Premarket Requirements for Nitric Oxide Delivery Systems and Gas Analyzers
This guidance document outlines requirements for premarket notification submissions for three types of devices: - Nitric Oxide Delivery Apparatus - Nitric Oxide Analyzer - Nitrogen Dioxide Analyzer These devices are used together as a system for delivering nitric oxide therapy to patients, while monitoring nitric oxide and nitrogen dioxide concentrations in the breathing circuit.
What You Need to Know? 👇
What are the key components of a nitric oxide delivery system for medical devices?
A complete nitric oxide delivery system consists of three component medical devices: a nitric oxide administration apparatus, a nitric oxide gas analyzer, and a nitrogen dioxide gas analyzer. Each component may be manufactured and distributed separately.
What accuracy requirements must nitric oxide analyzers meet according to FDA guidance?
Nitric oxide analyzers must measure concentrations as low as 1 ppm with accuracy within ±(0.5 ppm + 20% actual concentration) between 1-20 ppm, and ±(0.5 ppm + 10% actual concentration) above 20 ppm.
What are the electromagnetic compatibility requirements for nitric oxide delivery devices?
Devices must comply with CISPR 11 for emissions, withstand electrostatic discharge up to 8 kV, operate during electromagnetic fields up to 3 V/m (26 MHz-1 GHz), and meet specific conducted immunity requirements per MIL-STD-461D.
What backup power requirements apply to nitric oxide administration systems?
If the device requires electrical power and is used with ventilators having battery backup, it must include battery backup lasting at least 20 minutes or matching the ventilator’s duration, activating automatically within 5 seconds of power failure.
What nitrogen dioxide concentration limits are specified for nitric oxide delivery apparatus?
Devices must produce no more than 1.0 ppm nitrogen dioxide during administration of 40 ppm nitric oxide in 60% oxygen, with testing required under worst-case conditions for each compatible ventilator.
What software documentation is required for nitric oxide delivery devices in 510(k) submissions?
Software documentation must include requirements, hazard analysis, development process documentation, quality assurance activities, configuration management, verification/validation protocols and results, plus written affirmation that development followed stated procedures and met requirements.
What You Need to Do 👇
Recommended Actions
- Develop comprehensive test plan covering all performance, safety and EMC requirements
- Conduct design verification testing:
- NO delivery accuracy
- NO2 production
- Analyzer accuracy
- Environmental conditions
- EMC/electrical safety
- Endurance testing
- Prepare documentation package including:
- Device description and specifications
- Test reports and data
- Software documentation
- Risk analysis
- Labeling
- Validate compatibility with specified ventilators
- Develop training materials and installation instructions
- Implement quality system controls for:
- Design controls
- Document control
- Change management
- Device master record
- Submit 510(k) with complete documentation package demonstrating compliance with all requirements
- Maintain post-market surveillance system to monitor device performance and safety
Key Considerations
Non-clinical testing
- Testing must demonstrate accuracy and stability of NO delivery within 20% of set concentration
- Testing must verify NO2 production is less than 1.0 ppm during administration of 40 ppm NO in 60% oxygen
- Endurance testing required for 2000 hours with simulated use conditions
- Testing must verify accuracy of NO and NO2 analyzers across specified ranges
- Testing must demonstrate compatibility with specified ventilators
Human Factors
- Controls must be protected from inadvertent changes
- Controls must be clearly labeled and visible from 1 meter
- Connectors must prevent incorrect connections
- Device must minimize risk of patient strangulation from tubing/wires
Software
- Software documentation required per FDA software guidance
- Must include hazard analysis, verification and validation testing
- Software version control required
Labelling
- Must include prescription statement
- Must specify validated ventilators
- Must include installation instructions
- Must include warning about required training
- Must include specifications for accuracy and alarms
- Must identify medical gas cylinder connections
Biocompatibility
- Materials must be compatible with NO gas
- Must minimize health risks from leached substances
- Must verify material compatibility after endurance testing
Safety
- Must include battery backup power if used with ventilators having backup power
- Must include alarms for NO concentration, NO2 concentration, and power
- Must prevent catastrophic release of NO
- Must meet electrical safety requirements per IEC 601-1
- Must meet EMC requirements per specified standards
Other considerations
- Must include backup/reserve NO delivery system
- Must use gas-specific connectors with check valves
- Must operate within specs from 5-40°C and 15-95% humidity
- Surface temperatures must not exceed specified limits
Relevant Guidances 🔗
- Content of Premarket Submissions for Device Software Functions
- Applying Human Factors Engineering and Usability Engineering to Medical Devices
- Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
- 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 801-2: Electromagnetic compatibility for industrial-process measurement and control equipment
- CISPR 11: Industrial, scientific and medical equipment - Radio-frequency disturbance characteristics
- MIL-STD-461D: Requirements for the control of electromagnetic interference emissions and susceptibility
- ASTM F 1462-93: Standard Specification for Oxygen Analyzers
- CGA C-9-1982: Standard Color Marking of Compressed Gas Containers for Medical Use