Yet clinicians often prescribe adult-approved drugs for children, a practice known as off-label prescribing, (1) because most drugs have not been tested in children, and (2) because clinicians presume that the safety and effectiveness demonstrated with adults generally means that the drugs are also safe and effective for children. The Food and Drug Administration Amendments Act of 2007 (FDAAA, P.L. This report describes how and why Congress developed these initiatives. Specifically, the report
describes why research on a drug's pharmacokinetics, safety, and effectiveness in children might be necessary; presents why the marketplace has not provided sufficient incentives to manufacturers of drugs approved for adult use to study their effects in children; describes how BPCA provides extended market exclusivity in return for FDA-requested studies on pediatric use, and how PREA requires studies of drugs' safety and effectiveness when used by children ( Appendix B analyzes how BPCA and PREA evolved from FDA's administrative earlier efforts); analyzes the impact BPCA and PREA have had on pediatric drug research; and discusses issues, some of which Congress considered leading up to FDAAA, that may form the basis of oversight and evaluative activities along with reauthorization efforts in 2012. Manufacturers face many obstacles—economic, mechanical, ethical, and legal—that make them reluctant to conduct these tests. Congress has offered incentives to manufacturers for pediatric research for two main reasons. BPCA and PREA:Laws to Encourage Pediatric Drug Research

Although Congress has designed other laws (such as those affecting drug development, safety and effectiveness efforts, and general health care and consumer protection) to promote or protect the health of the entire population (including children), the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act (both sections of the Federal Food, Drug, and Cosmetic Act) authorize programs focused specifically on pediatric drug research. In 2007, Congress authorized their continuation for another five years. 355a) gives FDA the authority to offer manufacturers an additional six-month period of marketing exclusivity in return for FDA-requested pediatric use studies (including preclinical studies) and reports. Marketing exclusivity extends the time before which FDA grants marketing approval for a generic version of the drug. The law also has several public notice requirements for the Secretary, including the following:
notice of exclusivity decisions, along with copies of the written requests; public identification of any drug with a developed pediatric formulation that studies had shown were safe and effective for children that an applicant has not brought to market within one year; that, for a product studied under this section, the labeling include study results (if they do or do not indicate safety and effectiveness, or if they are inconclusive) and the Secretary's determination; dissemination of labeling change information to health care providers; and reporting on the review of all adverse event reports and recommendations to the Secretary on actions in response. 355c): Research into Pediatric Uses for Drugs and Biological Products. Their 2007 reauthorizations were paired in committee hearings and legislative vehicle (FDAAA) and Congress will likely consider them together in discussions of their 2012 reauthorizations. The House-passed bill for PREA 2007 would have eliminated PREA's link to the BPCA sunset provision; the Senate-passed bill continued it. Some researchers have examined the financial costs and benefits faced by manufacturers that receive pediatric exclusivity. Other manufacturers. Government. As Congress drafts language to continue BPCA and PREA, it could address whether FDA has adequate tools with which to assess, encourage, require, and enforce the development and dissemination of the information clinicians could use to reach better treatment decisions. By regulation, FDA requires pediatric-specific labeling in the following circumstances:
(B) If there is a specific pediatric indication different from those approved for adults that is supported by adequate and well-controlled studies in the pediatric population, …
(C) If there are specific statements on pediatric use of the drug for an indication also approved for adults that are based on adequate and well-controlled studies in the pediatric population, …
(D)(1) When a drug is approved for pediatric use based on adequate and well-controlled studies in adults with other information supporting pediatric use, …
(E) If the requirements for a finding of substantial evidence to support a pediatric indication or a pediatric use statement have not been met for a particular pediatric population, …
(F) If the requirements for a finding of substantial evidence to support a pediatric indication or a pediatric use statement have not been met for any pediatric population, …
(G) … FDA may permit use of an alternative statement if FDA determines that no statement described in those paragraphs is appropriate or relevant to the drug's labeling and that the alternative statement is accurate and appropriate. With each step of legislative and regulatory action over the years, Congress and FDA have tried to balance often conflicting goals:
drug development to address needs unique to children; tools to encourage drug manufacturers to test drugs for use in children, despite the expense, opportunity costs, and liability risk; protection of children as subjects of clinical research; public access to up-to-date and unbiased information on drug safety and effectiveness; and prioritizing agency activities in light of available resources. Current Law Evolved from Earlier Attempts
Before BPCA 2002 and PREA 2003, FDA attempted to spur pediatric drug research through administrative action. Food and Drug Administration Modernization Act of 1997
Three years later, Congress provided another approach to increasing pediatric labeling. FDAMA ( P.L. It provided drug manufacturers with an incentive to conduct pediatric use studies on their patented products. If a manufacturer completed a pediatric study according to FDA's written request, which included design, size, and other specifications, FDA would extend its market exclusivity for that product for six months. The Pediatric Rule mandated that manufacturers submit pediatric testing data at the time of all new drug applications to FDA. In October 2002, a federal court declared the Pediatric Rule invalid, noting that its finding related not to the rule's policy value but to FDA's statutory authority in promulgating it:
The Pediatric Rule may well be a better policy tool than the one enacted by Congress (which encourages testing for pediatric use, but does not require it)....
