Washington Editor

WASHINGTON - Drug companies that have fought against easy approvals for follow-on protein products aren't letting up these days, but their generic counterparts may be gaining some footholds as they clearly have their sights set on the lucrative and growing biopharmaceutical market.

Known under a litany of labels - biogenerics, follow-ons, generic biologicals - they "represent an extraordinary opportunity" for generic companies, said Kathleen Jaeger, the president and CEO of the Generic Pharmaceutical Association (GPhA). Eyed as "the future" by Bernard Hampl, the president and CEO of Sandoz U.S. Inc., biogenerics were a primary topic at the GPhA's first policy conference held here last week.

And it's easy to see why: Analysts estimate that $18 billion worth of the drugs will come off patent by 2010, by which point more than $60 billion in total sales are forecast for such products, but it's a market that innovators aren't readily ceding.

Still, in anticipation of that horizon, many generic and pioneer drug companies are awaiting much-anticipated guidance from the FDA and its accompanying white paper to provide a clearer view of biogeneric regulatory pathways. At this point, the agency's issuances are many months overdue, and it is catching flak for its delays.

Sen. Orrin Hatch (R-Utah), a longtime ally to the generic industry, is pressing the FDA on the matter. While he told conference attendees that biogenerics "are not front-burner issues" right now in Congress, he has inserted language into the FDA funding bill, which remains under committee consideration, to require the agency to report on its efforts to develop a biogeneric policy. Hatch added that FDA Commissioner Lester Crawford recently assured him that the agency would issue guidance "hopefully by the end of this year."

But Hatch cautioned that opposing language attached to the same appropriations bill could preclude the FDA from exploring whether an existing approval mechanism, Section 505 (b)(2) of the Food, Drug and Cosmetic Act, can be applied to biogenerics. He also acknowledged that many, if not all, biogenerics "will require at least some form of truncated human clinical testing."

That concession mirrored comments from the FDA's Steven Kozlowski, its acting director of the Office of Biotechnology Products. "There may be certain circumstances where [clinical trials] can't be replaced," he said.

Issues of safety at the risk-averse agency are a clear factor in establishing a biogeneric approval policy.

"I think the consideration of each product and product class, based on risk profile and other things, is going to determine the best steps to take," Kozlowski told BioWorld Today, adding that a "broad distinction" between different types of products could lead to a case-by-case system of evaluating biogenerics. He declined, though, to put a timeline on guidance documents from the FDA.

Hatch said that in the end, a biogeneric approval pathway might require legislation along the lines of that which passed more than 20 years ago, the generic drug industry-enabling Hatch-Waxman Act. Rep. Henry Waxman (D-Calif.) also spoke at the conference and told attendees that "the uniqueness of biological products suggests that we need a case-by-case approach for evaluating each type of product."

To that end, Waxman advocated a system similar to that being set up in Europe, where product-specific guidances are being established for biogeneric approvals. He also criticized brand-name pharmaceutical firms for seeking "loopholes" to block generic companies from entering the market, and later singled out abuses of the Citizens Petitions process as an example.

Many GPhA members have charged that the vetting process is improperly employed by innovator companies to delay the FDA from establishing a biogeneric regulatory pathway. Such feelings were echoed by a new face at the FDA who could prove most friendly to generic companies. Sheldon Bradshaw, the agency's new chief counsel, noted that misuse of Citizens Petitions represents attempts "to delay unnecessarily approval of competitors' products," adding that such a practice has "jumped out" at him and is "particularly troublesome."

He suggested putting Citizens Petitions on a separate review track from that of marketing applications to save the review process from lengthy delays. "Frankly, I've been considering whether or not we can implement something that would allow the agency to point out for all the world to see when Citizens Petitions are specious, untimely, or otherwise appear intended to delay competition," said Bradshaw, who previously worked in the Department of Justice, "rather than to assist the agency to review and approve drug applications in accordance with the law and sound science."

Economic forces also could force the issue. The GPhA has said that a one-day supply of biological drugs costs an average of $45, compared to a $1.66 daily average price of traditional small-molecule drugs. With the federal government set to become the biggest buyer of all drugs when Medicare's drug-benefit plan kicks in Jan. 1, the potential cost savings of biogenerics also could force a change in policy.

"Cost factors alone compel a full examination of public discussion of the merits of developing and implementing a fast-track review and approval system that can reduce the price of biopharmaceuticals once patents expire," Hatch said. He later hedged his comments by saying that "much groundwork" needs to be done before any biogeneric approval process is adopted. "I believe it should always be the goal of government to employ the least burdensome regulatory approach, without compromising other important considerations, such as in this case patient safety and intellectual property."

Those latter points continue to underlie arguments against shortened biogeneric approval pathways. According to Charles Lucas, a vice president and the general counsel at the Biotechnology Industry Organization (BIO), patient safety cannot be assured because product equivalence is not possible. Heterogeneity issues cloud precise characterization and comparison of pioneer biologicals to biogenerics, he told conference attendees. He also argued against the use of an innovator company's clinical data in considering a biogeneric marketing application, and charged that the FDA cannot use trade secrets in establishing its guidance as that would violate the constitutional "takings clause," the same section of federal law that permits eminent domain.

But several other speakers countered that scientific progress has advanced to the point of showing structural equivalence, while others disagreed with BIO's stance on the takings clause. With that back-and-forth continuing, both sides continue to await the FDA's determination.

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