ADVANCED ORTHOPEDIC TECHNOLOGIES, IMPLANTS AND REGENERATIVE PRODUCTS

Transcription

1 ADVANCED ORTHOPEDIC TECHNOLOGIES, IMPLANTS AND REGENERATIVE PRODUCTS HLC052C August 2014 Melissa Elder Project Analyst ISBN: BCC Research 49 Walnut Park, Building 2 Wellesley, MA USA (toll-free within the USA), or (+1) information@bccresearch.com

2 TABLE OF CONTENTS CHAPTER 1 INTRODUCTION 2 STUDY GOALS AND OBJECTIVES 2 REASONS FOR DOING THE STUDY 2 CONTRIBUTION OF THE STUDY AND INTENDED AUDIENCE 2 SCOPE OF THE REPORT 3 METHODOLOGY 3 PREVIOUS EDITIONS 4 RELATED BCC RESEARCH REPORTS 4 ANALYST'S CREDENTIALS 4 BCC RESEARCH WEBSITE 5 DISCLAIMER 5 CHAPTER 2 SUMMARY 7 SUMMARY TABLE GLOBAL MARKET FOR ADVANCED ORTHOPEDICS BY PRODUCT SEGMENT, THROUGH 2019 ($ MILLIONS) SUMMARY FIGURE ADVANCED ORTHOPEDIC TECHNOLOGY, IMPLANTS AND REGENERATIVE PRODUCTS, ($ MILLIONS) 9 9 CHAPTER 3 INDUSTRY OVERVIEW 11 HISTORY OF THE ORTHOPEDIC INDUSTRY 11 ADVANCED ORTHOPEDIC MARKET DEVELOPMENT 11 GOVERNMENT REGULATION OF DEVICES 11 REGULATION, COST AND CLASSIFICATION OF DEVICES BY REGION 12 Costs 12 U.S. (FDA) (k) Exemptions 13 TABLE 1 PARTS OF 21 CFR 14 Humanitarian Device Exemption (U.S.) 14 TABLE 2 LISTING OF ORTHOPEDIC-RELATED CDRH HUMANITARIAN DEVICE EXEMPTIONS, THROUGH MARCH 2014 Investigational Device Exemption 17 Changes in FDA Advisor Roles 17 Canada (Health Canada) 18 Europe (MDD) 18 Japan 20 TABLE 3 NUMBER OF MEDICAL DEVICES APPROVED WITH CLINICAL DATA REVIEW, Japanese Medical Device Nomenclature (JMDN) Codes for Orthopedic Devices TABLE 4 JAPANESE MEDICAL DEVICE NOMENCLATURE CODES FOR ORTHOPEDIC DEVICES Australia 23 Reclassification of Specific Orthopedic Implants 23 TREATMENT SETTINGS 24 Ambulatory Treatment Facilities 24 TABLE 5 U.S. AMBULATORY VISITS ALL AGES BY FACILITY TYPE,

3 TABLE 6 U.S. EMERGENCY ROOM VISITS BY INJURY LOCATION AND SPORT/ACTIVITY, 2008 DATA TABLE 7 U.S. EMERGENCY ROOM VISITS BY BODY SITE, 2010 DATA (THOUSANDS) 25 Orthopedic Rehabilitation Facilities and Physical Therapy 25 Orthopedic Surgeons 26 TABLE 8 ACTIVE U.S. PHYSICIANS BY SELECTED SPECIALTY, (THOUSANDS) CHAPTER 4 ISSUES AFFECTING THE MARKET 28 INSURANCE AND REIMBURSEMENT ISSUES 28 TABLE 9 MEDICARE REIMBURSEMENT RATES FOR COMMON ORTHOPEDIC PROCEDURES, NATIONAL PAYMENT AMOUNT, 2009 AND 2014 (DOLLARS) ECONOMICS AND HEALTH CARE 30 TABLE 10 HEALTH EXPENDITURES AS PERCENTAGE OF GDP BY SELECT COUNTRY, (%) FIGURE 1 HEALTH EXPENDITURES AS PERCENT OF GDP BY COUNTRY: (%) MEDICAL DEVICE PRICING TRENDS 32 MARKETING AND ADVERTISING ISSUES AND TRENDS 32 LEADING MANUFACTURERS' STRATEGIES 33 Manufacturing, Distribution and Supply 33 TABLE 11 ADVANCED ORTHOPEDIC MANUFACTURING AND SUPPLY FACILITIES 34 Alphatec 35 ArthroCare 35 Biomet Inc. 36 DJO Surgical 36 Exactech 36 Genzyme BioSurgery 36 LifeCell 36 NuVasive 37 Smith & Nephew 37 Stryker 37 Wright Medical 37 Zimmer Holdings 38 Sales and Marketing 38 TABLE 12 ADVANCED ORTHOPEDIC SALES AND MARKETING EXPENDITURES BY MANUFACTURER FOR FISCAL YEAR ($ MILLIONS) FIGURE 2 ADVANCED ORTHOPEDIC SALES, MARKETING AND ADMINISTRATIVE EXPENDITURES BY MANUFACTURER FOR FISCAL YEAR ($ MILLIONS) Alphatec 40 ArthroCare 40 Biomet Inc. 41 Conmed 41 Exactech 41 Integra Life Sciences 41 Smith & Nephew 41 Stryker 42 Wright Medical 42 Zimmer Holdings

