REMS Barriers: US FDA Takes 'Foundational Step' To Improve Generic Access

Generic firms might be able to purchase branded drugs for bioequivalence studies from Europe under concepts that FDA is considering. Commissioner Gottlieb says FDA may allow generic firms to seek wavier of shared REMS to avoid protracted negotiations. 

US FDA Commissioner Scott Gottlieb is keeping a spotlight on the agency's efforts to curb brand company abuses of the Risk Evaluation and Mitigation Strategy (REMS) system that block generic entry.

In a Nov. 8 statement announcing FDA's release of a draft guidance for use of a single drug master file in a shared REMS submission, Gottlieb took the opportunity to emphasize that FDA is exploring new steps to reduce the likelihood that branded drug companies can use the existence of REMS to slow the entry of generic competition. Specifically, he said the agency is considering allowing generic drug applicants to request a waiver from the requirement that they use a shared REMS with the innovator company.

The draft guidance, "Use of A Drug Master File for Shared System REMS Submissions," recommends how applicants can submit collective sets of files to FDA that represent all participating firms.

"My hope is that the use of a standardized process for collecting information in the new REMS document template will help streamline the drafting and review of shared system REMS making it easier for companies to engage in a shared REMS," Gottlieb stated. "Today's action is a foundational step toward reforms we may implement in the near future."

"My message is this: end the shenanigans" – FDA Commissioner Gottlieb

The statement coincided with Gottlieb's appearance at a Federal Trade Commission workshop on competition in prescription drug markets, at which he reiterated his concern about branded companies who "game" the system by taking advantage of rules or exploiting loopholes to delay generic approval. He cited the branded companies use of REMS to prevent generic firms from acquiring doses of branded drugs to conduct bioequivalence studies as an example.

Gottlieb told the FTC workshop: "My message is this: end the shenanigans."

Bypassing Shared REMS

In his statement on REMS, Gottlieb noted that the agency will be providing information on how and when generic drug applicants can request a waiver from using a shared system REMS with the innovator company and the factors that FDA intends to consider.

The law currently requires branded and generic companies to reach agreement on the implementation of a single, shared REMS and any generic drug application referencing a branded drug with a REMS with elements to assure safe use (ETASU) must use a single, shared REMS with the innovator unless FDA waives the requirement.

Gottlieb said the agency knows that negotiations to reach agreement on shared system REMS can take extended periods of time and block the timely entry of a generic competitor.

"A waiver would free generic entrants from the requirement that they reach agreement with a branded firm for a shared system REMS," he stated. "This can obviate the ability of branded sponsors to use these negotiations as a way to slow generic entry."

Gottlieb has previously raised the possibility of allowing generics to develop their own REMS in testimony at Congressional hearings. (Also see "Brand Exclusivity 'Gaming' To Be Addressed At US FDA Meeting" - Pink Sheet, 25 May, 2017.)

Collaborating With Other Agencies

Gottlieb has made it a priority to foster more robust generic competition since taking the helm of the agency in May. He has repeatedly criticized the tactics brand companies have used to block generic entry, including their use of REMS to deny generic companies' access to purchase branded drugs for use in bioequivalence studies. The issue was discussed at a public meeting in July on ensuring the Hatch-Waxman Act continues to balance access and innovation. (Also see "FDA Exploring Whether Public Shaming Can Stop REMS Abuses" - Pink Sheet, 18 Jul, 2017.)

Gottlieb addressed the topic again when he spoke at the National Press Club in Washington, DC. Nov. 3. He noted that it takes between 2,000 and 5,000 doses of a branded drug to run a bioequivalence study comparing the generic drug to the branded drug and that many generic companies have told FDA they cannot get access to the drugs to do these studies to file their applications.

"Oftentimes we see branded companies selling drugs through a tight supply chain. They might sell through a single specialty pharmacy with tight control of who the drug can be sold to," Gottlieb said. "I believe they have rules in place that make it difficult for the pharmacy or the distributor or whoever's handling the drug to actually make the sale to a generic company, or a sale in bulk fashion to a generic company."

Gottlieb noted that brand activities do not always fall within the purview of FDA and that he is willing to think of ways to collaborate with other agencies to address this.

Allowing Purchase Of Branded Drugs In Europe

Gottlieb also noted that the agency has talked about potentially allowing generic companies to go to Europe to buy the branded drugs.

Asked what the Association for Accessible Medicines thinks about this idea, AAM President and CEO Chip Davis Jr. said the best option, and the one that AAM supports, is for Congress to pass legislation like the CREATES Act.

"Should that not happen, using non-US reference products as samples for bioequivalence testing might be an option, if FDA feels comfortable relying on such products as having been demonstrated to be the same as the reference product," Davis said. "Simply put, a large and diverse set of stakeholders have come to realize that the current gaming of the system needs to be rectified. As such, the FDA and the Administration should use whatever tools they have to their fullest extent."

The Creating and Restoring Equal Access to Equivalent Samples (CREATES) Act, S. 974, would allow generic sponsors to sue innovators if a generic firm has obtained a covered product authorization from FDA and the brand company fails to provide "sufficient quantities" of the REMS-covered product. A similar bill introduced in the House, the Fair Access for Safe and Timely (FAST) Generics Act, H.R. 2051, would prohibit innovators from restricting access to covered products to eligible product developers for the purpose of avoiding generic competition.