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Design of Biomedical Devices
and Systems
Design of Biomedical Devices
and Systems
Fourth Edition

Paul H. King, Richard C. Fries, and Arthur T. Johnson

CRC Press
Taylor & Francis Group
6000 Broken Sound Parkway NW, Suite 300
Boca Raton, FL 33487-2742

© 2019 by Taylor & Francis Group, LLC

CRC Press is an imprint of Taylor & Francis Group, an Informa business

No claim to original U.S. Government works

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International Standard Book Number-13: 978-1-138-72306-1 (Hardback)

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Library of Congress Cataloging‑in‑Publication Data

Names: King, Paul H., 1941- author. | Fries, Richard C., author. | Johnson,
Arthur T. (Arthur Thomas), 1941- author.
Title: Design of biomedical devices and systems / Paul H. King, Richard C.
Fries, Arthur T. Johnson.
Description: Fourth edition. | Boca Raton: Taylor & Francis, 2018. | “A CRC
title, part of the Taylor & Francis imprint, a member of the Taylor &
Francis Group, the academic division of T&F Informa plc.” |
Includes bibliographical references and index.
Identifiers: LCCN 2018025828 | ISBN 9781138723061 (hardback: alk. paper)
Subjects: LCSH: Biomedical engineering.
Classification: LCC R856 .K53 2018 | DDC 610.28—dc23
LC record available at https://lccn.loc.gov/2018025828

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 Whose friendship, support, and love
make me whole.
Richard C. Fries
and
In appreciation for the special people in my life who
have greatly helped me to get this far.
Arthur T. Johnson
Contents
Preface..........................................................................................................................................xxvii
Acknowledgments..........................................................................................................................xxxi
Authors........................................................................................................................................ xxxiii

Chapter 1 Introduction to Biomedical Engineering Design..........................................................1

1.1 What Is Design?..................................................................................................1
1.2 What Is the Thrust of This Text?........................................................................2
1.3 What Might Be Designed?.................................................................................2
1.4 The Essentials of Design—Overview................................................................3
1.5 Biomedical Engineering Design in an Industrial Context................................. 3
1.6 An Overview of the Industrial Design Process..................................................5
1.7 How This Text Is Structured..............................................................................7
1.8 The Real Purpose of This Text...........................................................................7
1.9 Case Study..........................................................................................................7
Homework Exercises.....................................................................................................9
Notes���������������������������������������������������������������������������������������������������������������������������10

Chapter 2 Fundamental Idea Generation Techniques, Process Analysis Tools, and

Evaluation Methods..................................................................................................... 11
2.1  undamental Idea Generation Techniques....................................................... 11
F
2.1.1 Immersion........................................................................................... 11
2.1.2 Removal............................................................................................... 12
2.1.3 Group Brainstorming.......................................................................... 12
2.1.4 Method 635.......................................................................................... 13
2.1.5 Delphi Method (Expert Opinion Extraction)...................................... 13
2.1.6 Synectics.............................................................................................. 13
2.1.7 Thinking Caps..................................................................................... 14
2.1.8 Conventional Solution Searches.......................................................... 14
2.1.8.1 Web-Based and Print Literature.......................................... 14
2.1.8.2 Solutions in Nature and Analogies...................................... 15
2.1.9 SCAMPER.......................................................................................... 15
2.1.10 Beyond SCAMPER, Design Cards..................................................... 17
2.1.11 Introduction to TRIZ........................................................................... 17
2.1.12 Extended TRIZ Design Techniques.................................................... 18
2.1.12.1 The Use of Innovation Workbench...................................... 18
2.1.12.2 Ideation Process................................................................... 19
2.1.12.3 Summary............................................................................. 22
2.2 Function Analysis............................................................................................. 22
2.2.1 Simple Process Charts......................................................................... 23
2.2.2 Clinic Flowcharts................................................................................ 23
2.2.3 Flowcharts with Decision Points.........................................................24
2.2.4 Case Study: Cancer Clinic Charting...................................................26
2.2.4.1 Background..........................................................................26
2.2.4.2 Problem Statement...............................................................26
2.2.4.3 Problem Solution.................................................................26

vii
viii Contents

2.3  lementary Decision-Making Techniques.......................................................26

E
2.3.1 Selection Chart....................................................................................28
2.3.2 Evaluation Charts................................................................................ 29
2.4 Objective Trees................................................................................................. 29
2.5 Introduction to QFD Diagrams........................................................................ 30
2.6 Prototyping....................................................................................................... 32
2.7 Summary.......................................................................................................... 32
Homework Exercises................................................................................................... 32
Suggested Reading...................................................................................................... 33

Chapter 3 Design Team Management, Reporting, and Documentation...................................... 35

3.1 Design Team Construction and Management (Industry-Based)...................... 35
3.1.1 Definition of a Team............................................................................ 36
3.1.2 Characteristics of Teams..................................................................... 36
3.1.3 Team Success Factors.......................................................................... 37
3.1.4 The Team Leader................................................................................ 38
3.1.5 The Design Team................................................................................ 39
3.1.5.1 The Core Product Team....................................................... 39
3.1.5.2 The Working Design Team..................................................40
3.2 Student Design Team Construction and Management.....................................40
3.2.1 Definition of a Student Team..............................................................40
3.2.2 Characteristics of Student Teams........................................................40
3.2.3 Team Success Factors.......................................................................... 41
3.2.4 The Team Leader................................................................................ 41
3.2.5 Special Considerations for Student Design Teams.............................. 41
3.3 Reporting Techniques: Presentations, Posters, Reports, and Websites............ 42
3.3.1 Progress Reports: Written................................................................... 42
3.3.1.1 P rogress Report: EKG Transmitter Project—
Week 7 of 11�������������������������������������������������������������������� 42
3.3.1.2 Progress Report: Transmitter Project, Week 12 of 11
(Sorry This Is Late!)����������������������������������������������������������� 43
3.3.2 Oral Reporting.................................................................................... 43
3.3.3 Poster Presentations............................................................................44
3.3.4 Websites............................................................................................... 45
3.3.5 Expectations for Communications...................................................... 45
3.4 Introduction to Design Project Data Management........................................... 47
3.4.1 Excel Spreadsheets.............................................................................. 47
3.4.2 Databases............................................................................................. 47
3.4.3 Example 3.1: Pain Clinic Database Development............................... 48
3.4.4 R EDCap.............................................................................................. 49
Homework Exercises................................................................................................... 51
Suggested Reading...................................................................................................... 51

Chapter 4 Product Definition....................................................................................................... 53

4.1  hat Is a Medical Device?............................................................................... 53
W
4.1.1 Food and Drug Administration Definition.......................................... 53
4.1.2 The European Union Medical Device Directives Definition.............. 54
4.2 The Product Definition Process........................................................................ 54
4.2.1 Surveying the Customer...................................................................... 54
Contents ix

4.2.2 Defining the Company’s Needs........................................................... 55

4.2.3 What Are the Company’s Competencies?........................................... 55
4.2.4 What Are the Outside Competencies?................................................ 55
4.2.5 Completing the Product Definition..................................................... 55
4.3 The QFD Process............................................................................................. 56
4.3.1 The Voice of the Customer.................................................................. 56
4.3.2 The Technical Portion of the Matrix................................................... 56
4.3.3 Overview of the QFD Process............................................................. 58
4.4 Summary of QFD............................................................................................. 61
4.5 Requirements, Design, Verification, and Validation........................................ 62
4.5.1 Refinement of Requirements...............................................................64
4.5.2 Assimilation of Requirements.............................................................64
4.5.3 Requirements Versus Design.............................................................. 65
4.6 The Product Design Specification....................................................................66
4.7 The Student Product Specification................................................................... 68
4.8 Conclusion........................................................................................................ 70
Homework Exercises................................................................................................... 70
Suggested Reading...................................................................................................... 70
Suggested Web References.......................................................................................... 71

Chapter 5 Product Documentation............................................................................................... 73

5.1 Documents........................................................................................................ 74
5.1.1 The Business Proposal........................................................................ 74
5.1.1.1 Project Overview, Objectives, Major Milestones, and
Schedule������������������������������������������������������������������������������ 74
5.1.1.2 Market Need and Market Potential..................................... 75
5.1.1.3 Product Proposal.................................................................. 76
5.1.1.4 Strategic Fit.......................................................................... 76
5.1.1.5 Risk Analysis and Research Plan........................................ 76
5.1.1.6 Economic Analysis.............................................................. 77
5.1.1.7 Core Project Team............................................................... 77
5.1.2 Product Specification.......................................................................... 78
5.1.3 Design Specification............................................................................ 79
5.1.4 Software Quality Assurance Plan.......................................................80
5.1.4.1 Purpose................................................................................80
5.1.4.2 Reference Documents..........................................................80
5.1.4.3 Management........................................................................80
5.1.4.4 Documentation.....................................................................80
5.1.4.5 Standards, Practices, Conventions, and Metrics..................80
5.1.4.6 Review and Audits...............................................................80
5.1.4.7 Test....................................................................................... 81
5.1.4.8 Problem Reporting and Corrective Action.......................... 81
5.1.4.9 Tools, Techniques, and Methodologies................................ 81
5.1.4.10 Code Control........................................................................ 81
5.1.4.11 Media Control...................................................................... 81
5.1.4.12 Supplier Control................................................................... 81
5.1.4.13 Records Collection, Maintenance, and Retention............... 81
5.1.4.14 Training............................................................................... 81
5.1.4.15 Risk Management................................................................ 81
5.1.4.16 Additional Sections as Required......................................... 81
x Contents

5.1.5
 oftware Requirements Specification................................................. 81
S
5.1.5.1 Purpose................................................................................ 82
5.1.5.2 Scope.................................................................................... 82
5.1.5.3 Definitions, Acronyms, and Abbreviations......................... 82
5.1.5.4 References............................................................................ 82
5.1.5.5 Overview.............................................................................. 82
5.1.5.6 Product Perspective............................................................. 82
5.1.5.7 Product Functions................................................................ 82
5.1.5.8 User Characteristics............................................................. 82
5.1.5.9 General Constraints............................................................. 83
5.1.5.10 Assumptions and Dependencies.......................................... 83
5.1.5.11 Specific Requirements......................................................... 83
5.1.6 Software Design Description.............................................................. 83
5.1.6.1 Introduction......................................................................... 83
5.1.6.2 References............................................................................84
5.1.6.3 Decomposition Description.................................................84
5.1.6.4 Dependency Description......................................................84
5.1.6.5 Interface Description...........................................................84
5.1.6.6 Detailed Design Description...............................................84
5.2 Records.............................................................................................................84
5.2.1 The DHF..............................................................................................84
5.2.2 The DMR............................................................................................ 86
5.2.3 The DHR............................................................................................. 86
5.2.4 The TDF.............................................................................................. 86
5.3 A Comparison of the Medical Device Records................................................ 87
5.4 Expectations for Student Project Documentation............................................ 87
5.4.1 Example 5.1 Design Notebook Grading��������������������������������������������� 87
5.4.2 Final Design Project Written Report Grading Sheet Example 5.2........ 90
5.4.3 Senior Design Project Poster and Paper Grading Sheet, ABET
Based, Example 5.3���������������������������������������������������������������������������� 91
Homework Exercises...................................................................................................92
Suggested Reading......................................................................................................92

Chapter 6 Product Development.................................................................................................. 95

