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This is a draft guidance. Not for implementation.
What You Need to Know? 👇
What are flow restrictors and how do they enhance child safety for liquid medications?
Flow restrictors are packaging components that control liquid flow from medicine bottles, limiting the amount children can access during unintentional ingestion. They complement child-resistant packaging by restricting volume delivery over time, significantly reducing the risk of harmful pediatric exposures to oral liquid medications.
Which types of flow restrictors should manufacturers consider for different drug products?
Manufacturers should consider closed flow restrictors for narrow therapeutic index drugs, as they limit access to single-unit volumes. Open flow restrictors allow controlled continuous flow and are suitable for other products. The choice depends on drug toxicity, viscosity, and target restriction effects.
What are the FDA’s recommended restriction effects for common OTC liquid medications?
FDA recommends restricting flow to prevent harmful doses in 5 minutes for a 2-year-old child: acetaminophen ≤2,400mg, dextromethorphan ≤90mg, diphenhydramine ≤90mg, ibuprofen ≤2,400mg, and pseudoephedrine ≤144mg. These limits are based on toxicity thresholds requiring emergency evaluation.
What human factors considerations are essential when designing restricted delivery systems?
Key considerations include material compatibility with drug formulations, inclusion of compatible dosing devices, leak prevention, performance testing through 1.5x the maximum doses, and ensuring the system isn’t easily removable. Manufacturers should balance restrictiveness with ease of use to prevent improper usage.
How should labeling requirements be addressed for products with restricted delivery systems?
Products must include adequate directions for using the restricted delivery system. For OTC products, non-graphical instructions should be added to Drug Facts labeling. A toll-free number or email for replacement parts should be provided. Graphical instructions may require separate labeling inserts.
What regulatory pathway should manufacturers follow when implementing restricted delivery systems?
Manufacturers should engage with appropriate FDA review divisions early in development. For OTC products under monograph review, FDA generally won’t object to appropriate systems with proper labeling. For prescription products requiring premarket review, submission requirements should be discussed with relevant review divisions.
What You Need to Do 👇
Recommended Actions
- Evaluate need for restricted delivery system based on product toxicity profile and target population
- Select appropriate type of flow restrictor (open vs closed) based on:
- Product’s therapeutic index
- Toxicity profile
- Viscosity characteristics
- Conduct performance testing to verify:
- Flow restriction meets toxic dose prevention targets
- Compatibility with dosing devices
- Durability over product life
- No leakage
- Develop appropriate labeling including:
- Clear usage instructions
- Contact information for replacement parts
- Any required graphical instructions
- Perform human factors studies to validate:
- Ease of use
- Label comprehension
- Overall system effectiveness
- Contact appropriate FDA division early in development process to discuss:
- Testing requirements
- Submission information needs
- Labeling requirements
- 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
- Consider viscosity of liquid formulation
- System should not leak when used
- Must include compatible dosing device if required
- Flow restrictor should not compromise child-resistant packaging requirements
Relevant Guidances 🔗
- Essential Drug Delivery Outputs for Drug Delivery Devices and Combination Products (Draft)
- Applying Human Factors Engineering and Usability Engineering to Medical Devices
- Human Factors Information Needed in Medical Device Marketing Submissions (Draft)
- Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
- Design Considerations for Medical Devices Intended for Home Use
Related references and norms 📂
- 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 ID: 41359cb60f7c7aa5696958e7108618de