Update: On June 20, 2012, the House of Representatives passed, by voice vote and under suspension of the rules, S. 3187 (EAH), the Food and Drug Administration Safety and Innovation Act, as amended. This bill would reauthorize the FDA prescription drug and medical device user fee programs (which would otherwise expire on September 30, 2012), create new user fee programs for generic and biosimilar drug approvals, and make other revisions to other FDA drug and device approval processes. It reflects bicameral compromise on earlier versions of the bill (S. 3187 [ES], which passed the Senate on May 24, 2012, and H.R. 5651 [EH], which passed the House on May 30, 2012). The following CRS reports provide overview information on FDA's processes for approval and regulation of drugs:
CRS Report R41983, How FDA Approves Drugs and Regulates Their Safety and Effectiveness, by [author name scrubbed]. CRS Report RL33986, FDA's Authority to Ensure That Drugs Prescribed to Children Are Safe and Effective, by [author name scrubbed]. CRS Report R42130, FDA Regulation of Medical Devices, by [author name scrubbed]. CRS Report R42508, The FDA Medical Device User Fee Program, by [author name scrubbed].
(Note: The rest of this report has not been updated since November 10, 2011.)
With the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA), Congress authorized the Food and Drug Administration (FDA) to offer drug manufacturers financial and regulatory incentives to test their products for use in children. Congress extended both programs with the FDA Amendments of 2007 (FDAAA) and, because of the programs' sunset date, must act before October 1, 2012, to continue them. This report presents the historical development of BPCA and PREA, their rationale and effect, and FDAAA's impact. The report also discusses pediatric drug issues that remain of concern to some in Congress.
Most prescription drugs have never been the subject of studies specifically designed to test their effects on children. In these circumstances, clinicians, therefore, may prescribe drugs for children that FDA has approved only for adult use; this practice is known as off-label prescribing. Although some clinicians may believe that the safety and effectiveness demonstrated with adults would hold for younger patients, studies show that the bioavailability of drugs—that is, how much gets into a patient's system and is available for use—varies in children for reasons that include a child's maturation and organ development and other factors. The result of such off-label prescribing may be that some children receive ineffective drugs or too much or too little of potentially useful drugs; or that there may be side effects unique to children, including effects on growth and development.
Drug manufacturers are reluctant to test drugs in children because of economic, ethical, legal, and other obstacles. Market forces alone have not provided manufacturers with sufficient incentives to overcome these obstacles. BPCA and PREA represent attempts by Congress to address the need for pediatric testing. FDA had tried unsuccessfully to spur pediatric drug research through administrative action before 1997. With the FDA Modernization Act of 1997 (FDAMA, P.L. 105-115), Congress provided an incentive: if a manufacturer completed pediatric studies that FDA requested, the agency would extend the company's market exclusivity for that product for six months, not approving the sale of another manufacturer's product during that period. In 2002, BPCA (P.L. 107-109) reauthorized this program for five years.
In 1998, to obtain pediatric use information on the drugs that manufacturers were not studying, FDA published the Pediatric Rule, which required manufacturers to submit pediatric testing data at the time of all new drug applications. In 2002, a federal court declared the rule invalid, holding that FDA lacked the statutory authority to promulgate it. Congress gave FDA that authority with PREA (P.L. 108-155). PREA covers drugs and biological products and includes provisions for deferrals, waivers, and the required pediatric assessment of an approved marketed product.
In extending BPCA and PREA in 2007, Congress considered several issues: Why offer a financial incentive to encourage pediatric studies when FDA has the authority to require them? How does the cost of marketing exclusivity—including the higher prices paid by government—compare with the cost of the needed research? What percentage of labeling includes pediatric information because of BPCA and PREA? Do existing laws provide FDA with sufficient authority to encourage pediatric studies and labeling? Is FDA doing enough with its current authority? The 112th Congress will likely consider those questions as well as others: What information do clinicians and consumers need and how could industry and government develop and disseminate it? How can Congress balance positive and negative incentives to manufacturers for developing pediatric information to use in labeling? How could Congress consider cost and benefit when it deals with reauthorizing legislation in 2012?