Law Firm Challenges FDA on Combination Product Appeals

Regulatory NewsRegulatory News
| 09 March 2017 | By Michael Mezher 

Healthcare law firm Epstein Becker & Green (EBG) is calling on the US Food and Drug Administration (FDA) to improve how it handles challenges to its designation decisions for combination products.

In a citizen petition sent to FDA last week, the firm says that lengthy delays for such appeals negatively affects both product sponsors and patients by delaying the launch of new combination products.


Combination products, or products that combine two or more different types of FDA-regulated products, including drugs, biologics and medical devices, are regulated by FDA based on their primary mode of action.

For example, a drug and device combination could end up being regulated as a drug and reviewed by the Center for Drug Evaluation and Research (CDER), or as a device and reviewed by the Center for Devices and Radiological Health (CDRH), depending on FDA's determination of its primary mode of action.

Because this determination can have a significant impact on a product's development, sponsors can request a designation from FDA before filing for approval by submitting a RFD to the Office of Combination Products (OCP) in cases where it's unclear how the product will be classified, or if they anticipate a dispute over its classification with FDA. OCP then has 60 days to review the request and issue a letter of designation.

If a sponsor disagrees with the outcome of the request, they can ask the agency to reconsider its decision through a request for reconsideration that FDA has 15 days to act on. If the sponsor disagrees with the outcome of the reconsideration, they can appeal the decision up the agency's chain of command.

Sponsors may also request informal, non-binding, feedback from FDA regarding their product's designation, which the agency has begun to shape into a process of its own, called "pre-RFD."

Citizen Petition

In its citizen petition, EBG says that a lack of formalized timelines for FDA to act on appeals to its request for designation (RFD) decisions leads to significant delays for combination products.

Unlike initial requests for reconsideration, FDA is not held to a particular timeline for responding to appeals, though the agency says it "expects to respond to [an] appeal within 30 days."

"The lack of timelines for review makes the agency unaccountable for egregious delays in decision-making, and it has proven by its inaction that, without accountability, it cannot be counted on to act," EBG writes.

According to EBG, one such appeal has been "under consideration" at FDA for a year and a half. This, the firm says, is too long, as RFD submissions and requests for reconsideration are limited to 15 pages and five pages, respectively.

As such, EBG is calling on FDA to amend its regulations to hold itself to review combination product designation appeals within 60 calendar days.

James Boiani, a partner at EBG, told Focus he thinks 60 days is a reasonable timeframe for the agency to act on these appeals.

"If FDA makes it a priority, they can take care of it. The agency handles extremely complex appeals for various issues within 30 days.  It's just a matter of getting everyone on the same page regarding timing, and make it a priority for personnel, so it does not sit on someone's desk," Boiani said.

He also said it's difficult to tell how often companies appeal designation decisions.

"It's hard to say because it's confidential," Boiani added. "I would expect that it is rare, but could become more common in the future as FDA starts working through the new provisions of 21st Century Cures regarding designation decisions."

The 21st Century Cures Act introduces a number of changes to FDA's oversight of combination products, including provisions that restrict the agency from determining a product's primary mode of action "solely because the combination product has any chemical action within or on the human body."

In the past, industry has criticized FDA for leaning towards designating combination products as drugs or biologics when the product relies on any chemical action to achieve its intended effect.

Additionally, when companies and FDA disagree on the designation of a combination product, the act allows sponsors to propose studies—nonclinical or clinical—to "establish the relevance, if any, of the chemical action in achieving the primary mode of action."

FDA is also required to collaborate with the sponsor on the design of such studies and attempt to reach agreement with the sponsor on the studies within 90 days.

Citizen Petition


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