4 Research and Development Trends 43 TABLE 13 RESEARCH AND DEVELOPMENT EXPENDITURES FOR ADVANCED ORTHOPEDIC MANUFACTURERS AND SUPPLIERS, ($ MILLIONS) FIGURE 3 RESEARCH AND DEVELOPMENT EXPENDITURES FOR ADVANCED ORTHOPEDIC MANUFACTURERS AND SUPPLIERS, ($ MILLIONS) Acquisitions, Alliances and Agreements 44 Alphatec 44 Conmed 45 Exactech 45 Integra Life Sciences 45 Medtronic 45 NuVasive 46 Smith & Nephew 46 Stryker 46 Wright Medical 46 Zimmer Holdings 47 Employee Snapshot and Distribution 47 TABLE 14 EMPLOYEE DISTRIBUTION FOR ORTHOPEDIC MANUFACTURERS AND SUPPLIERS, 2013 (NUMBER) MEDICAL TOURISM IMPACT ON THE ORTHOPEDIC MARKET 48 TABLE 15 HIP REPLACEMENT: GLOBAL COST VARIATIONS, 2008 DATA ($ MILLIONS/NUMBER) FIGURE 4 HIP REPLACEMENT: GLOBAL COST VARIATIONS ($ MILLIONS/NUMBER) 49 TABLE 16 U.S. HEALTH INSURANCE COVERAGE BY AGE GROUP (%) 50 FIGURE 5 U.S. HEALTH INSURANCE COVERAGE BY AGE GROUP (%) 51 PUBLIC HEALTHCARE SYSTEMS AROUND THE WORLD 51 TABLE 17 WORLD HEALTH ORGANIZATION RANKING OF HEALTHCARE SYSTEMS, TOP 50, 2000 DEMOGRAPHICS AND AGING POPULATIONS 53 Global Demographics 53 TABLE 18 ESTIMATED WORLD POPULATION BY SELECTED AGE GROUP AND SELECTED YEARS, THROUGH 2030 (MILLIONS) FIGURE 6 ESTIMATED WORLD POPULATION BY SELECTED AGE GROUP AND SELECTED YEARS, ($ MILLIONS) TABLE 19 GLOBAL POPULATION BY SELECTED COUNTRY, THROUGH 2015 (MILLIONS) FIGURE 7 GLOBAL POPULATION BY SELECTED COUNTRY, 2010 AND PROJECTED 2015 (MILLIONS) U.S. Demographics 56 TABLE 20 U.S. POPULATION ESTIMATES AND PROJECTIONS BY AGE GROUP (THOUSANDS) FIGURE 8 U.S. POPULATION ESTIMATES AND PROJECTIONS BY AGE GROUP, (THOUSANDS) Gender, Age and Life Expectancy 57 TABLE 21 ESTIMATES OF EXPECTED U.S. LIFE EXPECTANCY AT BIRTH WITH PROJECTIONS BY GENDER, 2000 AND 2020 (YEARS) FIGURE 9 ESTIMATES OF EXPECTED U.S. LIFE EXPECTANCY AT BIRTH WITH PROJECTIONS BY GENDER, 2000 AND 2020 (YEARS) TABLE 22 GLOBAL LIFE EXPECTANCY AT BIRTH BY SELECTED COUNTRY, 1980 AND 2013 (YEARS)

