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 Contents

Preface xxxi
Asia Regulatory Professional Association xxxiii

1. How to Train University Students in Regulatory Affairs 1

Raymond K. Y. Tong

1.1 Introduction 1
1.2 A Sample of Regulatory Affairs Exercises for Students 2
1.2.1 Background 2

Part 1 Introduction
2. The Evolution of the Regulatory Professional: Perspectives on
the Skill Sets and Capabilities That Will Define the Next
Generation of Regulatory Professionals 7
David Martin and Neil Lesser

2.1 Introduction 7
2.2 Drivers of Change 8
2.3 Historical Role and Skill Set of a Regulatory
Professional 10
2.4 Changing Role and Skill Set of the Regulatory
Professional 12
2.5 Develop as a Center of Intelligence 12
2.6 Advance Toward Strategic Relationship
Management 13
2.7 Develop as a Strategic Business Partner 13
2.8 Conclusion: What Will It Take to Get There? 14
vi Contents

3. Ensuring Smooth Product Launch: Regulatory Interfaces

with Marketing and Supply Chain 17
Alok Mishra
3.1 Introduction 17
3.2 New Product Pipeline 18
3.3 Planned Launch Dates 18
3.4 New Product Forecasts 19
3.5 New Product Approval Dates 19
4. What Is the Right Thing to Do? 21
Jack Wong
4.1 Right Job 21
4.2 Two Key Challenges in Our Job 22
4.2.1 Quality 22
4.2.2 Speed 22
4.3 Regulatory Affairs Job Is a Combination of Science,
Legal Affairs, and Moral 22
4.4 Persons versus Things 22
5. Affordable Access to Medical Devices in Developing
Countries 25
Rosanna W. Peeling and Tikki Pang
5.1 Introduction 25
5.2 Why Is Affordable Access to Medical Devices
Important for Developing Countries? 26
5.2.1 Emergency Preparedness 27
5.2.2 Efficiency and Effectiveness of Health Systems 27
5.2.3 Health Equity 28
5.3 Case Studies 29
5.3.1 Delay in Eligibility to Treatment for HIV 29
5.3.2 Delay in Access to Early Diagnosis of
Tuberculosis 29
5.3.3 Misleading Claims of Test Performance for
Dengue Rapid Tests 30
5.3.4 Case Study — Access versus Performance: Basis
for FDA Approval of the First Over-the-Counter
Rapid HIV Test in the United States 31
 Contents vii

5.3.4.1 Background 31
5.3.4.2 Performance expectations 31
5.3.4.3 Risk beneit analysis 32
5.4 The Way Forward 33
6. A Story of Attention to Detail 35
Richard Liu

P 2 M D  S    R  ISO S 

7. Biomedical Devices: Overview 39
Piu Wong
7.1 Historic Aspect of Medical Devices 39
7.2 Biomedical Market Environment 41
7.3 Orthopedics 42
7.3.1 Market 42
7.3.2 Materials 43
7.3.3 Biocompatibility 43
7.3.4 Fabrication 44
7.3.5 Polyethylene Fabrication 44
7.4 Vision Care 46
7.4.1 Market 46
7.4.2 Diagnostic Devices 46
7.4.3 Treatment 47
7.5 Diabetics 48
7.6 Obesity 48
7.7 Vascular Disease 48
7.8 Concluding Remarks 49
8. Labeling, Label, and Language: A Truly Global Matter 53
Evangeline D. Loh and Jaap L. Laufer
8.1 Introduction 53
8.2 Deinition of Labeling 55
8.3 Elements of Labeling 56
8.4 Risk Management, Clinical Evaluation and Labeling:
The Core Triangle for Safe and Effective Use of
the Device 59
8.5 Labeling and Promotion 60
viii Contents

8.6 e-Labelling, Web Sites, Internet, and Social Media:

A Brave New World for Labeling 61
8.7 Language, Language Level and Intended User 63
8.8 Conclusion 64
9. Clinical Trials: Legal and Ethical Considerations of
Increasing Globalization 67
Paula Celine Trepman
9.1 Introduction 67
9.2 The Increasing Trend of Offshore Clinical Trials 68
9.3 International Standards to Protect Patients 69
9.4 Breaches of Clinical Trial Legality 70
9.5 Issues of Informed Consent 71
9.6 Cultural and Social Factors 71
9.7 Vulnerable Patient Populations 72
9.8 Economic Considerations 72
9.9 Comparison of Trial Population to Target
Population 73
9.10 Conclusion 75
10. Regulatory Affairs for Medical Device Clinical Trials in
Asia Pacific 79
Seow Li-Ping Geraldine
10.1 Introduction 79
10.2 Medical Device Clinical Trials versus
Pharmaceutical Clinical Trials 80
10.3 Regulation of Clinical Trials 83
10.4 Country Regulations 87
10.4.1 Australia 89
10.4.2 China 91
10.4.3 Hong Kong 91
10.4.4 India 91
10.4.5 Malaysia 92
10.4.6 New Zealand 92
10.4.7 Singapore 93
10.4.8 South Korea 94
 Contents ix

10.4.9 Taiwan 95
10.4.10 Thailand 96
10.5 Moving Ahead as Regulatory Affairs Professionals 96
11. Medical Device Classification Guide 101
Patricia Teysseyre
11.1 How to Carry Out Medical Device Classification 101
11.1.1 Scope 101
11.1.2 Definitions 102
11.2 Main Classifications 103
11.2.1 Medical Devices 103
11.2.2 Active Devices 103
11.2.3 IVD Devices 104
11.2.4 IVD Case Study 106
11.2.4.1 US FDA 107
11.2.4.2 Canada 107
11.2.4.3 EU 108
11.2.4.4 Singapore 109
11.3 Medical Device Classification: Practical
Examples 109
12. ISO 13485:2003 Medical Devices — Quality Management
Systems — Requirements or Regulatory Purposes 125
Ann Goodall and Gert Bos
12.1 Introduction 125
12.2 Background and Origins of ISO 13485:2003 126
12.3 Management Systems Standard 128
12.4 Quality Management Systems 129
12.5 ISO 9000 and ISO 13485 Quality Management
System Family of Standards 130
12.6 ISO 13485:2003 and Regulatory Requirements
Around the World 131
12.7 Good Reasons to Implement an ISO 13485:2003
Quality Management System 132
12.8 Process Approach 132
12.9 Planning the Implementation 133
 Contents

12.10 Scope, Exclusions and Non-Applicability 134

12.11 Document Control 134
12.12 Record Completion and Control 135
12.13 Management Responsibility 135
12.14 Resource Management 136
12.15 Product Realisation 136
12.16 Risk Management 136
12.17 Design and Development 137
12.18 Purchasing and Supplier Control 138
12.19 Production and Service Provision 138
12.20 Monitoring and Measuring, Including
Internal Audits and Management Review 139
12.21 Control of Non-Conforming Product 140
12.22 Analysis of Data 140
12.23 Improvement: Corrective Action and
Preventive Action 140
12.24 Purpose and Goal of ISO 13485:2003
Certification 141
12.25 Achieving Certification and Continuing to
Maintain Certification 141
13. ISO 14971: Application of Risk Management to
Medical Devices 145
Tony Chan and Raymond K. Y. Tong
13.1 Introduction 145
13.2 The Foundation of a Risk Management (RM)
Framework: Policy, Plan, Team, Process, and
Documentation 149
13.2.1 Policy 149
13.2.2 Plan 149
13.2.3 Team 149
13.2.4 Process 150
13.2.5 Documentation 150
13.3 The RM Process 150
13.3.1 Analyze Risk 150
13.3.2 Evaluate Risk 151
 Contents xi

13.3.3 Control Risk 151

13.3.4 Feedback from Production and
Post-Production Information 153
13.4 Conclusion 154
13.5 Case Study — An Example to Illustrate Risk
Management on a Medical Device: Functional
Electrical Stimulation System for Walking 154
13.5.1 Risk Management Process 156
Part 3 Harmonization of Medical Devices in Asia
14. Medical Devices in the World Health Organization 165
Adriana Velazquez Berumen and Jack Wong

