Submission Requirements for Terminally Sterilized Medical Devices
This guidance focuses on reviewing 510(k) submissions for devices labeled as sterile that undergo industrial terminal sterilization processes based on microbial inactivation (e.g., radiation, steam, ethylene oxide, new technology sterilization processes). It excludes sterilizers themselves, microbial exclusion processes, sterilization of devices with animal/human tissues, liquid chemical sterilants, and reprocessing of single-use or reusable devices.
What You Need to Know? 👇
What are the established sterilization methods recognized by FDA for medical devices?
FDA recognizes two categories: Established Category A (dry heat, EO, steam, radiation, vaporized hydrogen peroxide) with FDA-recognized consensus standards, and Established Category B (ozone, flexible bag systems) with published validation information but no dedicated FDA-recognized standards.
When does FDA require a pre-clearance inspection for sterile medical devices?
FDA intends to inspect manufacturing facilities before clearing 510(k) submissions for devices sterilized using novel sterilization methods, as these carry substantial risk of inadequate sterility assurance and potential serious risk to human health if not conducted properly.
What sterility assurance level (SAL) should be achieved for sterile medical devices?
FDA recommends SAL of 10⁻⁶ for devices labeled as sterile, except for devices intended only for contact with intact skin, which should achieve SAL of 10⁻³. Alternative SALs require direct consultation with FDA.
Which medical devices require pyrogenicity testing according to FDA guidance?
Devices requiring pyrogen limit specifications include implants, devices contacting cardiovascular/lymphatic systems or cerebrospinal fluid, and devices labeled as non-pyrogenic. FDA recommends 20 EU/device for general medical devices and 2.15 EU/device for cerebrospinal fluid contact.
What additional documentation is required for novel sterilization methods in 510(k) submissions?
Beyond standard requirements, novel methods need comprehensive process descriptions, validation protocols, complete sterilization validation data, and identification of applicable scientific literature. FDA may request additional information based on the specific device.
What sterilization processes are excluded from this FDA guidance document?
Exclusions include sterilizers as medical devices, microbial exclusion processes (filtration, aseptic processing), devices with animal/human tissues, liquid chemical sterilants, reprocessor validation, and healthcare facility reprocessing of reusable devices.
What You Need to Do 👇
Recommended Actions
- Determine if your sterilization method is “Established Category A,” “Established Category B,” or “Novel”
- Prepare comprehensive sterilization documentation package including:
- Description of sterilization method and validation approach
- SAL determination and justification
- Pyrogenicity testing plan if applicable
- Package integrity validation plan
- For novel methods:
- Prepare for facility inspection
- Compile complete validation data package
- Consider pre-submission meeting with FDA
- Ensure labeling complies with pyrogenicity terminology requirements
- Verify compliance with appropriate sterilization standards
- Document sterilant residuals and their safety justification for chemical sterilization methods
- Implement appropriate batch testing for endotoxins if required
- Prepare packaging validation protocol and documentation
Key Considerations
Non-clinical testing
- Validation of sterilization cycle using appropriate methods (e.g., half-cycle method)
- Sterility Assurance Level (SAL) of 10-6 required for most devices (10-3 acceptable for devices contacting only intact skin)
- For chemical sterilants: maximum residual levels must be determined and justified
- For established Category B and novel methods: complete validation protocol and data required
Labelling
- Must indicate if device is non-pyrogenic
- Recommend using “non-pyrogenic” or “meets pyrogen limit specifications” instead of “pyrogen free”
Biocompatibility
- Pyrogenicity testing required for:
- Implants
- Devices contacting cardiovascular system, lymphatic system, or cerebrospinal fluid
- Devices labeled non-pyrogenic
- Endotoxin limits: 20 EU/Device for general medical devices, 2.15 EU/Device for CSF-contacting devices
Safety
- Package integrity testing required to ensure sterility maintenance
- For novel sterilization methods: comprehensive process description and validation data required
- Manufacturing facility inspection required for novel sterilization methods
Other considerations
- Sterilization site must be identified
- For radiation sterilization: radiation dose must be specified
- For chemical sterilants: residual levels must be specified and justified
Relevant Guidances 🔗
- Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
- Reprocessing Instructions for Reusable Medical Devices and Non-Sterile Single-Use Devices - Development and Validation
- Biological Indicators for Healthcare Facility Sterilization Process Monitoring - 510k Submission Requirements
- Liquid Chemical Sterilants and High Level Disinfectants - Content and Format of 510k Submissions
Related references and norms 📂
- ISO 10993-7: Biological Evaluation of Medical Devices – Part 7: Ethylene Oxide Sterilization Residuals
- ISO 22441: Sterilization of health care products - Low temperature vaporized hydrogen peroxide
- ANSI/AAMI ST72: Bacterial endotoxins – Test methods, routine monitoring, and alternatives to batch testing
- AAMI/ANSI/ISO 11607: Packaging for terminally sterilized medical devices