Anna Eshoo and Henry Waxman go head-to-head over drug regulation. Credit: S. J. FERRELL/CONGRESSIONAL QUARTERLY/NEWSCOM

Makers of biological drugs and their would-be generic competitors drew new battle lines on Capitol Hill last week, in a long-simmering debate over when and how generic versions of these large, complex drugs will enter the US market. Two California Democrats have introduced duelling bills in the House of Representatives; which one emerges as the winner — or what compromise is struck between the two — will indicate how much power and influence the industry lobby has.

In his proposed budget for 2010, President Barack Obama supports allowing the US Food and Drug Administration (FDA) to approve generic versions of biologicals, also known as biosimilars. As he seeks to cut soaring health costs, the high prices of biological drugs present an attractive target. Last year, the Congressional Budget Office estimated that a Senate bill creating a regulatory pathway for biosimilars would cut spending on prescription drugs in the United States by $25 billion between 2009 and 2018.

Other countries have set a precedent for such approval. The European Union opened up a regulatory pathway for biosimilars in 2005, and since then its European Medicines Agency has approved 13 such drugs. A number of the European guidelines have been adopted in Australia, and Japan this month issued its own guideline for the regulation of biosimilars.

In the United States, Anna Eshoo, the Democrat who represents California's biotech-heavy Silicon Valley in Congress, has introduced the Pathway for Biosimilars Act with leading co-sponsor Joe Barton (Republican, Texas). And on 11 March, Henry Waxman, the energy and commerce committee chairman from Los Angeles, introduced the Promoting Innovation and Access to Life-Saving Medicines Act, co-sponsored by Nathan Deal (Republican, Georgia) and others.

Both groups agree that a law allowing the FDA to approve biosimilars should preserve patient safety while opening up the market to healthy competition — all without squelching incentives to innovation. But they agree on almost nothing in the legislative details of how to achieve this. "The biotechnology industry has endorsed the Eshoo bill, and the generic industry has endorsed the Waxman bill. It doesn't get more extreme than that," says Mark Schoenebaum, a biotechnology analyst in New York for Deutsche Bank.

Source: M. Schoenebaum

The starkest difference between the two bills — and probably the point of most heated contention in the upcoming congressional debate — is the period of market exclusivity they grant. Under Waxman, an innovator company would be guaranteed at most six years of competition-free market access. Under Eshoo, it would receive at least 12 years, and up to 14.5 years. With annual sales of leading biologicals such as Amgen's Epogen — set to come off its patents in the United States beginning in 2012 (see table) — at more than $2.4 billion, the stakes in what number is finally settled on are huge.

Significantly, Waxman has given ground from earlier versions of his bill, which guaranteed innovators no period of market exclusivity. Eshoo's bill, by contrast, remains essentially the same as it was in the last Congress, when a bipartisan group of leading senators also endorsed a 12-year exclusivity period. This year other senators are also expected to introduce a bill that, like Waxman's, endorses a 6-year period.

The Eshoo bill also proceeds more cautiously on other key issues, such as whether a biosimilar is interchangeable with the innovator drug, which could allow pharmacists and health plans to switch patients without a doctor's go-ahead. Before the FDA could allow this for a given biosimilar, Eshoo's bill would require the FDA to issue a 'guidance' document — an often-lengthy and public process — establishing the scientific grounds for allowing the change. Waxman's bill has no such requirement.

"Cost saving is obviously a goal here," says Sandi Dennis, the deputy general counsel for health care at the US Biotechnology Industry Organization. "But you can't make decisions purely on cost savings without first assuring that the appropriate data are there for a new product to assure patients' safety. The science has to precede the economics."

Generics makers argue that such requirements are stalling tactics. "In these tough economic times, the Eshoo–Barton bill is a dead end for consumers," says Kathleen Jaeger, president and chief executive of the Generic Pharmaceutical Association in Arlington, Virginia. "It's just riddled with barriers. Consumers are not going to get timely access to affordable medicines."

Both bills give discretion to the FDA to work out approval requirements, such as whether clinical trials are needed to win access to the market. Brand-name makers argue that trials are crucial because biosimilars, unlike generic copies of small-molecule drugs, are not exact copies of innovator biologicals and could thus cause unexpected safety problems, such as immunological reactions. Generics makers retort that the FDA has sufficient scientific expertise to judge when trials are needed — and shouldn't be required to impose them.