15. Asian Harmonization Working Party 169

Saleh Al Tayyar
15.1 Introduction 169
15.2 Future Directions 170
16. Asia-Pacific Economic Cooperation 173
Lindsay Tao
16.1 Introduction 173
16.1.1 Trade and Investment Liberalization 174
16.1.2 Business Facilitation 175
16.1.3 Economic and Technical Cooperation 175
16.2 APEC LSIF: Life Sciences Innovation Forum
(Reports to Committee on Trade and Investment) 176
16.3 APEC LSIF/RHSC: Regulatory Harmonization
Steering Committee 178
17. Harmonization of Medical Device in ASEAN 183
Petahn McKenna
17.1 Introduction 183
17.1.1 Medical Device Market in ASEAN 183
17.1.2 Medical Device Regulatory Environment
in ASEAN 184
17.2 ASEAN Medical Device Directive and
Harmonization 184
xii Contents

17.2.1 Provisions of the AMDD 185

17.2.2 Definition of a Medical Device 186
17.2.3 Medical Device Classification 187
17.2.4 Common Submission Dossier Template 187
17.2.5 Post-Market Alert System 188
17.2.6 AMDD Status 188
17.2.7 Future of ASEAN Harmonization 189
18. Regulatory Affairs Professionals Society 191
Sherry Keramidas and Zachary Brousseau
18.1 Introduction 191
18.2 Importance in Today’s Global Environment 192
18.3 The Global Regulatory Community 193
18.4 Building Knowledge and Competencies 194
18.5 The RAC Credential 195
18.6 Professional Knowledge and Standards 196
18.7 News and Information 197
19. Expediting Innovation in Singapore with Regulatory
Knowledge 199
Patricia Ho and Jui Lim
19.1 The Biodesign Innovation Process 201
19.1.1 Identify 202
19.1.2 Invent 202
19.1.3 Implement 204
19.2 The Innovator’s Resource 204
19.3 Current Direction 207
Part 4 Medical Device Regulatory System in the United
States and the European Union
20. United States Medical Device Regulatory Framework 211
Carole C. Carey
20.1 Introduction 211
20.2 The FDA Center for Devices and Radiological
Health 213
20.3 Total Product Life Cycle Approach 213
 Contents xiii

20.4 Legislation and Device Laws 214

20.4.1 FDA Law vs. FDA Regulations vs. FDA
Guidance 215
20.5 The Regulatory Environment for Bringing a
Medical Device to Market 215
20.6 Regulatory Considerations to Market and Keep
Devices in Distribution 216
20.6.1 Definition of Medical Devices 216
20.6.2 Classification of Medical Devices 217
20.6.3 Adulteration and Misbranding 218
20.6.4 Establishment Registration and Medical
Device Listing 219
20.6.5 Premarket Notification (510(k)) 220
20.6.5.1 Kits 221
20.6.5.2 Predicate device and
substantial equivalence 221
20.6.5.3 Planning and assembling the
510(k) submission process 223
20.6.6 Premarket Approval (PMA) 225
20.6.7 Investigational Device Exemption (IDE) 226
20.6.8 Labeling 226
20.6.9 Quality System (QS) Regulation/Good
Manufacturing Practices (GMP) 227
20.6.10 Medical Device Reporting (MDR) 227
20.6.11 User Fees 228
20.7 Summary 229
21. European Union: Medical Device Regulatory System 233
Patricia Teysseyre
21.1 Glossary of Terms 233
21.2 European Union: History and Structure 234
21.3 New Approach — Global Approach Concepts 235
21.4 Harmonized Standards and Presumption of
Conformity 239
21.5 European Associations 243
21.6 Overview of Medical Devices Directives 243
xiv Contents

21.7 Guidelines 244

21.8 Definitions 245
21.8.1 Medical Device 245
21.8.2 CE Mark 245
21.8.3 Competent Authority 246
21.8.4 Notified Body: Conformity Assessment
Body 247
21.8.5 Legal Manufacturer 248
21.8.6 Authorized Representative 249
21.9 Classification 249
21.9.1 Medical Devices 249
21.9.2 Active Implantable Medical Devices 250
21.9.3 In vitro and Diagnostics Medical Devices 251
21.10 Conformity Assessment Procedures 252
21.11 Essential Requirements 255
21.12 Labelling 257
21.13 Technical Documentation 258
21.14 Quality Management System 258
21.15 Risk Management 264
21.16 Clinical Evaluation 264
21.17 CE Mark Certificate and Declaration of
Conformity 266
21.18 Post-Market Surveillance 267
21.19 Recent Changes of MDD 93/42/EEC and
Impacts 268
21.20 Trends 270
21.21 Overview of All Interactions and Key
Terminology 271
22. Regulation of Combination Products in the United States 275
John Barlow Weiner and Thinh X. Nguyen
22.1 Introduction 275
22.2 What Products Are Considered Combination
Products 276
22.3 The Standards for Determining If a Product Is a
Combination Product 276
 Contents xv

22.4 The Standards for Determining Which FDA

Component has Primary Responsibility for
Regulating a Combination Product 277
22.5 Requests for Designation 280
22.6 Premarket Review Considerations 280
22.7 Post-Market Regulatory Considerations 281
22.8 Role of Office of Combination Products 282
22.9 Near-Term Developments That May Arise in
the US 284
22.10 International Harmonization and Coordination
Activities with Foreign Counterparts 284
22.11 FDA Resources for Obtaining Additional
Information 285
23. Regulation of Combination Products in the European
Union 287
Janine Jamieson and Elizabeth Baker
23.1 Introduction: Legal Basis 287
23.1.1 Definitions 288
23.1.1.1 Medical device 288
23.1.1.2 Medicinal product 289
23.1.1.3 Combination products:
Principal mode of action 290
23.1.1.4 Borderline products:
MEDDEV 2.1/3 291
23.1.1.5 Borderline products: Manual
of decisions 291
23.2 Combination Products Regulated as Medicinal
Products 291
23.2.1 Examples of Combination Products
Regulated as Medicinal Products 292
23.3 Combination Products Regulated as Medical
Devices 292
23.3.1 Examples of Combination Products
Regulated as Drug-Delivery Devices 292
23.4 Combination Products Regulated as Devices
Incorporating, as an Integral Part, an Ancillary
Medicinal Substance 293
xvi Contents

23.4.1 Examples of Devices Incorporating an

Ancillary Medicinal Substance 293
23.4.2 Examples of Drug Substances Incorporated
into Devices 294
23.4.3 Assessment of the Medicinal Substance
Aspects of a Device Incorporating an
Ancillary Medicinal Substance 294
23.5 The Consultation Process 294
23.6 Information to Be Provided on the Ancillary
Medicinal Substance 295
23.6.1 General 295
23.6.2 Quality, Safety, Usefulness (Clinical
Benefit/Risk) 295
23.6.2.1 Quality 295
23.6.2.2 Safety and usefulness
(clinical benefit/risk) 296
23.6.2.3 Guidance 296
23.7 Other Combination Products 297

Part 5 Medical Device Regulatory System

in Asia-Pacific Region
24. Australian Medical Device Regulations: An Overview 301
Petahn McKenna
24.1 Introduction 301
24.1.1 Medical Device Market in Australia 301
24.2 Medical Device Regulations 302
24.2.1 Overview 302
24.2.2 Regulating Authority 303
24.2.3 Legislation and Guidance 303
24.3 Definition of Medical Device 303
24.4 Classification of Medical Devices 304
24.4.1 Classification of IVD Medical Devices 304
24.5 Inclusion of Medical Devices on the ARTG 306
24.5.1 Process for Supplying a Medical Device in
Australia 306
 Contents xvii

24.5.2 Process for Including Class 1 IVD Medical

Devices (Other Than Export Only) in the
ARTG 307
24.5.3 Process for Including IVD Medical Devices
(Other Than Class 1) in the ARTG 310
24.6 Same Kind of Medical Device (SKMD) 312
24.7 Unique Product Identifier 312
24.8 In vitro Diagnostic UPIs 313
24.9 Renewal 314
24.10 Documentation Requirements 314
24.10.1 Conformity Assessment Applications 314
24.11 Application Audits 315
24.12 Access to Unapproved Medical Devices 316

