Draft Guidance for Industry provided by FDA: Clarification of Orphan Designation of Drugs and Biologics for Pediatric Subpopulations of Common Diseases.
This guidance is intended for sponsors of drugs and biological products (hereafter ‘drugs’)1 that submit orphan drug designation requests under section 526 of the Federal Food, Drug, and Cosmetic Act (FD&C Act). The Food and Drug Administration (FDA) no longer intends to grant orphan drug designation to drugs for pediatric subpopulations of common diseases (i.e., diseases or conditions with an overall prevalence of over 200,000), unless the use of the drug in the pediatric subpopulation meets the regulatory criteria for an orphan subset,2 or unless the disease in the pediatric subpopulation is considered a different disease from the disease in the adult population.
Congress enacted the Orphan Drug Act (ODA) to provide sponsors with incentives to develop drugs for rare diseases and conditions.3 FDA has historically granted orphan drug designation to drugs for use in pediatric subpopulations of common diseases or conditions (i.e., diseases or conditions with an overall prevalence of over 200,000 in the U.S.) if the prevalence in the pediatric subpopulation in the U.S. is below 200,000 (hereinafter, this practice is referred to as “pediatric-subpopulation designation”).4,5 Examples of pediatric-subpopulation designations include designations of drugs for pediatric ulcerative colitis and pediatric HIV. Each of these diseases (e.g., ulcerative colitis or HIV) is common, i.e., the total prevalence exceeds 200,000 in the U.S., but because the prevalence of the disease in the pediatric population in the U.S. falls below 200,000, FDA has granted pediatric-subpopulation designation for drugs for use in pediatric subpopulations in these diseases.
FDA began this practice of pediatric-subpopulation designation before pediatric-specific legislation to promote the study of drugs in the pediatric population was enacted. Because sponsors had historically failed to include pediatric populations in the research and development of their drugs for common diseases or conditions at that time, FDA applied orphan drug development incentives to promote the development of drugs for indications with a prevalence greater than 200,000 in the total population but less than 200,000 in the pediatric population for use in those pediatric populations.6
Since the time that FDA began granting pediatric-subpopulation designation to incentivize pediatric studies, Congress created several programs that promote pediatric studies and changed the regulatory landscape. In 1997, the Food and Drug Administration Modernization Act of 1997 (FDAMA) created a pediatric exclusivity provision that provided an additional six months of market exclusivity when a sponsor submits reports of pediatric studies that fairly respond to a written request from FDA and are conducted in accordance with generally applicable scientific principles and protocols. In 2002, this incentive program was reauthorized under the Best Pharmaceuticals for Children Act (BPCA).7 In 2003 Congress passed the Pediatric Research Equity Act (PREA), codifying a similar FDA regulation that had been struck down by the courts that required that certain marketing applications for new active ingredients, new indications, new dosage forms, new dosing regimens or new routes of administration contain an assessment of safety and effectiveness (including dosing information) for the proposed indication in all relevant pediatric subpopulations.8 The Food and Drug Administration Safety and Innovation Act (FDASIA) permanently reauthorized the BPCA and PREA in 2012.9 The FDA Reauthorization Act of 2017 (FDARA) extended the scope of PREA to require pediatric studies of certain adult oncology drugs that are directed at a molecular target that the Secretary determines to be substantially relevant to the growth or progression of a pediatric cancer.10
The successful completion of pediatric studies under BPCA and PREA, both of which have now been reauthorized without sunset dates, has led to the addition of new pediatric information in labeling for over 600 products since the enactment of these two laws.11 These initiatives have proven successful in promoting pediatric studies of drugs that are used in children. Additionally, the Rare Pediatric Disease (RPD) Priority Review Voucher (PRV) program, established under FDASIA, rewards sponsors that attain marketing approval for new drugs for use in rare pediatric diseases with vouchers for priority review of future marketing applications, in order to provide an added incentive for studies of rare pediatric diseases.
To read the full guidance, click here.