Medical Device Validation Handbook
vi Regulatory Affairs Professionals Society (RAPS)
Figure 7-14. I-MR Chart of Seal Strength by Stage......................................................................... 112
Figure 7-15. Waterfall Model (Verification and Validation). ............................................................113
Figure 7-16. Traditional PQ Model.................................................................................................. 113
Figure 7-17. MPQ Approach Model................................................................................................ 114
Figure 9-1. Examples of Typical Reusable Medical Devices. ..........................................................125
Figure 9-2. Notebook Studies Can Provide Data to Build Appropiate Validation Activities.......... 129
Figure 9-3. Automated Cleaning Equipment Typically Should be Validated Prior to Use............. 132
Figure 11-1. Organizational Involvement in UDI Implementation.................................................. 164
Figure 11-2. GHTF Process Validation Decision Tree. ....................................................................170
Figure 12-1. The Equipment Verification and Validation Cycle, Simplified. ....................................174
Figure 12-2. Application of Design Controls to Waterfall Design Process....................................... 176
Figure 12-3. Suggested/Possible V&V Test Case/Script Format...................................................... 181
Figure 12-4. Typical Product Development Milestones With V&V Tasks....................................... 184
Figure 13-1. Application of Design Controls to Waterfall Design Process....................................... 188
Figure 13-2. Typical Operating Characteristic Curve (OC). ............................................................190
Figure 13-3. Equivalence. .................................................................................................................192
Figure 14-1. Example of a Discretized Solid Model......................................................................... 203
Figure 14-2. Fatigue Test of Femoral Knee Condyle. .......................................................................204
Figure 14-3. Load and Constraint Applied to a Finite Element Model of a Femoral Knee and
Maximum Principal Stress in the Implant.................................................................... 204
Figure 14-4. Contour Plot of von Mises Equivalent Stress Distribution in a Carotid Artery
Wall After Stent Expansion. ........................................................................................205
Figure 14-5. Credibility Factors for Modeling and Simulation......................................................... 210
Figure 14-6. Sample Credibility Assessment With Threshold Shown in Dark Gray and
Achieved Scores in Light Gray..................................................................................... 210
Figure 15-1. Additive Manufacturing Process and Related Draft Guidance Sections. .....................216
Figure 17-1. Validation Elements. ....................................................................................................244
Figure 17-2. Surgical Tool Assembly and Laser Seam Weld............................................................. 245
Figure 17-3. PQ Components........................................................................................................... 246
Figure 17-4. Fixed Input Factors. .....................................................................................................247
Figure 17-5. Variable Input Factor Range......................................................................................... 247
Figure 17-6. DoE ANOVA Results.................................................................................................. 248
Figure 17-7. Marginal Means Graph for Burst Pressure................................................................... 248
Figure 17-8. Optimized Laser Welding Parameters.......................................................................... 249
Figure 17-9. PQ Challenge Laser-Welding Parameters.................................................................... 249
Figure 17-10. Weld Location Measurement....................................................................................... 250
Figure 17-11. Z-Test Results, PQ Challenge Test.............................................................................. 250
Figure 18-1. Disinfectant Application Technique............................................................................. 256
Figure 18-2. Triple Cleaning Effectiveness Demonstrated by Viable Particulate Surface
Sampling....................................................................................................................... 257
Figure 18-3. Cleaning Required for New Build Certification........................................................... 257
Figure 18-4. Example of Pressure Differentials Through an Aseptic Facility.................................... 258
vi Regulatory Affairs Professionals Society (RAPS)
Figure 7-14. I-MR Chart of Seal Strength by Stage......................................................................... 112
Figure 7-15. Waterfall Model (Verification and Validation). ............................................................113
Figure 7-16. Traditional PQ Model.................................................................................................. 113
Figure 7-17. MPQ Approach Model................................................................................................ 114
Figure 9-1. Examples of Typical Reusable Medical Devices. ..........................................................125
Figure 9-2. Notebook Studies Can Provide Data to Build Appropiate Validation Activities.......... 129
Figure 9-3. Automated Cleaning Equipment Typically Should be Validated Prior to Use............. 132
Figure 11-1. Organizational Involvement in UDI Implementation.................................................. 164
Figure 11-2. GHTF Process Validation Decision Tree. ....................................................................170
Figure 12-1. The Equipment Verification and Validation Cycle, Simplified. ....................................174
Figure 12-2. Application of Design Controls to Waterfall Design Process....................................... 176
Figure 12-3. Suggested/Possible V&V Test Case/Script Format...................................................... 181
Figure 12-4. Typical Product Development Milestones With V&V Tasks....................................... 184
Figure 13-1. Application of Design Controls to Waterfall Design Process....................................... 188
Figure 13-2. Typical Operating Characteristic Curve (OC). ............................................................190
Figure 13-3. Equivalence. .................................................................................................................192
Figure 14-1. Example of a Discretized Solid Model......................................................................... 203
Figure 14-2. Fatigue Test of Femoral Knee Condyle. .......................................................................204
Figure 14-3. Load and Constraint Applied to a Finite Element Model of a Femoral Knee and
Maximum Principal Stress in the Implant.................................................................... 204
Figure 14-4. Contour Plot of von Mises Equivalent Stress Distribution in a Carotid Artery
Wall After Stent Expansion. ........................................................................................205
Figure 14-5. Credibility Factors for Modeling and Simulation......................................................... 210
Figure 14-6. Sample Credibility Assessment With Threshold Shown in Dark Gray and
Achieved Scores in Light Gray..................................................................................... 210
Figure 15-1. Additive Manufacturing Process and Related Draft Guidance Sections. .....................216
Figure 17-1. Validation Elements. ....................................................................................................244
Figure 17-2. Surgical Tool Assembly and Laser Seam Weld............................................................. 245
Figure 17-3. PQ Components........................................................................................................... 246
Figure 17-4. Fixed Input Factors. .....................................................................................................247
Figure 17-5. Variable Input Factor Range......................................................................................... 247
Figure 17-6. DoE ANOVA Results.................................................................................................. 248
Figure 17-7. Marginal Means Graph for Burst Pressure................................................................... 248
Figure 17-8. Optimized Laser Welding Parameters.......................................................................... 249
Figure 17-9. PQ Challenge Laser-Welding Parameters.................................................................... 249
Figure 17-10. Weld Location Measurement....................................................................................... 250
Figure 17-11. Z-Test Results, PQ Challenge Test.............................................................................. 250
Figure 18-1. Disinfectant Application Technique............................................................................. 256
Figure 18-2. Triple Cleaning Effectiveness Demonstrated by Viable Particulate Surface
Sampling....................................................................................................................... 257
Figure 18-3. Cleaning Required for New Build Certification........................................................... 257
Figure 18-4. Example of Pressure Differentials Through an Aseptic Facility.................................... 258