Background of the Act

Federal legislation and regulations of the U.S. Food and Drug Administration (FDA) require that drugs be tested for safety and efficacy for use in a specific population, at a specific dosage, and for a specific time period, before the drugs can be approved for clinical use. Use in situations not included in this testing is considered to be "off-label" uses.

Over the years, several practical problems and difficulties have discouraged the testing of drugs in pediatric populations due to:

• A range of ethical issues, including parental permission and the child's assent
• Lack of necessary technology to monitor patients and assay very small amounts of blood
• Lack of incentives for pharmaceutical companies to study drugs in neonates, infants, and children
• Unforeseeable nature of some clinical responses in immature individuals
• Possibility of catastrophic unanticipated reactions
• Threat of effect on growth or health long after the drug's administration
• Difficulty in predicting dose-response or concentration-response relationships by extrapolation of data obtained from adults
• Ethical considerations for conducting non-therapeutic research in children
• Lack of suitable infrastructure for conducting pediatric pharmacology research

As a result, the majority of medications used in children today are done so off label, in most cases, without adequate understanding of appropriate dose, safety, or efficacy.

The Pediatric Rule of 1994, issued by FDA, allowed the labeling of drugs for pediatric use based on extrapolation of efficacy in adults and additional pharmacokinetics, pharmacodynamics, and safety studies in pediatric patients, if the course of the disease and the response to the drug are similar in children as in adults. Although designed to improve pediatric labeling, only a small number of well-designed and well-conducted studies resulted from this rule.

Additional legislation passed in1997 as part of the FDA Modernization Act (FDAMA) provided extra incentive to pharmaceutical companies for pediatric testing, namely an additional six-month exclusivity period for marketing. As a result of this program, many drugs have and continue to receive pediatric labeling under this provision.

The Best Pharmaceuticals for Children Act of 2002 (BPCA 2002) provided mechanisms for studying on- and off-patent drugs in children. The BPCA 2002 directed the Secretary of the Department of Health and Human Services (DHHS), acting through the Director of the National Institutes of Health (NIH), to establish a program for pediatric drug development. The Director of the NIH delegated to the Director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) the authority and responsibility for establishment and conduct of the pediatric drug development activity set forth under Part B, Title IV, Section 409I (a) and (b) of the Public Health Service Act (PHS Act). Under this legislation, the NICHD developed a priority list of drugs needing further study in pediatric practice (see Federal Register 71(9):23931-23936). Since the inception of the BPCA 2002, the NICHD has awarded fifteen (15) individual projects to organizations and institutions for the purpose of gathering information to improve labeling of drugs that are used in children.

The BPCA Reauthorization of 2007
Title V of Public Law 110-85 was enacted on September 27, 2007, as part of the Food and Drug Administration Amendments Act of 2007. Please refer to website www.fda.gov for details regarding this reauthorization.

The legislation reauthorizes the BPCA and extends the provision providing additional patent exclusivity for currently on-patent drugs that are being tested for pediatric use. The act extends and expands the research program at the NIH, which was established in the BPCA of 2002. The NICHD administers the research program and works cooperatively with other NIH Institutes and Centers (ICs) with significant pediatric research portfolios.

An overview of the changes to Section 409I (Program for Pediatric Studies of Drugs) in the new legislation includes the following:

• Instead of developing an “annual list of approved drugs,” the NIH must publish a “priority list of needs in pediatric therapeutics, including drugs or indications that require study,” beginning one year from enactment and every three years thereafter;
• The NIH shall, as appropriate, submit a Proposed Pediatric Study Request (PPSR) to the Food and Drug Administration (FDA) for additional studies that are needed to assess the safety and effectiveness of the use of the drug in the pediatric population. (A PPSR is a draft Written Request (WR) that describes the elements of the pediatric clinical trials needed to improve pediatric labeling). The submission shall be for drugs that have an approved application under section 505 (j) of the Federal Food, Drug, and Cosmetic Act and where there is no patent protection or market exclusivity protection for at least one form of the drug. A WR can be issued by the FDA to the holders of the New Drug Application (NDA) or abbreviated NDA (aNDA) for the drug. If a response to the WR is not received by the FDA within 30 days, the NIH must publish a Request for Proposal (RFP) for conducting this research;
• Within one year of enactment, the NIH must do a feasibility study on a compilation of information on drugs for pediatric use;
• Pediatric pharmacologists are to be specifically included in existing NIH career development and loan repayment programs;
• The new legislation also includes devices and biologics as potential therapeutic areas for research activities.