5 FIGURE 10 GLOBAL LIFE EXPECTANCY AT BIRTH BY SELECTED COUNTRY, 1980 AND 2013 (YEARS) INCIDENCE OF ORTHOPEDIC CONDITIONS 59 Osteoarthritis 59 Rheumatoid Arthritis 60 Ankylosing Spondylitis 60 Fibromyalgia 60 Gout 60 Scleroderma 61 Lupus 61 Bursitis and Tendonitis 61 Osteoporosis 61 Low Bone Mass 62 TABLE 23 ESTIMATED* PREVALENCE/INCIDENCE OF CONDITIONS AFFECTING THE GLOBAL ORTHOPEDIC INDUSTRY, AVERAGE FIGURE, (MILLIONS) FIGURE 11 ESTIMATED* PREVALENCE/INCIDENCE OF CONDITIONS AFFECTING THE GLOBAL ORTHOPEDIC INDUSTRY, AVERAGE FIGURE, (MILLIONS) ORTHOPEDIC PROCEDURE VOLUMES IN THE U.S. 63 FIGURE 12 NUMBER OF U.S. HIP REPLACEMENT PROCEDURES, (NUMBER) FIGURE 13 NUMBER OF U.S. KNEE REPLACEMENT PROCEDURES, (NUMBER) FIGURE 14 NUMBER OF U.S. SPINAL FUSION PROCEDURES, (NUMBER) 65 FIGURE 15 NUMBER OF U.S. PHYSICIAN VISITS FOR ROTATOR CUFF PROBLEMS, (MILLIONS) RISING ORTHOPEDIC INCIDENCE AND EVOLVING LIFESTYLE TRENDS 66 Overweight and Obesity 66 TABLE 24 U.S. AGE-ADJUSTED PERCENT DISTRIBUTION OF BODY MASS INDEX (BMI) AMONG PERSONS, 18 YEARS AND OVER, BY SELECTED CHARACTERISTICS FIGURE 16 OBESITY BY COUNTRY (%) 67 Smoking 69 TABLE 25 PERCENT OF SMOKERS IN THE U.S. POPULATION, 18 AND OLDER, BY AGE AND GENDER, 2009 (%) TABLE 26 DAILY TOBACCO CONSUMPTION BY COUNTRY: 1990 COMPARED TO 2009* (TOTAL % SMOKERS) FIGURE 17 DAILY TOBACCO CONSUMPTION BY COUNTRY: 1990 COMPARED TO 2009* (TOTAL % SMOKERS) Sedentary Lifestyle 72 TABLE 27 PERCENT OF U.S. ADULTS ENGAGING IN PHYSICAL ACTIVITY AND FITNESS BY SELECTED CHARACTERISTICS, 2008 (%) Nutrition 73 COMPARISON OF BONE MINERAL DENSITY LEVELS IN POPULATIONS CHAPTER 5 TECHNOLOGY 76 INTRODUCTION 76 PATENT TRENDS 76 ORTHOPEDIC PATENTS BY YEAR 76 TABLE 28 NUMBER OF ORTHOPEDIC PATENTS ISSUED BY YEAR, * 77 FIGURE 18 NUMBER OF ORTHOPEDIC PATENTS ISSUED BY YEAR, * 77 INTERNATIONAL PATENTS BY COUNTRY OF ORIGIN 77

6 TABLE 29 ORTHOPEDIC PATENTS BY COUNTRY OF ORIGIN, * (NO. OF PATENTS) FIGURE 19 ORTHOPEDIC PATENTS BY COUNTRY OF ORIGIN, * (NO. OF PATENTS) PATENT TRENDS BY ASSIGNEE 79 TABLE 30 ADVANCED ORTHOPEDIC PATENT INFORMATION BY ASSIGNEE 80 Biomet 83 ConMed 83 DePuy 83 DJO Surgical 84 Exactech 84 Medtronic 84 Smith & Nephew 84 Stryker 85 Synthes 85 Warsaw Orthopedic 86 Wright Medical 86 Zimmer Holdings 86 ADVANCED ORTHOPEDIC TECHNOLOGIES 87 Bone-Growth Stimulation Devices 87 Orthopedic Growth Factors 88 Transcutaneous Electrical Nerve Stimulation Units 88 Light Therapy (Light-Emitting Diodes and Infrared) 88 Thermal Imaging 90 Nanotechnology and Microprocessors 90 Digital X-rays 90 Bone Density Improvements 91 High-resolution Cartilage Imaging 91 Stem Cells 91 Government Limitations 92 Embryonic Stem Cells 92 Adult Stem Cells 92 Bone Technology and Stem Cells 93 Synthetic Bone Grafting 93 Bone Modeling for Osteoporotic Spinal Fracture Testing 93 Advanced Mechanical Implant Creation CHAPTER 6 BONE REPAIR AND REGENERATIVE PRODUCTS 96 SEGMENT OVERVIEW 96 BONE GRAFTS 96 TABLE 31 BONE GRAFT PRODUCTS AND MATERIALS 97 Procedures Using Bone Grafts 98 PRODUCT DESCRIPTIONS 98 HUMAN BONE PRODUCTS 98 TABLE 32 HUMAN BONE PRODUCTS AND COMPETITORS 98 Biomet 99 DePuy 100 Exactech 100