25. China: Medical Device Regulatory System 317

Jack Wong
25.1 Introduction 317
25.2 Market Overview 318
25.3 Overview of Regulatory Environment and What
Laws/Regulations Govern the Medical Devices 318
25.3.1 Measuring Function 319
25.3.2 Standards 319
25.4 Regulatory Body 320
25.5 Regulatory Overview 321
25.5.1 Definition of Medical Device 321
25.5.2 Classification of Medical Device 321
25.5.3 Registration Process 322
25.5.3.1 Medical devices registration
certificate 322
25.4.5.2 Product testing 323
25.5.3.3 Clinical trials 324
25.5.3.4 Exemption of clinical trial data
for Class II devices 325
25.5.3.5 Enforcing GMPs 325
25.5.3.6 Timeframes 326
xviii Contents

25.5.3.7 The CCC mark 327

25.6 Monitoring Adverse Events 328
25.7 Managing Recalls 329
26. Hong Kong: Medical Device Regulatory System 331
Jack Wong
26.1 Market Overview 331
26.1.1 Market Environment 331
26.2 Overview of Regulatory Environment and What
Laws/Regulations Govern Medical Devices 332
26.3 Regulatory Body 333
26.4 Regulatory Overview 335
26.4.1 Definition of Medical Device (It Follows
GHTF) 334
26.4.2 The Classification of Medical Devices 335
26.4.3 Role of Distributors or Local Subsidiaries 336
26.4.4 Product Registration or Conformity
Assessment Route and Time Required 337
26.4.4.1 Suggested registration
routes/steps 338
26.4.4.2 Technical material
requirement 338
26.4.4.3 The labelling requirement of
medical device 338
26.4.4.4 Post-marketing surveillance
requirement 338
26.4.4.5 Manufacturing-related regulation:
Do manufacturers need
registration/authorization? 339
26.4.4.6 Clinical trial-related regulation:
Are medical device clinical trials
regulated? 339
26.4.4.7 Is there a procedure for mutual
recognition of foreign marketing
approval or international
standards? 339
 Contents xix

26.5 Commercial Aspect 339

26.6 Next Steps 340
27. India: Medical Device Regulatory System 341
Kulwant S. Saini
27.1 Market Overview 341
27.1.1 Market Environment 341
27.1.2 Overview of Regulatory Environment and
What Laws/Regulations Govern Medical
Devices 342
27.1.3 Functions Undertaken by DCGI and Central
Government 346
27.1.3.1 Statutory functions 346
27.1.3.2 Other functions 346
27.1.4 Functions Undertaken by the FDA and
State Governments 347
27.1.4.1 Statutory functions 347
27.1.5 Guidance Documents 348
27.1.6 Indian Pharmacopoeial Commission 349
27.1.7 Detail of Key Regulator(s) 349
27.2 Regulatory Overview 352
27.2.1 Definition of Medical Device 352
27.2.2 Classification of Medical Device 353
27.2.3 Role of Distributors or Local Subsidiaries
(LRP) 353
27.2.4 Product Registration or Conformity
Assessment Route and Time Required 354
27.2.5 Quality System Regulation 356
27.2.6 Product Registration and Quality System
Regulation for Combined Device–Drug
Product 356
27.2.7 Registration Fee 356
27.2.8 Technical Material Requirement 357
27.2.9 The Labelling Requirement of Medical
Device 358
27.2.10 Post-Marketing Surveillance Requirement 359
xx Contents

27.2.11 Manufacturing-Related
Regulation 359
27.2.12 Clinical Trial-Related
Regulation 360
27.2.13 Is There a Procedure for Mutual Recognition
of Foreign Marketing Approval or
International Standards? 361
27.3 Commercial Aspect 361
27.3.1 Any Price Control of Medical Device 361
27.3.2 Are Parallel Imports Allowed? 362
27.3.3 Any Advertisement Regulation of
Medical Device? 362
27.4 Upcoming Regulation Changes 362
27.5 Related Agencies/Departments and Ministries 363

28. Indonesia: Medical Device Regulatory System 365

Mita Rosalina
28.1 Introduction 365
28.2 Regulating Authority 367
28.3 Definition of Medical Device 367
28.4 Classification of Medical Devices 368
28.5 Registration of Medical Devices 369
28.5.1 Process 368
28.5.2 Documents Required 370
28.5.3 Official Registration Fee 370
28.5.4 Time Line 370
28.5.5 Validity of Product License 371
28.5.6 Indonesian Labeling Requirement 371
28.5.7 Regulatory Action for Changes and
Device Modifications 371
28.6 Post Market Surveillance System 372
29. Japan: Medical Device Regulatory System 387
Atsushi Tamura
29.1 Introduction 387
29.2 Regulatory Agency in Japan 388
 Contents xxi

29.2.1 The Ministry of Health, Labour and

Welfare 388
29.2.2 Pharmaceuticals and Medical Devices
Agency 388
29.2.3 Shared Responsibility of MHLW and PMDA
on Medical Device Regulation 388
29.3 Legislation of Medical Devices 391
29.3.1 Classiication of Medical Devices 392
29.3.2 Type of Product’s Registration 393
29.3.2.1 Notiication 393
29.3.2.2 Pre-market certiication
(third-party certiication) 393
29.3.2.3 Pre-market approval 394
29.3.3 Marketing Authorization Holder 394
29.3.4 Manufacturer License (Art. 13)/
Accreditation of Foreign Manufacturer
(Art. 13-3) 394
29.4 Related Requirements 396
29.4.1 Quality Management System 396
29.4.1.1 QMS conformity as an
essential requirement 396
29.4.1.2 QMS inspections 397
29.4.2 Good Quality Practices 397
29.5 MAH’S Obligations during Post-Market Phase 397
29.5.1 Collection, Analysis and Reporting of
Safety Information 399
29.5.2 Recall 399
29.5.3 Post-Marketing Safety Management 400
29.6 PMDA’s Obligations during Post-Market Phase 400
29.6.1 New Challenge 401
29.6.2 Information Services 401
30. Jordan: Medical Device Regulatory System 403
Anan Abu Hassan
30.1 Jordan Food and Drug Administration:
Introduction 403
xxii Contents

30.1.1 Vision 403

30.1.2 Mission 404
30.1.3 Overview of Structure of Jordan Food and
Drug Administration 404
30.2 Medical Device Market in Jordan 404
30.3 Overview of Regulatory Environment and What
Laws/Regulations Govern the Medical Devices 404
30.4 Data about Jordan 409
30.5 Price Control of Medical Device 409
30.6 Priorities 409
31. Republic of Korea (South Korea): Medical Device
Regulatory System 421
Peter Lee
31.1 Market Overview 421
31.1.1 Facts about South Korea 421
31.1.2 Medical Device Market Scale in South
Korea 422
31.1.3 Definition of Medical Device 422
31.1.4 Detail of Key Regulator 423
31.2 Introduction to Korea Medical Device Regulatory
System 424
31.2.1 History 424
31.2.2 Procedures 425
31.2.3 KGMP: Quality Management System 426
31.2.4 Product Notification: Class I Devices 429
31.2.5 Product License: Class II, III, and
IV Devices 430
31.2.6 Technical File 430
31.2.7 Clinical Trials 431
31.2.8 Device Notification/License 432
31.2.9 Technical File Review 433
31.2.10 Type Testing (Mandatory for Class II, III,
and IV Devices) 434
31.2.11 KFDA-Registered 13 Laboratories 436
 Contents xxiii

31.2.12 Applying for a Product License 437

31.2.13 Business License 437
31.2.14 Audit of Quality Management System
(KGMP Certification) 438
31.2.15 Post-Market Surveillance System 438
31.3 Importer’s Note 439
31.3.1 Import Labelling 439
31.3.2 Import Packaging 439
31.3.3 Import Documentation 439
31.3.4 Other Agencies 440
31.3.5 Medical Device Advertisements 441
31.3.6 Contacts 439
32. Malaysia: Medical Device Regulatory System 445
Yean Ting Ong
32.1 Market Overview 445
32.2 Regulating Authority 446
32.3 Definition of Medical Device 447
32.4 Classification of Medical Devices 447
32.5 Registration of Medical Devices 449
32.5.1 Market Environment 450
32.5.2 Conformity Assessment Process 451
32.5.3 Combination Products 453
32.6 Post-Market Surveillance and Vigilance 453
32.6.1 Mandatory Reporting 453
32.6.2 Field Corrective Action 454
32.6.3 Recall 454
32.6.4 Labeling 455
32.7 Regulatory Action for Changes and Device
Modifications 455
33. Philippines: Medical Device Regulatory and Licensing 457
Mary Claire Cacanindin and Jennifer Cheah
33.1 Market Overview 457
33.2 Regulatory Overview 458
xxiv Contents

