Software as a Medical Device
Second Edition
xiii Regulatory Affairs Professionals Society
Defectiveness of Software as a Product. ...................................................................................................................................212
Manufacturer of a Defective Product and Other Potential Defendants. ..................................................................................214
Fault-Based Liability.....................................................................................................................................................................215
Not Complying with Legal Requirements, Acting Unreasonably............................................................................................215
Links Between the PLD and MDR/IVDR. ............................................................................................................................217
Medical Accidents, Liability of Medical Professionals. ............................................................................................................217
Liability in Contract......................................................................................................................................................................217
Product Liability in the US. ..........................................................................................................................................................218
Conclusion. ...................................................................................................................................................................................218
Acknowledgment .........................................................................................................................................................................219
Index. ...........................................................................................................................................................................221
Figures
Figure 2-1. Regulatory Fragmentation of Software as a Medical Device. .........................................................................................5
Figure 2-2. App to Detect Fever. ......................................................................................................................................................6
Figure 2-3. Categories of SaMD and SiMD ...................................................................................................................................9
Figure 2-4. A PACS System With Two Plugins. ............................................................................................................................10
Figure 2-5. Scenario 1: Wearable and Software Are an Integral Part of a Medical Device. ............................................................11
Figure 2-6. Scenario 2: Wearable Is an Accessory for SaMD/MDSW...........................................................................................11
Figure 2-7. Scenario 3: Software as an Accessory for Medical Device Wearable. ...........................................................................12
Figure 2-8. Scenario 4: Only Software Is a Medical Device, Wearable Not Subject to Regulation.................................................13
Figure 2-9. Scenario 5: Wearable and Software Are Placed on the Market as a System. ................................................................13
Figure 3-1. Decision Steps to Assist Qualification as an IVD or MD MDSW for the EU. ..........................................................16
Figure 3-2. Example of FDA IVD Generic Device Type Regulation. ............................................................................................22
Figure 3-3. Example of FDA Product Classification Database Search and Results. .......................................................................23
Figure 4-1. Illustration of a Selection of FDA Product Codes That Comprise Software Applications ..........................................32
Figure 4-2. Overview of EU IVDR Classification Rules. ...............................................................................................................34
Figure 4-3. Overview of EU MDR Classification Rules.................................................................................................................35
Figure 4-4. Digital Thermometer With a Fever Alert Function......................................................................................................36
Figure 4-5. Insulin Dose Calculator App That Drives an Insulin Pump. ........................................................................................36
Figure 4-6. An X-Ray System Comprised of Dependent and Independent Software. ...................................................................37
Figure 4-7. An Accessibility App for Patients With Locked-In Syndrome....................................................................................38
Figure 4-8. Illustration of How EU MDR Rule 11a Maps on the IMDRF SaMD Risk Framework ...........................................39
Figure 4-9. Examples of SaMD Mapped Against IMDRF Risk Framework.................................................................................40
Figure 4-10. Industry Interpretation of SaMD Risk Framework....................................................................................................41
Figure 4-11. Conformity Assessment Procedures Under EU MDR Article 52..............................................................................42
Figure 4-12. Illustration of the Extent of Notified Body Review for Increasing Device Classification...........................................43
Figure 4-13. Path to Market in the US According to Device Class. ...............................................................................................44
Figure 5-1. Clinical Evaluation Process...........................................................................................................................................50
Figure 5-2. Clinical Evidence Components for SaMD...................................................................................................................51
Figure 6-1. Sequence of Events for an IVD Device. .......................................................................................................................65
Figure 6-2. Figure Assertion Programming. ...................................................................................................................................69
Figure 7-1. SaMD Security.............................................................................................................................................................74
Figure 7-2. Security Monitoring Flowchart. ...................................................................................................................................78
Figure 8-1. Software Development According to the Waterfall Approach. ....................................................................................86
Figure 8-2. Software System Decomposition Into Software Items. ................................................................................................89
Figure 8-3. IEC 62304 Development Processes for Incremental Execution. ..................................................................................90
Figure 8-4. Mapping IEC 62304 Software Development Process Steps to Agile Increments........................................................91
Figure 8-5. IEC 62304 and IEC 62366-1 Development Processes for Incremental Execution......................................................92
Figure 8-6. Figure 2 of the FDA’s Proposed Regulatory Framework for Modifications to Artificial Intelligence/
Machine Learning......................................................................................................................................................................96
Figure 9-1. Device Use Concept. ..................................................................................................................................................103
Figure 10-1. Types of Controllability. ...........................................................................................................................................108
Figure 10-2. Transparency and Interpretability of an AI system’s output.................................................................................................110
Figure 10-3. Design for Happiness ..............................................................................................................................................111
Figure 10-4. Relationship Between User Needs, Requirements, and Design Specifications ........................................................113
