As patents protecting first-generation biologic innovations begin to expire, the creation of generic versions of biologic medicines -- or at least very similar versions -- seems technically possible.

The nature of biologics virtually rules out exact generic copies, but biotech companies seem both eager and capable of creating their own versions of off-patent biologic drugs, which increasingly are known as biosimilars.

The high cost of most biologics makes them a prime target for lower-priced biosimilars.

But larger biologics tend to be produced as diverse mixtures of molecules that differ very slightly from one another. Biologics also tend to have unique structural organization patterns that affect the way they work.

Arguments between the branded and generic industries have centered around the issue: If a biologic is a complex mixture that cannot be easily identified or characterized, can it be approved as equivalent to the originator's product without lengthy new clinical trials?

That question, among others, has kept biosimilars largely stalled in the United States, where the FDA has chosen to wait for guidance from Congress, which thus far has not been forthcoming.

A bill introduced in late 2006 by Rep. Henry Waxman, Sen. Hillary Clinton and others that would provide a pathway for FDA review and approval of generic biologic drugs went nowhere. It was reintroduced in the new Congress on Feb. 14, 2007.

The FDA in 2006 did approve Omnitrope, a "generic” recombinant human growth hormone produced by Sandoz. But the FDA took the position that Omnitrope is a "follow-on" product -- a product comparable to a previously approved biologic -- but not a bioequivalent generic substitute for the original biologic.

In Europe, where the European Commission created a legal framework for "similar biological medicinal products" or biosimilars in 2003, the EMEA in mid-2006 gave regulatory approval to Omnitrope and also BioPartners’ Valtropin as Europe's first two biosimilars.

Both drugs are based on Somatropin, a recombinant DNA growth hormone. They will compete on the market with products sold by Novo Nordisk, Eli Lilly, Genentech and Serono.

But the United States is clearly well behind the European Union in addressing the issue of biogenerics or biosimilars, and many believe it probably will be at least several more years before many biosimilars make it to the market.