10. Roadmap of the Submission Process of a Clinical Trial

10.1 Clinical Trial with Investigational Medicinal Product

The NIH has provided the following roadmap:

10.2 Pediatric Investigation Plan (PIP)

The FDA and the European Medicines Agency (EMA) have jointly produced a Pediatric Study Plan/Pediatric Investigation Plan template. See below:

In May 2023, the FDA issued two draft guidances for the industry entitled, Pediatric Drug Development: Regulatory Considerations – Complying with PREA and Qualifying for Pediatric Exclusivity Under the BPCA and Pediatric Drug Development Under the Pediatric Research Equity Act and the Best Pharmaceuticals for Children Act: Scientific Considerations. Both guidances, once finalized, will provide recommendations to support the approval of drugs, biological products, and vaccines under the Pediatric Research Equity Act (PREA) and/or the Best Pharmaceuticals for Children Act (BPCA). The guidance documents revise and replace the draft guidance for industry How to Comply with the Pediatric Research Equity Act. PREA and BPCA aim to provide pediatric-specific labeling information for drugs, biological products, and vaccines used in children. PREA gives FDA the authority to require pediatric studies of drugs, biological products, and vaccines under certain circumstances. BPCA provides an incentive of additional marketing exclusivity to sponsors who voluntarily complete pediatric clinical studies as requested by the FDA.

• Pediatric Drug Development: Regulatory Considerations – Complying with PREA and Qualifying for Pediatric Exclusivity Under the BPCA - This guidance is intended to assist industry sponsors who are developing drugs, biological products, and vaccines, to comply with the pediatric study requirements under PREA, and to describe the process for qualifying for pediatric exclusivity and the protections that pediatric exclusivity offers under BPCA. In addition to addressing the PREA topics covered in the earlier draft guidance (i.e., the pediatric assessment, pediatric plan, waivers and deferrals, compliance issues, and pediatric exclusivity provisions), this guidance addresses statutory requirements related to adverse event reporting, pediatric study plans (PSPs), deferral extensions, and noncompliance with requirements under PREA. 
• Pediatric Drug Development Under the Pediatric Research Equity Act and the Best Pharmaceuticals for Children Act: Scientific Considerations - This guidance addresses selected clinical, scientific, and ethical issues regarding the development of drugs, biological products, and vaccines for pediatric use under PREA and/or BPCA.

These guidances do not replace, Pediatric Study Plans: Content of and Process for Submitting Initial Pediatric Study Plans and Amended Initial Pediatric Study Plans or any other pediatric guidance document already published.

Additional Resources:

• Division of Pediatrics and Maternal Health
• Pediatric Labeling Changes Information Database (PREA/BPCA/Pediatric Rule)
• Pediatric Guidances

10.3 Clinical Study (Interventional or Observational)

See the FDA’s guidance entitled “E8(R1) General Considerations for Clinical Studies. Guidance for Industry” (April 2022).