Table Of ContentDesign Controls for the
Medical Device Industry
Design Controls for the
Medical Device Industry
Third Edition
Marie B. Teixeira
CRC Press
Taylor & Francis Group
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Contents
Preface .................................................................................................................xi
Author ..............................................................................................................xiii
Chapter 1 Introduction ..................................................................................1
Chapter 2 Device classification ...................................................................5
Chapter 3 Overview of design controls .....................................................9
Applicability .......................................................................................................9
Design controls and the bottom line ...............................................................9
When might design controls be considered? ...............................................11
What are the benefits of design control other than the obvious
mandate? ...........................................................................................................11
An idea is born .................................................................................................12
Ask the customer .............................................................................................12
Design controls and the customer .................................................................13
Design and development phases ...................................................................13
The first phase: Definition—i.e., design input ........................................14
The second phase: Develop outputs—i.e., design and development ......15
The third phase: Design verification ........................................................16
The fourth phase: Design validation ........................................................17
The fifth phase: Product release ................................................................17
The sixth phase: Improvement and optimization ..................................18
Chapter 4 Design and development planning .......................................19
Do we really need a plan? ...............................................................................19
Design and development planning requirements ......................................20
Key elements of a design and development plan? ......................................24
Planning techniques ........................................................................................25
Gantt charts ..................................................................................................25
When is a good time to use a Gantt chart? .........................................27
When might a Gantt chart not be appropriate? .................................27
v
vi Contents
PERT charts ..................................................................................................27
What are the advantages of using PERT? ...........................................27
When might PERT not be appropriate? ...............................................28
Project planning—How do I get started? .....................................................28
Chapter 5 Design inputs: Part I .................................................................31
The concept document ....................................................................................31
Design input .....................................................................................................33
What are design inputs? ..................................................................................35
Design input requirements .............................................................................35
Where do design inputs come from? ............................................................37
How do we document our inputs? ................................................................38
Chapter 6 Design inputs: Part II ...............................................................41
Performance characteristics—e.g., user requirements ...............................42
Indications for use .......................................................................................42
Clinical procedure for use .........................................................................43
Relevant use setting/environment ...........................................................44
Medical specialty of the user .....................................................................45
Patient population—inclusion/exclusion criteria ...................................45
User interface/ergonomic considerations ................................................46
Product characteristics—i.e., product requirements ...................................47
Physical characteristics ...............................................................................48
Chemical characteristics.............................................................................49
Biological characteristics ............................................................................50
Selection of tests......................................................................................52
Environmental characteristics ...................................................................53
Transport and storage ............................................................................53
Use environment ....................................................................................54
Sterilization and sterile barrier characteristics .......................................55
Methods of sterilization.........................................................................55
Aseptic processing .................................................................................56
Reusable medical devices ......................................................................56
Packaging and labeling characteristics ....................................................58
Equipment interface characteristics .........................................................60
Safety and reliability characteristics ........................................................63
Marketing requirements .................................................................................64
Intended marketplace .................................................................................64
Contractual requirements ..........................................................................65
Claims ...........................................................................................................65
Labeling requirements ...............................................................................67
Patents, trademarks, and licensing agreements ......................................70
Clinical information ....................................................................................70
Contents vii
Regulatory and quality assurance requirements ........................................71
Classification ................................................................................................71
Device approval requirements ..................................................................71
Relevant regulatory or harmonized standards ......................................71
Labeling ........................................................................................................72
Contractual agreements .............................................................................72
Financial requirements ...................................................................................72
Design specifications .......................................................................................73
One more step ...................................................................................................73
Chapter 7 Design outputs ...........................................................................75
Design output requirements ..........................................................................76
Typical design outputs ....................................................................................77
Device master record .......................................................................................78
Chapter 8 Design review ............................................................................81
Not another meeting! ......................................................................................81
FDA and design review ...................................................................................81
Design review requirements ..........................................................................82
Design team members .....................................................................................83
Design review focus ........................................................................................83
Design review elements ..................................................................................84
Design review meetings..................................................................................85
Phase 1—Design input phase review .......................................................86
Phase 2—Design and development phase review .................................87
Phase 3—Design verification phase review ............................................88
Phase 4—Design validation phase review ..............................................89
