FDA's decision not to release follow-on biologics documents in the near future suggests proponents of such products may turn their focus to Congress or the courts in an effort to establish a clear regulatory framework.

During a Food & Drug Law Institute teleconference Oct. 3, FDA Deputy Commissioner for Medical & Scientific Affairs Scott Gottlieb said he is "not sure" FDA is "going to have much more to say on" follow-on biologics "in the near future in terms of actual paper or policies that we announce."

A number of questions - scientific, legal and regulatory - need to be addressed before the agency will be prepared to issue further guidance on follow-on biologics, Gottlieb said.

"The science will continue to be developed, and we'll continue to work through some of the policy questions, some of the legal questions and regulatory questions that exist around exactly what the authority is there and what the appropriate framework and policy environment is to enable that," he said.

The agency's decision to back off earlier promises to release a historical paper and guidance documents could create more pressure on Congress to set forth a clear statutory pathway, even if the legislators have not been eager to move on the issue.

Five days before Gottlieb's remarks, Rep. Henry Waxman (D-Calif.) predicted Congress would be unlikely to act in the near future on generic biologics because of the politically divisive atmosphere on Capitol Hill.

"I have to say that I can't be optimistic" that generic biologics legislation will be passed "with the way Congress has been operating in the last five to 10 years," Waxman said at the Sixth Annual Generic Drugs Summit in Washington, D.C. Sept. 29. Such legislation would need bipartisan support and "we see almost no bipartisanship, almost none at all," he added.

Concerns over drug safety also may have factored into Congress' decision to put follow-on biologics on the backburner (¹ Also see "Generic Biologics Legislation Unlikely, But Issue Not Going Away" - Pink Sheet, 16 May, 2005., p. 4).

On the legal front, brand and generic firms are monitoring a lawsuit that seeks a judicial declaration that Section 505(b)(2) can be used as an approval pathway for follow-on biologics regulated under the FD&C Act.

Sandoz' lawsuit seeks FDA approval for its human growth hormone Omnitrope through the 505(b)(2) route (² Also see "Omnitrope Lawsuit Could Further Delay FDA “Follow-On” Biologics Guidance" - Pink Sheet, 19 September, 2005., p. 21).

FDA has been working on documents concerning follow-on biologics for years (³ Also see "FDA Generic Biologics Short-Term Plan Includes Immunogenicity Document" - Pink Sheet, 7 March, 2005., p. 35). As recently as August, the agency announced intentions to release a historical "white paper" by "late summer to fall."

While scientific tools necessary to characterize relatively simple biologics currently exist, tools to characterize more complex biologics - such as monoclonal antibodies - are not currently available, Gottlieb said during the FDLI call.

"For very simple biologics, very short-chain peptides or very short-chain proteins...a method to demonstrate either similarity for some of the proteins or even sameness" exists using available tools, he said.

However, "when you move up the continuum of complexity of biologics, your ability to demonstrate different levels of similarity starts to fall off quite significantly. When you get to something as complex as a monoclonal antibody, your ability to demonstrate any similarity without clinical data really doesn't exist in any significant fashion," he added.

Gottlieb said that FDA does not believe it "has the legal authority to approve follow-on versions of existing biologics under the Public Health Service Act."

While he acknowledged that FDA has said 505(b)(2) may be a viable pathway for follow-on biologics regulated under the FD&C Act, the deputy commissioner emphasized that a number of hurdles remain. "I think it is a question that remains very much open both from a legal and regulatory standpoint, from a policy standpoint," he said.

Questions exist about the "scope" of FDA's legal authority to approve products under 505(b)(2), Gottlieb said. "I don't think the agency is in a position to have anything to say on that in the near future," he added.

Follow-Ons Off? FDA Shelves Near-Term Plans For Biologics Documents

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