Second Edition
xiii Regulatory Affairs Professionals Society
Defectiveness of Software as a Product. ...................................................................................................................................212
Manufacturer of a Defective Product and Other Potential Defendants. ..................................................................................214
Fault-Based Liability.....................................................................................................................................................................215
Not Complying with Legal Requirements, Acting Unreasonably............................................................................................215
Links Between the PLD and MDR/IVDR. ............................................................................................................................217
Medical Accidents, Liability of Medical Professionals. ............................................................................................................217
Liability in Contract......................................................................................................................................................................217
Product Liability in the US. ..........................................................................................................................................................218
Conclusion. ...................................................................................................................................................................................218
Acknowledgment .........................................................................................................................................................................219
Index. ...........................................................................................................................................................................221
Figures
Figure 2-1. Regulatory Fragmentation of Software as a Medical Device. .........................................................................................5
Figure 2-2. App to Detect Fever. ......................................................................................................................................................6
Figure 2-3. Categories of SaMD and SiMD ...................................................................................................................................9
Figure 2-4. A PACS System With Two Plugins. ............................................................................................................................10
Figure 2-5. Scenario 1: Wearable and Software Are an Integral Part of a Medical Device. ............................................................11
Figure 2-6. Scenario 2: Wearable Is an Accessory for SaMD/MDSW...........................................................................................11
Figure 2-7. Scenario 3: Software as an Accessory for Medical Device Wearable. ...........................................................................12
Figure 2-8. Scenario 4: Only Software Is a Medical Device, Wearable Not Subject to Regulation.................................................13
Figure 2-9. Scenario 5: Wearable and Software Are Placed on the Market as a System. ................................................................13
Figure 3-1. Decision Steps to Assist Qualification as an IVD or MD MDSW for the EU. ..........................................................16
Figure 3-2. Example of FDA IVD Generic Device Type Regulation. ............................................................................................22
Figure 3-3. Example of FDA Product Classification Database Search and Results. .......................................................................23
Figure 4-1. Illustration of a Selection of FDA Product Codes That Comprise Software Applications ..........................................32
Figure 4-2. Overview of EU IVDR Classification Rules. ...............................................................................................................34
Figure 4-3. Overview of EU MDR Classification Rules.................................................................................................................35
Figure 4-4. Digital Thermometer With a Fever Alert Function......................................................................................................36
Figure 4-5. Insulin Dose Calculator App That Drives an Insulin Pump. ........................................................................................36
Figure 4-6. An X-Ray System Comprised of Dependent and Independent Software. ...................................................................37
Figure 4-7. An Accessibility App for Patients With Locked-In Syndrome....................................................................................38
Figure 4-8. Illustration of How EU MDR Rule 11a Maps on the IMDRF SaMD Risk Framework ...........................................39
Figure 4-9. Examples of SaMD Mapped Against IMDRF Risk Framework.................................................................................40
Figure 4-10. Industry Interpretation of SaMD Risk Framework....................................................................................................41
Figure 4-11. Conformity Assessment Procedures Under EU MDR Article 52..............................................................................42
Figure 4-12. Illustration of the Extent of Notified Body Review for Increasing Device Classification...........................................43
Figure 4-13. Path to Market in the US According to Device Class. ...............................................................................................44
Figure 5-1. Clinical Evaluation Process...........................................................................................................................................50
Figure 5-2. Clinical Evidence Components for SaMD...................................................................................................................51
Figure 6-1. Sequence of Events for an IVD Device. .......................................................................................................................65
Figure 6-2. Figure Assertion Programming. ...................................................................................................................................69
Figure 7-1. SaMD Security.............................................................................................................................................................74
Figure 7-2. Security Monitoring Flowchart. ...................................................................................................................................78
Figure 8-1. Software Development According to the Waterfall Approach. ....................................................................................86
Figure 8-2. Software System Decomposition Into Software Items. ................................................................................................89
Figure 8-3. IEC 62304 Development Processes for Incremental Execution. ..................................................................................90
Figure 8-4. Mapping IEC 62304 Software Development Process Steps to Agile Increments........................................................91
Figure 8-5. IEC 62304 and IEC 62366-1 Development Processes for Incremental Execution......................................................92
Figure 8-6. Figure 2 of the FDA’s Proposed Regulatory Framework for Modifications to Artificial Intelligence/
Machine Learning......................................................................................................................................................................96
Figure 9-1. Device Use Concept. ..................................................................................................................................................103
Figure 10-1. Types of Controllability. ...........................................................................................................................................108
Figure 10-2. Transparency and Interpretability of an AI system’s output.................................................................................................110
Figure 10-3. Design for Happiness ..............................................................................................................................................111
Figure 10-4. Relationship Between User Needs, Requirements, and Design Specifications ........................................................113