Premarket Notification Requirements for Aerosol Delivery Devices: Nebulizers, Metered Dose Inhalers, Spacers and Actuators
This guidance document is intended for FDA staff reviewing 510(k) premarket notifications for aerosol delivery devices including nebulizers, metered dose inhalers (MDIs), spacers and actuators. It outlines the required information and testing to demonstrate substantial equivalence to legally marketed devices. The guidance specifically covers devices regulated by CDRH (nebulizers, spacers, and MDIs for ventilator circuits) while MDIs and actuators are reviewed by CDER.
Recommended Actions
- Determine if device falls under CDRH or CDER jurisdiction based on intended use
- Prepare comprehensive device description including:
- Engineering drawings
- Materials
- Operating principles
- Specifications
- Conduct required performance testing:
- Particle size distribution using multiple methods
- Spray pattern/plume geometry for MDIs
- Life-cycle testing if reusable
- Environmental testing for portable devices
- Perform biocompatibility testing per ISO 10993-1
- Develop complete labeling including:
- Instructions for use
- Prescription statement
- Warnings/cautions
- Drug compatibility information
- For software-driven devices, prepare complete software documentation
- Prepare comparison to predicate devices showing substantial equivalence
- Conduct clinical trials if required (especially for spacers)
- Submit 510(k) with all required testing data and documentation
- Include either 510(k) summary or statement per SMDA requirements
Key Considerations
Clinical testing
- Small in vivo confirmational trials required for spacers to assess relative safety and effectiveness compared to MDI alone
- At least two trials per drug classification type needed:
- One trial for effectiveness
- One trial for safety
- Clinical trials must follow 21 CFR Part 812, Part 50, and Part 56 requirements
Non-clinical testing
- Particle size distribution testing required using at least two different methods
- Cascade impactor testing mandatory to determine:
- Total drug mass released
- Drug quantity at each impactor location
- Mass median aerodynamic diameter (MMAD)
- Geometric standard deviation (GSD)
- For MDIs/actuators:
- Spray pattern and plume geometry testing
- Testing at different fill levels (full, half, end of life)
- Potency testing for each claimed drug
- Life-cycle testing for reusable devices
Labelling
- Must include prescription statement per 21 CFR 801.109
- Instructions for use including:
- Operating principles
- Drug-specific instructions if applicable
- Cautionary statements
- Single use/reuse statements
- Patient and physician instructions as needed
Software
- For software-driven devices:
- Hazard analysis
- Software requirements and design information
- Test plans/protocols with data
- Development process documentation
- Quality assurance activities
- Configuration management plan
- Verification activities
Biocompatibility
- Testing per ISO 10993-1 requirements
- Must include test protocols, pass/fail criteria, results and analysis
Safety
- Electrical safety testing for electronic devices
- Environmental testing for portable/home use devices
- Sterility information if applicable
Other considerations
- Device description including engineering drawings
- Comparison to predicate devices
- Performance testing in intended environment
- Documentation of Good Laboratory Practices compliance
Relevant Guidances
- Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
- Content of Premarket Submissions for Device Software Functions
- Content and Decision-Making Process for 510k Submissions: Determining Substantial Equivalence
- Refuse to Accept Policy for 510k Submissions: Minimum Threshold Requirements for Administrative and Technical Review
- Electromagnetic Compatibility for Medical Devices and Accessories: Testing, Documentation, and Labeling Requirements
Related references and norms
- IEC 601-1: Medical electrical equipment, Part 1: General Requirements for Safety
- IEC 529: Classification of Degrees of Protection Provided by Enclosures
- ISO 10993-1: Biological evaluation of medical devices
- CISPR 11: Limits and Methods of Measurement of Radio-Interference Characteristics
- IEC 68: Environmental Testing
Original guidance
- Premarket Notification Requirements for Aerosol Delivery Devices: Nebulizers, Metered Dose Inhalers, Spacers and Actuators
- HTML
- Issue date: 1993-09-30
- Last changed date: 2020-03-17
- Status: FINAL
- Official FDA topics: Medical Devices, Premarket
- ReguVirta summary file ID: 5e5a2edb6562aefea4d9931d24497794
This post is licensed under CC BY 4.0 by the author.