33.3 History of Medical Device Regulation 460

33.4 Regional Medical Device Harmonization under
Development through ASEAN 461
33.5 Definition of Medical Device in Philippines 462
33.6 Registration with BFAD 463
33.6.1 License to Operate 463
33.6.2 License to Operate: Requirements 464
33.6.3 Certificate of Product Registration 465
33.6.4 Certificate of Product Registration:
Technical Requirements 465
33.6.5 Certificate of Product Registration: Legal
Requirements 466
33.7 Import Labeling 466
33.8 Import Documentation 467
33.9 Summary of Regulatory System 467
33.10 Contacts 468
34. Saudi Arabia: Medical Device Regulation System 469
Ali M. Al Dalaan

34.1 Introduction 469

34.2 Legislative Responsibilities 470
34.3 Executive Responsibilities 470
34.4 Surveillance Responsibilities 471
34.5 Regulation Overview 472
34.6 Registration Requirements 473
34.7 Information to Be Provided to SFDA 473
34.8 Medical Device Marketing Authorization
(MDMA) 476
34.9 Medical Device Listing 478
34.10 Registration Fees 478
34.11 General Information and Documentary
Evidence to Be Provided to SFDA 480
34.12 Labeling Requirement for Medical Device 481
34.13 Post-Market Surveillance Requirement 481
 Contents xxv

35. Singapore: Medical Device Regulatory System 487

Lee Ching Hwee
35.1 Market Overview Introduction: An Explanation of
the Process and Approach 487
35.1.1 Market Environment 487
35.1.2 Overview of Regulatory Environment and
What Laws/Regulations Govern Medical
Devices 488
35.1.2.1 Phase I implementation 489
35.1.2.2 Phase II implementation 489
35.1.2.3 Phase III implementation 489
35.2 Detail of Key Regulator(s) 491
35.3 Regulatory Overview 492
35.3.1 The Definition of Medical Device 492
35.3.2 Classification of Medical Devices
(Classes A, B, C, and D) 493
35.3.2.1 Principle 493
35.3.2.2 Classification 493
35.3.2.3 Determination 494
35.4 Product Grouping 494
35.4.1 Single 494
35.4.2 Family 495
35.4.3 System 495
35.4.4 Group 496
35.4.5 IVD Cluster 496
35.5 Product Registration and Time Required 496
35.5.1 Application Process: Product Registration
for Higher Risk Medical Devices (Class B, C,
and D) 496
35.5.2 Product Registration for Lower Risk Medical
Devices (Class A) 497
35.5.3 Evaluation Routes 498
35.6 Product Registration for Combined Device–Drug
Product 499
35.7 Application Fee 499
xxvi Contents

35.8 Technical Material Requirement 499

35.9 Labeling Requirement of Medical Devices 501
35.10 Post-Marketing Surveillance Requirement 502
35.11 Manufacturing-, Importing-, and Wholesaling-
Related Regulation 503
35.12 Good Distribution Practice for Medical Devices 504
35.13 Clinical Trial-Related Regulation 504
35.14 Special Access 505
35.15 Commercial Aspect 506
35.15.1 Any Price Control of Medical Device 506
35.15.2 Are Parallel Imports Allowed? 506
35.15.3 Any Advertisement Regulation of Medical
Device? 507
35.16 Upcoming Regulatory Implementation 507
35.16.1 Regulatory Framework for Cell- and
Tissue-Based Therapeutic Products 507
36. Taiwan: Medical Device Regulatory System 513
Li-Ling Liu

36.1 Market Overview 513

36.1.1 Overview of Structure and Funding of
Local Healthcare System 513
36.1.2 Overview of Regulatory Environment and
Laws/Regulations Governing Medical
Devices 515
36.1.3 Detail of Key Regulator(s) 517
36.2 Regulatory Overview 517
36.2.1 Definition of Medical Device 517
36.2.2 Classification of Medical Device 517
36.2.3 Role of Distributors or Local Subsidiaries 518
36.2.4 Products Registration, Technical Material
Requirement, and Time Required 518
36.3 Quality System Regulation 519
36.4 Combined Device–Drug Product 520
36.5 Registration Fee 520
 Contents xxvii

36.6 Labeling Requirements of Medical Devices 520

36.7 Any Post-Marketing Surveillance Requirement 521
36.8 Manufacturing-Related Regulation 521
36.9 Clinical Trial-Related Regulation 521
36.10 International Cooperation 522
36.11 Commercial Aspects 522
36.11.1 Price Control of Medical Device 522
36.11.2 Parallel Imports 523
36.11.3 Any Advertisement Regulation of Medical
Devices? 523
37. Thailand: Regulatory and Medical Device Control 525
Patanawong Yuwadee

37.1 Market Overview 525

37.2 Medical Device Regulations and Regulators 526
37.3 Definition of a Medical Device 527
37.4 Classification of Medical Devices 529
37.5 Product Registration 529
37.5.1 Licensed Medical Devices and Notified
Medical Devices 529
37.5.2 General Medical Devices 530
37.5.3 Review Period (as Promulgated in 2012) 531
37.5.4 Fees and Validity of Granting or Issued
Document 532
37.6 Labeling 532
37.7 Advertisement Control 533
38. UAE: Overview of Medical Device/IVD Regulatory System 535
Amin Al Amiri

38.1 Ministry of Health 535

38.1.1 Registration and Drug Control Department 535
38.1.2 Mission Statement 536
38.1.3 Medical Device Registration 536
38.2 Introduction to Md/ivd Regulatory System in Uae 537
xxviii Contents

38.3 Medical Devices Marketing Approval Flow Chart 538

38.4 Approval on Importation Level 539
38.5 Definition of a Medical Device 540
38.6 Classification of Medical Device/IVD 540
38.7 Authorized Representative Concept 541
38.8 Company Registration 542
38.8.1 Medical Devices Classified as
Nonpharmaceutical Dosage Form 542
38.8.2 Medical Devices Classified as Containing
Pharmaceutical Ingredients 543
38.9 Product Registration 543
38.9.1 Medical Devices Subject for Listing 543
38.9.2 Product Registration: Main Documents 544
38.9.3 Required Attachments per Device Class 545
38.10 Pricing 546
38.11 Parallel Importation 546
39. Vietnam: Medical Device Regulatory System 547
Thuy Nguyen Thi Thu

39.1 Market Overview 547

39.2 Overview of Regulatory Environment and Laws/
Regulations Governing Medical Devices 548
39.2.1 Detail of Key Regulator(s) 548
39.3 Regulatory Overview 549
39.3.1 Definition of Medical Device 549
39.4 Classification of Medical Devices (Class A, B, C, D) 550
39.5 Role of Distributors or Local Subsidiaries 550
39.6 Product Registration or Conformity Assessment
Route and Time Required 550
39.6.1 Quality System Regulation 551
39.6.2 Product Registration and Quality System
Regulation for Combined Device–Drug
Product 551
39.6.3 Registration Fee 551
 Contents xxix

39.6.4 Technical Material Requirement 552

39.6.5 Labeling Requirements for Medical Devices 552
39.6.6 Post-Marketing Surveillance Requirement 552
39.6.7 Manufacturing-Related Regulation 552
39.6.8 Clinical Trial-Related Regulation 552
39.6.9 Is There a Procedure for Mutual
Recognition of Foreign Marketing
Approval or International Standards? 552
39.7 Commercial Aspects 553
39.7.1 Any Control over Prices of Medical
Devices? 553
39.7.2 Are Parallel Imports Allowed? 553
39.7.3 Any Regulation Regarding Advertisement
of Medical Devices? 553
39.8 Upcoming Events 553

Appendix 555
Index 575
This page intentionally left blank
 Preface

Medical device regulation in Asian markets has become important.

