Patent Baristas

Legislators are stepping up the pressure in the long running saga of getting generic versions of biotech drugs to market. The FDA approves generic versions of pharmaceutical (small molecule) drugs once the patents for brand-name products expire. But complex biotech drugs do not have such an approval process.

Representative Henry Waxman and Senator Orrin Hatch gave a talk to the Generic Pharmaceutical Association on the need for legislation that would balance the interests of generic drug makers and brand-name manufacturers who shoulder staggering drug development costs.

Waxman said he plans to introduce a bill to spur the U.S. Food and Drug Administration into action on the long-overdue FDA guidelines for manufacturers to follow to produce generic versions of biotechnology drugs. Hatch, on the other hand, said that the issue is too important to try to pass before the Senate recess, expected at the end of next week. Also see the letter that Hatch and Waxman sent to the FDA earlier this year.

While the FDA has approved Novartis AG’s Omnitrope hormone, there has not been a change in the stance taken by the FDA on generic biotechnology drugs. Omnitrope was approved only after a federal judge ordered the FDA to decide after a long delay. Also, Omnitrope is considered less complicated than most other biologics.

Under both the Federal Food Drug and Cosmetic Act and the Food Prescription Drug User Fee Act, the FDA is required to either approve or reject new drug applications. However, no biogenerics (or follow-on proteins) have yet been approved in the US pharmaceutical market beyond Omnitrope. It is argued that the 505(b)(2) provision of the Hatch-Waxman Act (the Hatch-Waxman amendments of the Federal Food, Drug and Cosmetic Act) lays out an abbreviated approval pathway (ANDA) for generic versions of small molecule drugs) provides a route for the FDA to approve a biological therapy that is different from the originator product, yet relies on data filed by the innovator as part of the original NDA.

The reason for the lack of a regulatory pathway for approval of biogenerics lies in the complexity of the biological products themselves. Biologics are large, complex, heterogeneous molecules for which the manufacturing process can be a determinant of the end product. Demonstrating that a generic version of the product is as safe and effective as the brand name product would be a difficult at best since, for example, establishing that immunogenicity had not been altered and that any undetected differences in the product would not impact safety and efficacy would be problematic without conducting extensive clinical trials.

But the stakes are high, given biotech drug sales are expected to top $60 billion by 2010. Biogeneric companies need an abbreviated approval pathway to avoid undertaking the same large scale clinical development process as the originator companies, and thus allow them to market their product at a discount to the brand while maintaining a healthy profit margin.

With Omnitrope, the FDA, however, went out of its way to say that Omnitrope is not a generic biologic stating that “Omnitrope is not rated as therapeutically equivalent to (and therefore substitutable for) any of the other approved human growth hormone products. Omnitrope is more appropriately characterized as a “follow-on protein product.”

The FDA indicated that the approval of Omnitrope in a 505(b)(2) application does not establish a pathway for approval of follow-on products for biological products licensed under section 351 of the Public Heath Service Act, nor does it mean that more complex and/or less well understood proteins approved as drugs under the Food, Drug, and Cosmetic Act could be approved as follow-on products.

Just the same, brand name biotech companies may want to get a hold of a copy of Cutting Edge Information’s report “Combating Generics: Pharmaceutical Brand Defense for 2007,” which includes strategies to retain market share and defend patents including, among others, patent litigation and authorized generics and corporate generics subsidiaries. (More at Philip Brooks’ Patent Infringement Updates)