Washington Editor

WASHINGTON - Companies developing biologics that could be used off-label in children may end up having to run pediatric clinical trials.

Working in conjunction with the Bush administration, lawmakers are expected this week to introduce legislation that would force biotechnology and pharmaceutical companies to conduct pediatric trials on adult drugs that could be used for the same purpose in children.

Such a regulation, known as the Pediatric Rule, was issued in 1998 by the FDA, but was later challenged by "right-wing" groups, Mark McClellan, the FDA commissioner, told a House Appropriations subcommittee Thursday. In October, a federal district court struck down the rule, finding that the FDA did not have the authority to require such tests.

In response, the federal government has decided against pursuing the matter in court, McClellan said. Instead, the administration will take the faster route through Congress, he said. (The American Academy of Pediatrics in Chicago and the Elizabeth Glaser Pediatric AIDS Foundation in Washington are appealing the court decision.)

The American Academy of Pediatrics (AAP), which has lobbied for 40 years to get drug makers to test products in children, is hoping the much-anticipated legislation will mirror the 1998 rule.

Marjorie Tharp, AAP's public affairs manager in Washington, told BioWorld Today the Pediatric Rule was meant to "capture" any medicines (i.e., biologics) that were not included in the Best Pharmaceuticals for Children Act of 1997.

"Best Pharmaceuticals says that if you are a drug company and you know your medication is often prescribed to kids and you want to test it in the pediatric population, then go ahead and work with the FDA. Once you've finished [and received approval in the pediatric population] the FDA will give you an additional six months of patent exclusivity," Tharp said. "That law is voluntary."

Tharp said AAP and others responded to Best Pharmaceuticals by continuing to lobby for a stronger measure. And that's how they got the Pediatric Rule.

In a nutshell, it required manufacturers of certain new and already-marketed drugs and biologics to conduct studies to ensure that their products were adequately labeled for children. (For example, it would not apply to an Alzheimer's drug or biologic.)

Biologics were covered because a significant portion of therapeutics used in children, including many cancer treatments, are biological products, a prepared statement from AAP said.

Meanwhile, the groups responsible for winning the lawsuit are standing their ground against any legislation that would force companies to conduct pediatric trials of adult drugs. The groups are the Competitive Enterprise Institute, of Washington; Association of American Physicians and Surgeons, of Tucson, Ariz.; and Consumer Alert, of Washington.

"If a drug comes into widespread use and it has been shown to be safe in the market in adults, then you might want to test it in children. There are guidelines for figuring out what dose children should have [off-label]," Jane Orient, executive director the Association of American of Physicians and Surgeons, told BioWorld Today. "The attending physician should decide if the drug should be used off-label without the huge expense of doing pediatric trials just to get it to market."

Furthermore, she argued that adults should bear the brunt of testing and early marketing. "All new drugs are dangerous in children, and kids are not at a lower risk just because they are in an experimental group."

The Competitive Enterprise Institute issued a statement saying a pediatric testing mandate would lengthen the drug-approval process, resulting in fewer new drugs overall.

"The Pediatric Rule constituted a drastic change in the drug-approval process, and it should not be replicated by Congress," a prepared statement by Sam Kazman, the institute's general counsel and expert on FDA policy, said. "The end result could be a far riskier and costly approval process, and ultimately, fewer drugs. No one would benefit from that."

Under the Pediatric Rule, companies could seek a waiver if a product did not represent a meaningful therapeutic benefit over existing treatment options and if it was not likely to be used in a substantial number (5,000) of children. Also, waivers could be issued if pediatric studies were impractical or dangerous.

Companies also could seek deferrals if waiting for the pediatric studies would delay availability for adults.