Governments and regulatory bodies of countries across the region
have placed new regulatory systems or refined the existing ones.
Regulatory affairs (RA) is a science of how to get a medical product
registered with different countries’ health authorities. A registered
product would demand a lot of technical documentation to prove
its efficacy, safety, and quality. To successfully and smoothly register
a product, many soft skills are required for dealing with various
key stakeholders in governments, testing centers, hospitals, and
medical doctors.
The handbook is the first to cover medical device regulatory
affairs in Asia. It is enriched by contributions by authors working
with several regulatory bodies, including the US Food and Drug
Administration (FDA), UK Medicines and Healthcare Products
Regulatory Agency (MHRA), Japan Pharmaceuticals and Medical
Devices Agency (PMDA), Saudi Food and Drug Authority (SFDA),
Korea Testing Laboratory (KTL), Taiwan FDA, World Health
Organization (WHO), Asian Harmonization Working Party (AHWP),
Regulatory Affairs Professionals Society (RAPS), and British
Standards Institution (BSI). Each chapter provides substantial
background materials relevant to a particular area to provide the
reader a better understanding of regulatory affairs. The text also
presents in-depth discussion on requirements for medical device
registration in China and India.
Government bodies will find this book useful to understand the
global regulatory environment to help enhance their regulatory
systems. The medical device industry can use it to better understand
and access the Asian market. Academics and students will find this
book very important for their careers in biomedical engineering and
medical device–related fields. In research and development, with
the help of this book, companies can plan their projects and ensure
that the developed medical devices adhere to the global regulatory
environment.
xxxii Preface

The chapters have been grouped into five main parts as follows:
• Part 1 explains what RA is, how to be a good RA professional,
how a RA professional works with other team members,
and some associated soft skills.
• Part 2 focuses on medical device fundamentals, such as
history, labeling requirement, clinical trial requirement,
how to do classification, and two important standards for
medical device regulatory (ISO 13485 and ISO 14971).
• Part 3 introduces key global (WHO, APEC, RAPS) and
regional (AHWP, ASEAN) organizations.
• Part 4 discusses the US and EU regulatory systems in detail.
We also invite two experts from the US FDA and the UK
MHRA to share their experience on combinational product
regulatory. Their experience will be very helpful for Asia.
• Part 5 is the core of this book. It describes the regulatory
system in the Asia-Pacific market, with contributions from
regulatory authorities, testing laboratories, and industries.
This book would not have been possible without contributions
from outstanding experts in various topics discussed in it. We wish
to express our gratitude to all of them for their precious efforts
and strong support.
Fifty percent of the revenue from this book will be donated to the
Asia Regulatory Professional Association and the remaining 50% to
the Interdisciplinary Division of Biomedical Engineering in Hong
Kong Polytechnic University for future regulatory professionals’
development.
Finally, many thanks to our families (Jack Wong’s mother, Cheung
Shim Kuen, wife, Sherry Kwan Suet Sum, and son, Jay Wong Yat;
Raymond Tong’s wife, Wai-nga Lam, and daughter and sons, Lok-
ching, Lok-tin, and Lok-ting), for their support, encouragement, and
patience. They have been our driving forces.

Jack Wong
Asia Regulatory Professional Association
Raymond Kai-yu Tong
Professor, The Hong Kong Polytechnic University
Hong Kong Academy Chair, Asia Regulatory Professional Association
 Asia Regulatory Professional Association xxxiii

Asia Regulatory Professional Association

The Asia Regulatory Professional Association (ARPA) is an

organization of Healthcare Regulatory Affairs professionals in Asia.
ARPA aims to raise the standard and social recognition of Regulatory
Professionals as part of healthcare team.
We are working with different regulatory expertise globally to
achieve the above objectives. ARPA created this first Regulatory
textbook in Asia and arranged a number of Regulatory Certificate
courses in order to raise the standard of Regulatory Professionals.
You will also get awareness from key regulatory bodies, including
the US Food and Drug Administration, the Japan Pharmaceuticals
and Medical Devices Agency, Korea Testing Laboratory, and Taiwan
FDA, and regulatory organizations, including the World Health
Organization, Regulatory Affairs Professionals Society, and British
Standards Institution, which support this book and endorse the
importance of Regulatory Professional development.
The ARPA membership is free. Anyone who is interested in
the Asia regulatory affairs can join ARPA. For more details, visit
http://www.healthcare.org.hk/Health2.aspx?id=1&Cid=0.

Jack Wong
General Manager
Asia Regulatory Professional Association
[email protected]
This page intentionally left blank
Chapter 1

How to Train University Students in

Regulatory Affairs

Raymond K. Y. Tong
Hong Kong Polytechnic University, Hung Hom, Hong Kong
Asia Regulatory Professional Association (ARPA)
[email protected]

This chapter focuses on how to design a regulatory course to train

university students in regulatory affairs.

1.1 Introduction
Medical device regulations are coming up in many Asian markets.
The course should be suitable for students who are studying
biomedical engineering, healthcare, or medical device engineering.
These students should have some experience in a health- or
engineering-related field and should wish to start working in
the growing field of regulatory affairs. The course in regulatory
affairs aims to give both factual and practical knowledge of what is
regulatory requirement and how to handle future regulatory tasks.

Handbook of Medical Device Regulatory Affairs in Asia

Edited by Jack Wong and Raymond K. Y. Tong
Copyright © 2013 Pan Stanford Publishing Pte. Ltd.
ISBN 978-981-4411-21-9 (Hardcover), 978-981-4411-22-6 (eBook)
www.panstanford.com
 How to Train University Students in Regulatory Affairs

On completion of the course, students will be able to demonstrate

their understanding of how to meet the standards and regulatory
requirements, and they will be able to handle regulatory tasks,
including classification, risk management, ISO standard, product
registration, and commercial materials review.
Students will be trained to understand the global, regional, and
local medical device regulatory requirements and trends. Besides
conducting lectures, students will be arranged into a small group to
work on a medical device and practice preparing a medical device
registration submission to a competent authority. The competent
authority is a body that has authority to act on behalf of the
government to ensure that the requirements of the medical device
directives are transposed into the national law and are applied.
Guest lecturers with regulatory experience and network will be
invited to share their experience. Students who finish the course
will be eligible for attending related medical device regulatory
examination conducted by external bodies, such as notified bodies
and the Asia Regulatory Professional Association.

1.2 A Sample of Regulatory Affairs Exercises

for Students
1.2.1 Background
Consider this case. You have just been recruited by a manufacturing
company, Poly Technologies Corporation (PTC), as project manager
under its newly found business section for medical and healthcare
products. The company has little, if any, experience in designing and
manufacturing medical devices. Your primary duty is to provide
internal consultancy to the top management of the company on new
business development analysis and management of medical device
design and manufacturing projects.
Last month your company’s top management signed a business
agreement to collaborate with an overseas client, which is a global
distributor of medical products. Under this collaboration agreement,
your client and PTC will co-develop a series of medical devices for
global markets. Your client has proposed to start a project with the
sterile disposable hypodermic syringes with needles — for single-
dose hypodermic injection (Fig. 1.1).
 A Sample of Regulatory Affairs Exercises for Students 

Figure 1.1 Various sizes of hypodermic syringes.

To begin with, your client has suggested designing and

manufacturing the products for the US and EU markets and,
if possible, extend the market to China in future.

Task 1: Classification
Your first task is to brief your management about the product
classifications of the device. For more details, see Chapter 11,
“Medical Device Classification Guide.”
Classification
rules applied
What are to the product
the US FDA under EU Notified body
Target Device regulation medical device involvement for
market classification numbers directive CE marking?
EU
US
China

Task 2: Risk Analysis

(For more details, see Chapter 13 on ISO14971.)
During the design phase of the device, suggest hazards for the
product that the product design team has to include in the design
input considerations.
Suggest the severity and occurrence for the suggested hazards.
Ensure that you have provided your own table and definition of
different levels of severity and occurrence.

Task 3: Risk Evaluation and Risk Control

(For more details, see Chapter 13 on ISO14971.)
 How to Train University Students in Regulatory Affairs

You have to develop a risk graph (group for risk regions and decide
the risk acceptability) and risk matrix (put all the above risks in your
device)
Implement risk control measures for all of your hazards. After
all risk control measures have been implemented and verified, the
manufacturer shall decide whether the overall residual risk posed
by the medical device is acceptable using the criteria defined in the
risk management plan.

Task 4: Medical Device Registration Submission

Prepare a medical device registration submission to your competent
authority.