Phase 5—Design release and approval for sale (i.e., product launch) ...89
Phase 6—Use design review meeting ......................................................90
Documenting the design review ...................................................................91
Meeting dynamics ...........................................................................................91
Communication skills .................................................................................91
Did they get it? .............................................................................................92
Listen and validate ......................................................................................93
Accept the bad news ...................................................................................94
Monitor and measure .................................................................................94
Don’t confuse motion with progress ........................................................95
Meeting minutes..........................................................................................95
Making decisions that solve problems .....................................................95
Chapter 9 Design verification ....................................................................99
What is the purpose of design verification? .................................................99
What is design verification?............................................................................99
Design verification—Definitions ...................................................................99
viii Contents
Design verification requirements ................................................................100
Design verification process ...........................................................................101
Verification activities .....................................................................................101
A word of advice ............................................................................................104
Chapter 10 Risk management ....................................................................105
Why? ................................................................................................................105
How does risk management fit into design and development? ..............105
What is risk management? ...........................................................................107
The risk management process ......................................................................107
Risk analysis ...................................................................................................108
Human factors and the risk management process ...................................109
Risk evaluation ...............................................................................................112
Risk control ......................................................................................................113
Risk review ......................................................................................................115
Post-production risk management ...............................................................116
Chapter 11 Design validation ....................................................................119
Why validate? ..................................................................................................119
What is design validation? .............................................................................119
Design validation requirements ..................................................................120
Design validation process .............................................................................124
Validation activities .......................................................................................126
Design validation results ..............................................................................126
Risk assessment of medical device materials and the finished device ......127
Chapter 12 Biocompatibility ......................................................................129
Duration of use ...............................................................................................130
Degree of invasiveness ..................................................................................130
Biological effects/end points ........................................................................132
Biological testing considerations .................................................................132
Regulatory aspects of biocompatibility ......................................................134
Biocompatibility testing programs ..............................................................139
Phases of biocompatibility testing ...............................................................140
Screening tests ................................................................................................142
Systemic toxicity .............................................................................................142
Cytotoxicity and cell cultures ......................................................................144
Evaluation using extracts .........................................................................144
Evaluation by direct contact ....................................................................145
Evaluation by indirect contact .................................................................146
USP biological tests ........................................................................................146
Irritation tests..................................................................................................147
Sensitization tests ...........................................................................................148
Contents ix
Hemocompatibility tests ...............................................................................148
Implantation tests ...........................................................................................150
Mutagenicity tests (genotoxicity) .................................................................150
Supplemental testing .....................................................................................151
Carcinogenicity testing .................................................................................152
Reproductive and developmental toxicity .................................................152
Biodegradation ...............................................................................................153
Chapter 13 Design transfer ........................................................................155
Importance of design transfer ......................................................................155
Design transfer requirements ......................................................................156
Design transfer ...............................................................................................157
The design transfer checklist .......................................................................157
Design release .................................................................................................159
Chapter 14 Design change ..........................................................................161
Why control design changes .........................................................................161
Design change examples ................................................................................161
Design change requirements........................................................................163
Design change procedure .............................................................................163
Evaluation of design changes .......................................................................163
Documenting design changes ......................................................................165
Chapter 15 Design history file ...................................................................167
Why do we need a design history file? ........................................................167
What is a design history file? ........................................................................167
Design history file requirements ..................................................................167
Design history file elements .........................................................................168
Chapter 16 The FDA inspection technique ............................................171
Oh no! The FDA investigator is here ...........................................................171
General design control requirements..........................................................171
Design and development planning ........................................................171
Design input ...............................................................................................172
Design output ............................................................................................172
Design review ............................................................................................173
Design verification ....................................................................................173
Design validation .......................................................................................174
Design transfer ...........................................................................................174
Design changes ...........................................................................................174
Design history file ......................................................................................174
