Software as a Medical Device
Second Edition
viii Regulatory Affairs Professionals Society
Analytical Performance of IVD SaMD......................................................................................................................................27
Clinical Performance of IVD SaMD. ........................................................................................................................................27
Conclusion. .....................................................................................................................................................................................28
Chapter 4: Classification of Medical Device Software. .....................................................................................................31
Koen Cobbaert, MSc
Introduction. ...................................................................................................................................................................................31
Code-Based Classification...............................................................................................................................................................31
Rule-Based Classification................................................................................................................................................................31
Classification Following EU MDR and EU IVDR. .......................................................................................................................31
Medical Device Software. ...............................................................................................................................................................32
Implementing Rules in EU MDR. .................................................................................................................................................33
Administration Medical Device Classification Catalog .................................................................................................................33
Definition of Drive or Influence the Use.........................................................................................................................................34
Types of Drive or Influence the Use................................................................................................................................................35
Dependent MDSW. ..................................................................................................................................................................35
Independent MDSW.................................................................................................................................................................36
Classification Rule 11......................................................................................................................................................................37
Scope of Rule 11a.......................................................................................................................................................................37
Interpretation of Rule 11a. .........................................................................................................................................................38
Interpretation of IMDRF SaMD Risk Framework. .......................................................................................................................38
Interpretation Issues of IMDRF SaMD Risk Framework. .............................................................................................................39
Rule 11b. .........................................................................................................................................................................................40
Rule 11c..........................................................................................................................................................................................40
Impact of Rule 11............................................................................................................................................................................40
Classification Rule 12......................................................................................................................................................................40
Classification Rule 15......................................................................................................................................................................41
Classification Rule 22......................................................................................................................................................................41
Helsinki Procedure. .........................................................................................................................................................................43
Class Implications. ..........................................................................................................................................................................44
Conclusion. .....................................................................................................................................................................................45
Chapter 5: Clinical Evaluation of Software...................................................................................................................... 49
Zuzanna Kwade, PhD, MSc
Introduction. ...................................................................................................................................................................................49
General Principles of Clinical Evaluation. ......................................................................................................................................49
Specific Guidelines for SaMD Clinical Evaluation.........................................................................................................................50
Considerations for Artificial Intelligence. .......................................................................................................................................52
Regulations......................................................................................................................................................................................53
Conclusion. .....................................................................................................................................................................................56
Chapter 6: Safety Risk Management of Software. ............................................................................................................59
Mikael Dahlke, MSc, and Robert Ginsberg, MSc
Introduction. ...................................................................................................................................................................................59
The History of Software Safety Risk Management.........................................................................................................................60
1985-1987: Therac-25: Software Controlling a Therapy Device.................................................................................................60
2001: Multidata, National Cancer Institute, Panama City: Radiation Planning Software. ........................................................60
2020: COVID-19 Tests..............................................................................................................................................................61
Summary. ...................................................................................................................................................................................61
Aspects of Software in Risk Management According to ISO 14971. .............................................................................................61
Hazardous Situation Example....................................................................................................................................................61
Examples. ...................................................................................................................................................................................62
Challenges With Software Risk Assessment...................................................................................................................................62
Challenges With Analyzing Hazards Causing Indirect Harm...................................................................................................62
Challenges Related to ML Medical Devices..............................................................................................................................63
Challenges With Probability Estimates for Software.................................................................................................................63
Second Edition
viii Regulatory Affairs Professionals Society
Analytical Performance of IVD SaMD......................................................................................................................................27
Clinical Performance of IVD SaMD. ........................................................................................................................................27
Conclusion. .....................................................................................................................................................................................28
Chapter 4: Classification of Medical Device Software. .....................................................................................................31
Koen Cobbaert, MSc
Introduction. ...................................................................................................................................................................................31
Code-Based Classification...............................................................................................................................................................31
Rule-Based Classification................................................................................................................................................................31
Classification Following EU MDR and EU IVDR. .......................................................................................................................31
Medical Device Software. ...............................................................................................................................................................32
Implementing Rules in EU MDR. .................................................................................................................................................33
Administration Medical Device Classification Catalog .................................................................................................................33
Definition of Drive or Influence the Use.........................................................................................................................................34
Types of Drive or Influence the Use................................................................................................................................................35
Dependent MDSW. ..................................................................................................................................................................35
Independent MDSW.................................................................................................................................................................36
Classification Rule 11......................................................................................................................................................................37
Scope of Rule 11a.......................................................................................................................................................................37
Interpretation of Rule 11a. .........................................................................................................................................................38
Interpretation of IMDRF SaMD Risk Framework. .......................................................................................................................38
Interpretation Issues of IMDRF SaMD Risk Framework. .............................................................................................................39
Rule 11b. .........................................................................................................................................................................................40
Rule 11c..........................................................................................................................................................................................40
Impact of Rule 11............................................................................................................................................................................40
Classification Rule 12......................................................................................................................................................................40
Classification Rule 15......................................................................................................................................................................41
Classification Rule 22......................................................................................................................................................................41
Helsinki Procedure. .........................................................................................................................................................................43
Class Implications. ..........................................................................................................................................................................44
Conclusion. .....................................................................................................................................................................................45
Chapter 5: Clinical Evaluation of Software...................................................................................................................... 49
Zuzanna Kwade, PhD, MSc
Introduction. ...................................................................................................................................................................................49
General Principles of Clinical Evaluation. ......................................................................................................................................49
Specific Guidelines for SaMD Clinical Evaluation.........................................................................................................................50
Considerations for Artificial Intelligence. .......................................................................................................................................52
Regulations......................................................................................................................................................................................53
Conclusion. .....................................................................................................................................................................................56
Chapter 6: Safety Risk Management of Software. ............................................................................................................59
Mikael Dahlke, MSc, and Robert Ginsberg, MSc
Introduction. ...................................................................................................................................................................................59
The History of Software Safety Risk Management.........................................................................................................................60
1985-1987: Therac-25: Software Controlling a Therapy Device.................................................................................................60
2001: Multidata, National Cancer Institute, Panama City: Radiation Planning Software. ........................................................60
2020: COVID-19 Tests..............................................................................................................................................................61
Summary. ...................................................................................................................................................................................61
Aspects of Software in Risk Management According to ISO 14971. .............................................................................................61
Hazardous Situation Example....................................................................................................................................................61
Examples. ...................................................................................................................................................................................62
Challenges With Software Risk Assessment...................................................................................................................................62
Challenges With Analyzing Hazards Causing Indirect Harm...................................................................................................62
Challenges Related to ML Medical Devices..............................................................................................................................63
Challenges With Probability Estimates for Software.................................................................................................................63