Although there are active patents on the insulin analogs—lispro (Humalog), aspart (NovoLog), and glargine (Lantus)—the patents have already run out on recombinant human insulins. So, with billions of dollars at stake, why haven’t generic manufacturers rushed to make generic versions of recombinant human insulin? And why are only two U.S.-based manufacturers (Eli Lilly and Company and, more recently, Sanofi-Aventis) manufacturing insulin?

So far, in this country, there are no generic versions of biologic drugs (genetically engineered versions of naturally made substances such as hormones and antibodies). Probably the most compelling reason is that biologics and their manufacturing processes are too complex for most generic manufacturers to readily replicate. Further, the approval of generic versions of biologic drugs is in a sort of regulatory “gray zone.” Because the manufacturing of a biologic drug often depends on living organisms (such as bacteria and yeast) and complex procedures, it is much more difficult to determine how comparable the generic biologic or its manufacturing methods are to the original. Biologics are so different from other drugs (most of the drugs you know are simple molecules produced through chemical interactions) that it raises the question of whether the Hatch–Waxman Act, with its simplified approval process for generics, should apply to them.

However, as more and more patents on biologics expire, generic manufacturers are increasing pressure on government regulatory agencies. In mid-2003, the European Union passed legislation allowing companies to apply for permission to sell generic versions of genetically engineered drugs. Meanwhile, in the United States, generic drug companies have been pushing to have generic versions of biologics approved through the Hatch–Waxman Act. The Biotechnology Industry Organization has fought back by petitioning the U.S. Food and Drug Administration (FDA) to make approval of generic biologics more difficult, citing safety and legal issues.

To add another wrinkle to an already complicated business, there is a little-known regulatory loophole that may help speed generic versions of biologics through the approval process. Under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, a generic drug doesn’t have to be an exact duplicate of the brand-name original to be approved, which allows the FDA some flexibility. Under this rule, the manufacturer doesn’t have to conduct its own studies of safety and effectiveness (relying instead on previously published studies or the original drug’s studies), nor does it have to provide some of the data required for the approval of traditional generics. According to some sources, the FDA will probably consider using this regulation to approve generic biologics on a case-by-case basis.