MEDICAL DEVICE DESIGN FOR SIX SIGMA

MEDICAL DEVICE DESIGN FOR SIX SIGMA A Road Map for Safety and Effectiveness BASEM S. EL-HAIK KHALID S. MEKKI WILEY- INTERSCIENCE A JOHN WILEY & SONS, INC., PUBLICATION

CONTENTS Foreword Preface xvii xix 1 Medical Device Design Quality 1 1.1 Introduction, 1 1.2 The Essence of Quality, 2 1.3 Quality Operating System and the Device Life Cycle, 5 1.3.1 Stage 1: Idea Creation, 6 1.3.2 Stage 2: Voice of the Customer and Business, 7 1.3.3 Stage 3: Concept Development, 8 1.3.4 Stage 4: Preliminary Design, 9 1.3.5 Stage 5: Design Optimization, 9 1.3.6 Stage 6: Verification and Validation, 9 1.3.7 Stage 7: Launch Readiness, 10 1.3.8 Stage 8: Mass Production, 10 1.3.9 Stage 9: Consumption, 11 1.3.10 Stage 10: Disposal or Phaseout, 11 1.4 Evolution of Quality, 11 1.4.1 Statistical Analysis and Control, 12 1.4.2 Root-Cause Analysis, 13 1.4.3 Total Quality Management, 13 1.4.4 Design Quality, 14 1.4.5 Process Simplification, 15 1.4.6 Six Sigma and Design for Six Sigma, 15

viii CONTENTS 1.5 Business Excellence: A Value Proposition, 17 1.5.1 Business Operation Model, 17 1.5.2 Structure of the Medical Device Quality Function, 18 1.5.3 Quality and Cost, 22 1.5.4 Quality and Time to Market, 23 1.6 Summary, 23 2 Design for Six Sigma and Medical Device Regulation 25 2.1 Introduction, 25 2.2 Global Perspective on Medical Device Regulations, 25 2.3 Medical Device Classification, 28 2.4 Medical Device Safety, 29 2.5 Medical Device Quality Management Systems Requirements, 31 2.6 Medical Device Regulation Throughout the Product Development Life Cycle, 34 2.6.1 Design and Development Plan, 36 2.6.2 Design Input, 42 2.6.3 Design Output, 44 2.6.4 Design Review, 46 2.6.5 Design Verification and Validation, 47 2.6.6 Design Transfer, 49 2.6.7 Design Changes, 50 2.6.8 Design History File, 50 2.6.9 QSIT Design Control Inspectional Objectives, 51 2.7 Summary, 52 3 Basic Statistics 53 3.1 Introduction, 53 3.2 Common Probability Distributions, 53 3.3 Methods of Input and Output Analysis, 56 3.4 Descriptive Statistics, 58 3.4.1 Measures of Central Tendency, 59 3.4.2 Measures of Dispersion, 61 3.5 Inferential Statistics, 63 3.5.1 Parameter Estimation, 63 3.5.2 Hypothesis Testing, 65 3.5.3 Experimental Design, 69 3.6 Normal Distribution and Normality Assumption, 70 3.6.1 Violating the Normality Assumption, 72 3.7 Summary, 72

4 The Six Sigma Process 73 4.1 Introduction, 73 4.2 Six Sigma Fundamentals, 73 4.3 Process Modeling, 74 4.3.1 Process Mapping, 74 4.3.2 Value Stream Mapping, 75 4.4 Business Process Management, 76 4.5 Measurement Systems Analysis, 77 4.6 Process Capability and Six Sigma Process Performance, 78 4.6.1 Motorola's Six Sigma Quality, 82 4.7 Overview of Six Sigma Improvement, 84 4.7.1 Phase 1: Define, 84 4.7.2 Phase 2: Measure, 84 4.7.3 Phase 3: Analyze, 85 4.7.4 Phase 4: Improve, 85 4.7.5 Phase 5: Control, 85 4.8 Six Sigma Gose Upstream: Design for Six Sigma, 86 4.9 Summary, 86 Appendix 4A: Cause-and-Effect Tools, 87 5 Medical Device Design for Six Sigma 89 5.1 Introduction, 89 5.2 Value of Designing for Six Sigma, 91 5.3 Medical Device DFSS Fundamentals, 94 5.4 The ICOV Process in Design, 96 5.5 The ICOV Process in Product Development, 98 5.6 Summary, 100 6 Medical Device DFSS Deployment 101 6.1 Introduction, 101 6.2 Medical Device DFSS Deployment Fundamentals, 102 6.3 Predeployment Phase, 103 6.3.1 Predeployment Considerations, 105 6.4 Deployment Phase, 125 6.4.1 Training, 126 6.4.2 Project Financials, 127 6.5 Postdeployment Phase, 128 6.6 DFSS Sustainability Factors, 129 6.7 Black Belts and the DFSS Team: Cultural Change, 132 6.8 Summary, 135 7 Medical Device DFSS Project Road Map 137 7.1 Introduction, 137 7.2 Medical Device DFSS Team, 139 ix

