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This is a draft guidance. Not for implementation.
What You Need to Know? 👇
What reliability specifications does FDA recommend for emergency-use injectors?
FDA recommends emergency-use injectors include design control specifications for successful injection reliability of 99.999% with a 95% level of confidence. This target is equivalent to post-market detection of failure to successfully inject in 1/100,000 injection attempts.
What regulatory pathway applies to emergency-use injectors?
Emergency-use injectors are regulated as combination products submitted under BLA, NDA, or ANDA pathways. They’re assigned to CDER or CBER based on the drug’s primary mode of action and must comply with both drug CGMPs and specific device QS regulation provisions.
What should be included in a reliability report for emergency-use injectors?
The reliability report should include combination product definition, reliability specifications, fault tree analysis, reliability test plan and data, total product life cycle reliability plan, conclusions, and supporting appendices. This facilitates efficient FDA review of reliability data.
How should manufacturers handle design changes affecting emergency-use injector reliability?
Manufacturers must evaluate if changes impact design output specifications or fault tree analysis basic events. If changes create new design outputs or risks, the reliability report should be updated with change data and included in premarket submissions.
What preconditioning factors should be considered for reliability testing?
Preconditioning should include shipping, aging, storage conditions, vibration, shock resistance, temperature extremes, altitude/pressure effects, and air particulates. Testing must adequately challenge the injector’s ability to withstand real-world stressors throughout its use-life.
When should manufacturers request FDA meetings for emergency-use injector development?
FDA strongly encourages early development meetings (Pre-IND or Pre-ANDA) and subsequent IND meetings throughout development. These meetings can clarify reliability requirements and discuss alternative approaches for demonstrating emergency-use injector reliability specifications.
What You Need to Do 👇
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