Combination products without regulatory precedent will be assigned to the FDA center with the most expertise in evaluating the products' primary safety and efficacy concerns, according to a proposed rule published in the May 7 Federal Register.

The regulation will facilitate more timely approval of combo products by identifying the proper center for review assignment, FDA says.

The proposed rule defines "primary mode of action," which determines whether a product is assigned to the agency's device, drug or biologics center, as "the single mode of action of a combination product that provides the most important therapeutic action of the combination product."

Should a combo product be too early in its development to identify its PMOA, or should its actions be independent of each other, the agency recommends assignment to the center that regulates comparable products, unless there is no precedent.

As an example, the rule refers to a contact lens combined with a drug to treat glaucoma. Because the lens' function is vision correction and the drug's function is the treatment of glaucoma, they are independent of each other.

Since no combination product has been submitted for these functions, there is no precedent to follow in assignment of review center.

However, the drug's safety and effectiveness issues are more significant than those of the contact lens, which are "considered routine." Therefore, the glaucoma-treating lens would be regulated by CDER, the proposed rule explains.

Conversely, drug-eluting stents will still be regulated by CDRH because the function of the drug is secondary and supportive to the function of the stent, which is to open an artery.

Office of Combination Products Director Mark Kramer noted his office considered roughly 300 combination products that had been reviewed over the last 13 years in developing the algorithms used within the rule.

During a May 6 teleconference unveiling the proposal, Kramer stressed that existing FDA regs allow a review assignment to be changed during product development if data show that a product is incorrectly assigned, creating a public health concern.

FDA issued the proposed rule against industry appeals. In February, AdvaMed urged the agency to "not move hastily to codification " of PMOA, urging OCP to first draft guidance defining the concept (¹ Also see "AdvaMed Cautions FDA Against Rush To “Primary Mode of Action” Rule" - Medtech Insight, 8 March, 2004., p. 18).

FDA also addresses review speed in a separate draft guidance on formal dispute resolution requests for combo products, suggesting requests be filed after applicable performance goal timelines have passed.

Exceptions may apply if a sponsor receives advance notice that a center will not meet a pertinent deadline. In those cases, a resolution request to OCP would be acceptable, as it would "further the goal of obtaining review as quickly as possible," the May 4 ² guidance explains.

Formal dispute resolution requests are inappropriate either before the review segment has been initiated or after it has been completed, the agency notes. OCP dispute resolution requests made after the portion of the review in question has been completed "would do nothing to further the goal" of expediting the review. However, the office is open to receiving comments related to slow reviews, OCP notes.

"Prospective concerns about [a] reviewing agency's ability to meet performance goals in the future" should be addressed through "informal procedures outside the scope of this guidance," the document states.

OCP stresses that it will continue to help sponsors work through regulatory confusion surrounding combination product submissions and facilitate communication with review centers, significantly decreasing the likelihood of timeliness complaints.

Combination product submissions reviewed under a single premarket application are subject only to the performance goals associated with that application. For products requiring two application types, performance goals established at each center would apply.

MDUFMA established premarket timeliness dispute resolution as a responsibility of OCP at its inception. However, the office has yet to receive a complaint that would fall into that category, staffers say. Comments on the proposed rule and the draft guidance are due July 6.

Combo Product Dispute Resolution, Primary Mode Of Action Detailed By OCP

More from Archive

More from Medtech Insight