6.1  roduct Requirements...................................................................................... 95
P
6.2 Design and Development Planning..................................................................96
6.2.1 Design and Development Plan............................................................97
6.2.1.1 Program Goals.....................................................................97
6.2.1.2 Design and Development Elements.....................................97
6.2.1.3 Organizational and Key Interfaces...................................... 98
6.2.1.4 Deliverables and Responsibilities........................................ 98
6.2.1.5 Design and Development Schedule..................................... 98
6.2.1.6 Approve Design and Development Plan..............................99
6.2.1.7 Incorporate Updates to Design and Development Plan.......99
6.3 System Requirements Specification.................................................................99
6.4 Design Input.....................................................................................................99
6.4.1 Product Requirements....................................................................... 100
6.5  esign Output................................................................................................. 100
D
6.5.1 Intermediate Design Output.............................................................. 101
6.5.2 Final Design Output.......................................................................... 101
Contents xi

6.6  ormal Design Review................................................................................... 102

F
6.6.1 Action Tracking and Issue Resolution............................................... 102
6.7 Design Verification......................................................................................... 102
6.7.1 Design Verification Plan.................................................................... 102
6.7.2 Design Verification Test Methods..................................................... 102
6.7.3 Design Verification Report................................................................ 103
6.8 Design Validation........................................................................................... 103
6.8.1 Design Validation Plan...................................................................... 103
6.8.2 Design Validation Test Methods....................................................... 104
6.8.3 Design Validation Report.................................................................. 105
6.9 Design Transfer.............................................................................................. 105
6.10 Role of the Intern............................................................................................ 105
6.11 Student Project Development Expectations.................................................... 105
Homework Exercises................................................................................................. 106
Suggested Reading.................................................................................................... 106
Web References......................................................................................................... 107

Chapter 7 Hardware Development Methods and Tools............................................................. 109

7.1  esign for Six Sigma...................................................................................... 109
D
7.2 Methodologies................................................................................................ 110
7.3 Structure......................................................................................................... 111
7.4 DFSS Tools..................................................................................................... 111
7.4.1 Robust Design................................................................................... 112
7.4.1.1 Why Use the Robust Design Methodology?...................... 112
7.4.1.2 Typical Problems Addressed By Robust Design............... 112
7.4.1.3 Robustness Strategy........................................................... 113
7.4.1.4 Quality Measurement........................................................ 113
7.4.1.5 S/N Ratio........................................................................... 114
7.4.2 Quality Function Deployment........................................................... 115
7.4.3 Robust Design Failure Mode and Effects Analysis.......................... 115
7.4.3.1 Benefits of a Robust DFMEA............................................ 116
7.4.3.2 The Parameter Diagram.................................................... 116
7.4.3.3 Performing a Robust DFMEA........................................... 117
7.4.3.4 Conclusion......................................................................... 121
7.4.4 Axiomatic Design.............................................................................. 121
7.4.4.1 What is Axiomatic Design?............................................... 121
7.4.4.2 Mapping of Axiomatic Design.......................................... 122
7.5 Component Derating...................................................................................... 124
7.6 Safety Margin................................................................................................. 125
7.7 Load Protection.............................................................................................. 126
7.8 Environmental Protection............................................................................... 126
7.9 Product Misuse............................................................................................... 126
7.10 Reliability Prediction...................................................................................... 127
7.10.1 Parts Count Prediction...................................................................... 127
7.10.2 Parts Count Example......................................................................... 129
7.10.3 Summary of Reliability Prediction................................................... 132
7.11 Design for Variation....................................................................................... 133
7.12 Design of Experiments................................................................................... 133
7.12.1 The Taguchi Method......................................................................... 133
7.13 Design Changes.............................................................................................. 133
xii Contents

7.14 D esign for Manufacturability......................................................................... 134

7.14.1 The DFM Process............................................................................. 135
7.15 Design for Assembly...................................................................................... 135
7.15.1 Overall Design Concept.................................................................... 135
7.15.2 Component Mounting....................................................................... 136
7.15.3 Test Points......................................................................................... 136
7.15.4 Stress Levels and Tolerances............................................................. 136
7.15.5 Printed Circuit Boards....................................................................... 136
7.15.6 Miscellaneous.................................................................................... 136
7.15.7 DFA Process...................................................................................... 136
7.16 Design Reviews.............................................................................................. 137
7.17 Expectations for Student Projects................................................................... 138
Homework Exercises................................................................................................. 138
Suggested Reading.................................................................................................... 139
Web References......................................................................................................... 139

Chapter 8 Software Development Methods and Tools............................................................... 141

8.1  oftware Design Levels.................................................................................. 141
S
8.2 Design Alternatives and Tradeoffs................................................................. 142
8.3 Software Architecture.................................................................................... 142
8.4 Choosing a Methodology................................................................................ 144
8.5 Structured Analysis........................................................................................ 144
8.6 Object-Oriented Design.................................................................................. 145
8.7 Choosing a Language..................................................................................... 145
8.8 Software Risk Analysis.................................................................................. 147
8.9  he RTM........................................................................................................ 147
T
8.10 S oftware Review............................................................................................. 148
8.11 Design Techniques.......................................................................................... 150
8.12 P erformance Predictability and Design Simulation....................................... 150
8.13 M odule Specifications.................................................................................... 151
8.14 C  oding............................................................................................................ 151
8.14.1 Structured Coding Techniques.......................................................... 151
8.14.2 Single-Entry, Single-Exit Constructs................................................ 152
8.14.3 Good Coding Practices..................................................................... 152
8.14.3.1 Review Every Line of Code............................................... 152
8.14.3.2 Require Coding Sign-Offs................................................. 154
8.14.3.3 Route Good Code Examples for Review........................... 154
8.14.3.4 Emphasize that Code Listings are Public Assets.............. 154
8.14.3.5 Reward Good Code........................................................... 154
8.14.3.6 One Easy Standard............................................................ 154
8.14.4 The Coding Process.......................................................................... 155
8.14.4.1 Start with a PDL................................................................ 155
8.14.4.2 Writing the Routine Declaration........................................ 155
8.14.4.3 Turning the PDL into High-Level Comments................... 155
8.14.4.4 Fill in the Code below Each Comment.............................. 155
8.14.4.5 Check the Code Informally............................................... 155
8.14.4.6 Clean Up the Leftovers...................................................... 156
8.14.4.7 Check the Code Formally.................................................. 156
8.14.5 Using Static Analysis to Check Code................................................ 156
8.14.6 Implementation Checklist................................................................. 158
Contents xiii

8.14.7 C oding Examples.............................................................................. 158

8.14.7.1 Example 1.......................................................................... 158
8.14.7.2 Example 2.......................................................................... 159
8.14.7.3 Example 3.......................................................................... 159
8.15 Design Support Tools..................................................................................... 160
8.16 Design as the Basis for Verification and Validation Activity......................... 160
8.17 Design Case Study 8.1.................................................................................... 160
8.18 Notes to Students............................................................................................ 161
8.19 Conclusion...................................................................................................... 161
Homework Exercises................................................................................................. 162
Suggested Reading.................................................................................................... 162
Web References......................................................................................................... 162

Chapter 9 Human Factors.......................................................................................................... 163

9.1 What Is Human Factors?................................................................................ 163
9.2 The Human Element in Human Factors Engineering.................................... 164
9.3 The Hardware Element in Human Factors..................................................... 165
9.4 Software Element in Human Factors.............................................................. 167
9.5 The Human Factors Process........................................................................... 168
9.6 Planning.......................................................................................................... 169
9.7 Analysis.......................................................................................................... 169
9.8 Conduct User Studies..................................................................................... 169
9.8.1 Observations...................................................................................... 169
9.8.2 Interviews.......................................................................................... 170
9.8.3 Focus Groups..................................................................................... 170
9.8.4 Task Analysis.................................................................................... 171
9.8.5 Benchmark Usability Test................................................................. 171
9.8.6 Write User Profile.............................................................................. 171
9.8.7 Setup an Advisory Panel................................................................... 171
9.9 Set Usability Goals......................................................................................... 171
9.10 Design User Interface Concepts..................................................................... 172
9.10.1 Develop Conceptual Model............................................................... 172
9.10.2 Develop User Interface Structure...................................................... 172
9.10.3 Define Interaction Style..................................................................... 172
9.10.4 Develop Screen Templates................................................................ 172
9.10.5 Develop Hardware Layout................................................................. 173
9.10.6 Develop a Screenplay........................................................................ 173
9.10.7 Develop a Refined Design and Final Design..................................... 173
9.11 Model the User Interface................................................................................ 173
9.12 Test the User Interface.................................................................................... 173
9.13 Specify the User Interface.............................................................................. 174
9.13.1 Style Guide........................................................................................ 174
9.13.2 Screen Hierarchy Map....................................................................... 174
9.13.3 Screenplay......................................................................................... 174
9.13.4 Specification Prototype..................................................................... 174
9.13.5 Hardware Layouts............................................................................. 174
9.14 Additional Human Factors Design Considerations........................................ 175
9.14.1 Consistency and Simplicity............................................................... 175
9.14.2 Safety................................................................................................. 175
9.14.3 Environmental/Organizational Considerations................................. 175
xiv Contents

9.14.4 Documentation.................................................................................. 176

9.14.5 Anthropometry.................................................................................. 176
9.14.6 Functional Dimensions...................................................................... 177
9.14.7 Psychological Elements..................................................................... 178
9.14.8 Workstation Design Considerations.................................................. 178
9.14.9 Alarms and Signals........................................................................... 179
9.14.10 Labeling............................................................................................. 181
9.14.11 Software............................................................................................ 182
9.14.12 Data Entry......................................................................................... 182
9.14.13 Displays............................................................................................. 183
9.14.14 Interactive Control............................................................................. 184
9.14.15 Feedback............................................................................................ 184
9.14.16 Prompts............................................................................................. 185
9.14.17 Defaults............................................................................................. 185
9.14.18 Data Correction................................................................................. 185
9.15 Fitts’ Law........................................................................................................ 185
9.15.1 The Model......................................................................................... 186
Homework Exercises................................................................................................. 186
Suggested Reading.................................................................................................... 187

Chapter 10 Industrial Design....................................................................................................... 189

10.1 Set Usability Goals......................................................................................... 190
10.2 Design UI Concepts........................................................................................ 190
10.2.1 Develop Conceptual Model............................................................... 191
10.2.2 Develop UI Structure........................................................................ 192
10.2.3 Define Interaction Style..................................................................... 192
10.2.4 Develop Screen Templates................................................................ 193
10.2.5 Develop Hardware Layout................................................................. 193
10.2.6 Develop a Screenplay........................................................................ 193
10.2.7 Develop a Refined Design................................................................. 193
10.2.8 Develop a Final Design..................................................................... 193
10.3 Model the UI.................................................................................................. 193
10.4 Test the UI...................................................................................................... 194
10.5 Specify the UI................................................................................................ 195
10.5.1 Style Guide........................................................................................ 195
10.5.2 Screen Hierarchy Map....................................................................... 195
10.5.3 Screenplay......................................................................................... 195
10.5.4 Specification Prototype..................................................................... 195
10.5.5 Hardware Layouts............................................................................. 195
10.6 Additional Industrial Design Considerations................................................. 195
10.6.1 Consistency and Simplicity............................................................... 195
10.6.2 Safety................................................................................................. 196
10.6.3 Environmental/Organizational Considerations................................. 196
10.6.4 Documentation.................................................................................. 196
10.6.5 Alarms and Signals........................................................................... 197
10.6.6 Displays............................................................................................. 199
10.6.7 Interactive Control.............................................................................200
10.6.8 Software............................................................................................ 201
10.6.9 Data Entry......................................................................................... 201
10.6.10 Feedback............................................................................................202
Contents xv