7 Integra Life Sciences 100 LifeCell Inc. 101 Medtronic 101 Orthofix 101 Wright Medical 102 Zimmer Holdings 102 BONE-GROWTH STIMULATORS 102 TABLE 33 BONE-GROWTH STIMULATOR (BIOLOGICAL) PRODUCTS AND COMPETITORS TABLE 34 BONE-GROWTH STIMULATOR (ELECTRICAL/ULTRASOUND DEVICES) PRODUCTS AND COMPETITORS Biomet 103 Bioventus 104 DJO Global 104 Medtronic 104 NuVasive 105 Orthofix International 106 Stryker 106 SYNTHETIC BONE REPLACEMENTS 107 TABLE 35 SYNTHETIC BONE-REPLACEMENT PRODUCTS AND COMPETITORS 107 Baxter 108 Biomet 108 DePuy Synthes 108 Exactech 109 Integra Life Sciences 109 Medtronic 109 Orthofix 109 Smith & Nephew 109 Stryker 109 Wright Medical 110 Zimmer Holdings 110 MARKET ANALYSIS 110 MARKETS BY PRODUCT TYPE 111 TABLE 36 BONE REPAIR AND REGENERATIVE PRODUCTS MARKET, THROUGH 2019 ($ MILLIONS) FIGURE 20 BONE REPAIR AND REGENERATIVE PRODUCTS MARKET ($ MILLIONS) SALES DISTRIBUTION BY PROCEDURE TYPE 113 TABLE 37 REVENUE DISTRIBUTION FOR BONE REPAIR AND REGENERATIVE PRODUCTS BY PROCEDURE TYPE, 2014 ($ MILLIONS) FIGURE 21 REVENUE DISTRIBUTION FOR BONE REPAIR AND REGENERATIVE PRODUCTS BY PROCEDURE TYPE, 2014 ($ MILLIONS) MARKETS BY REGION 114 TABLE 38 REVENUE DISTRIBUTION FOR BONE REPAIR AND REGENERATIVE PRODUCTS BY REGION, 2014 (%) FIGURE 22 REVENUE DISTRIBUTION FOR BONE REPAIR AND REGENERATIVE PRODUCTS BY REGION, 2014 (%) LEADING SUPPLIERS AND PARTICIPANTS

8 TABLE 39 SUMMARY OF BONE REPAIR AND REGENERATIVE PRODUCTS BY COMPETITOR REVENUES, 2014 ($ MILLIONS) FIGURE 23 SUMMARY OF BONE REPAIR AND REGENERATIVE PRODUCTS BY COMPETITOR REVENUES, 2014 ($ MILLIONS) CHAPTER 7 CARTILAGE AND OTHER SOFT TISSUE REPAIR AND REGENERATIVE PRODUCTS SEGMENT OVERVIEW 120 PRODUCT DESCRIPTIONS 121 FIXATION SYSTEMS AND OTHER SPECIALIZED DEVICES 121 TABLE 40 FIXATION SYSTEMS AND OTHER SPECIALIZED DEVICES AND MARKETERS 121 Arthrex 122 ArthroCare 123 Biomet 123 Conmed Linvatec 123 Corin Group 124 Covidien 124 DePuy Synthes 124 Integra Life Sciences 124 Ortheon Medical 125 Smith & Nephew 125 Stryker 125 Zimmer Holdings 125 BIOLOGICS AND BIOMATERIALS 125 TABLE 41 CARTILAGE AND SOFT TISSUE BIOLOGICS AND BIOMATERIALS SEGMENT 126 Aesculap 126 Biomet 126 DePuy 126 Integra Life Sciences 127 LifeCell Inc. 127 Sanofi 127 Stryker 127 Wright Medical 127 Zimmer Holdings 128 MARKET ANALYSIS 128 MARKETS BY PRODUCT TYPE 128 TABLE 42 CARTILAGE AND OTHER SOFT TISSUE REPAIR AND REGENERATIVE PRODUCTS MARKET, THROUGH 2019 ($ MILLIONS) FIGURE 24 CARTILAGE AND OTHER SOFT TISSUE REPAIR AND REGENERATIVE PRODUCTS MARKET, ($ MILLIONS) MARKETS BY REGION 130 TABLE 43 GLOBAL DISTRIBUTION OF REVENUES FROM CARTILAGE AND OTHER SOFT TISSUE REPAIR AND REGENERATIVE PRODUCTS BY REGION, 2014 (%/$ MILLIONS) FIGURE 25 GLOBAL DISTRIBUTION OF REVENUES FROM CARTILAGE AND OTHER SOFT TISSUE REPAIR AND REGENERATIVE PRODUCTS BY REGION, 2014 (%) LEADING SUPPLIERS AND PARTICIPANTS 132 TABLE 44 SUMMARY OF CARTILAGE AND OTHER SOFT TISSUE REPAIR AND REGENERATIVE PRODUCTS BY COMPETITOR REVENUES, 2014 (%/$ MILLIONS)

