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.
Recommended Actions
- Assess need for long-term neurodevelopmental safety evaluation early in product development
- 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
- Engage with FDA review division early to align on approach
- Implement strategies for participant retention and data quality
- Include plan for clinical referrals if developmental issues identified
- Consider adjunctive assessments (biomarkers, imaging) when warranted
- Ensure appropriate collection of covariate data
- Use validated assessment tools appropriate for population
- Plan for minimum 2-year follow-up with potential longer duration based on specific concerns
- 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
- Consider timing of exposure relative to developmental stages
- Account for disease state characteristics
- Evaluate route of administration impacts
- Consider regional differences in healthcare systems
- Collect data on relevant covariates (demographics, socioeconomic factors, etc.)
Relevant Guidances
- Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
- Biological Evaluation of Medical Devices Standards in the Accreditation Scheme for Conformity Assessment (ASCA) Pilot Program
Related references and norms
- 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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