10.6.11 Error Management/Data Protection..................................................202

10.7 FDA Thoughts................................................................................................202
10.8 Lessons for Students.......................................................................................203
Homework Exercises.................................................................................................204
Suggested Readings...................................................................................................204
Web References.........................................................................................................205

Chapter 11 Biomaterials and Material Testing............................................................................207

11.1  he FDA and Biocompatibility......................................................................208
T
11.2 ISO 10993....................................................................................................... 211
11.3 Device Category and Choice of Test Program............................................... 213
11.4 Preparation of Extracts................................................................................... 214
11.5 Biological Control Tests................................................................................. 215
11.5.1 Microbiological Control Tests........................................................... 215
11.5.2 Tests for Endotoxins.......................................................................... 215
11.5.3 Test for Nonspecific Toxicity............................................................. 216
11.6 Tests for Biological Evaluation....................................................................... 216
11.6.1 Cytotoxicity....................................................................................... 216
11.6.2 Sensitization...................................................................................... 216
11.6.3 Skin Irritation.................................................................................... 217
11.6.4 Intracutaneous Reactivity.................................................................. 217
11.6.5 Acute Systemic Toxicity.................................................................... 217
11.6.6 Genotoxicity...................................................................................... 218
11.6.7 Implantation...................................................................................... 218
11.6.8 Hemocompatibility............................................................................ 218
11.6.9 Subchronic and Chronic Toxicity...................................................... 219
11.6.10 Carcinogenicity................................................................................. 219
11.7 Animal Testing............................................................................................... 219
11.7.1 Animal Models.................................................................................. 220
11.8 Nanotechnology.............................................................................................. 220
11.9 Alternative Test Methods............................................................................... 222
11.10 Endnote........................................................................................................... 223
Homework Exercises................................................................................................. 223
References................................................................................................................. 223
Suggested Readings...................................................................................................224
Web References.........................................................................................................224

Chapter 12 Risk Analysis—Devices and Processes.................................................................... 225

12.1  afety.............................................................................................................. 225
S
12.2 Risk................................................................................................................. 226
12.3 Deciding on Acceptable Risk......................................................................... 228
12.4 Factors Important for Medical Device Risk Assessment............................... 228
12.4.1 Device Design and Manufacture....................................................... 229
12.4.2 Materials............................................................................................ 229
12.4.3 Device Users...................................................................................... 229
12.4.4 Human Factors.................................................................................. 229
12.4.5 Medical Device Systems................................................................... 230
12.5 Risk Management........................................................................................... 230
12.6 The Risk Management Process...................................................................... 230
xvi Contents

12.6.1 Identifying the Risk Factors.............................................................. 230

12.6.2 Assessing Risk Probabilities and Risks on the Project..................... 231
12.6.3 Developing Strategies to Mitigate Identified Risks........................... 232
12.6.4 Monitoring Risk Factors................................................................... 232
12.6.5 Invoking a Contingency Plan............................................................ 232
12.6.6 Managing the Crisis.......................................................................... 233
12.6.7 Recovering from the Crisis............................................................... 233
12.7 Tools for Risk Estimation............................................................................... 233
12.7.1 Hazard/Risk Analysis....................................................................... 233
12.7.2 Failure Mode and Effects Analysis................................................... 235
12.7.3 Fault Tree Analysis............................................................................ 237
12.7.3.1 The FTA Process............................................................... 237
12.7.3.2 Example of an FTA........................................................... 238
12.8 Risk Analysis and Systems............................................................................. 239
12.8.1 Medical Case Example......................................................................240
12.8.2 Safety in Design................................................................................ 242
12.8.3 Medical Case Example—Revisited.................................................. 243
12.8.4 Process Improvement........................................................................244
12.8.5 Miscellaneous Issues......................................................................... 245
12.9 ISO 14971....................................................................................................... 245
12.10 Other Process Issues.......................................................................................246
12.11 Risk and the FDA........................................................................................... 247
12.12 MAUDE and MDR.........................................................................................248
12.13 Summary........................................................................................................ 249
Homework Exercises................................................................................................. 249
Notes�������������������������������������������������������������������������������������������������������������������������249
Suggested Reading.................................................................................................... 250
Web References......................................................................................................... 250

Chapter 13 Testing....................................................................................................................... 251

13.1 Testing Defined............................................................................................... 251
13.2 Parsing Test Requirements............................................................................. 252
13.3 Test Protocol................................................................................................... 253
13.4 Test Methodology........................................................................................... 254
13.4.1 Time Testing...................................................................................... 254
13.4.2 Event Testing..................................................................................... 254
13.4.3 Stress Testing.....................................................................................254
13.4.4 Environmental Testing...................................................................... 254
13.4.5 Time Related..................................................................................... 254
13.4.6 Failure Related.................................................................................. 255
13.5 Purpose of the Test......................................................................................... 255
13.6 Failure Definition........................................................................................... 255
13.7 Determining Sample Size and Test Length.................................................... 256
13.7.1 Example 13.1..................................................................................... 256
13.7.2 Example 13.2..................................................................................... 257
13.8 Types of Testing.............................................................................................. 258
13.8.1 Verification........................................................................................ 258
13.8.2 Validation.......................................................................................... 258
13.8.3 Black Box.......................................................................................... 258
13.8.4 White Box......................................................................................... 258
Contents xvii

13.8.5 Hardware Testing.............................................................................. 258

13.8.6 Software Testing................................................................................ 259
13.8.7 Functional Testing............................................................................. 259
13.8.8 Robustness Testing............................................................................260
13.8.9 Stress Testing..................................................................................... 261
13.8.10 Safety Testing.................................................................................... 261
13.8.11 Regression Testing............................................................................. 262
13.9 Highly Accelerated Stress Testing.................................................................. 263
13.10 Highly Accelerated Life Testing....................................................................264
13.11 Other Accelerated Testing..............................................................................266
13.11.1 Increased Sample Size.......................................................................266
13.11.2 Increased Test Severity......................................................................266
13.11.2.1 Example 13.3....................................................................266
13.11.2.2 Example 13.4.................................................................... 267
Homework Exercises................................................................................................. 268
Suggested Reading.................................................................................................... 269
Web References......................................................................................................... 269

Chapter 14 Analysis of Test Data................................................................................................ 271

14.1 T he Definition of Reliability.......................................................................... 271
14.2 Types of Reliability........................................................................................ 272
14.2.1 Electronic Reliability........................................................................ 272
14.2.1.1 Infant Mortality................................................................. 272
14.2.1.2 Useful Life......................................................................... 273
14.2.1.3 Wear-Out........................................................................... 273
14.2.2 Mechanical Reliability...................................................................... 273
14.2.3 Software Reliability.......................................................................... 274
14.2.4 System Reliability............................................................................. 276
14.3 Failure Rate.................................................................................................... 277
14.3.1 Example 14.1..................................................................................... 277
14.3.2 Example 14.2..................................................................................... 277
14.4 Mean Time Between Failures......................................................................... 278
14.4.1 Time Terminated, Failed Parts Replaced.......................................... 278
14.4.1.1 Example 14.3..................................................................... 278
14.4.2 Time Terminated, No Replacement.................................................. 279
14.4.3 Failure Terminated, Failed Parts Replaced....................................... 279
14.4.3.1 Example 14.4..................................................................... 279
14.4.4 Failure Terminated, No Replacement...............................................280
14.4.5 No Failures Observed........................................................................280
14.4.5.1 Example 14.5..................................................................... 281
14.5 Reliability....................................................................................................... 281
14.5.1 Example 14.6..................................................................................... 281
14.5.2 Example 14.7..................................................................................... 282
14.6 Confidence Level............................................................................................ 282
14.6.1 Example 14.8..................................................................................... 282
14.7 Confidence Limits.......................................................................................... 282
14.7.1 Time-Terminated Confidence Limits................................................ 283
14.7.1.1 Example 14.9...................................................................... 283
14.7.2 Failure-Terminated Confidence Limits.............................................284
14.8 Minimum Life................................................................................................284
xviii Contents

14.9 Graphical Analysis.........................................................................................284

14.9.1 Pareto Analysis..................................................................................284
14.9.2 Graphical Plotting............................................................................. 285
14.9.2.1 Example 14.10.................................................................... 285
14.9.2.2 Weibull Plotting................................................................. 286
Homework Exercises................................................................................................. 286
Suggested Reading.................................................................................................... 287
Web References......................................................................................................... 287

Chapter 15 Product Liability and Accident Investigations.......................................................... 289

15.1 P  roduct Liability Laws................................................................................... 289
15.1.1 Negligence......................................................................................... 289
15.1.2 Strict Liability...................................................................................290
15.1.3 Breach of Warranty........................................................................... 291
15.1.3.1 Implied Warranties............................................................ 291
15.1.3.2 Exclusion of Warranties..................................................... 291
15.1.4 Defects............................................................................................... 292
15.1.5 Failure to Warn of Dangers............................................................... 293
15.1.6 Plaintiff’s Conduct............................................................................ 293
15.1.7 Defendant’s Conduct......................................................................... 293
15.1.8 Defendant-Related Issues.................................................................. 294
15.1.9 Manufacturer’s and Physician’s Responsibilities.............................. 294
15.2 Accident Reconstruction and Forensics......................................................... 295
15.2.1 Medical Device Accident Investigations........................................... 295
15.2.2 Biomechanics and Traffic Accident Investigations........................... 299
15.3 Conclusion......................................................................................................300
Homework Exercises.................................................................................................300
Note��������������������������������������������������������������������������������������������������������������������������301
Suggested Reading.................................................................................................... 301

Chapter 16 The FDA and Devices............................................................................................... 303

16.1 H istory of Device Regulation......................................................................... 303
16.2 Device Classification...................................................................................... 305
16.2.1 Class I Devices.................................................................................. 305
16.2.2 Class II Devices................................................................................. 305
16.2.3 Class III Devices...............................................................................306
16.3 Registration and Listing.................................................................................307
16.4 The 510(k) Process.........................................................................................307
16.4.1 Determining Substantial Equivalency..............................................307
16.4.2 Types of 510(k)s................................................................................307
16.4.3 The Traditional 510(k).......................................................................309
16.4.3.1 The 510(k) Format............................................................. 310
16.4.4 The Special 510(k)............................................................................. 311
16.4.4.1 Special 510(k) Content....................................................... 312
16.4.5 The Abbreviated 510(k)..................................................................... 312
16.4.5.1 Abbreviated 510(k) Content............................................... 313
16.5 Declaration of Conformance to a Recognized Standard................................ 313
16.6 The PMA Application.................................................................................... 314
Contents xix

16.6.1 The PMA Process............................................................................. 314

16.6.2 Contents of a PMAA......................................................................... 314
16.7 Investigational Device Exemption.................................................................. 315
16.7.1 Institutional Review Board................................................................ 315
16.7.2 IDE Format........................................................................................ 316
16.8 Good Laboratory Practices............................................................................. 316
16.9 Quality System Regulation............................................................................. 316
16.9.1 Design Control.................................................................................. 317
16.10 The FDA and Software................................................................................... 318
16.10.1 Software Classification...................................................................... 319
16.11 Human Factors............................................................................................... 319
16.12 Good Manufacturing Practices...................................................................... 321
16.13 Unique Device Identifier................................................................................ 321
16.14 The FDA Inspection....................................................................................... 322
16.15 Advice on Dealing with the FDA................................................................... 322
Homework Exercises................................................................................................. 323
Suggested Reading.................................................................................................... 323
FDA Website Documents.......................................................................................... 324

Chapter 17 FDA History and Relevant Non-Device Regulations................................................ 325

