Clinical Research: Phase 1 - Phase 4

Understanding Recent Regulatory Changes for Pediatric Oncology Trials

Of the 1.7 million new cases of cancer in the U.S. in 2018, 10,590 involved children aged 14 or younger.[1] While children typically have a better cure rate for cancer, biopharma companies have traditionally shied away from pediatric oncology trials, resulting in fewer treatment options. However, the regulatory landscape is evolving, and the demand for innovative therapies for pediatric cancers is becoming increasingly vocal.

Until recently, the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act of 2003 (PREA) constituted the primary legislation on pediatric trials in the U.S. The objective of PREA, in conjunction with BPCA, was to increase the availability of evidence for pediatric medication use by giving regulatory agencies the authority to require sponsors to conduct pediatric testing and to produce formulations appropriate for children.[2] These regulations are intended to not only support the need for pediatric safety, efficacy, and dosing information but also to provide increased transparency into the drug approval process.

  • PREA requires sponsors to submit an initial pediatric study plan (iPSP) for each investigational new drug (IND) application submitted to the Food and Drug Administration (FDA) unless a waiver is granted, even if the application is intended only for adults. Pediatric studies can be deferred post-approval, but the sponsor must provide the FDA with its pediatric assessment by the final due date.
  • BPCA legislation offers an incentive of additional marketing exclusivity to manufacturers who voluntarily conduct pediatric studies of medicines with potential uses for children in response to a written request from the FDA.[3] As of September 6, 2019, the FDA had granted pediatric exclusivity to 253 approved drugs.[4]

Of note, prior to 2017, PREA legislation allowed for exemptions for orphan drugs. In the past, sponsors have sought orphan designations for pediatric subpopulations of common diseases in order to be exempt from having to conduct pediatric studies when seeking approval of the adult indication.[5]

Introducing the RACE for Children Act

On August 18, 2018, the Research to Accelerate Cures and Equity (RACE) for Children Act was signed into law as part of the 2017 FDA Reauthorization Act, which amended PREA. The purpose of the RACE for Children Act is to promote the development and reach of new cancer treatments for children. Per this legislation, PREA exemptions for orphan drugs have been eliminated and pediatric investigation is required if the drug or biologic product is intended for the treatment of an adult cancer and directed at a molecular target substantially relevant to the growth or progression of a pediatric cancer.

The FDA, with input from the National Cancer Institute and the pediatric cancer research community, has compiled and published a list of relevant pediatric molecular targets [PDF] to provide guidance to industry in planning for new submissions. However, it’s important for sponsors to keep in mind that designation as a relevant pediatric molecular target is neither an absolute nor the only requirement for pediatric evaluation. Studies may still be required for products directed at targets that do not appear on the list, and waivers may still be possible for products directed at relevant targets.

When the RACE for Children Act goes into effect on August 18, 2020, all sponsors of new oncology drugs (orphan or not) intended for both adult and pediatric populations should plan to include an iPSP as part of their submission to the FDA. The EU has long required such sponsors to submit and discuss their pediatric investigational plans (PIPs) before completion of human pharmacokinetic (PK) studies. With this new legislation, sponsors working in both the US and the EU should seek a partner with the appropriate regulatory consulting expertise to align these pediatric strategies in order to streamline the clinical development process.


[1] National Cancer Institute. Cancer in Children and Adolescents. https://www.cancer.gov/types/childhood-cancers/child-adolescent-cancers-fact-sheet. Accessed September 26, 2019.

[2] U.S. Food and Drug Administration. FDAAA-Title IV: Pediatric Research Equity Act of 2007 (PREA) and Title V: Best Pharmaceuticals for Children Act 2007 (BCPA). http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/UCM049870.pdf. Accessed September 26, 2019.

[3] U.S. Food and Drug Administration. Best Pharmaceuticals for Children Act (BPCA). https://www.fda.gov/drugs/development-resources/best-pharmaceuticals-children-act-bpca. Accessed September 26, 2019.

[4] U.S. Food and Drug Administration. Drugs to Which FDA has Granted Pediatric Exclusivity for Pediatric Studies under Section 505A of the Federal Food, Drug, and Cosmetic Act. https://www.fda.gov/drugs/development-resources/pediatric-exclusivity-granted. Accessed September 26, 2019.

[5] RAPS. FDA Closes Loophole Companies Used to Skirt Pediatric Study Requirements. https://www.raps.org/regulatory-focus™/news-articles/2017/12/fda-closes-loophole-companies-used-to-skirt-pediatric-study-requirements. Accessed September 26, 2019.