From X-Rays to AI: Navigating US Regulations in Radiological Health
iv Regulatory Affairs Professionals Society (RAPS)
Table 2-4. Selected Device Problems Reported in the FDA’s Medical Device Reporting (MDR)
Database Between 2018 and 2023 ....................................................................................34
Table 2-5. Summary of the FDA’s Post-Marketing Surveillance System for Diagnostic X-ray
Systems. .............................................................................................................................35
Table 3-1. Ten-Year Review of MRI Adverse Events: Breakdown by Category. ................................50
Table 4-1. Technical specifications of the five commercial DBT systems ..........................................63
Table 5-1. Well-established ultrasound modes of operation utilizing longitudinal waves .................72
Table 5-2. Acoustic Output Exposure Levels for Diagnostic Ultrasound Devices.............................. 75
Table 6-1. Product Codes Under 21 CFR §892.5050 (Medical Charged-particle Radiation
Therapy System) and 21 CFR §892.5060 (Fludeoxyglucose F18-Guided Radiation
Therapy System)................................................................................................................. 85
Table 6-2. Product Codes Under 21 CFR §892.5730 (Radionuclide Brachytherapy Source). ...........87
Table 7-1. Radiological Health Software Regulations, Product Codes, Device Types, Device
Classes ...............................................................................................................................99
Table 7-2. Consensus Standards and Other Documents Relevant to Radiological Health
Software. ..........................................................................................................................101
Table 7-3. Possible IMDRF Framework for Risk Categorization of SaMD ..................................111
Table 8-1. Terms, Abbreviations and Definitions Related to AI and ML Technologies ..................116
Table 8-2. Examples of Key Performance Metrics Evaluated by the FDA During the Clearance
of recent Computer-Assisted Detection (CADe) Devices............................................... 123
Table 8-3. Examples of FDA-Cleared AI/ML Devices for Cardiology ...........................................124
Table 8-4. Good Machine Learning Practice for Medical Device Development: Guiding
Principles.......................................................................................................................... 126
Table 8-5. Key Considerations for Successful CAD Regulatory Documentation ............................127
Table 8-6. Summary of Key Digital Health Activities. .....................................................................132
Figures
Figure 2-1. The OHT8B is Responsible for Reviewing Radiological Imaging Device Technologies... 16
Figure 2-2. Typical System Configuration Integrated with the Auto ROI Components. ....................29
Figure 3-1. Magnetic Resonance Diagnostic Device Regulation 21 CFR §892.1000.......................... 40
Figure 3-2. Understanding MRI Safety Labeling................................................................................. 43
Figure 3-3. MRI Scanning Tips for Implants....................................................................................... 44
Figure 3-4. MRI Burn Prevention. .......................................................................................................45
Figure 5-1. The OHT8C is Responsible for Reviewing Diagnostic Ultrasound Systems. ...................70
Figure 6-1. Simplified Schema of a Typical Radiotherapy Clinical Workflow in a Patient
Diagnosed with Cancer...................................................................................................... 80
Figure 6-2. Gantry-Based Radiotherapy System .................................................................................81
Figure 6-3. Brachytherapy for Prostate Cancer ....................................................................................82
Figure 6-4. Number of 510(k) Approvals Per Year in the Main Product Codes Related to
Radiation Therapy Devices................................................................................................. 86
Figure 6-5. Number of 510(k) Approvals Per Year in the Main Product Codes Related to
Brachytherapy ...................................................................................................................88
Figure 6-6. Components of a Nuclear Medicine Device. .....................................................................90
Figure 7-1. General Overview of the FDA’s Thinking on Whether a Clinical Decision Support
Software is a Device. ........................................................................................................104
Figure 7-2. OTS and SOUP are not equivalent. A software component can be OTS but not
SOUP, and vice versa........................................................................................................ 106
Figure 7-3. Healthcare and Public Health Sector Coordinating Council (HSCC) Product Security
Framework ......................................................................................................................108