17.1 A Brief History of the FDA Relevant to Food and Drugs.............................. 325
17.2 Drug Development.......................................................................................... 329
17.2.1 Native Drug Development and Use................................................... 329
17.2.2 Sampling the Environment................................................................ 329
17.2.3 Manipulation of Known Reactants................................................... 330
17.2.4 Plants and Animals as Factories for Drug Manufacture................... 330
17.2.5 Computer-Aided Development of New Drugs Using Chemical
Modeling of Structures��������������������������������������������������������������������� 330
17.2.6 Other Approaches: Nanoparticle, and Microparticle Hybrids
with Drugs���������������������������������������������������������������������������������������� 330
17.2.7 The Role of Imaging in Preclinical and Clinical Drug
Development������������������������������������������������������������������������������������� 330
17.3 Drug Testing................................................................................................... 331
17.3.1 Initial Screenings.............................................................................. 331
17.3.2 Primary Animal Studies................................................................... 331
17.3.3 Investigational New Drug Application and Human Subject
Solicitation���������������������������������������������������������������������������������������� 332
17.3.4 Drug Testing in Humans, Phases I, II, and III.................................. 333
17.3.4.1 Phase I................................................................................ 333
17.3.4.2 Phase II.............................................................................. 333
17.3.4.3 Phase III............................................................................. 333
17.4 FDA Post Production Oversight and Enforcement......................................... 334
17.5 The Future of Drug Therapy?......................................................................... 334
17.6 The FDA and Combination Products............................................................. 334
17.7 Veterinary Medicine....................................................................................... 335
17.8 The FDA and Cosmetics................................................................................ 335
17.9 Summary and Conclusions............................................................................. 337
Homework Exercises................................................................................................. 338
Notes�������������������������������������������������������������������������������������������������������������������������338
xx Contents

Chapter 18 Biological Engineering Designs................................................................................ 339

18.1 W hat Is a Biological System?......................................................................... 339
18.2 Special Issues When Dealing with Nonhuman Subjects...............................340
18.2.1 Difficult or No Direct Communication.............................................340
18.2.1.1 Imaging..............................................................................340
18.2.2 Awareness Issues...............................................................................340
18.2.3 Presumption of Status....................................................................... 341
18.2.4 Unintended Consequences................................................................ 341
18.2.5 Environmental Interactions............................................................... 342
18.3 Biological Principles....................................................................................... 343
18.3.1 The Basic Principle: Survival and Reproduction.............................. 343
18.3.2 Flexibility.......................................................................................... 343
18.3.3 Redundancy.......................................................................................344
18.3.4 Competition and Cooperation...........................................................344
18.3.5 Optimization.....................................................................................344
18.3.6 Communication................................................................................. 345
18.3.7 Characteristics of Biomaterials......................................................... 345
18.3.8 Information Legacy...........................................................................346
18.3.9 Sustainability..................................................................................... 347
18.4 D esign Objectives........................................................................................... 347
18.4.1 Effectiveness..................................................................................... 347
18.4.2 Economics......................................................................................... 347
18.4.3 Sustainability..................................................................................... 347
18.4.4 Resistance Avoidance........................................................................ 347
18.4.4.1 Refuge Plots.......................................................................348
18.4.5 Redundancy.......................................................................................348
18.5 Information Sources....................................................................................... 349
18.6 Useful Techniques.......................................................................................... 349
18.6.1 Biomimetics....................................................................................... 349
18.6.2 Scaling............................................................................................... 350
18.6.3 Directed Evolution............................................................................. 351
18.6.4 Genetic Modifications....................................................................... 351
18.6.5 Use Internal Potentials...................................................................... 352
18.7 R  egulations and Standards ............................................................................ 352
18.7.1 Regulations........................................................................................ 352
18.7.2 Standards........................................................................................... 352
18.7.3 Agencies with Relevant Regulations or Standards............................ 353
18.8 E  thics.............................................................................................................. 353
18.8.1 Reverence for Life............................................................................. 354
18.8.2 Human Centered............................................................................... 354
18.8.3 Sentience........................................................................................... 354
18.8.4 Suffering............................................................................................ 354
18.8.5 Animal Rights................................................................................... 355
18.8.6 DNA Modification............................................................................. 355
18.8.7 Cloning.............................................................................................. 356
18.8.8 Synthetic Biology.............................................................................. 356
18.8.9 Artificial Intelligence and Robotics.................................................. 356
18.9 Biological Engineering Design Examples...................................................... 357
18.9.1 Groundwater System Contaminated with Methyl Tert-Butyl
Ether and Petroleum Hydrocarbons������������������������������������������������� 357
Contents xxi

18.9.1.1 Solution Approach............................................................. 358

18.9.2 M inimizing Damage to a Salt Marsh................................................ 358
18.9.2.1 Solution Approach............................................................. 358
18.9.3 Freezing Hamburger.......................................................................... 358
18.9.3.1 Solution Approach............................................................. 359
18.9.4 Drying Yew Materials....................................................................... 359
18.9.4.1 Solution Approach.............................................................360
18.9.5 Cystic Fibrosis Gene Delivery...........................................................360
18.9.5.1 Solution Approach............................................................. 361
18.9.6 Green Roof Design............................................................................ 361
18.9.6.1 Solution Approach............................................................. 361
Homework Exercises................................................................................................. 361
Suggested Reading.................................................................................................... 366

Chapter 19 International Regulations and Standards.................................................................. 369

19.1 S tandards........................................................................................................ 369
19.2 Definition of a Medical Device...................................................................... 370
19.3 The MDDs...................................................................................................... 371
19.3.1 The MDDs Process........................................................................... 371
19.3.2 Choosing the Appropriate Directive................................................. 371
19.3.2.1 Active Implantable Medical Devices Directive................. 371
19.3.2.2 Medical Devices Directive................................................ 371
19.3.2.3 In Vitro Diagnostic Medical Devices Directive................ 371
19.3.3 Identifying the Applicable Essential Requirements.......................... 372
19.3.4 Identification of Corresponding Harmonized Standards.................. 372
19.3.4.1 Horizontal Standards......................................................... 373
19.3.4.2 Semi-horizontal Standards................................................ 373
19.3.4.3 Vertical Standards............................................................. 373
19.3.5 Assurance That the Device Meets the Essential Requirements
and Harmonized Standards and Documentation of the Evidence�������374
19.3.5.1 Essential Requirement 1.................................................... 374
19.3.5.2 Essential Requirement 2.................................................... 376
19.3.5.3 Essential Requirement 3.................................................... 376
19.3.5.4 Essential Requirement 4.................................................... 377
19.3.6 Classification of the Device............................................................... 378
19.3.7 Decision on the Appropriate Conformity Assessment Procedure...... 380
19.3.7.1 Medical Devices Directive................................................ 380
19.3.7.2 Active Implantable Medical Devices Directive................. 381
19.3.7.3 In Vitro Diagnostic Medical Devices Directive................ 381
19.3.8 Type Testing...................................................................................... 381
19.3.9 Identification and Choice of a Notified Body.................................... 382
19.3.10 Establishing a Declaration of Conformity........................................ 384
19.3.11 Application of the CE Mark.............................................................. 385
19.3.11.1 Declaration Of Conformity............................................... 385
19.3.12 Conclusion......................................................................................... 386
19.4 ISO Standards................................................................................................. 386
19.4.1 ISO 13485.......................................................................................... 386
19.4.2 ISO 14971.......................................................................................... 387
19.5 European Regulations and Standards............................................................. 387
19.5.1 The Impact of Brexit on EU Regulations.......................................... 389
xxii Contents

19.6 Russian and Asian Regulations and Standards.............................................. 389

19.6.1 Russian Regulations and Standards.................................................. 389
19.6.1.1 Registration Certificate...................................................... 390
19.6.1.2 Medical Device Testing and Clinical Data
Requirements in Russia���������������������������������������������������� 390
19.6.2 Japanese Regulations and Standards................................................. 390
19.6.3 Chinese Regulations and Standards.................................................. 391
19.6.3.1 Registration for Medical Devices...................................... 392
19.6.3.2 Quality Management for Medical Products in China....... 392
19.6.3.3 China Quality Control/Quality Assurance for
Medical Devices��������������������������������������������������������������� 392
19.6.3.4 Challenges to Meeting GMP Standards in China............. 393
19.7 North American Regulations and Standards.................................................. 393
19.8 Software Standards and Regulations.............................................................. 393
19.9 Medical Informatics....................................................................................... 394
Homework Exercises................................................................................................. 394
Suggested Reading.................................................................................................... 395
Web References......................................................................................................... 395

Chapter 20 Intellectual Property: Patents, Copyrights, Trade Secrets, and Licensing................ 397
20.1 P atents............................................................................................................. 397
20.1.1 What Qualifies as a Patent?............................................................... 398
20.1.1.1 Patentable Subject Matter.................................................. 398
20.1.1.2 Usefulness.......................................................................... 398
20.1.1.3 Novelty............................................................................... 399
20.1.1.4 Nonobviousness................................................................. 399
20.1.1.5 Improvement of an Existing Invention.............................. 399
20.1.1.6 A Design Patent................................................................. 399
20.1.2 The Patent Process (Utility)..............................................................400
20.1.3 Patent Claims.................................................................................... 401
20.1.4 Protecting Your Rights as an Inventor..............................................402
20.1.5 Patent Infringement...........................................................................402
20.1.6 A Word or Four of Warning..............................................................403
20.2 Copyrights......................................................................................................404
20.2.1 What Can Be Copyrighted?..............................................................405
20.2.2 The Copyright Process......................................................................406
20.2.2.1 Copyright Notice...............................................................406
20.2.2.2 Copyright Registration.......................................................406
20.2.3 Copyright Duration...........................................................................407
20.2.4 Protecting Your Copyright Rights.....................................................407
20.2.5 Infringement......................................................................................407
20.3 Trademarks.....................................................................................................407
20.3.1 Selecting a Trademark.......................................................................408
20.3.1.1 What Is a Distinctive Trademark?.....................................408
20.3.2 The Trademark Process.....................................................................409
20.3.3 Intent to Use Registration.................................................................. 410
20.3.4 Protecting Your Trademark Rights................................................... 410
20.4 Trade Secrets.................................................................................................. 410
20.4.1 What Qualifies for Trade Secrecy?................................................... 411
20.4.2 Trade Secrecy Authorship................................................................. 411
Contents xxiii

20.4.3
 ow Trade Secrets Are Lost............................................................. 411
H
20.4.4
Duration of Trade Secrets................................................................. 411
20.4.5
Protecting Your Trade Secret Rights................................................. 412
20.4.6A Trade Secrecy Program................................................................. 412
20.4.7 Use of Trade Secrecy with Copyrights and Patents.......................... 413
20.4.7.1 Trade Secrets and Patents.................................................. 413
20.4.7.2 Trade Secrets and Copyrights............................................ 413
20.5 Licensing........................................................................................................ 413
Homework Exercises................................................................................................. 413
Suggested Reading.................................................................................................... 414

Chapter 21 Manufacturing and Quality Control.......................................................................... 415

