As the US Congress debates a re-authorization of key US Food and Drug Administration (FDA; Rockville, MD) regulations, the biotechnology industry is preparing to fight an effort to permit the FDA to more readily approve knock-off versions of recombinant products.

Although the FDA can approve generic small-molecule drugs on the basis of bioequivalence data only, generic biologics are required to go through the expensive and painstaking clinical trial process. The generic drug industry, led by Barr Laboratories (Pomona, NY), is lobbying lawmakers to consider changes in the FDA's rules to bring the approval of generic biologics into line with that of small molecules.

At stake are billions: analyst Timothy Coan of ABN AMRO (New York) estimates recombinant products worth more than $10 billion in annual sales will lose patent protection by 2006, including blockbusters such as Amgen's anemia treatment Epogen and Biogen's multiple sclerosis drug Avonex. Without changes in the way the FDA operates, those billions will be safe from the quickly growing generic drug industry, which says the regulatory hurdles give biotech companies an unfair monopoly on their drugs, even after the patents expire. “It seems to me that any situation where there is a de facto monopoly set up, it has to be challenged,” says Wayne Mulcahy, the senior director of scientific and professional affairs at Teva North America (North Wales, PA), a maker of generic drugs.

The biotechnology industry, however, is working to keep that effort from getting off the ground. The Biotechnology Industry Organization (BIO; Washington, DC) successfully fought attempts to add similar provisions to FDA-related bills last year by writing to influential members of Congress. This year, BIO expects to resume the fight, says Steve Lawton, the group's chief lobbyist on the issue.

For BIO, it is a matter of safety, says Lawton. Unlike traditional drugs, biologics are more than just pure chemical preparations: small changes to the manufacturing process can lead to clinical differences in the way products work. That makes it impossible to tell whether the same protein made by two different manufacturers will work in the same way, says Lawton. “As of now, the manufacturing is just too complex to support generic biologics,” he says, echoing the group's pitch to lawmakers. Lawton cites the example of Johnson & Johnson's (New Brunswick, NJ) problems with Eprex, the version of erythropoietin the company sells in Europe. That drug has been linked to a rare cause of anemia known as pure red-cell aplasia in 40 patients, but Amgen (Thousand Oaks, CA) has seen a similar problem with its version Epogen only once. That suggests, says Lawton, that the two molecules made by two different companies, although same in name, do not have identical effects on the body.

Nevertheless, the FDA has already drafted a possible pathway for a few older recombinant products (such as recombinant insulin and human growth hormone) to win approval without a full complement of clinical testing. Although the generic drug industry says the scientific challenges in creating copies of more complex recombinant drugs can be overcome, the FDA proposal raised the hackles of industry and drew a sharp rebuke from Amgen, which wrote to the agency in December calling the effort "a direct threat to patient health and safety."

However, further regulatory changes concerning more complex generic biologics are inevitable, says Coan. Because biotechnology products are generally more expensive than drugs (with a year's supply of Avonex or of Immunex's rheumatoid arthritis treatment Enbrel, for example, each running more than $10,000), US legislators seeking to bring down health care spending may look to generic biologics. He says that although the FDA itself does not focus on drug pricing, legislators aware of the strain of rising medical spending on the government's insurance program are likely to push for the changes.