Determining and Managing Off-Label Use Concerns in 510k Submissions
This guidance outlines CDRH staff procedures for determining the intended use of devices in 510(k) submissions, focusing on how to handle situations where there is a reasonable likelihood of off-label use that could cause harm.
Recommended Actions
- Review all proposed labeling materials thoroughly to clearly define intended use
- Document any potential off-label uses identified during review
- Assess likelihood of off-label use and potential harm
- If off-label use concerns exist:
- Escalate to senior division management
- Contact Premarket Notification Section Chief
- Prepare for possible consultation with Office Director
- Consider device modifications if off-label use concerns are raised
- Implement any required labeling limitations exactly as specified in SE letter
- Submit new 510(k) for any modifications to imposed labeling limitations
- Maintain documentation of all decisions and communications regarding intended use determination
Key Considerations
Labelling
- Intended use must be determined by the proposed labeling for the product
- Labeling includes the actual label and any accompanying information such as directions for use and promotional materials
- When limitations are imposed due to off-label use concerns, they must be included in Precautions, Warnings, Contraindications, or other appropriate sections
- Any modification to labeling limitations requires a new 510(k) submission
Safety
- Must evaluate if there is a reasonable likelihood of off-label use that could cause harm
- If off-label use concerns exist, specific limitations may be imposed through an “SE with limitations” letter
Other considerations
- Office Director must personally evaluate and cannot delegate responsibilities regarding off-label use determinations
- Consultation between Office Director and 510(k) submitter may be required
- Manufacturers have the option to modify device design to address off-label use concerns
Relevant Guidances
- General vs. Specific Indications for Use in Medical Device Substantial Equivalence Determinations
- 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
- Device Labeling Requirements and Content for Premarket Approval Applications
Related references and norms
- 21 CFR 807.87(e): Requirements for 510(k) submission content regarding labeling
Original guidance
This post is licensed under CC BY 4.0 by the author.