EpiPen Generics: Woodcock Explains Injector Studies

In response to Congressional questions about whether FDA is a barrier to competition for the epinephrine product, CDER Director lays out what could be required to prove an injector device problem is fixed.

For potential EpiPen competitors, it appears FDA's requirements to fix problems with the device may not be extensive.

Center for Drug Evaluation and Research Director Janet Woodcock outlined to Senators Sept. 21 the potential steps that could be involved to ensure injector issues, such as ensuring it delivers the proper dose, were resolved.

While she did not mention any potential sponsors that may be affected, Woodcock described what could be the process that Teva Pharmaceutical Industries Ltd., as well as Sanofi, might be able use to help their potential alternatives to Mylan NV's EpiPen (epinephrine) reach the market and hopefully force price competition.

EpiPen's heavily criticized price increases also was the subject of a House Oversight and Government Reform Committee hearing the same day (Also see "Scrutiny Of EpiPen Pricing Invited By Mylan Lobbying, Congressman Says" - Pink Sheet, 21 Sep, 2016.)

Along with the public shaming of Mylan, members of Congress have written the company asking for justification of the price increase.

Legislators have also asked FDA for an explanation of why generic competition has not entered the market. (Also see "Mylan's EpiPen Nightmare Not Over Yet, But Will Congress Just Write?" - Pink Sheet, 30 Aug, 2016.)

During Woodcock's appearance at the Senate Appropriations Agriculture, Rural Development, FDA and Related Agencies Subcommittee hearing on FDA's role in the generic market, Ranking Member Sen. Jeff Merkley, D-Ore., pushed the line of questioning, asking about FDA's requirements for a generic EpiPen. He wanted to know whether FDA was a barrier to generic competition in the space.

Merkley also asked what would be required for a company to resubmit an application after the product was pulled from the market because of a manufacturing problem with its injector device, an apparent reference to Sanofi's Auvi-Q epinephrine product.

Woodcock emphasized that she was answering in theoretical terms, and said the company would have to prove to FDA that the injector device works as intended, but likely would not have to conduct clinical trials that would take years.

"Depending how they change their auto-injector, they might have to do a human factor study again to make sure people can use it properly," Woodcock told the subcommittee. "Or they might not, depending on if the change was just inside, they might not have to do that. But if the change was how you went about injecting yourself, they might have to test that again on people to make sure that it would work for them."

Auvi-Q has been approved, but it was voluntarily recalled after potential problems with the device delivering the proper dose. (Also see "Mylan’s EpiPen Exclusivity Saved Again As Teva Reports CRL" - Pink Sheet, 1 Mar, 2016.)

Device Patents The Issue, Woodcock Says

Indeed, it is the injector device that seems to present the biggest problem for a generic EpiPen.

Woodcock said the agency has approved four auto-injectors, but an EpiPen ANDA must include a similar device while not violating its patents.

"It's not easy to make a generic that doesn't infringe upon those patents and still works," she said.

The device has four patents listed in the Orange Book, which do not expire until 2025.

Teva submitted an ANDA for an EpiPen generic and had a device prepared that was similar but not identical to EpiPen.

Mylan filed a citizen petition as part of a fight to keep it off the market, arguing that a generic should not be approved unless comparative performance tests show that patients can operate the Teva device with EpiPen instructions. (Also see "Mylan’s EpiPen Defense Against Generics Focuses On Device Design" - Pink Sheet, 22 Jan, 2015.)

Mylan's petition also included a study conducted by a third party comparing a prototype Teva injector device to EpiPen that concluded patients could not use it like an EpiPen.

Teva later said its ANDA received a complete response letter with major deficiencies (Also see "EpiPen Familiarity May Prove Tough Hurdle For Generics" - Pink Sheet, 12 Sep, 2016.)

Auvi-Q Would Not Need Prioritization

Merkley also asked whether an EpiPen generic application could be prioritized under FDA rules, given the volume of pending generic applications on its books.

Woodcock said that should the Auvi-Q application be resubmitted, it would be an NDA and therefore be subject to prescription drug user fee review goals, which already are speedy.

FDA also has the ability to expedite an ANDA for EpiPen using its policies to push first-generics and competitors for sole-source drugs to the market as quickly as possible. (Also see "Drug Pricing Panacea Or Just PR Victory? Expedited ANDAs May Have Limited Impact" - Pink Sheet, 21 Mar, 2016.)