It was only a matter of time before the issue of generic biologics arose for the biotech industry - a matter of time about as long as the patent life of a biologic.

It is unfortunate that the issue has arisen in the context of a dispute between two companies in the sector, Amgen Inc. and Transkaryotic Therapies Inc., rather than as part of a reasoned discussion of the scientific and regulatory issues involved in creating generic biologics. Nevertheless, now that the question is before the industry, it makes sense to take a look at the technological and regulatory issues before rushing to judgement about political and business strategies that could have long-term and unforeseen effects on the entire sector.

Lawyers and lobbyists representing some of America's most successful biotech and pharmaceutical companies last week debated the merits and implications of AMGN's proposals to persuade Congress to modify the Waxman-Hatch Amendments (see Amgen Presses Ahead, A5). Waxman-Hatch made today's generic drug industry possible by allowing generic manufacturers to engage in R&D using others' patented drugs without fear of litigation, and to gain marketing approval on the basis of bioequivalence rather than full-blown clinical trials.

AMGN (Thousand Oaks, Calif.) wants to prevent TKTX (Cambridge, Mass.) from using Waxman-Hatch to shield GA-EPO, a rival version of AMGN's Epogen erythropoietin (EPO) from patent infringement litigation during the clinical development period (see BioCentury, Sept. 21).

While third parties do not want to become entangled in the dog fight, the dispute turns up the temperature on a simmering issue: generic and second-generation biologics. Patent terms on several important biotech products such as tPA and some of the interleukins will expire around the turn of the century and some companies are already positioning themselves to produce bioequivalent products. At the same time, companies like TKTX are developing products that they claim represent a second generation that could have superior efficacy and/or safety.

Barriers to biologic generics

The argument over biologic generics hinges on several interrelated issues, including the complexity of proteins, the fact that the actual makeup of a protein will vary depending on how it is manufactured, and other residues of the manufacturing process, all of which may affect side effects and efficacy.