor to reach agreement on the study design."
Note that the section of the Food, Drug, and Cosmetic Act on combination products states that a product is a device if it "does not achieve its primary intended purposes through chemical action within or on the body of man" and "is not dependent upon being metabolized for the achievement of its primary intended purposes."
The FDA Law Blog says that the agency already provided a rationale for its decisions and sponsors could submit feedback, though the bill, which it describes as "a good start", would formalize the process.
The attorneys write that a study challenging the FDA's ruling would add to the regulatory burden and is unlikely to succeed: "Since the study must prove a negative, i.e., that chemical action does not play a role--or at least more than a minor role--it is easy for the OCP to dismiss almost any such study as insufficient."
Instead, they propose changing the governing statute, writing "a root cause solution to the problem does not require a new procedure; it requires a revision to the statute to shift the burden of proof (to the FDA) and to require that the chemical or metabolic action be the primary mechanism for achieving the product's primary purpose."
The combination product arena has long kept food and drug lawyers busy. The FDA Law Blog attorneys even suggested changing the aforementioned statute from "primary purposes" to "primary purpose."
"This distinction, believe it or not, has been a subject of litigation," they write.
Last year, the U.S. District Court for the District of Columbia rejected the FDA's attempt to classify Prevor's Diphoterine Skin Wash as a drug rather than a device for the second time, dealing industry a victory in the contentious combination product arena.
The approved House version of the comprehensive 21st Century Cures Act requires the FDA to issue final guidance documents on the role of each agency center (such as its drugs, devices and biologics arms) in reviewing combination products, according to Covington & Burling.
Don't be surprised if the Senate version of the bill contains more ambitious provisions to address the regulation of combination products.