Drug Research and Children : What's Spurring the Research?

by Food and Drug Administration (FDA)

(Page 2 of 3)

The FDA has taken a carrot-and-stick approach to encourage pediatric studies, says William Rodriguez, M.D., the FDA's science director for pediatrics. The carrot is the voluntary pediatric exclusivity provision of the Food and Drug Administration Modernization Act of 1997 (FDAMA). And the stick has been the FDA's "pediatric rule," which required pediatric studies and was finalized in 1998. Here's an overview of each initiative:

The Pediatric Exclusivity Provision of FDAMA

The pediatric exclusivity provision has done more to spur pediatric studies than any other regulatory or legislative initiative so far. The provision extends patent protection to give companies an additional six months of marketing exclusivity if they do the studies in children requested by the FDA.

Patents protect a company's investment by giving it the sole right to sell a drug while the patent is in effect. When patents or other periods of exclusive marketing for brand-name drugs are close to expiring, other drug companies can apply to the FDA to sell generic versions, without having to repeat the original developer's clinical trials. So the trade-off is that by giving companies additional months of exclusivity, there is a delay in the availability of lower-cost generic drugs.

The FDA has interpreted the provision so that the six months of exclusivity isn't only added to the drug that was studied in the pediatric population, but also to any of the drug company's formulations, dosage forms, and indications that contain the same active part of a molecule (moiety) and have existing marketing exclusivity or patent life. So if a company markets an oral formulation and a topical cream containing the same moiety, the six months of marketing exclusivity will be added to any existing exclusivity or patent protection for both products.

The process can be initiated either by a drug company or the FDA. A drug company may submit a proposal to conduct pediatric studies to the FDA. If the FDA agrees that studying a drug may produce health benefits for children, the agency will issue a "Written Request" addressing the type of studies to be conducted, study design and goals, and the age groups to be studied. Or the agency may issue a Written Request on its own initiative when it identifies a need for pediatric data. No matter how the studies are initiated, if the FDA determines that the data submitted fairly respond to the Written Request, then the company will be granted six months of pediatric exclusivity.

The exclusivity provision also requires the FDA to publish an annual list of approved drugs for which additional pediatric information may produce health benefits.

More than 60 drugs have been granted exclusivity so far. As of Sept. 30, 2002, 601 studies had been requested and 256 Written Requests issued. The FDA estimates that about 80 percent of the studies outlined in Written Requests will be conducted.

Kauffman says the exclusivity is proof that economics plays a large role in the lack of pediatric studies. "Once the economic disincentive was removed," he says, "the dam broke completely open."

The exclusivity provision was renewed in January 2002 and extended through 2007 under the Best Pharmaceuticals for Children Act (BPCA). Some categories of drugs and age groups have remained inadequately studied. The incentive under FDAMA did not apply to old antibiotics and other drugs that lack marketing exclusivity or patent protection. For these products, the BPCA provides a contract mechanism through the NIH to fund pediatric studies. If a company that has a drug with existing exclusivity or patent protection chooses not to conduct the requested pediatric studies, this new mechanism through BPCA allows the Foundation for the National Institutes of Health to award grants so that third parties can conduct the needed studies.

The FDA's Pediatric Rule

In the early 1990s, the FDA implemented voluntary measures to encourage pediatric studies, but they were mostly unsuccessful. In 1997, the FDA published a proposed regulation that for the first time required manufacturers of new drug and biological products to conduct pediatric studies in some circumstances. The rule was finalized in 1998, and the first studies were required to be submitted starting December 2000.

But the rule had its critics. In December 2000, the Association of American Physicians and Surgeons, the Competitive Enterprise Institute and Consumer Alert filed a lawsuit against the pediatric rule, challenging the FDA's legal authority to require pediatric studies. And in October 2002, a federal district court overturned the pediatric rule.

HHS Secretary Tommy G. Thompson responded in mid-December 2002 by announcing that his department will push for rapid passage of legislation that would give the FDA authority to require pharmaceutical manufacturers to conduct appropriate pediatric clinical trials on drugs.

"The fastest and most decisive route for establishing clear authority in this area is to work with Congress for new legislation," Thompson said in a prepared statement. "Children need to have access to drugs that can benefit them, and these drugs need to be properly tested for pediatric use, not prescribed and sold without testing. Congress alone can speak clearly on the authority that FDA needs ..."

Kauffman says turning the pediatric rule into law would be the ideal scenario. "The exclusivity provision sunsets again in 2007, with no guarantees of being renewed. We need something permanent so that we don't lose all the ground we've gained."

The pediatric rule was intended to address some of the gaps left by the pediatric exclusivity provision. Unlike the exclusivity provision, the pediatric rule was a requirement and covered both drugs and biologics — medical products derived from living sources such as vaccines, blood and blood derivatives, and new treatments for cancers.

Under the pediatric rule, the FDA could require pediatric studies of a drug submitted in a new drug application if the FDA determined the product was likely to be used in a substantial number of pediatric patients, or if the product would provide a meaningful benefit in the pediatric population over existing treatments. At the same time, the pediatric rule did not delay the availability of drugs for adults.

"The exclusivity provision and the rule have worked in tandem," says the FDA's Dianne Murphy. "We have told sponsors who submit a new drug application and who are required under the rule to conduct pediatric studies that they also may qualify for pediatric exclusivity."

Gorman says the exclusivity provision is the one that has the drug industry's attention, but he has been most excited about the pediatric rule. "The exclusivity provision has been important for helping children play catch-up and that's important, but the pediatric rule puts children at the table very early in the development of drugs."

About the Author

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FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.