Regulators struggle with generic biodrugs
The first generic version of a biotechnology drug may still be years away for American patients, but new developments in Washington could help break the logjam on the contentious issue.
A federal judge in the District of Columbia this month ordered US drug regulators to act on a long-delayed approval application for Omnitrope, a generic version of a human growth hormone. The drug's maker, Sandoz Inc., had sued the Food and Drug Administration for letting the application languish for more than two years without deciding whether to approve it.
In a strongly worded opinion, US District Judge Ricardo Urbina called the delay egregious and ordered the FDA to give the company some kind of response.
Though his opinion can be appealed, it marked a rare decisive moment in a long, closely watched debate that pits the biotechnology companies that develop new drugs against generic drug makers and insurance payers, who would like to see cheaper versions reach the market.
The debate is fueled by a curious fact: Although low-priced generic versions of traditional pills have been available for years, no such option exists for drugs produced using recombinant genetics and other sophisticated biotechnology techniques.
As so-called ''biotech drugs" become an increasingly large part of the nation's healthcare budget, costing billions of dollars a year, drug companies and lawmakers are trying to solve the question of how to develop and test generic versions.
''With the rapid spread of biologics and the meteoric rise in the price of these products, I believe that it is simply no longer possible for Congress to stand by and do nothing," Representative Henry Waxman, Democrat of California, said to a gathering of generic drug manufacturers in a speech last month.
Waxman, who cowrote the 1984 law that created an approval pathway for generic versions of traditional drugs, said he is looking into writing a new law that would do the same for biologicals.
In doing so, he and his supporters will encounter some serious scientific obstacles.
Generic versions of traditional ''small molecule" drugs -- the kind that come in a pill -- are cheaper partly because generics manufacturers are allowed to skip much of the human-safety research that name-brand drug makers must conduct. A company seeking to make a generic version of a pill such as Viagra or Lipitor must simply show that the chemical substance of the copy is identical to the original pill. Because they are spared the expense of conducting detailed human tests, the generic makers can introduce them at much lower prices after the patent on the original drug expires.
By contrast, biotech drugs such as hormones, enzymes, and antibodies are more scientifically complicated, and often made in bioreactors with living cell cultures. It is much harder to prove that a copy is identical to the original, and opponents contend it would be unsafe to push a complex human protein through the same simplified approval process that makes generic drugs inexpensive.
''You're very likely to not be able to replicate the drug exactly, and the question is, how close do the regulators want it to be?" said Michael Peskoe, a former FDA official who is now a lawyer with Edwards Angell Palmer & Dodge in Boston.
Peskoe, who worked with the drug company Wyeth when it fended off generic challenges to its Premarin hormone in 1997, said scientific techniques cannot yet show that two similar-looking biotech molecules don't have subtle but possibly dangerous differences.
''Are we going to have similar efficacy and safety? These are big question marks," he said.
On one issue, all sides seem to be reaching agreement: Some biotech molecules are more difficult to copy than others. Insulin and human growth hormone are two examples of relatively simple biotech molecules. European regulators have issued guidelines for drug makers looking for approval of both insulin and growth hormone, and last week Europe approved Sandoz's request to sell Omnitrope, which is a generic version of a hormone called Genotropin, made by Pfizer.
US regulators, however, appear not to have moved closer to issuing such guidelines. Although the FDA started work on guidelines for insulin and growth hormones in 2002, the agency wrote a letter to Waxman and Senator Orrin Hatch, Republican of Utah, last month saying the plan is off the table, and that the agency is instead working on guidelines that are ''more broadly applicable" to all types of biotech drugs.
Where that leaves the generic manufacturers is not yet clear. Many believe that they will be stymied until the FDA produces specific guidelines for each family of biotech drug.
For the biotechnology companies producing the original name-brand protein drugs, Peskoe said, a law would carry real risks. Many are relatively young companies whose profits depend on just one or two high-value molecules.
''With a generic in the market, it just turns off the [revenue] spigot," he said.
Stephen Heuser can be reached at sheuser@globe.com. 