21.1 G ood Manufacturing Practices...................................................................... 415
21.2 The GMP Regulation...................................................................................... 416
21.2.1 Design Controls................................................................................. 416
21.2.2 Purchasing Controls.......................................................................... 416
21.2.3 Servicing Controls............................................................................. 417
21.2.4 Changes in Critical Device Requirements........................................ 417
21.2.5 Harmonization................................................................................... 417
21.3 Design for Manufacturability......................................................................... 417
21.3.1 The DFM Process............................................................................. 418
21.4 Design for Assembly...................................................................................... 418
21.4.1 DFA Process...................................................................................... 419
21.5 Highly Accelerated Stress Screening............................................................. 420
21.6 Highly Accelerated Stress Audit.................................................................... 421
21.7 The Manufacturing Process........................................................................... 421
21.7.1 Preproduction Activity...................................................................... 421
21.7.2 The Pilot Run Build.......................................................................... 422
21.7.3 The Production Run.......................................................................... 423
21.7.4 Customer Delivery............................................................................ 423
21.8 UDI................................................................................................................. 423
Homework Exercises................................................................................................. 424
Suggested Reading.................................................................................................... 425
Web References......................................................................................................... 425

Chapter 22 Miscellaneous Issues................................................................................................. 427

22.1 I ntroduction.................................................................................................... 427
22.2 Learning from Failure (and Lies)................................................................... 427
22.3 Design for “X”................................................................................................ 428
22.3.1 Design for Failure.............................................................................. 428
22.3.2 Design for Convenience.................................................................... 429
22.3.3 Design for Assembly......................................................................... 429
22.3.4 Design for the Environment.............................................................. 430
22.3.5 Design for Developing Countries...................................................... 430
22.3.6 Design to Combat Customer Misuse................................................. 432
22.3.7 Design for Manufacturability............................................................ 432
22.3.8 Design for Serviceability................................................................... 433
22.4 Universal Design............................................................................................ 433
22.5 Prevention through Design............................................................................. 433
xxiv Contents

22.6 P oka-Yoke....................................................................................................... 434

22.7 Product Life Issues......................................................................................... 434
22.7.1 Analysis of Field Service Reports..................................................... 434
22.7.1.1 The Database..................................................................... 435
22.7.1.2 Data Analysis..................................................................... 436
22.7.2 Failure Analysis of Field Units.......................................................... 438
22.7.3 Warranty Analysis............................................................................. 438
22.8 Product Testing Issues.................................................................................... 439
Homework Exercises................................................................................................. 439
Notes�������������������������������������������������������������������������������������������������������������������������439
Bibliography..............................................................................................................440

Chapter 23 Professional Issues.................................................................................................... 441

23.1 B ME-Related Professional Societies.............................................................. 441
23.1.1 Biomedical Engineering Societies.................................................... 441
23.2 Standards Setting Groups...............................................................................444
23.3 Professional Engineering Licensure............................................................... 445
23.3.1 Engineering Internship......................................................................446
23.4 Registration as a Professional Engineer.........................................................446
23.5 Rules of Professional Conduct........................................................................ 447
23.6 Codes of Ethics............................................................................................... 447
23.7 Forensics and Consulting...............................................................................448
23.7.1 Consulting Example 23.1.................................................................. 450
23.7.2 Consulting Example 23.2.................................................................. 450
23.7.3 Forensics Example............................................................................ 450
23.8 Continuing Education..................................................................................... 451
Homework Exercises................................................................................................. 451

Chapter 24 Concept to Product?.................................................................................................. 453

24.1 I ntroduction.................................................................................................... 453
24.2 Prepare Yourself Prior to Any Further Developments................................... 453
24.2.1 Web Resources.................................................................................. 454
24.2.2 Written Sources................................................................................. 454
24.2.3 Personal Contacts—Networking and Conferences........................... 454
24.2.4 Introspect........................................................................................... 455
24.3 Find Funding Sources..................................................................................... 455
24.3.1 Family............................................................................................... 455
24.3.2 University.......................................................................................... 455
24.3.3 Government....................................................................................... 456
24.3.4 Private Agencies................................................................................ 456
24.3.5 Angel Investors.................................................................................. 456
24.3.6 The Web............................................................................................ 456
24.4 Next Steps....................................................................................................... 456
24.5 Case Study 24.1: Pathfinder Technologies...................................................... 457
24.6 NCIIA Examples............................................................................................ 457
24.6.1 Case Study 24.2: The Epicard E-Team............................................. 458
24.6.2 Case Study 24.3: Nanografts............................................................. 458
24.7 Case Study 24.4: Multitool............................................................................. 459
24.8 Case Study 24.5: Development of Max-Mobility Corp.................................. 461
Contents xxv

24.9 Conclusion...................................................................................................... 463

Suggested Reading.................................................................................................... 463
Appendix 1: χ2 Table....................................................................................................................465
Appendix 2: Percent Rank Tables............................................................................................... 467
Appendix 3: 40 Inventive Principles, Engineering Parameters, and Conflict Matrix........... 477
Appendix 4: Glossary................................................................................................................... 493
Index............................................................................................................................................... 499
Preface
The design and functional complexity of medical devices and systems has increased during the past
50 years, evolving from the use of a metronome circuit for the initial cardiac pacemaker to functions
that include medical bookkeeping, electrocardiogram analysis, delivery of anesthesia, laser surgery,
magnetic resonance imaging, and intravenous delivery systems that adjust dosages based on patient
feedback. As device functionality becomes more intricate, concerns arise regarding efficacy, safety,
and reliability. Both the user and the patient want the device to operate as specified, perform in
a safe manner, and continue to perform over a long period without failure. To be successful, the
designer of medical devices must ensure that all devices meet these requirements.
Medical device design is a complex process that requires careful integration of diverse disci-
plines, technical activities, standards, regulatory requirements, and administrative project controls.
The need for systematic approaches to product development and maintenance is necessary to ensure
a safe and effective device for the user and the patient, an economical and competitive success for
the manufacturer, and a reliable, cost-effective investment for the user.
This edition of the book is aimed generally at senior bioengineering students who are in the
formative stages of deciding what to do for a senior design project and who need to consider what
the societal factors are that may or may not impact their project now or in the future if brought to a
useful conclusion. Portions of the book may be used in lower level classes, such as the sections on
brainstorming and elementary idea generation techniques. Portions of the book may be used in early
graduate-level classes if one has had little exposure to the Food and Drug Administration (FDA)
and CE mark information. The book is meant to be comprehensive, so that the needs of a variety of
students working on a variety of topics (from databases to process analysis to device improvement)
may have adequate information to begin a fairly comprehensive project. Additionally, it is aimed
at design engineers new to the medical device industry who have not had access to such a compre-
hensive book or course in their background. This book should prove to be an excellent resource for
those individuals as they enter the workforce.
The emphasis of the book is on the practical, hands-on approach to device design. The layout
of the book follows the typical design process. The mathematics included here is that which is
necessary to conduct everyday tasks. Equations, where needed, are merely given, not derived. It is
assumed that the reader has a basic knowledge of statistics. References are given at the end of each
chapter for those wishing to delve more deeply into the subject.
The first three chapters are a general introduction to the subject. Chapter 1 introduces the reader
to biomedical engineering (BME) design. Chapter 2 is an outline of some fundamental ideas, gener-
ation techniques, and design decision and comparison tools with a brief introduction to the process
of inventive (TRIZ) problem-solving. Fundamental to successful design processes is the generation
of a good design team and the management thereof; this is introduced in Chapter 3. This section
then naturally segues into the need for documentation techniques and requirements, and the use of
databases in this endeavor. Reporting techniques are briefly covered in discussion on posters, oral
presentations, and progress reports.
Fundamental to a good design is correct and customer-driven product definition. Chapter 4
summarizes the product definition process and reiterates and concludes on the use of QFD in this
process.
Product documentation, record keeping, and levels of effort mandated by FDA quality regula-
tions and medical device regulations are discussed in Chapter 5.
Chapter 6 gives an overview of hardware and software design techniques that ensue from the ear-
lier product specification tasks. Specifically covered is the FDA concept of the product development
process, which outlines the links from product requirements to design transfer, with intermediate
links such as design verification and validation.

xxvii
xxviii Preface

Hardware development methods and tools are reviewed in Chapter 7. Overviewed are such topics
as design for Six Sigma, robust design, failure modes and effect considerations, axiomatic design,
design improvements via component derating, reliability prediction and improvement, and several
design for “X” methodologies. The chapter concludes with a discussion of design reviews.
Chapter 8 is an introduction to software development methods and tools. Because software dif-
fers from hardware, methods and tools used for software development are very different from those
used in hardware development, but constraints on verification and validation as mandated by the
FDA are paramount.
Chapter 9 overviews human factor issues. Several of the techniques used to guard against human-
caused errors are reviewed, as are techniques to increase usability. Workstation design and human
expectations are also discussed, as are the methods used to test these in use.
Chapter 10 discusses industrial design, including developing user interface concepts, designing a
conceptual model, developing screen templates and a screenplay, and testing the design.
Biomaterials and materials selection are the theme of Chapter 11, with heavy coverage of the
various FDA (and some international) tests and test methods used for materials that may come into
contact with users. Tests for toxicity, hemocompatibility, irritation, reactivity, and sensitization are
summarized.
Chapter 12 covers risk analysis of devices and systems, including some safety topics not dealt
with elsewhere in the text, specifically addressing safety as a component of the design process and
one of several structured approaches to the consideration of safety in a design.
Once the design is completed, it must be tested to prove whether it meets its requirements. The
subject of testing is summarized in Chapter 13. Types of tests, parsing test requirements, establish-
ing a test protocol, and defining failure are all discussed in detail. The chapter also discusses the
methodology for determining test sample size and test length.
Once the testing is completed, the test data must be analyzed to determine the success or failure
in testing. Chapter 14 explains the mathematical basis of analyzing test data. Metrics that are cov-
ered here include failure rate, reliability, mean time between failures, confidence level, confidence
limits, and minimum life. There is also a discussion of graphical analysis of data, including Pareto
charts.
Chapter 15 discusses the legal ramifications of medical device development and failure. Topics
include negligence, breach of warranty, failure to warn of dangers, accident reconstruction, and
forensics.
Chapter 16 discusses the FDA and its role in the regulation of medical devices. Device classifica-
tion, manufacturer registration, and types of registration and listing are among the topics discussed.
Chapter 17 discusses FDA history and relevant non-device regulations. A comprehensive his-
tory of the FDA is followed by a discussion of drug enforcement and postproduction oversight and
enforcement.
Chapter 18 discusses biological engineering design. The emphasis of the chapter is on biological
systems impacted by engineering.
Chapter 19 discusses international regulations and standards. Medical devices sold in the United
States must meet FDA regulations and US standards. Those devices sold in other parts of the world
must meet regulations and standards from those areas where they will be sold.
Good design will likely generate intellectual property. Chapter 20 gives a summary of the pro-
tection of intellectual property, including licensing, patents, copyrights, and trademarks.
Chapter 21 covers manufacturing and quality control. This chapter discusses manufacturing pro-
cesses and how quality control issues continue during this phase of the design process and how they
must be addressed.
Chapter 22 covers a few miscellaneous issues not relevant to other chapters, specifically such
issues as learning from failure and designing for failure.
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 CHAPTER V.
THE ELECTORATE OF HANOVER.

The House of Hanover ranges itself against France—Ernest Augustus

created Elector—Domestic rebellion of his son Maximilian—His
accomplice, Count von Moltke, beheaded—The Electors of Germany.

