Content and Decision-Making Process for 510k Submissions: Determining Substantial Equivalence
This guidance provides recommendations for industry and FDA staff about the content of 510(k) submissions and the decision-making process for determining substantial equivalence of medical devices reviewed under the 510(k) program. It covers key aspects like predicate devices selection, intended use determination, technological characteristics evaluation, and performance data requirements.
What You Need to Know? 👇
What is the difference between a predicate device and a reference device in 510(k) submissions?
A predicate device is a legally marketed device used to demonstrate substantial equivalence through comparison of intended use and technological characteristics. A reference device provides scientific methodology or technical information after Decision Point 4 and cannot be used to address the primary substantial equivalence determination.
When does FDA typically request clinical data for 510(k) submissions?
FDA requests clinical data in less than 10% of 510(k) submissions, typically when non-clinical testing is insufficient, when technological differences are significant but don’t warrant NSE determination, or when non-clinical methods are limited or inappropriate for the specific indications or device technology.
Can multiple predicate devices be used in a single 510(k) submission?
Yes, multiple predicates can be used when combining features from different devices with the same intended use, seeking multiple indications under the same intended use, or when a single predicate cannot adequately support substantial equivalence. However, FDA recommends identifying a primary predicate to simplify review.
What constitutes a “new intended use” that would make a device ineligible for 510(k) review?
A new intended use occurs when changes in indications raise different questions of safety and effectiveness that preclude meaningful comparison with the predicate device, or when changes significantly increase safety/effectiveness concerns beyond those addressed by the predicate device.
How does the “least burdensome” principle apply to 510(k) performance data requests?
FDA follows a stepwise approach: first considering descriptive information, then non-clinical bench testing, followed by animal/biocompatibility studies, and finally clinical data only when other methods are insufficient. The principle ensures information requests reflect the minimum required for substantial equivalence determination.
What are the key requirements for a compliant 510(k) Summary under 21 CFR 807.92?
The 510(k) Summary must include submitter information, device identification, predicate device details, device description with technological characteristics, intended use statement, comparison with predicate, performance data discussion (if applicable), and conclusions demonstrating substantial equivalence in sufficient detail for public understanding.
What You Need to Do 👇
Recommended Actions
- Clearly identify appropriate predicate device(s) and document comparison
- Determine if intended use is the same as predicate device
- Compare technological characteristics with predicate device
- Determine appropriate testing requirements based on differences from predicate:
- Non-clinical testing
- Clinical testing if needed
- Performance data requirements
- Prepare comprehensive 510(k) Summary following requirements
- Consider pre-submission meeting with FDA if guidance unclear
- Ensure compliance with applicable standards and regulations
- Document scientific rationale for use of reference devices if applicable
- Follow least burdensome approach while ensuring safety and effectiveness
- Maintain clear documentation of substantial equivalence justification
Key Considerations
Clinical testing
- Clinical data may be needed when:
- New/modified indications for use need validation
- Technological differences require clinical validation
- Non-clinical testing methods are limited/inappropriate
- Less than 10% of 510(k)s require clinical data
- Clinical data must constitute valid scientific evidence
- Clinical studies must comply with IDE regulations as applicable
Non-clinical testing
- Non-clinical bench performance testing includes:
- Mechanical, electrical, biological engineering performance
- EMC testing
- Sterility testing
- Stability/shelf life testing
- Software validation
- Must comply with GLP regulations as applicable
- Should follow recognized consensus standards when available
Software
- Software validation required based on level of concern
- Documentation should follow FDA software guidance
- Software changes affecting patient data analysis may require clinical validation
Labelling
- Must include indications for use statement
- Should be consistent with proposed labeling
- 510(k) Summary must include detailed device description and labeling information
Biocompatibility
- Testing should follow ISO 10993 standards
- Must consider duration and type of tissue contact
- Material specifications should be provided
Safety
- Safety evaluation based on:
- Technological characteristics comparison
- Performance testing results
- Risk analysis
- Clinical data when needed
Other considerations
- Multiple predicates may be used if appropriate justification provided
- Reference devices can support scientific methodology
- 510(k) Summary must be comprehensive and accurate
- Least burdensome approach should be followed
Relevant Guidances đź”—
- Content of Premarket Submissions for Device Software Functions
- Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
- Recommended Format and Content for Non-Clinical Bench Performance Testing in Medical Device Premarket Submissions
- Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for Medical Devices
- Least Burdensome Principles for Medical Device Regulation
Related references and norms đź“‚
- IEC 60601-1: Medical electrical equipment - General requirements for basic safety and essential performance
- IEC 60601-1-2: Medical electrical equipment - EMC requirements
- ISO 10993: Biological evaluation of medical devices
- ASTM F-67: Standard Specification for Unalloyed Titanium for Surgical Implant Applications