References

1. ISO 13485 (Medical devices — Quality management systems —

Requirements for regulatory purposes).
2. ISO 14971 (Medical devices — Application of risk management to
medical devices).
3. EU Directive 93/42/EEC regarding medical devices.
4. MDCO, http://www.mdco.gov.hk/eindex.html.
5. AHWP, http://www.ahwp.info/.
6. GHTF, http://www.ghtf.org/.
7. Asia Regulatory Professional Association (ARPA) http://www.
healthcare.org.hk/E_Doctors/Health2.aspx?id=1&Cid=0.
8. International Organization for Standardization, http://www.iso.ch/
iso/.
 Part 1

Introduction
This page intentionally left blank
Chapter 2

The Evolution of the Regulatory

Professional: Perspectives on the Skill
Sets and Capabilities That Will Define
the Next Generation of Regulatory
Professionals

David Martin and Neil Lesser

Deloitte Consulting LLP
[email protected], [email protected]

2.1 Introduction
Historically, the role of the regulatory affairs function within
companies that develop and sell medical devices has been more
tactical than strategic. While this tactical focus has served the
industry well in the past, regulatory authorities around the world
are raising the bar for market access. Regulatory reforms as well
as the increased availability of real-world safety and efficacy data
continue to alter the path to approval and the underlying investment
case for medical devices. Globalization will also play a key role in
shifting regulatory requirements — New regulatory frameworks
are evolving and regional partnerships will be the main driver
of harmonization going forward, especially in the Asia-Pacific
market area.

Handbook of Medical Device Regulatory Affairs in Asia

Edited by Jack Wong and Raymond K. Y. Tong
Copyright © 2013 Pan Stanford Publishing Pte. Ltd.
ISBN 978-981-4411-21-9 (Hardcover), 978-981-4411-22-6 (eBook)
www.panstanford.com
 The Evolution of the Regulatory Professional

In response, manufacturers are seeking a new type of regulatory

professional that can continuously adapt to this more complex
regulatory environment. The new regulatory professional will
continue to execute tactical requirements and will also own strategic
relationships with regulators and thought leaders that can help
shape future policies. Guiding the regulatory professional will be
a fluent understanding of the organization’s strategy and active
participation in product development and commercialization,
making them a more robust business partner to the clinical and
commercial functions.

2.2 Drivers of Change

The regulatory environment in the global medical device industry
is and will continue to undergo major shifts. In December 2011, the
Asia-Pacific Economic Cooperation group announced a new plan to
harmonize regulations for medical devices by 2020. The proposal is
based on the Global Harmonization Task Force (GHTF) — recently
re-formed into the International Medical Devices Regulators’
Forum (IMDRF) — and intends to create a predicable regulatory
framework for device manufacturers. This large-scale initiative will
require an unprecedented level of cooperation across national health
authorities. If successful, the harmonization will eliminate some
of the unknowns in the regulatory environment, but getting there
will challenge manufacturers that must reconcile the harmonized
promise of tomorrow against the fragmented regulatory landscape
of the near term. In addition, regulations have a history of lagging
behind the rate of product innovation, meaning there will be a
continued need for sophistication in the regulatory affairs function
to navigate the evolution of the national, regional, and global
regulatory environment. Regulatory professionals in the medical
device and diagnostics industry must become aware of the three main
influencers to the environment: rapid change, harmonization on a
global scale, and increased safety and effectiveness requirements.
First, the regulatory environment is changing rapidly and
professionals must be able to gauge how new developments will
affect the future environment. New regulations with far-reaching
ramifications have emerged in only the last few months; in January
of 2012, Chinese officials issued a set of rules to deal with the conflict
of interest of healthcare government officials in connection with
 Historical Role and Skill Set of a Regulatory Professional 

pharmaceutical and device manufacturers, and released a new Five

Year Plan for the pharmaceutical and medical device industries.
Second, as firms increasingly develop a global footprint, the
comparative global regulatory frameworks must be taken into
account. These regulatory frameworks are embarking on a period
of standardization, led predominantly by the Global Harmonization
Task Force, founded in 1992 with the stated goal of achieving
greater uniformity between national medical device regulatory
systems. This agency is playing a key role in driving standardization
and continues to leverage existing international organizations
(such as the Association of Southeast Asian Nations (ASEAN)) to
achieve greater coordination. For example, the Malaysian Medical
Device Control Division has drafted guidelines for the in vitro
diagnostics sector which are based on recommendations from GHTF
and ASEAN guidelines. In addition, these regulatory frameworks
are also currently going through a period of change. The GHTF itself
has recently announced a successor organization, the International
Medical Devices Regulatory Forum (IMDRF) which will continue the
goal of acceleration of harmonization, but will also assemble ad hoc
working groups comprised of various stakeholders to discuss key
issues.
Third, there has been an increased emphasis placed on safety
and effectiveness in the data required for clinical trials. Several
developing nations are incorporating adverse event reporting
capabilities and requirements into their regulatory frameworks,
including India and China. Singapore is also planning to introduce
regulations for medical device clinical trials in 2012. This trend is of
increased importance, as clinical data will become more crucial for
pre-market decisions due to the greater overall emphasis placed on
patient safety recently. However, this trend will need to be monitored
closely across the region as China has actually begun to relax clinical
trial regulations for specific medical device classes.

2.3 Historical Role and Skill Set of a

Regulatory Professional
Historically, the regulatory professional has served an important
operational role within a life sciences organization. The role could be
described as process oriented in nature: managing the submission
10 The Evolution of the Regulatory Professional

process, communicating to stakeholders and ensuring compliance

with rules and policies to secure the smooth delivery of a product
submission (see Fig. 2.1 below for an example of a job description
for a traditional regulatory position).

• Compile and format departmental documentation for inclusion in

regulatory submissions (IDE, 510(k), International Registrations).
• Participate in the complaint management process and ensure timely
completion of adverse event reporting as required by the FDA and
international regulatory agencies.
• Work closely with the Sr. Director of Regulatory and related
departments in order to support Regulatory submission activities.
• Coordinate and consult with other departments, including
Engineering, Manufacturing, Marketing and Quality, in order to
support the collection of documentation, review and assembly of
regulatory submissions.
• Ensure the quality, content and format of regulatory submissions to
state, federal and international agencies.
• Ensure consistency, completeness and adherence of standards for
all submissions. Submissions will include IDEs, 510(k)s, federal and
state establishment licensing applications, international regulatory
device licensing applications, etc.

Figure 2.1 Sample job description for a traditional regulatory professional

role.
The primary skill sets necessary for the completion of the above
tasks are excellent organizational and managerial skills as well
as a thorough understanding of standards and regulations. The
requirements for this position are more focused on adherence to
regulations and curating the appropriate compliance documentation,
with less emphasis on analyzing the larger regulatory-industry
environment to understand its far reaching implications.
While these process and organizational skills will remain
essential, tectonic shifts in the environment have manufacturers
seeking to unlock the strategic value of the regulatory function.
They are looking for their regulatory leaders to contribute outside
of their functional vertical and leverage their expertise across the
organization. This enhanced position requires a broader skill set
and leading manufacturers have already begun hiring for this
evolved regulatory role as evidenced in the job description below
(Fig. 2.2).
 Changing Role and Skill Set of the Regulatory Professional 11

• Independently lead global regulatory strategy development,

planning, and implementation for multiple complex programs and
platforms. Participate in identification of risk areas and develop
alternative courses of action including anticipation of regulators
responses through scenario planning and development of
contingency plans.
• Guide and influence technical groups in areas of product develop-
ment and lifecycle enhancement. Participate in potential and estab-
lished third part efforts (i.e. due diligence activities, joint ventures,
etc.).
• Initiate and maintain appropriate communication within the RA
function and represent Regulatory Affairs with business units and
other functions. Implement policies to ensure ongoing compliance
of regulatory requirements.
• Develop and implement regulatory strategy aligned with business
strategy. Assess impact of new regulations and implement
appropriate changes as well as lead development of company policy
and positions on draft regulation and guidance.
• Responsible for negotiating and decision making with regulators
and stakeholders with complex and high-risk projects.
• Provide direct supervision of individuals including mentoring,
performance management and staffing decisions.
• Represent company externally at appropriate industry associations.
May act as primary contact with regulatory authorities including
the planning and leadership of meetings. May participate in
management of budgets.