While Sophia Dorothea was daily growing more unhappy, her

father-in-law was growing more ambitious and the prospects of her
husband more brilliant. The younger branch of Brunswick was
outstripping the elder in dignity, and not merely an electoral but a
kingly crown seemed the prize it was destined to attain.
When Ernest’s elder brother, John Frederick, died childless, and
left him the principalities of Calemberg and Grubenberg, with
Hanover or a ‘residenz,’ he hailed an increase of influence which he
hoped to see heightened by securing the Duchy of Zell also to his
family. He had determined that George Louis should succeed to
Hanover and Zell united. In other words, he established
primogeniture, recognised his eldest son as heir to all his land, and
only awarded to his other sons moderate appanages whereby to
support a dignity which he considered sufficiently splendid by the
glory which it would receive, by reflection, from the head of the
house.
This arrangement by no means suited the views of one of
Ernest’s sons, Maximilian. He had no inclination whatever to borrow
glory from the better fortune of his brother, and was resolved, if it
might be, to achieve splendour by his own. He protested loudly
against the accumulation of the family territorial estates upon the
eldest heir; claimed his own share; and even raised a species of
domestic rebellion against his sire, to which weight, without peril,
was given by the alleged adhesion of a couple of confederates,
Count von Moltke and a conspirator of burgher degree.
Ernest Augustus treated ‘Max’ like a rude child. He put him
under arrest in the paternal palace, and confined the filial rebel to the
mild imprisonment of his own room. Maximilian was as obstinate as
either Henry the Dog or Magnus the Violent, and he not only
opposed his sire’s wishes with respect to the aggrandisement of the
family by the enriching of the heir-apparent, but went counter to him
in matters of religion. In after-years he was not only a good Jacobite,
but he also conformed to the faith of the Stuarts, and Maximilian
ultimately died, a tolerable Roman Catholic, in the service of the
Emperor.
In the meanwhile, his domestic antagonism against his father
was not productive of much inconvenience to himself. His arrest was
soon raised, and he was restored to freedom, though not to favour or
affection. It went harder, however, with his friend and confederate
Count von Moltke, against whom, as nothing could be proved, much
was invented. An absurd story was coined to the effect, that at the
time when Maximilian was opposing his father’s projects, Count von
Moltke, at a court entertainment, had presented his snuff-box to
Ernest Augustus. This illustrious individual having taken therefrom
the pungent tribute respectfully offered, presented the same to an
Italian greyhound which lay at his feet, who thereon suddenly
sneezed and swiftly died. The count was sent into close arrest, and
the courtly gossips forged the story to account for the result. The
unfortunate von Moltke was, indeed, as severely punished as though
he had been a murderer. He was judged in something of the old
Jedburgh fashion, whereby execution preceded judgment; and the
head of Count von Moltke had fallen before men could well guess
why he had forfeited it. The fact was that this penalty had been
enacted as a vicarious infliction on Prince Maximilian. The more
ignoble plotter was only banished, and in the death of a friend and
the exile of a follower, Maximilian, it was hoped, would see a double
suggestion from which he would draw a healthy conclusion. This
course had its desired effect. The disinherited heir accepted his ill-
fortune with a humour of the same quality, and, openly at least, he
ceased to be a trouble to his more ambitious than affectionate father.
The next important public circumstance was the raising Hanover
to an Electorate; and this was not effected without much bribery and
intrigue. In those warlike times, when France and the German
empire were in antagonism, the attitude assumed by such a state as
Hanover was matter of interest to the adverse powers. It is said that
the last argument which decided the Emperor’s course was a hint
from De Groot, the Hanoverian minister, that Ernest Augustus might
cast in his lot with France. A prince who had so often well served the
empire was not to be allowed to assist France for lack of flinging to
him the title of Elector. This title was granted, but under heavy
stipulations. The two Dukes of Hanover and Zell bound themselves,
as long as the war lasted, on the side of the Emperor against the
French and against the Turks, to pay annually 500,000 thalers, to
furnish a contingent amounting to 9,000 men, to uphold the claim of
the Arch-Duke Charles on the Spanish throne, and at any election of
a new Emperor to vote invariably for the eldest heir of the House of
Hapsburg. The 19th of December 1692 was the joyful day on which
Ernest Augustus was nominated Elector of Hanover.
The day, however, was anything but one of joy to the branch of
Brunswick-Wolfenbüttel. That elder branch felt itself dishonoured by
the august dignity which had been conferred upon the younger scion
of the family. The elder branch, and the Sacred College with it,
affirmed that the Emperor was invested with no prerogative by which
he could, of his own spontaneous act, add a ninth Elector to the
eight already existing. Originally there were but seven, and the
accession of one more to that time-honoured number was
pronounced to be an innovation by which ill-fortune must ensue.
Something still more deplorable was vaticinated as the terrible
consequence of a step so peremptorily taken by the Emperor, in
despite of the other Electors.
It was said by the supporters of the Emperor and Hanover that
the addition of a ninth and Protestant Elector was the more
necessary, that there were only two Electors on the sacred roll who
now followed the faith of the Reformed Church, and that the sincerity
of one, at least, of these was very questionable. The reformed states
of Germany had a right to be properly represented, and the Emperor
was worthy of all praise for respecting this right. With regard to the
nomination, it was stated that, though it had been made
spontaneously by the Emperor, it had been confirmed by the
Electoral College—a majority of the number of which had carried the
election of the Emperor’s candidate.
Now, this last point was the weak point of the Hanoverians; for it
was asserted by many adversaries, and not denied by many
supporters, that in such a case as this no vote of the Electoral
College was good unless it were an unanimous vote. To this
objection, strongly urged by the elder branch of Brunswick-
Wolfenbüttel, no answer was made, except, indeed, by praising the
new Elector, of whom it was correctly stated that he had introduced
into his states such a taste for masquerades, operas, and ballets as
had never been known before; and that he had made a merry and a
prosperous people of what had been previously but a dull nation, as
regarded both manners and commerce. The Emperor only thought of
the good service which Ernest Augustus had rendered him in the
field, and he stood by the ‘accomplished fact’ of which he was the
chief author.
The College was to the full as obstinate, and would not
recognise any vote tendered by the Elector of Hanover, or of
Brunswick, as he was at first called. For nearly sixteen years was
this opposition carried on. At length, on the 30th of June 1708, this
affair of the ninth electorate was adjusted, and the three colleges of
the empire resolved to admit the Elector of Hanover to sit and vote in
the Electoral College. In the same month, he was made general of
the imperial troops, then assembled in the vicinity of the Upper
Rhine.
His original selection by the Emperor had much reference to his
military services. The efforts of Louis XIV. to get possession of the
Palatinate, after the death of the Palatine Louis, had caused the
formation of the German Confederacy to resist the aggression of
France—an aggression not checked till the day when Marlborough
defeated Tallard, at Blenheim. Louis was hurried into the war by his
minister, Louvois, who was annoyed by his interference at home in
matters connected with Louvois’s department. It was to make the
confederation more firm and united that Ernest Augustus was
created, rather than elected, a ninth Elector. The three Protestant
Electors were those of Saxony, Brandenburg, and Hanover; the
three Roman Catholic, Bohemia, Bavaria, and the Palatinate; and
the three spiritual Electors, the Prince-Archbishops of Metz, Trèves,
and Cologne.
The history of the creation of the ninth Electorate would not be
complete without citing what is said in respect thereof by the author
of a pamphlet suppressed by the Hanoverian government, and
entitled ‘Impeachment of the Ministry of Count Munster.’ It is to this
effect: ‘During the war between Leopold I. and France, at the close
of the 17th century, Ernest Augustus, Duke of Brunswick, and
administrator of Osnabrück, father of George I., had been paid a
considerable sum of money on condition of aiding the French
monarch with ten thousand troops. The Emperor, aware of the
engagement, and anxious to prevent the junction of these forces with
the enemy, proposed to create a ninth electorate, in favour of the
Duke, provided he brought his levies to the imperial banner. The
degrading offer was accepted, and the envoys of Brunswick-
Luneberg received the electoral cap, the symbol of their master’s
dishonour, at Vienna, on the 19th of December 1692. From the
opposition of the college and princes, Ernest was never more than
nominally an Elector, and even his son’s nomination was with
difficulty accomplished in 1710. It was in connection with this new
dignity that Hanover, a name till then applied only to a principal and
almost independent city of the Dukedom of Brunswick, became
known in the list of European sovereignties.’
But while the Court of Hanover was engaged in the important or
trivial circumstances which have been already narrated, a notable
individual had been pursuing fortune in various countries of Europe,
and had made his appearance on the scene at Hanover, to play a
part in a drama which had a tragical catastrophe—namely, Count
Königsmark.
 CHAPTER VI.
THE KÖNIGSMARKS.

Count Charles John Königsmark’s roving and adventurous life—The great

heiress—An intriguing countess—‘Tom of Ten Thousand’—The murder of
Lord John Thynne—The fate of the count’s accomplices—Court influence
shelters the guilty count.

