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.
What You Need to Know? 👇
What is the primary purpose of the FDA’s 510(k) intended use determination guidance?
The guidance reflects the elimination of the sunset provision of Section 513(i)(1)(E), allowing CDRH staff to continue established procedures for determining intended use in 510(k) submissions and updates procedures with minor changes since implementation.
How does FDA determine the intended use of a medical device in 510(k) submissions?
FDA determines intended use primarily through evaluation of proposed labeling submitted in the 510(k), including labels, directions for use, and promotional materials. Only in rare cases might other information be considered.
What criteria must be met for FDA to impose limitations on off-label use?
The Office Director must determine there’s reasonable likelihood the device will be used for unidentified intended uses in proposed labeling, and such use could cause harm to patients or consumers.
Can manufacturers modify labeling limitations imposed through “SE with limitations” letters?
No, manufacturers must submit a new 510(k) before modifying or removing any labeling limitations required by Section 513(i)(1)(E), as these are mandated by federal law, not voluntary changes.
What consultation process occurs when FDA identifies potential off-label use concerns?
The Office Director consults with the 510(k) submitter via telephone or meeting. Following consultation, the firm may modify device design, request written determination, or receive an “SE with limitations” letter.
Who has authority to make off-label use determinations for 510(k) devices?
Only the Office Director has authority to make determinations regarding off-label use limitations under Section 513(i)(1)(E). This responsibility cannot be delegated to other FDA staff members.
What You Need to Do 👇
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 đź”—
- 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 đź“‚
- 21 CFR 807.87(e): Requirements for 510(k) submission content regarding labeling