Biological Indicators for Healthcare Facility Sterilization Process Monitoring - 510k Submission Requirements
This guidance document provides information for manufacturers preparing 510(k) submissions for Biological Indicators (BIs) intended to monitor sterilization processes used in healthcare facilities. BIs are Class II medical devices that accompany products being sterilized to monitor sterilization adequacy by demonstrating growth or no growth of known microorganisms. The guidance excludes physical/chemical sterilization indicators, BIs for manufacturing settings, and BIs for liquid chemical sterilization.
What You Need to Know? 👇
What are the key requirements for a 510(k) submission for biological indicators?
A 510(k) for biological indicators must include device comparison, detailed specifications, performance characteristics (D-value, Z-value, survival/kill window), shelf life data, labeling requirements, and validation studies conducted on at least 3 different spore lots from different crops.
Which microorganisms are recommended for different sterilization processes?
Steam sterilization uses Geobacillus stearothermophilus, dry heat and ethylene oxide use Bacillus atrophaeus, and hydrogen peroxide uses Geobacillus stearothermophilus. These organisms provide appropriate resistance characteristics for their respective sterilization methods.
Can biological indicator incubation time be reduced from the standard 7 days?
Yes, incubation time can be reduced if validated through specific methodology. Testing must demonstrate that 97% of biological indicators showing growth at 7 days also show growth at the proposed shorter incubation time.
What is the minimum Z-value requirement for thermal biological indicators?
FDA generally recommends that biological indicators have a minimum Z-value of 10°C for thermal sterilization processes. The Z-value represents the temperature change corresponding to a 10-fold change in D-value.
Are accelerated aging studies appropriate for biological indicator shelf life validation?
No, accelerated aging studies may be inappropriate for biological indicators because they may be unstable at elevated temperatures. Real-time shelf life studies are recommended, though preliminary data with ongoing study protocols may be acceptable.
What documentation is required for mail-in biological indicator monitoring services?
For biological indicators marketed as part of mail-in monitoring services, the handling protocol must be detailed in labeling and validated to ensure that required handling doesn’t adversely impact biological indicator resistance characteristics.
What You Need to Do 👇
Recommended Actions
- Conduct comprehensive performance testing including:
- Viable spore population assays
- Resistance characteristics studies
- Materials evaluation
- Recovery protocol validation
- Prepare detailed device documentation:
- Device comparison to predicate
- Complete specifications
- Test protocols and results
- Shelf life data
- Develop compliant labeling with:
- Clear intended use statement
- Complete device description
- Detailed instructions for use
- Required precautions
- Validate any associated components (incubators, test packs)
- Ensure conformity with applicable standards and maintain documentation in design history file
- Consider submitting preliminary shelf life data with ongoing study protocol if complete real-time data not available
Key Considerations
Non-clinical testing
- Viable spore population assay to demonstrate product meets specifications
- Resistance characteristics study using resistometer (D-value, Z-value for thermal processes, Survival/Kill window)
- Carrier and primary packaging materials evaluation
- Holding time assessment
- Recovery protocols validation
- Mail-in protocols validation if applicable
Labeling
- Must include intended use (sterilization method, cycle, exposure time, temperature, sterilant concentration)
- Device description (genus/species/strain, lot number, type of BI, D-value, Z-value, survival/kill time, spore count)
- Instructions for use (sterilization parameters, result interpretation, disposal, recovery)
- Precautions regarding D-value reproducibility
Safety
- Demonstrate specifications maintained throughout labeled shelf life
- Evaluate effect of sterilization process on recovery medium for self-contained BIs
- Validate incubator performance if sold as system
Other considerations
- Test packs if indicated for use must demonstrate equivalent performance to AAMI reference
- Minimum 3 different spore lots from different crops for testing
- Real-time shelf life data or preliminary data with ongoing study protocol
Relevant Guidances 🔗
- Regulatory Requirements for Medical Device Washers and Washer-Disinfectors
- Liquid Chemical Sterilants and High Level Disinfectants - Content and Format of 510k Submissions
- Refuse to Accept Policy for 510k Submissions: Minimum Threshold Requirements for Administrative and Technical Review
- Content and Decision-Making Process for 510k Submissions: Determining Substantial Equivalence
- Submission Requirements for Terminally Sterilized Medical Devices
Related references and norms 📂
- ANSI/AAMI/ISO TIR11139:2006: Sterilization of health care products-Vocabulary
- ANSI/AAMI/ISO ST11138-1:2006: Sterilization of health care products-Biological indicators-Part 1: General requirement
- ANSI/AAMI/ISO ST11138-4:2006: Sterilization of health care products-Biological indicators-Part 4: Biological indicators for dry heat sterilization processes
- ISO 18472:2006: Sterilization of health care products Biological and Chemical Indicators Test Equipment