Follow-On Biologics Pathway Unlikely Without Confirmed FDA Commissioner

FDA is unlikely to proceed with developing a follow-on biologics pathway until a permanent commissioner is confirmed, a Senate Health Committee staffer said at a Food & Drug Law Institute conference in Washington, D.C., Nov. 16.

Several major policy initiatives are on hold at the agency until a permanent replacement can be found for Acting Commissioner Andrew von Eschenbach, the Hill staffer suggested.

"Right now, there's a mandate that comes from Senate confirmation," the aide said. "No matter how good an acting director is-and we think Dr. von Eschenbach is very good-he's not" a confirmed commissioner. "It changes the way things" are handled.

The sudden departure of former Commissioner Lester Crawford in September is thought to have further stymied progress on the agency's plans to issue a historical "white paper" on biologic regulation and guidance documents on follow-on biologics (¹ , p. 3).

While von Eschenbach has continued to serve as director of the National Cancer Institute, he ceded day-to-day management of the NIH division to John Niederhuber (² , p. 7).

In October, FDA Deputy Commissioner for Medical & Scientific Affairs Scott Gottlieb suggested it was unlikely FDA would issue policy documents on follow-on biologics in the near future (³ (Also see "Follow-Ons Off? FDA Shelves Near-Term Plans For Biologics Documents" - Pink Sheet, 10 Oct, 2005.), p. 14).

As recently as August, the agency said it expected to release its historical white paper by fall, at the latest.

Interest in delineating a generic biologics approval pathway may prompt Congress to move before the agency initiates action on its own.

"We are in no way, shape or form obligated to wait on the agency," the Senate Health Committee staffer said.

"We've heard from other stakeholders. I think it's reasonable that we'd want to hear from FDA," given the agency's level of familiarity with the subject, the staffer said. However, "we can't wait forever."

Pfizer Senior Corporate Counsel Jeffrey Chasnow cautioned against Congress proceeding on a legislative route without FDA input.

He pointed to FDA's key role in the development of Waxman/Hatch.

"The bioequivalence principles that were adopted into Hatch/Waxman were incorporated from principles FDA then articulated itself," Chasnow said. "If Congress were to come out with its own principles first and FDA had not been involved in that," administration of that aspect of the statute could have been problematic, he said.

One possible solution could be to import part of the framework for follow-on biologics that is being developed in Europe. The European Medicines Agency is ahead of its U.S. counterpart in drafting guidelines for follow-on biologic products (⁴ , p. 30).

However, Covington & Burling partner Richard Kingham cautioned that there may be little to glean from EMEA's guidelines.

"While there may be interesting things to look at in the guidance that's under development in Europe, in terms of the legislative paradigm - the language that's needed to establish an overarching system with which FDA would work - we still need to do that from a fresh" perspective, Kingham said. "There's very little" in the EU guidelines that is "worth importing into our regulatory system."

Carole Ben-Maimon, president of Barr's Duramed Research subsidiary, suggested the current generic drug approval process, including the Waxman/Hatch patent challenge mechanism, could be modified for biologics.

"This is not about drugs versus biologics. This is about simple versus complex," she said.

"Not all generics are identical, but they perform the same. What we're really being charged with is demonstrating that the product that comes to the market will have the same effect and have a similar safety profile as the brand product," the Barr exec said. "If it achieves that, it doesn't really matter how you got there."