X CONTENTS 7.3 Medical Device DFSS Road Map, 143 7.3.1 Phase 1: Identify Requirements, 144 7.3.2 Phase 2: Characterize Design, 148 7.3.3 Phase 3: Optimize Requirements, 151 7.3.4 Phase 4: Verify/Validate the Design, 152 7.4 Software DFSS ICOV Process, 154 7.5 Summary, 157 8 Quality Function Deployment 159 8.1 Introduction, 159 8.2 History of QFD, 160 8.3 QFD Fundamentals, 161 8.4 QFD Methodology, 161 8.5 HQQ Evaluation, 164 8.6 HQQ 1: The Customer's House, 165 8.6.1 Kano Model, 167 8.7 HQQ 2: Translation House, 170 8.8 HQQ 3: Design House, 171 8.9 HQQ 4: Process House, 171 8.10 Application: Auto 3D, 172 8.11 Summary, 175 9 DFSS Axiomatic Design Method 177 9.1 Introduction, 177 9.2 Axiomatic Method Fundamentals, 179 9.3 Introduction to Axiom 1, 183 9.4 Introduction to Axiom 2, 185 9.5 Axiomatic Design Theorems and Corollaries, 189 9.6 Application: Medication Mixing Machine, 192 9.7 Application: Axiomatic Design Applied to Design Controls, 193 9.8 Summary, 196 Appendix 9A: Matrix Review, 196 10 DFSS Innovation for Medical Devices 198 10.1 Introduction, 198 10.2 History of the Theory of Inventive Problem Solving, 198 10.3 TRIZ Fundamentals, 200 10.3.1 Overview, 200 10.3.2 Analytical Tools, 204 10.3.3 Knowledge-Based Tools, 204 10.4 TRIZ Problem-Solving Process, 209 10.5 Ideal Final Result, 210

CONTENTS 10.5.1 Itself Method, 210 10.5.2 Ideality Checklist, 211 10.5.3 Ideality Equation, 211 10.6 Building Sufficient Functions, 212 10.7 Eliminating Harmful Functions, 212 10.8 Inventive Principles, 213 10.9 Detection and Measurement Concepts, 219 10.10 TRIZ Root Cause Analysis, 220 10.11 Evolution trends in Technological Systems, 221 10.12 TRIZ Functional Analysis and Analogy, 224 10.13 Application: Using Triads to Predict and Conceive Next-Generation Products, 225 10.14 Summary, 234 Appendix 10A: Contradiction Matrix, 234 11 DFSS Risk Management Process 240 11.1 Introduction, 240 11.2 Planning for Risk Management Activities in Design and Development, 241 11.3 Risk Assessment Techniques, 244 11.3.1 Preliminary Hazard Analysis, 245 11.3.2 Hazard and Operability Study, 245 11.3.3 Failure Mode and Effects Analysis, 245 11.3.4 Fault Tree Analysis, 246 11.4 Risk Evaluation, 248 11.5 Risk Control, 250 11.6 Postproduction Control, 250 11.7 Summary, 250 Appendix HA: Robust Design Failure Mode and Effects Analysis, 251 11A.1 Parameter Diagram, 252 11A.2 Robust Design FMEA Elements, 253 12 Medical Device Design for X 259 12.1 Introduction, 259 12.2 Design for Reliability, 262 12.3 Design for Packaging, 265 12.4 Design for Manufacture and Design for Assembly, 269 12.4.1 DFMA Approach, 269 12.4.2 DFMA in the ICOV DFSS Process, 271 12.4.3 DFMA Best Practices, 274 12.4.4 Example, 280 12.5 Design for Maintainability, 281 12.6 Design for Serviceability, 282

XII CONTENTS 12.6.1 DFS Guidelines, 282 12.6.2 Application: Pressure Recorder PCB Replacement, 285 12.7 Summary, 290 13 DFSS Transfer Function and Scorecards 291 13.1 Introduction, 291 13.2 Design Mapping, 292 13.2.1 Functional Mapping, 293 13.2.2 Process Mapping, 294 13.2.3 Design Mapping Steps, 297 13.3 Design Scorecards and the Transfer Function, 297 13.3.1 DFSS Scorecard Development, 299 13.3.2 Transfer Function Life Cycle, 299 13.4 Transfer Function Mathematics, 302 13.5 Transfer Function and Optimization, 306 13.6 Monte Carlo Simulation, 308 13.7 Summary, 309 14 Fundamentals of Experimental Design 311 14.1 Introduction, 311 14.2 Classical Design of Experiments, 314 14.2.1 Study Definition, 314 14.3 Factorial Experiment, 324 14.3.1 Mathematical Transfer Function, 325 14.3.2 Interaction Between Factors, 325 14.4 Analysis of Variance, 327 14.5 2 k Füll Factorial Designs, 332 14.5.1 Design Layout, 333 14.5.2 Data Analysis, 334 14.5.3 DOE Application, 334 14.5.4 The 2 3 Design, 341 14.5.5 The 2 3 Design with Center Points, 342 14.6 Fractional Factorial Designs, 343 14.6.1 The 2" Design, 344 14.6.2 Half-Fractional 2 k Design, 345 14.6.3 Design Resolution, 346 14.6.4 One-Fourth Fractional 2 k Design, 347 14.7 Other Factorial Designs, 349 14.7.1 Three-Level Factorial Design, 349 14.7.2 Box-Behnken Designs, 350 14.8 Summary, 350 Appendix 14A, 351 14A.1 Diagnostic Plots of Residuais, 351 14A.2 Pareto Chart of Effects, 351

