Recent data suggest that roughly two-thirds of all drugs prescribed to children have not been studied in a pediatric population and are not labeled for pediatric use. This dearth of information leaves children at risk of being exposed to ineffective treatments or improper dosing. The Best Pharmaceuticals for Children Act of 2002 (BPCA) is Congress’ attempt to address this issue and, since its passage, has led to nearly 800 studies involving more than 45,000 children. BPCA, codified as Section 505A of the Federal Food, Drug, and Cosmetic Act, encourages drug sponsors to conduct pediatric studies in exchange for marketing exclusivity for the studied product. BPCA, however, is set to expire on October 1, 2007.

As reported in the Tufts University Center for the Study of Drug Development survey, in 2006 companies conducting pediatric clinical studies under BPCA outsourced all of the clinical trials conducted under the Act. Thus, BPCA’s reauthorization affects both drugs sponsors and contract research organizations providing pediatric research services or having the capacity to provide such services to a drug sponsor.

The Best Pharmaceuticals for Children Act of 2002

BPCA was enacted in 2002 to encourage drug sponsors to conduct pediatric studies. The goal of the BPCA program is the development of clinical information regarding the safe and effective administration of drugs to children. BPCA renewed pediatric incentives originally granted under the Food and Drug Modernization Act of 1997 (FDAMA), which Congress allowed to expire on January 1, 2002.

In exchange for conducting the appropriate pediatric studies, a drug may receive six months of additional market exclusivity. This exclusivity, known as “pediatric exclusivity,” is granted by the Food and Drug Administration (FDA) under the authority of BPCA. FDA may only grant a drug pediatric exclusivity if the drug meets specified requirements, including that an existing patent or exclusivity currently covers the active moiety of the drug product, FDA makes a written request to the sponsor that pediatric studies be conducted, and the sponsor performs and submits pediatric studies that meet the terms specified in the written request issued by the FDA.

FDA will issue a written request to a drug sponsor to conduct pediatric drug studies where the Agency determines that the product may provide health benefits to children. A sponsor need not wait for FDA to send a written request; instead, it may attempt to prompt a written request from the Agency by submitting a proposed pediatric study request describing the pediatric study or studies the sponsor proposes to conduct in return for pediatric exclusivity. FDA may issue a written request in response to a proposed pediatric study request if it finds that the proposed study will provide information that may result in health benefits to children. The written request sent by FDA will outline the nature of the pediatric studies the drug sponsor must conduct to qualify for pediatric exclusivity and a time frame for completion of those studies.

Under BPCA, these written requests require a response from the drug sponsor of any on-patent product. Sponsors of products with no patent protection do not need to submit a response, but after 30 days, FDA assumes the request is declined. Following acceptance and submission of a study report in response to the written request, FDA has 90 days to complete its review to determine whether to grant pediatric exclusivity to the drug and/or to require product labeling changes. Even though pediatric exclusivity does not extend to drug products not currently covered by a patent or other exclusivity, other provisions of BPCA provide for the study of both on-patent and off-patent drugs a sponsor has declined to study. If the sponsor of an on-patent drug declines a written request, FDA may refer the product to the Foundation for the National Institutes of Health (FNIH), which may opt to fund a study. In addition, BPCA provides funding to the National Institutes of Health (NIH) to perform studies of off-patent drugs.

The exclusivity authorized under BPCA provides an additional six-month period during which the sponsor retains sole marketing rights to all forms of a drug product line containing the active moiety. The retention of this marketing control makes pediatric exclusivity a substantial financial incentive for advancing pediatric studies.

GAO Assessment of Studies Conducted Under BPCA

In a March 2007 report to the Committee on Health, Education, Labor, and Pensions of the U.S. Senate and the Committee on Energy and Commerce of the House of Representatives, the U.S. Government Accountability Office (GAO) provided an assessment of the effect of BPCA. In the report-entitled “Pediatric Drug Research: Studies Conducted under Best Pharmaceuticals for Children Act”-the GAO evaluated the extent to which pediatric drug studies were being conducted under BPCA for on-patent drugs, including studies conducted when the sponsor declines to perform the studies; the impact of BPCA on labeling drugs for pediatric use and the process by which the labeling changed; and the range of diseases treated by drugs studied under BPCA. The GAO’s assessment is based on data regarding FDA-requested studies between 2002-2005 and interviews of representatives of the federal government, the pharmaceutical industry, and public health advocates.

