Adding Imaging Contrast Indications to Medical Devices Used with Approved Imaging Drugs
This guidance assists developers of medical imaging devices and imaging drug/biological products in determining when new imaging contrast indications can be added to devices for use with approved imaging drugs without drug labeling modification, and what type of marketing submission(s) should be submitted for approval/clearance. The guidance aims to promote timely and effective premarket review and consistent regulation/labeling for imaging drugs and devices.
What You Need to Know? 👇
What are the key principles for determining when a device submission alone is sufficient for adding new contrast imaging indications?
A device submission alone is typically sufficient when the new indication uses an approved imaging drug at its approved formulation, dose, and administration route in a manner consistent with existing drug labeling, without requiring changes to drug characteristics or safety information.
When do both device and drug submissions become necessary for new imaging contrast indications?
Both submissions are required when device modifications affect drug-device interactions that impact safety or effectiveness, when new dosing or administration changes are needed, or when the modification creates labeling inconsistencies between products.
How does FDA determine the lead center for reviewing imaging device-drug combination products?
For most imaging products that don’t meet combination product definitions, device manufacturers submit to CDRH and drug manufacturers to CDER. For true combination products, the lead center is determined by primary mode of action under 21 CFR Part 3.
What types of clinical data are typically required to support new imaging contrast indications?
Clinical trials should demonstrate safety and effectiveness using both the imaging drug and device together. The data requirements follow existing FDA guidance on imaging drug development, focusing on the specific indication category and patient population.
What are the four broad imaging drug indication categories that FDA recognizes?
The four categories are: 1) Structural delineation, 2) Disease or pathology detection or assessment, 3) Functional, physiological or biochemical assessment, and 4) Diagnostic or patient management. Changes between categories constitute new indications.
How should manufacturers approach early communication with FDA for imaging product development?
Manufacturers should contact the appropriate lead center early for pre-IND/pre-IDE meetings, providing comprehensive discussion of the proposed indication, device technology, existing drug labeling, and proposed clinical studies to ensure efficient development and review processes.
What You Need to Do 👇
Recommended Actions
- Determine if proposed change requires device submission only or both device and drug submissions
- Engage in early communication with FDA to:
- Obtain feedback on required preclinical/clinical data
- Identify critical development issues
- Establish intercenter review team
- Design appropriate clinical trials considering:
- Drug class characteristics and differences
- Device settings and performance
- Safety monitoring requirements
- Prepare comprehensive submission including:
- Clinical trial data
- Preclinical test results
- Software/technology validation
- Proposed labeling changes
- Implement post-approval monitoring of:
- Drug labeling changes
- Safety reporting
- Required postmarket surveillance
- Maintain ongoing communication with FDA review team throughout development and review process
Key Considerations
Clinical testing
- Clinical trials should be appropriately designed to use both imaging drug and device
- Type and volume of data may vary based on indication, patient population, safety questions
- Trial designs should address differences within drug/device classes as appropriate
- Early studies should establish imaging drug dosing and device energy differences needed for labeling
Non-clinical testing
- Preclinical test results should be provided
- Device software or new technology validation when appropriate
Software
- Software validation required for device modifications
- Software changes that affect drug characteristics need additional review
Labeling
- Device and drug labeling should be generally consistent
- Labeling should reflect essential information establishing imaging contrast indication
- Indication statements should include clinical study description, device characteristics/settings, drug dosing regimen, target organ
Safety
- Safety profile of drug class should be considered in trial design
- Monitoring of approved drug’s labeling and changes required post-approval
- Postmarket surveillance may be required
Other considerations
- Early communication with FDA recommended
- Intercenter review team coordination needed
- Primary mode of action determines lead FDA center
- Device changes consistent with drug labeling may only need device submission
- Drug changes may require both drug and device submissions
Relevant Guidances 🔗
- Content of Premarket Submissions for Device Software Functions
- Benefit-Risk Determinations for Medical Device Premarket Review
- Postmarket Surveillance Studies Requirements for Medical Devices Under Section 522
- Q-Submission Program: Strategic Framework for FDA Interactions in Medical Device Development
Related references and norms 📂
- 21 CFR Part 3: Definition of Primary Mode of Action of a Combination Product
- 21 CFR 201.57: Labeling Requirements
- 21 CFR 814.20: Premarket Approval Application Content
- 21 CFR Part 803: Medical Device Reporting
- 21 CFR Part 822: Postmarket Surveillance