The circumstance of the sojourn of a Count Königsmark at Zell,

during the childhood of Sophia Dorothea, has been before noticed.
Originally the family of the Königsmarks was of the Mark of
Brandenburgh, but a chief of the family settled in Sweden, and the
name carried lustre with it into more than one country. In the army,
the cabinet, and the church, the Königsmarks had representatives of
whom they might be proud; and generals, statesmen, and prince-
bishops, all labouring with glory in their respective departments,
sustained the high reputation of this once celebrated name. From the
period, early in the seventeenth century, that the first Königsmark
(Count John Christopher) withdrew from the imperial service and
joined that of Sweden, the men of that house devoted themselves,
almost exclusively, to the profession of arms. This Count John is
famous as the subduer of Prague, in 1648, at the end of the Thirty
Years’ War. Of all the costly booty which he carried with him from
that city, none has continued to be so well cared for by the Swedes
as the silver book containing the Mœso-Gothic Gospels of Bishop
Ulphilas, still preserved with pride at learned Upsal.
John Christopher was the father of two sons. Otho William, a
marshal of France, a valued friend of Charles XII., and a gallant
servant of the state of Venice, whose government honoured his tomb
with an inscription, Semper Victori, was the younger. He was pious
as well as brave, and he enriched German literature with a collection
of very fervid and spiritual hymns. The elder son, Conrad
Christopher, was killed in the year 1673, when fighting on the Dutch
and imperial side, at the siege of Bonn. He left four children, three of
whom became famous. His sons were Charles John, and Philip
Christopher. His daughters were Maria Aurora (mother of the famous
Maurice of Saxony) and Amelia Wilhelmina. The latter was fortunate
enough to achieve happiness without being celebrated. If she has
not been talked of beyond her own Swedish fireside, she passed
there a life of as calm felicity as she and her husband, Charles von
Loewenhaupt, could enjoy when they had relations so celebrated,
and so troublesome, as Counts Charles John and Philip Christopher,
and the Countess Maria Aurora, the ‘favourite’ of Augustus of
Poland, and the only royal concubine, perhaps, who almost
deserved as much respect as though she had won greatness by a
legitimate process.
It was this Philip Christopher who was for a brief season the
playfellow or companion of Sophia Dorothea, in the young days of
both, in the quiet gardens and galleries of Zell. It is only told of him
that, after his departure from Zell, he sojourned with various
members of his family, travelled with them, and returned at intervals
to reside with his mother, Maria Christina, of the German family of
Wrangel, who unhappily survived long enough to be acquainted with
the crimes as well as misfortunes of three of her children.
In the year 1682, Philip Christopher was in England. The elder
brother, who had more than once been a visitor to this country, and a
welcome, because a witty, one at the Court of Charles II., had
brought his younger brother hither, in order (so it was said) to have
him instructed more completely in the tenets of the Protestant
religion, and ultimately to place him at Oxford. In the meantime
Charles John lodged Philip with a ‘governor,’ at the riding academy,
near the Haymarket, of that Major Foubert, whose second
establishment (where he taught ‘noble horsemanship’) is still
commemorated by the passage out of Regent Street, which bears
the name of the French Protestant refugee and professor of
equestrianism.
 The elder brother of these two Königsmarks was a superb
scoundrel. He had led a roving and adventurous life, and was in
England when not more that fifteen years of age, in the year 1674.
During the next half-dozen years he had rendered the ladies of the
Court of France ecstatic at his impudence, and had won golden
opinions from the ‘marine knights’ of Malta, whom he had
accompanied on a ‘caravane,’ or cruise, against the Turks, wherein
he took hard blows cheerfully, and had well-nigh been drowned by
his impetuous gallantry. At some of the courts of southern Europe he
appeared with an éclat which made the men hate and envy him; but
nowhere did he produce more effect than at Madrid, where he
appeared at the period of the festivities held to celebrate the
marriage of Charles II. with Maria Louisa of Orleans. The marriage of
the last-named august pair was followed by the fiercest and the
finest bull-fights which had ever been witnessed in Spain. At one of
these Charles John made himself the champion of a lady, fought in
her honour in the arena, with the wildest bull of the company, and got
dreadfully mauled for his pains. His horse was slain, and he himself,
staggering and faint, and blind with loss of blood, and with deep
wounds, had finally only strength enough left to pass his sword into
the neck of the other brute, his antagonist, and to be carried half-
dead and quite senseless out of the arena, amid the approbation of
the gentle ladies, who purred applause upon the unconscious hero,
like satisfied tigresses.
In 1681, at the age of twenty-two, master of all manly vices, and
ready for any adventure, he was once more in England, where he
seized the opportunity afforded him by the times and their events,
and hastened to join the expedition against Tangier. On the
conclusion of the warm affair at Tangier, he went as an amateur
against the Algerines, and without commission inflicted on them and
their ‘uncle’ (as the word dey implies) as much injury as though he
had been chartered general at the head of a destroying host. When
he returned to England, he was received with enthusiasm. His
handsome face, his long flaxen hair, his stupendous periwig for state
occasions, and his ineffable impudence, made him the delight of the
impudent people of those impudent times.
 Now, of all those people, the supercilious Charles John cared but
for one, and she, there is reason to believe, knew little and cared
less for this presuming scion of the House of Königsmark.
Joscelyn, eleventh Earl of Northumberland, who died in the year
1670—the last of the male line of his house—left an only daughter,
four years of age, named Elizabeth. Her father’s death made her the
possessor—awaiting her majority—of vast wealth, to which increase
was made by succession to other inheritances. Her widowed mother
married Ralph Montague, English ambassador in Paris. When the
widow of Joscelyn espoused Montague, her daughter Elizabeth went
to reside with the mother of Joscelyn, Dowager Countess of
Northumberland, and co-heiress to the Suffolk estate, destined to be
added to the possessions of the little Elizabeth. She was an
intriguing, indelicate, self-willed, and worthless old woman; and with
respect to the poor little girl of whom she was the unworthy guardian,
she made her the subject of constant intrigues with men of power
who wished for wealth, and with rich men who wished for rank and
power. Before the unhappy little heiress had attained the age of
thirteen, her grandmother had bound her in marriage with Henry
Cavendish, Earl Ogle. Though the ceremony was performed, the
parties did not, of course, reside together. The dowager countess
and the earl were satisfied that the fortune of the heiress was
secured, and they were further content to wait for what might follow.
That which followed was what they least expected—death; the
bridegroom died within a year of his union with Elizabeth Percy; and
this child, wife, and widow was again at the disposal of her wretched
grandmother. The heiress of countless thousands was anything but
the mistress of herself.
At this period the proprietor of the house and domain of
Longleat, in Wiltshire, was that Thomas Thynne, whom Dryden has
celebrated as the Issachar of his ‘Absalom and Achitophel.’ He was
the friend of the Duke of Monmouth, was spoken of as ‘Tom of Ten
Thousand,’ and was a very unworthy fellow, although the member of
a worthy house. Tom’s Ten Thousand virtues were of that metal
which the Dowager Countess of Northumberland most approved;
and her grand-daughter had not been many months the widow of
Lord Ogle, when her precious guardian united her by private
marriage to Thynne. The newly-married couple were at once
separated. The marriage was the result of an infamous intrigue
between infamous people, some of whom, subsequently to Thynne’s
death, sued his executors for money which he had bound himself to
pay for services rendered to further the marriage.
When Charles John Königsmark returned to England, in January
1682, all England was talking of the match wherein a poor child had
been sold, although the purchaser had not yet possession of either
his victim or her fortune. The common talk must have had deep
influence on the count, who appears to have been impressed with
the idea that if Thynne were dead, Count Charles John Königsmark
might succeed to his place and expectations.
On the evening of Sunday, the 12th of February 1682, Thynne
was in his coach, from which the Duke of Monmouth had only just
previously alighted, and was riding along that part of Pall-Mall which
abuts upon Cockspur Street, when the carriage was stopped by
three men on horseback, one of whom discharged a carbine into it,
whereby Tom of Ten Thousand was so desperately wounded that he
died in a few hours.
The persons charged with this murder were chiefly discovered
by means of individuals of ill repute with whom they associated. By
such means were arrested a German, Captain Vratz, Borosky a
Pole, and a fellow, half knave, half enthusiast, described as
Lieutenant Stern. Vratz had accompanied Königsmark to England.
They lodged together, first in the Haymarket, next in Rupert Street,
and finally in St. Martin’s Lane. Borosky had been clothed and armed
at the count’s expense; and Stern was employed as a likely tool to
help them in this enterprise. It was proved on the trial, that, after the
deed was committed, these men were at the count’s lodgings, that a
sudden separation took place, and that the count himself, upon
some sudden fear, took flight to the water-side; there he lay hid for a
while, and then dodged about the river, in various disguises, in order
to elude pursuit, until he finally landed at Gravesend, where he was
pounced upon by two expert thief-catchers.
 The confession of the accomplices, save Vratz, did not affect the
count. His defence took a high Protestant turn—made allusion to his
Protestant ancestors and their deeds in behalf of Protestantism,
lauded Protestant England, alluded to his younger brother, brought
expressly here to be educated in Protestant principles, and
altogether was exceedingly clever, but in no wise convincing. It was
known that the King would learn with pleasure that the count had
been acquitted. As this knowledge was possessed by judges who
were removable at the King’s pleasure, it had a strong influence; and
the arch-murderer, the most cowardly of the infamous company, was
acquitted accordingly. In his case, the verdict, as regarded him, was
given in, last. The other three persons were indicted for the actual
commission of the fact, Königsmark as accessory before the fact,
hiring them, and instigating them to the crime. Thrice he had heard
the word ‘Guilty’ pronounced, and, despite his recklessness, was
somewhat moved when the jury were asked as to their verdict
respecting him. ‘Not Guilty,’ murmured the foreman; and then the
noble count, mindful only of himself, and forgetful of the three
unhappy men whom he had dragged to death, exclaimed in his
unmanly joy, ‘God bless the King, and this honourable bench!’ The
meaner assassins were flung to the gallows. Vratz went to his fate,
like Pierre; declared that the murder was the result of a mistake, that
he had no hand in it, and that as he was a gentleman, God would
assuredly deal with him as such! This ‘gentleman’ accounted for his
presence at the murder as having arisen by his entertaining a quarrel
with Mr. Thynne, whom he was about to challenge, when the Pole,
mistaking his orders and inclinations, discharged his carbine into the
carriage, and slew the occupant. The other two confessed to the
murder, as the hired instruments of Vratz. Count Charles John
repaired to the Court of France, where he was received in that sort of
gentlemanly fashion which Vratz looked for in Paradise. His sword
gleamed in many an action fought in various battle-fields of Europe
during the next few years, at the head of a French regiment, of which
he was colonel. Finally, in 1686, he was in the service of the
Venetians in the Morea. On the 29th of August he was before Argos,
when a sortie was made by the garrison, and in the bloody struggle
which ensued he was mortally wounded. For Thynne’s monument in
Westminster Abbey a Latin inscription was prepared, which more
than merely hinted that Königsmark was the murderer of Tom of Ten
Thousand. ‘Small, servile, Spratt,’ then Dean of Westminster, would
not allow the inscription to be set up; and his apologists, who
advance in his behalf that he would have done wrong had he
allowed a man, cleared by a jury from the charge of murder, to be
permanently set down in hard record of marble as an assassin, have
much reason in what they advance.
The youthful maid, wife, and widow, Lady Ogle, remained at
Amsterdam (whither she had gone, some persons said fled), after
her marriage with Thynne, until the three of his murderers, who had
been executed, had expiated their crime, as far as human justice
was concerned, upon the scaffold. She then returned to England; but
the young lady did not ‘appear public,’ as the phrase went, for six or
seven weeks, and when she did so, it was found that she had just
married Charles Seymour, third Duke of Somerset—a match which
made one of two silly persons and a couple of colossal fortunes.
This red-haired lady died in the fifty-sixth year of her age, a.d.
1722; and the duke, then sixty-four, found speedy consolation for his
loss in a marriage with the youthful Lady Charlotte Finch, who was at
once his wife, nurse, and secretary. It is said of her, that she one day,
in the course of conversation, tapped her husband familiarly on the
shoulder with her fan; whereupon that amiable gentleman indignantly
cried out: ‘Madam, my first wife was a Percy, and she never took
such a liberty!’
Königsmark, whose fate was so bound up with that of Sophia
Dorothea, left England with his brother, and like his brother, he led
an adventurous and roving life, never betraying any symptom of the
Christian spirit of the religion of the Church of England, of which he
first tasted what little could be found in Major Foubert’s riding-school.
A portion of his time was spent at Hamburg with his mother and two
sisters. His renown was sufficient for a cavalier who loved to live
splendidly; and when he appeared at the Court of Hanover, in search
of military employment, he was welcomed as cavaliers are who are
so comfortably endowed. In 1688 we first hear of him in the electoral
capital, bearing arms under the Elector and a guest at the table of
George Louis and Sophia Dorothea. This was a year after the birth
of the second and last child of that ill-matched couple.
 CHAPTER VII.
KÖNIGSMARK AT COURT.

Various accomplishments of Count Philip Christopher Königsmark—The early

companion of Sophia Dorothea—Her friendship for him—An interesting
interview—Intrigues of Madame von Platen—Foiled in her machinations—
A dramatic incident—The unlucky glove—Scandal against the honour of
the princess—A mistress enraged on discovery of her using rouge—
Indiscretion of the princess—Her visit to Zell—The Elector’s criminal
intimacy with Madame von der Schulenburg—William the Norman’s
brutality to his wife—The elder Aymon—Brutality of the Austrian Empress
to ‘Madame Royale’—Return of Sophia, and reception by her husband.