Figure 2.2 Example job description for the changing regulatory pro-
fessional role.

2.4 Changing Role and Skill Set of the

Regulatory Professional
In light of the aforementioned shifts in the regulatory environment,
it is clear that an expansion of capabilities will be required in the
future within regulatory departments. These capabilities will go
beyond the traditional realm of regulatory affairs and move the
function closer to “heart of the business” issues that shape the
strategic direction of the organization. Regulatory professionals
that are able to make this leap will become trusted partners and
contributors as they will have found ways to unlock value in the
12 The Evolution of the Regulatory Professional

regulatory process. Described below are a few of the next-generation

capabilities that will empower the regulatory professional.

2.5 Develop as a Center of Intelligence

To adjust to the dynamic regulatory environment found in both
the Asia-Pacific region and the broader global environment,
the regulatory function should strive to operate as a center of
intelligence for the organization — proactively sensing signals of
change in the external environment and disseminating the insights
to the organization. Such a role requires that the professional be
capable of synthesizing data and trends from a variety of sources
and developing a recommendation that considers complex points of
view. To do this successfully requires that regulatory professionals
are able to capture intelligence from a variety of sources and detect
signals from extraneous noise.
Regulatory intelligence is available from myriad sources:
interactions with health authorities, conversations with key
opinion leaders (KOLs), in the presentations of academics, through
networking at conferences and summits, and from the outcome of
product submissions. The efficiency and certainty of signal detection
will improve with the collective experience of the regulatory
professional and the level of rigor used to assess and document
regulatory trends. In summary, the regulatory professional will
need to develop a process to collect data, perform trend analysis,
develop summary insights, and possess the ability to communicate
the findings to various stakeholders within the organization.

2.6 Advance Toward Strategic

Relationship Management
As the fundamental gatekeeper to market access, health authorities/
regulatory agencies play a “make or break” role in the success of
a product. For this reason, it is paramount that manufacturers
consider means to maximize the value of interactions with key
figures from a regulatory body. One such way to maximize value is
to implement a more thoughtful approach to interacting with key
figures in the approval process and those external stakeholders (e.g.,
 Conclusion: What Will It Take to Get There? 13

KOLs) that might influence it. By formulating a clear understanding

of its goals and needs, a manufacturer can align its outreach
efforts to effect more purposeful and productive conversations
with external figures. By cultivating advanced communication and
negotiation skills the organization can help shape the dialogue
around reforms and regulatory findings rather than being blocked
from the conversation. While not necessarily a cure-all or a quick
fix, an organization with a deep understanding of the landscape of
influencers and a network to match is more prepared to respond in
times of crisis or more able to pick up the phone and get an answer
to a burning question.

2.7 Develop as a Strategic Business Partner

Foundational to the aforementioned capabilities will be the expan-
sion of the regulatory professional as a strategic minded individual.
With primary access to regulators and a keen understanding of the
levers that guide their review and lines of inquiry, the regulatory
professional is in a unique position to add value to the organization.
By understanding where the key interests and points of debate
are for a health authority (e.g., efficacy, safety, cost) the regulatory
professional can help guide the direction of a clinical program or
a commercial campaign toward those areas most likely to satisfy a
regulators priorities while still serving the organization’s needs. Part
of this role will include actively participating in the strategic business
planning process to lend a perspective on feasibility and any prior
precedent. It will be critical for the internal expert to communicate
across the organization into both commercial and clinical functions
and serve as a strategic business partner that can help decipher
the “noise” to guide informed decision making for commercial and
clinical investment. Delivering in this expanded role will require
flexible strategic thinking, complex stakeholder management and a
firm understanding of the organization’s goals and plans.

2.8 Conclusion: What Will It Take to Get There?

Having laid out a few of the capabilities and skills that the regulatory
professional of the future will need, what follows is a discussion
14 The Evolution of the Regulatory Professional

of how one can attain the skills and experiences to best position
themselves for future success.
Primarily, one must gain the foundational strategic, analytical
and communication skills that will be required. This is best
accomplished through coursework in Strategy, Operations and
Communications. Further coursework in the fields of Negotiation
and Marketing would provide the necessary “big picture” view
required of the new regulatory role, a skill set in synthesizing
information and an understanding of how to manage multiple
shareholders and their diverse incentives.
To complement this coursework, one should pursue opportu-
nities to network with a wide array of students and professionals
from across life sciences, health care, and the government in order to
enrich one’s understanding of the needs and motivations of various
stakeholders in the system. Memberships in professional societies
and industry groups and attending summits and conferences should
be at the forefront of any career development strategy, but in this
case these associations are particularly important in order to gain a
viewpoint on the changing environment of regulation and develop a
network of colleagues throughout the industry.
Further, a rotational role within a life sciences organization
would be especially valuable. Such a role would provide exposure
to a broad spectrum of functions and stakeholders and their
diverse incentives and viewpoints. This position represents an ideal
experience for a professional in this industry seeking to become
fluent in the internal workings of an organization and competent in
a strategic partner role.
Ultimately, success in this field requires that professionals
recognize that the regulatory role is evolving and that this evolution
must be matched by a new, broader focus in their education and
career development. Fortunately, the resources exist to prepare
for this evolved position and to build a career in this challenging,
growing field — One might even say there has never been a more
exciting time to be on the regulatory side of the medical device and
diagnostics industry.

Acknowledgment
Contributions to this chapter have been made by Chris Nuesch, Bill
Chiodetti, and Riddhi Roy, all from Deloitte Consulting LLP.
 References 15

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specialist.
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regulatory-affairs-cmc-biologics.
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Chapter 3

Ensuring Smooth Product Launch:

Regulatory Interfaces with Marketing
and Supply Chain

Alok Mishra
Asia Pacific, Strategic Business Systems,
Johnson & Johnson Medical Singapore
[email protected]

3.1 Introduction
The Regulatory step is perhaps the most critical step in the New
Product Introduction process as it involves externalities — both
within and outside the organization. In a large multinational device
manufacturer, the product is often launched in geographies far
from the originating company and involves a variety of regulatory
and reimbursement authorities who can be quite different in their
priorities, processes, requirements, and approach. This is key
interfacial step in the launch and one that can create — or destroy
— the significant value for the corporation.
A rough calculation can highlight the impact of achieving speed
to market. Assume a product will achieve a forecast of $30 million

Handbook of Medical Device Regulatory Affairs in Asia

Edited by Jack Wong and Raymond K. Y. Tong
Copyright © 2013 Johnson & Johnson Medical Asia Pacific
ISBN 978-981-4411-21-9 (Hardcover), 978-981-4411-22-6 (eBook)
www.panstanford.com
18 Ensuring Smooth Product Launch

per year of peak sales. This translates to sales of over $82,000 per
day. The company would lose a million dollars for each 12 days
of delay! Alternatively, faster launch makes the company almost
$2.5 million extra per month.
What does this have to do with Marketing and Supply Chain? To
understand this, we need to look at interfaces and delays.
There are thus several areas where better communication
processes can improve efficiency, reduce time to market, and thus
have a positive impact on the bottom-line.

3.2 New Product Pipeline

In most cases, Marketing is exposed to new products in the
pipeline much before anyone else. However, quite often they fail to
convey this information to other parts of the organization — most
importantly, Regulatory Affairs and Supply Chain — which creates
suboptimal conditions later. Early information to regulatory affairs
is critical for their being able to establish key connections for the
documentation, providing heads up and getting feedback from
regulators regarding possible requirements and overall being able
to create appropriate Regulatory Strategy for the quickest path.
Information to Supply Chain is important as many new
products, especially biologics and drug–device combinations,
have unique storage requirements and its takes time to optimize
vendors and locations to handle such products. In one case, the
transportation cost of a biologic product was over 50% of the
product’s landed costs, and it took months of vendor negotiation to
bring it down to a reasonable level.

3.3 Planned Launch Dates

It is important for Marketing to develop launch dates in early
consultation with Regulatory Affairs as the latter are in the best
position to assess Regulatory difficulty and provide guidelines for
feasible dates. In addition, some products may have additional
requirements, e.g., mandatory clinical trials, which need detailed
budgeting and resource planning to be able to complete registration
requirements.
 New Product Approval Dates 19

3.4 New Product Forecasts

It is often said forecasting is difficult, especially of the future! The
new product forecast of a medical device is a challenging task
as it has several barriers that determine the growth rate. These
are summarized as 4A’s (Access, Adoption, Awareness, and
Affordability) (Fig. 3.1 ).

