A federal judge has ordered the U.S. Food and Drug Administration to decide after a long delay whether Novartis AG can market a version of human growth hormone as a bioequivalent to the one already sold by Pfizer Inc.

The order by Judge Ricardo Urbina of the U.S. District Court for the District of Columbia could put pressure on the FDA to come up with guidelines for approving generic copies of biotechnology drugs. The agency has said it was close to issuing such guidelines for years now. In January 2006, the European Medicines Agency (EMEA) announced draft guidelines for the first four biogeneric products – recombinant human insulin, somatropin, erythropoietin (EPO), and recombinant granulocyte colony-stimulating factor (rG-CSF). In December 2005, the EMEA reported that it had provided scientific advice to companies on the development of 15 other biosimilars. In contrast, the FDA has over the past year done almost nothing to move toward clearer biogeneric regulations.

Sandoz, the generics arm of Novartis, sued the FDA last September for leaving its copycat product in limbo, a move designed to break a logjam over so-called biogenerics. The FDA in November sought a dismissal of the suit, saying the charges were unfounded since its experts had not finished their review of the drug, Omnitrope.

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.

Sandoz filed its application for Omnitrope in July 2003. On Sept 2 2004, Sandoz announced that FDA had notified the company that the agency was unable to reach a decision on whether to approve the company’s application for Omnitrope. According to the FDA letter issued to Sandoz, the agency has completed its review of Omnitrope and did not identify any deficiencies in the application. However, the agency stated it had been unable to reach a final decision on the application due to uncertainty regarding scientific and legal issues. No action on the application has been taken since then.

No biogenerics (or follow-on proteins) have yet been approved in the US pharmaceutical market. 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 biological products. Biologics are large, complex, heterogeneous molecules, for which the manufacturing process can be a determinant of the end product. Demonstrating that its product was as safe and effective as the originator’s would be a difficult task, since 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 clinical trials.

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.

But, even if biogenerics are approved, don’t go spending all your projected savings just yet. The high barriers to market entry will necessitate a smaller price differential between brand and generic products than that seen in regular generics, and initial physician and patient reluctance to take up biogenerics may limit the impact of competition on originator companies.

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