Reliability Requirements for Emergency-Use Auto-Injectors (DRAFT)
This guidance focuses on emergency-use injectors marketed as combination products with emergency-use drugs for treating life-threatening conditions like anaphylaxis, opioid overdose, poisoning, or severe hypoglycemia. It provides recommendations for demonstrating reliability of these devices when submitted under BLA, NDA or ANDA applications.
This is a draft guidance. Not for implementation.
Recommended Actions
- Develop comprehensive reliability specifications targeting 99.999% reliability with 95% confidence
- Create detailed fault tree analysis documenting all potential failure modes
- Establish test protocols with statistically justified sample sizes
- Document preconditioning and use conditions for testing
- Implement procedures for maintaining reliability throughout product lifecycle
- Create plan for evaluating impact of design/manufacturing changes
- Establish quality control procedures and action limits
- Prepare reliability report following recommended format
- Request early development meetings with FDA to discuss reliability approach
- Maintain procedures for investigating failures and implementing corrective actions
Key Considerations
Non-clinical testing
- Reliability verification testing should be conducted on final finished combination product after appropriate preconditioning and use conditions
- Sample size for reliability testing should be statistically justified
- All test failures should undergo root cause analyses linked to fault tree analysis
- Testing should demonstrate 99.999% reliability with 95% confidence level
Safety
- Must consider use conditions and preconditioning factors like shipping, aging, storage, vibration, shock, temperature, altitude/pressure effects
- Need procedures for analyzing quality issues and complaints
- Must investigate potential causes of malfunctions and identify corrective actions
Other considerations
- Need fault tree analysis to model reliability
- Must maintain reliability throughout product lifecycle
- Changes to design or manufacturing require re-evaluation of reliability
- Need procedures for in-process controls and release testing
- Should establish action limits for rejection rates
Relevant Guidances
- Human Factors Studies and Related Analyses for Combination Products
- Early Development Considerations for Combination Products
- Current Good Manufacturing Practice Requirements for Combination Products
- Premarket Review Pathways for Combination Products
- Postmarketing Safety Reporting Requirements for Combination Products
- Obtaining FDA Feedback for Combination Products: Best Practices and Meeting Procedures
- Compliance Policy for Combination Product Postmarketing Safety Reporting Requirements
Related references and norms
- ISO 14971:2007: Medical Devices - Application of risk management to medical devices
- IEC 61078:2016: Reliability Block Diagrams
- IEC 61025:2006: Fault Tree Analysis (FTA)
- ISO 16269-6:2014: Statistical interpretation of data - Determination of statistical tolerance intervals
- ISO 3534-1:2006: Statistics - Vocabulary and symbols
Original guidance
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