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Safety Considerations for Flow Restrictors in Oral Liquid Drug Products to Prevent Accidental Ingestion by Children (DRAFT)

This guidance provides recommendations for manufacturers regarding the use of restricted delivery systems, particularly flow restrictors, to limit unintentional ingestion of oral liquid drug products by children. It applies to both prescription and over-the-counter oral liquid drug and biological products.

This is a draft guidance. Not for implementation.

  1. Evaluate need for restricted delivery system based on product toxicity profile and target population
  2. Select appropriate type of flow restrictor (open vs closed) based on:
    • Product’s therapeutic index
    • Toxicity profile
    • Viscosity characteristics
  3. Conduct performance testing to verify:
    • Flow restriction meets toxic dose prevention targets
    • Compatibility with dosing devices
    • Durability over product life
    • No leakage
  4. Develop appropriate labeling including:
    • Clear usage instructions
    • Contact information for replacement parts
    • Any required graphical instructions
  5. Perform human factors studies to validate:
    • Ease of use
    • Label comprehension
    • Overall system effectiveness
  6. Contact appropriate FDA division early in development process to discuss:
    • Testing requirements
    • Submission information needs
    • Labeling requirements
  7. Ensure compliance with child-resistant packaging requirements while implementing flow restrictor

Key Considerations

Non-clinical testing

  • Performance testing should include testing for 1.5x the maximum number of doses available in the container
  • Testing should be conducted at all specified orientations or all possible container orientations as defined by product label
  • Testing should assess product functionality for labeled use and performance to prevent unintentional ingestions

Human Factors

  • Balance degree of restrictiveness with ease of use
  • System should not be overly burdensome or discourage proper use
  • Consider human factors principles and usability studies during development
  • System should not be easily removed or pushed through bottle neck
  • Must be compatible with target consumer/patient/caregiver populations

Labelling

  • Must include adequate directions for using the drug product with the restricted delivery system
  • Should include toll-free number/email for obtaining replacement parts
  • For OTC products, include non-graphical instructions in Drug Facts labeling
  • If needed, graphical instructions can be provided in a separate insert
  • Verify target population comprehends additional labeling

Biocompatibility

  • Materials must be safe for oral, skin and mucosal contact
  • Must be compatible with drug formulation

Safety

  • Should reduce amount of liquid children can extract from bottles
  • Consider toxic dose calculations based on 50th percentile weight for 2-year-old child
  • System should restrict flow to prevent toxic dose access within 5 minutes
  • For narrow therapeutic index drugs, use closed flow restrictors

Other considerations

  • ASTM F3375-19: Test Method for Assessing Non-Metered Restricted Delivery Systems for Liquid Consumer Products

Original guidance

  • Safety Considerations for Flow Restrictors in Oral Liquid Drug Products to Prevent Accidental Ingestion by Children
  • HTML / PDF
  • Issue date: 2020-03-17
  • Last changed date: 2020-03-17
  • Status: DRAFT
  • Official FDA topics: Medical Devices, Device & Drug Safety, Drugs, Biologics
  • ReguVirta summary file ID: 41359cb60f7c7aa5696958e7108618de
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