How Best to Change FDA's Combination Product Regs?

Last month, senators proposed a bill to reform FDA's combination product regulations, but experts don't agree on the details of the legislation.

Last month, senators proposed a bill to reform FDA's combination product regulations, but experts don't agree on the details of the legislation.

Marie Thibault


Medical products that don't fit into just one bucket—say, drug, or device—are considered combination products and have a murkier path to market. In July, senators introduced a bill to tackle the regulation of combination products. But does the legislation strike the right approach, or does more need to be done?

As background, the "Combination Product Regulatory Fairness Act of 2015," sponsored by Senators Johnny Isakson (R–GA), Robert Casey (D–PA), and Pat Roberts (R–KS), would allow FDA to use previous safety and effectiveness data for the various components of the product, would designate a lead center to determine whether the combination product is reviewed as a device, drug, or biologic, and would have companies work together with FDA to create a plan for the regulatory requirements. 

In a contributed column to The Hill, former medtech executive Joseph Gulfo, a former medtech executive who is now an author and the executive director of the Rothman Institute of Innovation and Entrepreneuship at Fairleigh Dickinson University, writes that "we need to put the review plan before the regulatory path when it comes to combination products instead of vice versa."

Currently, the lead review center is supposed to depend on which part of the product contributes the primary mode of action (PMOA). One frequently-cited example is a drug-eluting stent—the device part is viewed as perfoming the PMOA, so CDRH should be the lead review center. 

But Gulfo writes that this doesn't match what is actually happening. He explains that "standards that differ from the statute are being applied, pushing review of combination products having a chemical action 'even in part' or 'that meaningfully contributes' to the primary intended purpose . . . to the FDA drugs center, as opposed to the devices center, as intended in the law."

The legislation "is a step in the right direction," Gulfo writes, because "it aims to create an innovation-friendly process by which the review plan . . . would dictate the regulatory path, rather than the abstract assignment of the path dictating the review plan."

On the other hand, some legal experts think that the legislation doesn't go far enough. Jeffrey K. Shapiro and Jeffrey N. Gibbs, directors at Hyman, Phelps and McNamara PC, write on the FDA Law Blog that "this bill is a good start, but more is needed."

Shapiro and Gibbs explain that the Office of Combination Products (OCP) views a medical product as a drug unless the product sponsors proves it is a device by explaining in detail why the product doesn't rely on chemical action or metabolization to work. They write that "this approach leads to inconsistency with historical agency classification decisions, so that a product intended to compete with other devices is forced to undergo much more burdensome drug regulation."

The lawyers write that the legislation's approach of making OCP explain the scientific rationale for assigning a combination product to a drug review and allowing the product sponsor to appeal a drug classification by designing a study to determine the importance of any chemical action, "is not likely to yield good fruit."

They elaborate: "It will not be difficult for the OCP to provide a rationale . . . it often does so now . . .it is difficult or impossible as a practical matter for the sponsor to challenge." What's more, product sponsors can already show data from studies trying to prove that the chemical action is not important enough to classify the product as a drug, but "it is easy for the OCP to dismiss almost any such study as insufficient," Shapiro and Gibbs write.

The experts want to turn the tables and make OCP show scientific proof for its decisions. They write, "the OCP should not be permitted to classify a product as a drug unless it proves that a product claimed to be a device actually uses chemical (or metabolic) action as the primary mechanism for achieving the product's primary purpose." 

It remains to be seen what will actually come of the combination products bill, which was referred to the Senate Committee on Health, Education, Labor, and Pensions in July.

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Marie Thibault is the associate editor at MD+DI. Reach her at and on Twitter @medtechmarie


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