Waxman is also skeptical that the Republican-controlled Congress would do anything to displease the brand-name drug industry, a major financial supporter of the GOP. "I think it would be fair to say the big drug companies don't want competition and will do whatever they can to stop it," he said. But others, including Sen. Charles E. Schumer (D-N.Y.), are seeking action this year.
The European Union is already moving forward with a regulatory process that would allow the simplest biologics to be copied. Regulators there are not reviewing applications yet, but their planning is conceded to be several years ahead of the United States'.
The crux of the argument centers on how biologics and traditional drugs are made. Most drugs invented before the last decade of the 20th century were discovered through chemistry and are made of small molecules that interact with living cells. The advent of biotechnology and the explosion of knowledge about genetics and the life sciences have begun to produce very different products -- large-molecule proteins and peptides that change the workings of a patient's body in complex and often variable ways.
Since passage of the Hatch-Waxman Act, generic-drug companies have analyzed thousands of small-molecule drugs that no longer have patent protection and have learned to manufacture them safely and cheaply. But making a large-molecule biologic is, by all accounts, more complicated, especially because many of the technologies involved are trade secrets. What's more, protein-based drugs can cause immune reactions that are more serious and long-lasting than the allergic reactions that chemistry-based drugs sometimes cause.
To create a pure and dependable drug, Centocor runs its biologics through nine major stages of processing. The healing proteins are first grown in sealed "bioreactors" of live cells and then spun out of the growth medium that sustains the cells exactly when ready about 60 days later, and refined several times over.
"We're using a unique line of living cells to make our product," said John Dingerdissen, who runs global biologics manufacturing for Centocor. "You make the slightest change with them or with our process, and you can end up with a very different result."
Johnson & Johnson decided to publicly discuss its own disturbing experience as a contribution to the debate: In 1998, the company changed a stabilizing chemical in Eprex, a protein drug that was marketed only outside the United States. The change was made to remove any cow-based material.
Within a year, reports began to trickle in of a small but significant number of patients who were not getting better with the drug but were developing a severe and rare form of anemia called pure red cell aplasia. It took almost four years, a team of about 100 researchers and many millions of dollars to figure out what had happened. It turned out that the new stabilizer was interacting with some rubber stoppers used in the syringes to inject the drug, creating a compound that stimulated the body to produce antibodies to Eprex.
"Only an innovator company has a deep enough knowledge of its product to know where to look effectively when there's a problem like this," said Audrey Phillips, a biopharmaceutical executive with Johnson & Johnson.
Gordon Johnston, GPhA vice president for regulatory affairs, acknowledged the Eprex lesson but said "it's never a good idea to set policy based on one problem or one success."
Some biotech companies are also skeptical that generic biologics would save consumers much money. That is because -- unlike chemistry-based drugs -- biologics require costly testing on a continuing basis. Generic-drug makers agree but say they can still reduce prices by 20 to 30 percent, said the GPhA's Jaeger, unless Congress and the FDA require too much testing.
But Johnson & Johnson's Phillips says that testing has to be extensive to make sure any follow-on product is safe and effective. "Given what we've experienced, we believe that standard has to be very high," she said.