The GAO found that sponsors initiated pediatric studies for most on-patent drugs, agreeing to study 173 of the 214 drugs for which FDA issued a written request for pediatric studies. However, the GAO determined that no drugs were being studied when the sponsor declined to perform the study even though a mechanism exists under BPCA whereby FDA can refer the study of these drugs to the FNIH. FDA has referred nine drugs as of December 2005 and FNIH has declined to fund the study of any of these drugs.

The GAO discovered that approximately 87% of drugs granted pediatric exclusivity experienced labeling changes based on information discovered in the pediatric studies, such as finding that children may be exposed to ineffective drugs, ineffective dosing, overdosing, or previously unknown side effects. However, the GAO noted that the time to implement the labeling changes based on the pediatric studies was lengthy, ranging from 238 to 1,055 days. Finally, the GAO reported that drugs were studied for many different diseases, from common to life-threatening, in 17 broad categories of disease.

Based on its assessment, GAO identified five strengths of BPCA through interviews with FDA and NIH officials, including: the economic incentives to conduct pediatric drug studies; the availability of summaries of pediatric drug studies; the broad scope of pediatric drug studies conducted under BPCA; the effective use of dispute resolution as a negotiating tool for ensuring labeling changes; and improved safety through focused pediatric safety reviews. However, the GAO also identified several areas of weakness and suggested changes to BPCA using a 2006 Institute of Medicine forum on pediatric research. These third-party suggestions include providing FDA with 180 days to review the results from pediatric drug studies; requiring submission of study results for pediatric exclusivity determination at least one year prior to patent expiration; making written requests and the receipt of study results by FDA public; and encouraging the study of off-patent drugs.

Reauthorization of BPCA

Congress is already considering reauthorization of some form of BPCA. A March 2007 hearing of the Senate Health, Education, Labor, and Pensions Committee chaired by Sen. Chris Dodd (D-CT) included testimony from industry, healthcare professionals, and patient advocates. The GAO report is among several Congressionally-requested analyses of BPCA that will be considered during reauthorization alongside academic and industry-sponsored assessments of the program.

In lauding the effects of BPCA during the recent hearing, Dr. Samuel Maldonado, vice president and head of the Pediatric Drug Development Center of Excellence at Johnson & Johnson, requested that Congress go further with this reauthorization and recommended reauthorizing BPCA without a five-year sunset provision. Dr. Maldonado stated such a change in the law would encourage greater participation by industry in BPCA by creating a consistent and predictable exclusivity provision. Dr. Maldonado opined that a stable exclusivity provision was necessary to garner enhanced industry support in light of the increasing cost, size, number, and complexity of pediatric studies, a finding reported by researchers at the Center for the Study of Drug Development at Tufts University.

The hearings held by Sen. Dodd precedes the introduction of any legislation on the matter and will be used when creating the mark-ups for reauthorization. One issue of current debate includes the potential for windfalls to companies with so-called “blockbuster” drug products for conducting pediatric studies under BPCA. Several members of Congress have voiced concern regarding the returns that blockbuster drugs receive under BPCA and have recommended limiting or changing the term of exclusivity provided. In drafting the reauthorization, Sen. Dodd is specifically considering whether to shorten the period of pediatric exclusivity from six months to three months for blockbuster drugs. However, advocates of an unchanged BPCA cite the tremendous leverage the current period of exclusivity has been in achieving program goals.

Both sponsors and CROs will want to monitor closely Congress’ posture and actions regarding the reauthorization of BPCA. Although it seems likely that Congress will reauthorize BPCA in some form, it remains to be seen whether the reauthorization will result in some change in the incentives for conducting pediatric drug studies. On the one hand, Congress wants to use a carrot to encourage pediatric drug studies; on the other hand, Congress cannot ignore the political and economical realities of drug pricing and the desire to accelerate access to generic medications, particularly blockbusters.

Gary C. Messplay is a partner in the Washington, D.C. office of Hunton & Williams LLP (www.hunton.com), where he is head of the law firm’s Food and Drug Practice. He can be reached at
gmessplay@hunton.com. Colleen Heisey is an attorney in the firm’s Food and Drug Practice.