Process for Clinical Investigations Involving Children Requiring Additional Safeguards
This guidance outlines FDA's process for handling clinical investigations involving children that require additional safeguards and have been referred for review under 21 CFR 50.54. It describes the procedures for IRBs, sponsors, and clinical investigators when a clinical investigation involving children does not meet the standard requirements and needs special consideration.
What You Need to Know? 👇
What is the purpose of 21 CFR 50.54 in pediatric clinical investigations?
21 CFR 50.54 provides additional safeguards for children in clinical investigations when an IRB determines the study doesn’t meet standard pediatric research criteria (50.51-50.53) but presents reasonable opportunity to address serious pediatric health problems.
How long does the FDA referral process under 21 CFR 50.54 typically take?
The FDA projects the referral process will take approximately six months to complete. Complex submissions, particularly those involving joint FDA-OHRP reviews, may require additional time for thorough evaluation and determination.
What documents must IRBs include when submitting a 21 CFR 50.54 referral?
IRBs must submit their finding that the study addresses serious pediatric health problems, explanation why standard criteria aren’t met, research protocol, IND/IDE numbers, informed consent documents, and supporting materials like IRB minutes.
Who participates in the Pediatric Ethics Subcommittee review process?
The Subcommittee includes at least two PAC members with relevant clinical expertise, plus invited experts in science, medicine, education, ethics, and law. FDA typically includes patient advocates, statisticians, and other specialists as needed.
Can multi-site studies continue at other sites during 21 CFR 50.54 review?
Yes, other sites may continue enrollment while one site’s IRB has made a referral, but IRBs should consider implications since the Commissioner might determine the study cannot proceed or requires protocol modifications.
How does public participation work in the 21 CFR 50.54 review process?
FDA establishes a public docket for each referral, solicits public comments (typically 4 weeks), holds open Subcommittee and PAC meetings, and makes all transcripts, recommendations, and final determinations publicly available online.
What You Need to Do 👇
Recommended Actions
- Consult with sponsor about possible protocol modifications before referring to FDA under 50.54
- Submit complete referral package to FDA’s Office of Pediatric Therapeutics including:
- IRB findings and explanation
- Research protocol
- IND/IDE number if applicable
- Informed consent documents
- Supporting documentation
- Ensure all documents are in “IRB-approvable” condition except for 50.54 issues
- For multi-site studies, notify all sites of the referral
- Prepare for participation in:
- Public comment period
- Pediatric Ethics Subcommittee meeting
- Pediatric Advisory Committee meeting
- Plan for approximately 6-month review timeline
- If joint FDA-HHS jurisdiction applies, prepare for coordinated review process
Key Considerations
Clinical testing
- Clinical investigations cannot proceed until Commissioner approval after IRB referral
- Multi-site clinical investigations may continue at other sites during review process
- IRB must document that investigation presents reasonable opportunity to further understanding/prevention/alleviation of serious problems affecting children’s health/welfare
Safety
- Must ensure protection of rights, safety and welfare of children
- Must be conducted according to sound ethical principles
- Adequate provisions required for obtaining child assent and parental permission
Other considerations
- Public review and comment required
- Expert panel consultation needed (science, medicine, education, ethics, law)
- Complete documentation package required for referral
- Joint FDA-HHS review process when investigation falls under both jurisdictions
- Approximately 6-month timeline for review process
Relevant Guidances 🔗
- Ethical Considerations for Clinical Investigations of Medical Products in Children (Draft)
- Process for Research Involving Children that Requires FDA and OHRP Review under 21 CFR 50.54 and 45 CFR 46.407 (Draft)
Related references and norms 📂
- 21 CFR Part 50 Subpart D: Additional Safeguards for Children in Clinical Investigations
- 45 CFR Part 46 Subpart D: Additional Protections for Children Involved as Subjects in Research
Original guidance
- Process for Clinical Investigations Involving Children Requiring Additional Safeguards
- HTML / PDF
- Issue date: 2006-12-01
- Last changed date: 2024-08-09
- Status: FINAL
- Official FDA topics: Medical Devices, Pediatric Product Development, Good Clinical Practice (GCP), Drugs, Biologics
- ReguVirta ID: 5cba51f1b4e6d89b0c50defce87d1d4c