CONTENTS xiii 14A.3 Square and Cube Plots, 351 14A.4 Interaction Plots, 352 15 Robust Parameter Design for Medical Devices 353 15.1 Introduction, 353 15.2 Robust Design Fundamentals, 354 15.2.1 Robust Design and DFSS, 355 15.3 Robust Design Concepts, 357 15.3.1 Concept 1: Output Classification, 357 15.3.2 Concept 2: Quality Loss Function, 358 15.3.3 Concept 3: Signal, Noise, and Control Factors, 361 15.3.4 Concept 4: Signal-to-Noise Ratios, 362 15.3.5 Concept 5: Orthogonal Arrays, 363 15.3.6 Concept 6: Parameter Design Analysis, 365 15.4 Application: Dynamic Formulation, 368 15.5 Summary, 376 16 Medical Device Tolerance Design 377 16.1 Introduction, 377 16.2 Tolerance Design and DFSS, 378 16.2.1 Application: Imprecise Measurements, 380 16.3 Worst-Case Tolerance, 382 16.3.1 Application: Internal Pressures in Disposable Tubing, 383 16.4 Statistical Tolerances, 388 16.4.1 Relationship of Tolerance to Process Capabilities, 389 16.4.2 Linear Statistical Tolerance, 389 16.4.3 Nonlinear Statistical Tolerance, 391 16.5 Taguchi's Loss Function and Safety Tolerance Design, 394 16.5.1 Nominal-the-Best Tolerance Design, 394 16.5.2 Smaller-the-Better Tolerance Design, 396 16.5.3 Larger-the-Better Tolerance Design, 397 16.6 High- vs. Low-Level Requirements' Tolerance Relationships, 398 16.6.1 Tolerance Allocation for Multiple Parameters, 399 16.7 Taguchi's Tolerance Design Experiment, 400 16.7.1 Application: Tolerance Design, 402 16.8 Summary, 404 17 Medical Device DFSS Verifikation and Validation 405 17.1 Introduction, 405 17.2 Design Verification Process, 408 17.2.1 Building a Verification Prototype, 416

xiv CONTENTS 17.2.2 Prototype Testing, 417 17.2.3 Confidence Interval of Small-Sample Veriflcation, 418 17.3 Production Process Validation, 419 17.3.1 Device Veriflcation Analysis, 427 17.4 Software Validation, 428 17.5 Design Validation, 429 17.6 Summary, 430 18 DFSS Design Transfer 431 18.1 Introduction, 431 18.2 Design Transfer Planning, 432 18.3 Process Control Plan, 433 18.4 Statistical Process Control, 434 18.4.1 Choosing the Control Chart, 435 18.4.2 Interpreting the Control Chart, 437 18.4.3 Taking Action, 438 18.5 Process Capability, 438 18.6 Advanced Product Quality Planning, 439 18.6.1 APQP Procedure, 440 18.6.2 Product Part Approval Process, 444 18.7 Device Master Record, 446 18.7.1 Document for Intended Employees, 449 18.7.2 Adequate Information, 451 18.7.3 Preparation and Signatures, 452 18.8 Summary, 453 19 Design Change Control, Design Review, and Design History File 454 19.1 Introduction, 454 19.2 Design Change Control Process, 455 19.2.1 Pre- and Postdesign Transfer CCP, 455 19.3 Design Review, 457 19.4 Design History File, 459 19.5 Summary, 460 20 Medical Device DFSS Case Study 462 20.1 Introduction, 462 20.2 DFSS Identify Phase, 462 20.3 DFSS Characterize Phase, 467 20.4 DFSS Optimize Phase, 470 20.4.1 DOE Optimization Analysis, 476 20.4.2 DOE Optimization Conclusions, 476 20.4.3 DOE Confirmation Run, 479

CONTENTS xv 20.5 DFSS Verify/Validate Phase, 480 20.6 Summary, 487 Glossary: DFSS Terminology 488 Appendix: Statistical Tables 497 References 510 Index 523