Figure 3.1 The four A’s.

It is thus essential that the Marketing manager works with

folks in Regulatory and Reimbursement to assess times and rates
of approval and build good assumptions around rate of adoption
and awareness to arrive at robust forecasts. The importance of this
cannot be overemphasized as there is no bigger embarrassment
than to have forecasted a wrong approval date and be sitting on
valuable inventory when other parts of the world have shortages.

3.5 New Product Approval Dates

Finally, Regulatory Affairs also has an important responsibility to
provide timely feedback to Marketing and Supply Chain so that they
can plan the launch effectively and not waste resources by planning
to early or miss revenue opportunity by not being prepared when
the product approval comes through.
Working together of Regulatory Affairs, Marketing, and
Supply Chain in a seamless fashion that identifies delays early and
responds to problems proactively, thus minimizing the time to
market, can be a key source of competitive advantage for a medical
device company (Fig. 3.2). It is not easy but is worth all the time and
money spent in making it happen.
20 Ensuring Smooth Product Launch

Marketing
M
Ͳ NewProductfo orecasts Ͳ NewProductpipeline
Ͳ Plannedlaunch hdates Ͳ Planned
dlaunchdates
Ͳ Pricinginformaation

Regulatorry
Suppllychain
Affairs

Figure 3.2 Team work for
 success.

Chapter 4

What Is the Right Thing to Do?

Jack Wong
Asia Regulatory Professional Association (ARPA)
[email protected]

4.1 Right Job

I am a health care professional who graduated as a pharmacist and
worked as a Regulatory Affairs officer in healthcare companies. I am
very proud of working in the health care sector as my products or
services are very important for people. My job as Regulatory Affairs
officer is to make available new medical products to patients by
utilizing scientific data from R&D, to ensure a good-quality system
in manufacturers, to liaise with the health authority, and finally
to obtain relevant certificates prior to supplying the products to
patients who need it. To provide high-quality medical products to
patients fast is my core job.

Handbook of Medical Device Regulatory Affairs in Asia

Edited by Jack Wong and Raymond K. Y. Tong
Copyright © 2013 Pan Stanford Publishing Pte. Ltd.
ISBN 978-981-4411-21-9 (Hardcover), 978-981-4411-22-6 (eBook)
www.panstanford.com
22 What Is the Right Thing to Do?

4.2 Two Key Challenges in Our Job

4.2.1 Quality
To ensure good quality, many international standard bodies (e.g.,
ISO and BSI) and local standard bodies in many countries such
as the United States, Japan, and China actively develop better
product standards for manufacturers so that products with
better specifications are manufactured. After a product with good
specifications has been developed, its production needs to be
done within a good system, too (e.g., GMP and ISO 13485), and the
process needs to be regularly audited by certification bodies and
governments. As regulatory professionals, we need to understand
this and explain this to relevant government bodies and finally
obtain relevant approvals before supplying the product to patients.

4.2.2 Speed
Taking medical devices as an example, it usually takes 90 working
days to get approval in the United States and Europe. Surprisingly,
it can take up to 1–2 years to get approval in Asia. Health care
sectors and governments in Asia are working hard to streamline the
process.

4.3 Regulatory Affairs Job is a Combination of

Science, Legal Affairs, and Moral
The following formula can explain our job aptly:
RA = (Science × Law)Moral
The Science and Legal parts may be obvious to readers. I would
like to explain the Moral part. To begin, I would like to start a story
of moral situation.

4.4 Persons versus Things

To explain the moral part of the Regulatory Affairs job, I would like
to start with a moral question/situation:
 Persons versus Things 23

Suppose you were a trolley car driver driving at 60 miles an

hour. Suddenly, you see five persons standing in your way. You
try to stop, but the brakes do not work. You feel bad as the
persons may die.
Then you notice a side track on your right hand side, but there
is a person standing there. You can turn right hitting that one
person but sparing the five.
What will you do? Sacrificing one life in order to save five seems
the right thing to do.
Now consider another version of the trolley car situation:
You are not the driver but an onlooker standing on a bridge
overlooking the track, and there is no side track this time. Along
the track, there are five persons. The trolley car cannot stop as
the brakes do not work, and it is about to crash into the five
persons. You feel desperate to help them. Suddenly, you notice a
heavy man standing next to you. You can push him off the bridge
into the path of the trolley car. He could die, but the five persons
would be saved. (Assume that this approach will work and the
option of you jumping onto the track will not help as you are too
small to stop the trolley).
Will you push the heavy man?

I studied some literature on human rights and philosophy to

look for an answer to this question and came up with the following
statement:
It is wrong to use people for the sake of the general welfare.
Pushing the heavy man onto the track to block the trolley uses him
as a means and, hence, fails to respect him and his dignity.
We value things not just “more” or “less,” but in qualitatively
higher and lower ways.

The Right Thing to Do

A human being is not an object but a person with dignity. As health
care professionals, our sole aim is to help them receive good medical
services/products fast. By respecting human dignity, we should
put human dignity first and minimize all administrative,
bureaucratic, and political issues. This drives our work in
Regulatory Affairs.
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Chapter 5

Affordable Access to Medical Devices in

Developing Countries

Rosanna W. Peelinga and Tikki Pangb

aLondon School of Hygiene and Tropical Medicine, London, UK
bWorld Health Organization, Geneva, Switzerland
[email protected], [email protected]

5.1 Introduction
National regulatory approval for drugs provides safeguards for the
safety and effectiveness of drugs used in a country. Most countries
have established a process for reviewing the evidence from drug
trials to support the introduction of new drugs. Over time, this
has improved the quality of drugs used in developing countries.
Unfortunately, in the developing world, apart from tests used for
blood banking, more than 50% of countries do not regulate in
vitro diagnostics (IVD) for infectious diseases [1, 2]. More broadly,
medical devices are often sold and used in most of the developing
world without any formal evaluation of their performance and
effectiveness. Access to good-quality medical devices is problematic
in these countries as companies with good-quality products are
often unable or reluctant to compete in a market that is flooded with
cheap, poor-quality products.

Handbook of Medical Device Regulatory Affairs in Asia

Edited by Jack Wong and Raymond K. Y. Tong
Copyright © 2013 Pan Stanford Publishing Pte. Ltd.
ISBN 978-981-4411-21-9 (Hardcover), 978-981-4411-22-6 (eBook)
www.panstanford.com
26 Affordable Access to Medical Devices in Developing Countries

In countries that do regulate medical devices, the regulatory

landscape is highly variable and continuously changing, resulting in
greater challenges associated with transparency, language barriers,
and costs. Regulatory reviews consist of technical and administrative
components which can vary significantly between countries, even
in the same region. Time frames for approval and the complexity of
the approval process vary widely. Because of the onerous process
and costs, companies tend to target countries with markets that
allow for a substantial return for investment. Smaller countries
in the developing world are currently paying significantly higher
prices for medical devices than countries with sizeable markets,
largely because of the many distribution channels that health
program and providers need to go through to access the products
that they need. Another important outcome of this scenario is that
these complex, lengthy and variable regulatory approval processes
have driven up the cost of goods making products unaffordable
and become a major disincentive to innovation.
Recent investments in the development of tools to improve
global health will soon lead to the commercialization of novel
classes of medical devices. However, regulatory directives have
not kept pace with technological development [3].
In recent years, the global economic crisis has led to drastic
cutback in health programs. Companies have less resources for
the research and development of medical devices. International
aid programs for HIV have declined from US$ 8.7 billion in 2009 to
US$ 7.6 billion in 2010. The Global Fund, one of the major sources
of support for global health, recently announced that no new
projects will be funded until 2014. But now more than ever,
affordable medical devices, in particular IVDs, are urgently needed
in the developing world and these products need to be accessible
and affordable to patients in the developing world.

5.2 Why Is Affordable Access to Medical

Devices Important for Developing Countries?
In times of the global financial crisis, limited resources and
competing priorities, affordable and sustainable access to medical
devices in developing countries represents a critical first step in
ensuring the optimal delivery of health care. In particular, access