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Long-Term Neurodevelopmental Safety Evaluation of Medical Products Used in Neonates

This guidance provides a framework for evaluating whether and what type of long-term neurologic, sensory and developmental evaluations are needed to assess safety of medical products (drugs, biologics, devices) used in neonates. It focuses specifically on long-term neurodevelopmental safety evaluations and does not cover effectiveness assessments, safety assessments for neuroprotective agents, toxicity to other organs, or clinical pharmacology studies.

  1. Assess need for long-term neurodevelopmental safety evaluation early in product development
  2. If needed, develop comprehensive evaluation plan considering:
    • Patient population characteristics
    • Product-specific factors
    • Timing and duration of follow-up
    • Appropriate assessment tools and domains
    • Standardization across sites
  3. Engage with FDA review division early to align on approach
  4. Implement strategies for participant retention and data quality
  5. Include plan for clinical referrals if developmental issues identified
  6. Consider adjunctive assessments (biomarkers, imaging) when warranted
  7. Ensure appropriate collection of covariate data
  8. Use validated assessment tools appropriate for population
  9. Plan for minimum 2-year follow-up with potential longer duration based on specific concerns
  10. Document scientific rationale for evaluation approach

Key Considerations

Clinical testing

  • Long-term neurodevelopmental safety evaluations should be conducted up to at least 2 years of age (adjusted for prematurity)
  • Controlled study design recommended whenever feasible
  • Need to ensure standardization across sites and examiners
  • Early consent for long-term follow-up recommended during initial enrollment
  • Plan needed for clinical referral if developmental problems identified

Non-clinical testing

  • Pre- and postnatal development studies needed
  • Embryo-fetal development studies may be warranted
  • Juvenile animal studies testing at critical brain development stages
  • Alternative non-animal testing methods supported when feasible

Human Factors

  • Consider patient/family burden and barriers to participation
  • Engage patient families and community leaders early
  • Maintain contact strategies to reduce missing data
  • Consider integrating data from routine care when appropriate
  • Plan for minimizing participant testing burden

Biocompatibility

  • For devices with tissue contact, biocompatibility evaluation needed to assess potential adverse responses
  • Both active ingredients and excipients should be evaluated for neurodevelopmental toxicity potential

Safety

  • Comprehensive assessment of neurologic function needed including:
    • Physical health
    • Sensory function
    • Motor skills
    • Cognition
    • Emotional/behavioral health
    • Communication/language
    • Social functioning
    • Adaptive functioning

Other considerations

  • ISO 10993-1: Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process

Original guidance

  • Long-Term Neurodevelopmental Safety Evaluation of Medical Products Used in Neonates
  • HTML / PDF
  • Issue date: 2024-10-17
  • Last changed date: 2024-10-17
  • Status: FINAL
  • Official FDA topics: Medical Devices, Pediatric Product Development, Drugs, Biologics, Clinical - Medical
  • ReguVirta summary file ID: f7c92b03491a0a29197f8522db83e875
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