iv Regulatory Affairs Professionals Society (RAPS)
Table 2-4. Selected Device Problems Reported in the FDA’s Medical Device Reporting (MDR)
Database Between 2018 and 2023 ....................................................................................34
Table 2-5. Summary of the FDA’s Post-Marketing Surveillance System for Diagnostic X-ray
Systems. .............................................................................................................................35
Table 3-1. Ten-Year Review of MRI Adverse Events: Breakdown by Category. ................................50
Table 4-1. Technical specifications of the five commercial DBT systems ..........................................63
Table 5-1. Well-established ultrasound modes of operation utilizing longitudinal waves .................72
Table 5-2. Acoustic Output Exposure Levels for Diagnostic Ultrasound Devices.............................. 75
Table 6-1. Product Codes Under 21 CFR §892.5050 (Medical Charged-particle Radiation
Therapy System) and 21 CFR §892.5060 (Fludeoxyglucose F18-Guided Radiation
Therapy System)................................................................................................................. 85
Table 6-2. Product Codes Under 21 CFR §892.5730 (Radionuclide Brachytherapy Source). ...........87
Table 7-1. Radiological Health Software Regulations, Product Codes, Device Types, Device
Classes ...............................................................................................................................99
Table 7-2. Consensus Standards and Other Documents Relevant to Radiological Health
Software. ..........................................................................................................................101
Table 7-3. Possible IMDRF Framework for Risk Categorization of SaMD ..................................111
Table 8-1. Terms, Abbreviations and Definitions Related to AI and ML Technologies ..................116
Table 8-2. Examples of Key Performance Metrics Evaluated by the FDA During the Clearance
of recent Computer-Assisted Detection (CADe) Devices............................................... 123
Table 8-3. Examples of FDA-Cleared AI/ML Devices for Cardiology ...........................................124
Table 8-4. Good Machine Learning Practice for Medical Device Development: Guiding
Principles.......................................................................................................................... 126
Table 8-5. Key Considerations for Successful CAD Regulatory Documentation ............................127
Table 8-6. Summary of Key Digital Health Activities. .....................................................................132
Figures
Figure 2-1. The OHT8B is Responsible for Reviewing Radiological Imaging Device Technologies... 16
Figure 2-2. Typical System Configuration Integrated with the Auto ROI Components. ....................29
Figure 3-1. Magnetic Resonance Diagnostic Device Regulation 21 CFR §892.1000.......................... 40
Figure 3-2. Understanding MRI Safety Labeling................................................................................. 43
Figure 3-3. MRI Scanning Tips for Implants....................................................................................... 44
Figure 3-4. MRI Burn Prevention. .......................................................................................................45
Figure 5-1. The OHT8C is Responsible for Reviewing Diagnostic Ultrasound Systems. ...................70
Figure 6-1. Simplified Schema of a Typical Radiotherapy Clinical Workflow in a Patient
Diagnosed with Cancer...................................................................................................... 80
Figure 6-2. Gantry-Based Radiotherapy System .................................................................................81
Figure 6-3. Brachytherapy for Prostate Cancer ....................................................................................82
Figure 6-4. Number of 510(k) Approvals Per Year in the Main Product Codes Related to
Radiation Therapy Devices................................................................................................. 86
Figure 6-5. Number of 510(k) Approvals Per Year in the Main Product Codes Related to
Brachytherapy ...................................................................................................................88
Figure 6-6. Components of a Nuclear Medicine Device. .....................................................................90
Figure 7-1. General Overview of the FDA’s Thinking on Whether a Clinical Decision Support
Software is a Device. ........................................................................................................104
Figure 7-2. OTS and SOUP are not equivalent. A software component can be OTS but not
SOUP, and vice versa........................................................................................................ 106
Figure 7-3. Healthcare and Public Health Sector Coordinating Council (HSCC) Product Security
Framework ......................................................................................................................108