The estimation in which Count Philip Christopher von Königsmark

was held at the Court of Hanover was soon manifested, by his
elevation to the post of Colonel of the Guards. He was the
handsomest colonel in the small electoral army, and passed for the
richest. His household, when thoroughly established, in 1690,
consisted of nine-and-twenty servants; and about half a hundred
horses and mules were stalled in his stables. His way of life was
warrant for the opinion entertained of his wealth, but more flimsy
warrant could hardly have existed, for the depth of a purse is not to
be discovered by the manner of life of him who owns it. He continued
withal to enchant every one with whom he came in contact. The
spendthrifts reverenced him, for he was royally extravagant; the few
people of taste spoke of him encouragingly, for at an era when little
taste was shown, he exhibited much both in his dress and his
equipages. These were splendid without being gaudy. The scholars
even could speak with and of him without a sneer expressed or
reserved, for Philip Christopher was intellectually endowed, had read
more than most of the mere cavaliers of his day, and had a good
memory, with an understanding whose digestive powers a
philosopher might have envied. He spelt, however, and he wrote little
better than his grooms. He was not less welcome to the soldier than
the scholar, for he had had experience in ‘the tented field,’ and had
earned in the ‘imminently deadly breach’ much reputation, without
having been himself, in the slightest degree, ‘illustriously maimed.’
Königsmark was as daring in speech as in arms. It is said of him that
when George Louis in crowded court once asked him why he had
quitted the Saxon service, Königsmark replied, ‘It moved me to
anger to see a prince poison the life and happiness of his lovable
young wife, by his connection with an impudent and worthless
mistress!’ The whole audience gaped with astonishment, and the
speech was reported in many a ball-room. But ball-rooms also re-
echoed with the ringing eulogiums of his gracefulness, and his witty
sayings are reported as having been in general circulation; but they
have not been strong enough to travel by the rough paths of time
down to these later days. He is praised, too, as having been satirical,
without any samples of his satire having been offered for our opinion.
He was daringly irreligious, for which free-thinkers applauded him as
a man of liberal sentiments, believing little, and fearing less. He was
pre-eminently gay, which, in modern and honest English, means that
he was terribly licentious; and such was the temper of the times, that
probably he was as popular for this characteristic as for all the other
qualities by which he was distinguished, put together.
There was nothing remarkable in the fact that he speedily
attracted the notice of Sophia Dorothea. She may, without fault, have
remembered with pleasure the companion of her romping youth; and
have ‘wished him well and no harm done,’ as Pierre says. He was
not a mere stranger; and the two met, just as the husband of Sophia
Dorothea had publicly insulted her by ostentatiously parading his
attachment and his bad taste for women, no more to be compared
with her in worth and virtue than Lais with Lucretia. Up to this time,
the only confidantes of her secret sorrows were her mother and her
faithful von Knesebeck. She had repulsed the affected sympathy of
the Countess von Platen; and had concealed her feelings, when her
jealousy was stirred by allusions to the countess’s sister and to
Ermengarda von der Schulenburg. The Countess von Platen, mature
of age, cast admiring eyes on Königsmark. It is asserted, that the
count had scarcely been made Colonel of the Guards when the
Countess von Platen fixed upon him as one of the instruments by
which she would ruin Sophia Dorothea, and relieve George Louis of
a wife whose virtues were a continual reproach to him.
The princess had been taking some exercise in the gardens of
the palace, returning from which she met her little son, George
Augustus, whom she took from his attendant, and with him in her
arms began to ascend the stairs which led to her apartments. Her
good will was greater than her strength, and Count Königsmark
happened to see her at the moment when she was exhibiting
symptoms of weakness and irresolution, embarrassed by her
burthen, and not knowing how to proceed with it. The count at once,
with ready gallantry, not merely proffered, but gave his aid. He took
the young prince from his mother, ascended the stairs, holding the
future King of England in his arms, and at the door of the apartment
of Sophia Dorothea again consigned him to maternal keeping. They
tarried for a few brief moments at the door, exchanging a few
conventional terms of thanks and civility, when they were seen by
the ubiquitous von Platen, and out of this simple fact she is
supposed to have gradually worked the subsequent terrible calamity
which may be said to have slain both victims, for Sophia Dorothea
was only for years slowly accomplishing death, which fell upon the
cavalier so surely and so swiftly.
This incident was reported to Ernest Augustus (Mon Sieur, as
the countess used to call him) with much exaggeration of detail, and
liberal suggestion not warranted by the facts. The conduct of the
princess was mildly censured as indiscretion, that of the count as
disloyal impertinence; and, thereto, a mountain of comment seems
to have been added, and a misty world of hints, which annoyed the
duke without convincing him.
Foiled in her first attempt to ruin Sophia Dorothea, von Platen
addressed herself to the task of cementing strict friendship with the
count; and he, a gallant cavalier, was nothing loth, nought
suspecting. Of the terms of this friendly alliance little is known. They
were only to be judged of by the conduct of the parties whom that
alliance bound. A perfect understanding appeared to have been
established between them; and the Countess von Platen was often
heard to rally the count upon the love-passages in his life, and even
upon his alleged admiration of Sophia Dorothea. What was said
jokingly, or was intended to seem as if said jokingly, was soon
accepted by casual hearers as a sober, and a sad as sober, truth.
The countess referred often to his visits paid to Sophia Dorothea as
‘rendezvous’; but at these, Fräulein von Knesebeck was (as she
subsequently affirmed) present from first to last; and two other
ladies-in-waiting, pages, women, and George Louis’ own servant,
Soliman (a Turk), had free and frequent ingress and egress.
This first step having been made, no time was lost in pursuing
the object for which it had been accomplished. At one of those
splendid masquerades, in which Ernest Augustus especially
delighted, Königsmark distinguished himself above all the other
guests by the variety, as well as richness, of his costume, and by the
sparkling talent with which he supported each assumed character.
He excited a universal admiration, and—so it was said by the
Countess von Platen—in none more than in Sophia Dorothea. This
may have been true, and the poor princess may possibly have found
some oblivion for her domestic trials in allowing herself to be amused
with the exercise of the count’s dramatic talent. She honestly
complimented him on his ability, and on the advantages which the
fête derived from his presence, his talent, and his good-nature. Out
of this compliment the countess forged another link of the chain
whereby she intended to bind the princess to a ruin from which she
should not escape. At this time the countess is said to have hated
the handsome Königsmark as much as she had previously admired
him. He had met her liberal advances with disregard, or had
disregarded her after reciprocating them. In either case, the offence
was deadly.
The next incident told is more dramatic of character, perhaps,
than any of the others. The countess had engaged the count in
conversation in a pavilion of the gardens in the Electoral Palace,
when, making the approach of two gentlemen an excuse for retiring,
they withdrew together. The gentlemen alluded to were George
Louis and the Count von Platen; and these entering the pavilion
which had just been vacated, the former picked up a glove which
had been dropped by the countess. The prince recognised it by the
embroidery, and perhaps by a crest, or some mark impressed upon
it, as being a glove belonging to his consort. He was musingly
examining it, when a servant entered the place, professedly in
search of a glove which the princess had lost. On some explanation
ensuing, it was subsequently discovered that Madame von Weyhe,
the sister of the Countess von Platen, had succeeded in persuading
Prince Maximilian to procure for her this glove, on pretext that she
wished to copy the pattern of the embroidery upon it, and that the
prince had thoughtlessly done so, leaving the glove of Madame von
Weyhe in its place. But this, which might have accounted for its
appearance in the pavilion, was not known to George Louis, who
would probably in such case have ceased to think more of the
matter, but that he was obligingly informed that Count Königsmark
had been before him in the pavilion where the glove was found; been
there, indeed, with the excellent Countess von Platen, who
acknowledged the fact, adding, that no glove was on the ground
when she was there, and that the one found could not have been
hers, inasmuch as she never wore Netherland gloves—as the one in
question was—but gloves altogether of different make and quality.
Königsmark had been there, and the glove of the Princess Sophia
Dorothea had been found there, and this German specimen of Mrs.
Candour knew nothing beyond.
Thenceforth, George Louis was not merely rude and faithless to
his wife, but cruel in the extreme—the degrading blow, so it was
alleged, following the harsh word. The Elector of Hanover was more
just than his rash and worthless son: he disbelieved the insinuations
made against his daughter-in-law. The Electress was less
reasonable, less merciful, less just, to her son’s wife. She treated her
with a coolness which interpreted a belief in the slander uttered
against her; and when Sophia Dorothea expressed a wish to visit her
mother, the electoral permission was given with an alacrity which
testified to the pleasure with which the Electress of Hanover would
witness the departure of Sophia Dorothea from her court.
 Sophia Dorothea, as soon as she descended at the gates of her
father’s residence, found a mother there, indeed, ready to receive
her with the arms of a mother’s love, and to feel that the love was
showered upon a daughter worthy of it. Not of like quality were the
old duke’s feelings. Communications had been made to him from
Hanover, to the effect that his daughter was obstinate, disobedient,
disrespectful to the Elector and Electress, neglectful of her children,
and faithless in heart, if not in fact, to their father. The Duke of Zell
had been, as he thought, slow to believe the charges brought
against his child’s good name, and had applied to the Elector for
some further explanation. But poor Ernest Augustus was just then
perplexed by another domestic quarrel. His son, the ever
troublesome Prince Maximilian, having long entertained a suspicion
that the Countess von Platen’s denial of the light offence laid to her
charge, of wearing rouge, was also a playful denial, mischievously
proved the fact one day, by not very gallantly ‘flicking’ from his finger
a little water in which peas had been boiled, and which was then a
popularly mischievous test to try the presence of rouge, as, if the
latter were there, the pea-water left an indelible fleck or stain upon it.
At this indignity, the Countess von Platen was the more enraged as
her denial had been disproved. She rushed to the feet of the Elector,
and told her complaint with an energy as if the whole state were in
peril. The Elector listened, threatened Prince Maximilian with arrest,
and wished his family were as easy to govern as his electoral
dominions. He had scarcely relieved himself of this particular source
of trouble, by binding Prince Maximilian to his good behaviour, when
he was applied to by the Duke of Zell on the subject of his daughter.
He angrily referred the duke to three of his ministers, who, he said,
were acquainted with the facts. Now these ministers were the men
who had expressly distorted them.
These worthy persons, if report may be trusted, performed their
wicked office with as wicked an alacrity. However the result was
reached, its existence cannot be denied, and its consequences were
fatal to Sophia Dorothea. The Electress Sophia is said to have at last
so thoroughly hated her daughter-in-law, as to have entered partly
into these misrepresentations, which acquired for her the temporary
wrath of her father. But of this enmity of her mother-in-law the
younger Sophia does not appear to have suspected anything.
Sophia Dorothea, at all events, bore her father’s temporary aversion
with a wondering patience, satisfied that ‘time and the hour’ would at
length do her justice.
The duke’s prejudice, however, was rather stubborn of character,
and he was guilty of many absurdities to show, as he thought, that
his obstinacy of ill-merited feeling against his own child was not ill-
founded. He refused to listen to her own statement of her wrongs, in
order to show how he guarded himself against being unduly biassed.
The mother of the princess remained her firmest friend and truest
champion. If misrepresentations had shaken her confidence for a
moment, it was only for a moment. She knew the disposition of
Sophia Dorothea too well to lend credit to false representations
which depicted her as a wife, compared with whom Petruchio’s
Katherine would have been the gentlest of Griseldas. As little did she
believe—and to the expression of her disbelief she gave much
indignant force of phrase—as little did she believe in the suggestions
of the ministers of the Elector that the familiar terms which, as they
alleged, existed between the Electoral Princess and Count
Königsmark were such as did wrong to her husband George Louis.
Those judges of morality had jumped to the conclusion that youth
and good looks were incompatible with propriety of conduct.
The worst that could have been alleged against Sophia Dorothea
at this period was, that some letters had passed between her and
Count Königsmark, and that the latter had once or twice had private
audience of the Electoral Princess. Whatever may be thought of
such things here in England, and in the present age, they have never
been accounted of in Germany but as common-place circumstances,
involving neither blame nor injury. A correspondence between two
persons of the respective ranks of the Electoral Princess and the
count was not an uncommon occurrence; save that it was not often
that two such persons had either the taste or capacity to maintain
such intercourse. As to an occasional interview, such a favour,
granted by ladies of rank to clever conversational men, was as
common an event as any throughout the empire; and as harmless as
the interviews of Leonora and that very selfish personage, the poet