FDA: Many barriers remain on generic biologics

Gottlieb told a roomful of generic industry heavyweights, including GPhA president and CEO Kathleen Jaeger and the high-profile Barr Pharmaceuticals president and CEO Bruce Downey, that among other goals, the FDA is trying to find ways to make the process of developing generics more predictable and more transparent for generic drug developers. "We know that generic drug manufacturers face the same challenges as any other developer, and they want a predictable and transparent process," said Gottlieb.

Another fundamental goal of the FDA, Gottlieb told the audience, is to develop better science around newer areas of generic drug development. The agency wants to do more to encapsulate advances in scientific thinking pertaining to demonstrating bioequivalence for the approval of generic drugs in guidance documents. Gottlieb rejected criticism with respect to the FDA's budget. "I don't know that improving the generic drug process at FDA is just about more money. It's also about process improvements that we can make at the agency." Gottlieb went on to note that the agency is working more collaboratively with the industry and that more applications have been approved on the first cycle than in the past, as a result of increases in staffing and more resources. On June 20 the Senate Agricultural Appropriations Subcommittee proposed an additional $10 million in funding for the Office of Generic Drugs (OGD).

On the issue of timely approvals, Gottlieb said, it's a question of science. There are places in the drug approval process where the science isn't very well developed for demonstrating therapeutic equivalence. For example, with metered dose inhalers, there is only one generic albuterol because of the difficulties of demonstrating bioequivalence with the current clinical trials in in vitro methodology. Also, the industry still needs methods for evaluating bioequivalence for nasal sprays. "We've made some progress and are working toward a guidance that generalizes the agency's scientific progress. We need additional work in that area." The third type of generic product that poses a special challenge, Gottlieb pointed out, are topical dermatologics that are applied directly to the skin and not substantially absorbed into the body.

In the area of follow-on protein products, Gottlieb said that the recent approval of Omnitrope (somatropin, Sandoz) doesn't qualify it as a generic biologic. He said that a product like Omnitrope is a follow-on version of existing protein products that have been approved through an agreement and pathway that relies on the prior finding of safety and effectiveness.

In a legal context, for the protein products that are regulated under the Food, Drug & Cosmetics Act, Gottlieb said there is authority under a section of that law that allows the FDA to approve follow-on protein products and an abbreviated process that relies on the earlier approval of the innovator product.

In contrast, Gottlieb said that the FDA does not believe such authority exists for follow-on biologics approved under section 351 of the Public Health Service Act, which includes the vast majority of protein products.

The approval of follow-on protein products under the Public Health Service Act, said Gottlieb, would require legislation. "These questions are quite apart from the scientific questions. Even our most recent approval of a follow-on protein product did not allow for that product to be rated as therapeutically equivalent to and therefore substitutable for an already approved similar product."

Gottlieb indicated that there remain substantial scientific obstacles to more widespread development of follow-on versions of existing proteins-"certainly for many of the more complex ones."