9 FIGURE 26 SUMMARY OF CARTILAGE AND OTHER SOFT TISSUE REPAIR AND REGENERATIVE PRODUCTS BY COMPETITOR REVENUES, 2014 ($ MILLIONS) 134 CHAPTER 8 JOINT REPLACEMENTS, IMPLANTS AND REGENERATIVE PRODUCTS 136 SEGMENT OVERVIEW 136 PRODUCT DESCRIPTION 138 HIP REPLACEMENTS 138 TABLE 45 HIP REPLACEMENT PRODUCT SUPPLIERS 138 Biomet 139 DePuy Synthes 139 DJO Global 140 Exactech 140 MicroPort Scientific Corp. 141 Smith & Nephew 141 Stryker 141 Zimmer Holdings 142 KNEE REPLACEMENTS 142 TABLE 46 KNEE REPLACEMENT PRODUCT SUPPLIERS 143 Biomet 143 DePuy Synthes 143 DJO Global 144 Exactech 144 MicroPort Scientific Corp. 144 Smith & Nephew 144 Stryker 145 Zimmer Holdings 145 SPINE REPLACEMENTS/FIXATION 146 TABLE 47 SPINE REPLACEMENT/FIXATION PRODUCT SUPPLIERS 146 Aesculap 147 Alphatec 147 Biomet Spine 147 DePuy Synthes Spine 148 Exactech 149 Globus Medical 149 Integra Life Sciences (Integra Spine) 149 LDR Spine 150 Medtronic 150 MicroPort Scientific Corp. 151 Orthofix International 151 Stryker 152 Zimmer Holdings 152 OTHER EXTREMITY REPLACEMENTS AND JOINT PRODUCTS 153 TABLE 48 OTHER EXTREMITY REPLACEMENTS, JOINT PRODUCT SUPPLIERS 153 Biomet 154 DePuy Synthes 154 DJO Global 155 Exactech 155 Small Bone Innovations 155

10 Stryker 155 Wright Medical 155 Zimmer Holdings 156 BIOLOGICAL JOINT PRODUCTS AND OTHER RELATED DEVICES 156 TABLE 49 BIOLOGICAL JOINT PRODUCTS AND OTHER RELATED DEVICES 157 Anika Therapeutics 157 Bioventus 157 Ferring Pharmaceuticals 158 Institut Biochimique SA 158 Mylan 158 Sanofi 159 Zimmer Holdings 159 MARKET ANALYSIS 159 MARKETS BY PRODUCT TYPE 160 TABLE 50 JOINT REPLACEMENT, IMPLANT AND REGENERATIVE PRODUCT MARKETS, THROUGH 2019 ($ MILLIONS) FIGURE 27 JOINT REPLACEMENT, IMPLANT AND REGENERATIVE PRODUCT MARKETS, ($ MILLIONS) MARKETS BY REGIONS 162 TABLE 51 GLOBAL REVENUE DISTRIBUTION FOR JOINT REPLACEMENTS, IMPLANTS AND REGENERATIVE PRODUCTS, 2014 (%/$ MILLIONS) FIGURE 28 GLOBAL REVENUE DISTRIBUTION FOR JOINT REPLACEMENTS, IMPLANTS AND REGENERATIVE PRODUCTS, 2014 (%) LEADING SUPPLIERS AND PARTICIPANTS 163 TABLE 52 SUMMARY OF JOINT REPLACEMENTS, IMPLANTS AND REGENERATIVE PRODUCTS BY COMPETITOR REVENUES, 2014 (%/$ MILLIONS) FIGURE 29 SUMMARY OF JOINT REPLACEMENTS, IMPLANTS AND REGENERATIVE PRODUCTS BY COMPETITOR REVENUES, 2014 ($ MILLIONS) CHAPTER 9 MARKET SUMMARY 168 GLOBAL MARKET ANALYSIS 168 TABLE 53 GLOBAL MARKET FOR ADVANCED ORTHOPEDICS BY PRODUCT SEGMENT, THROUGH 2019 ($ MILLIONS) FIGURE 30 GLOBAL MARKET FOR ADVANCED ORTHOPEDICS BY PRODUCT SEGMENT, THROUGH 2019 ($ MILLIONS) GEOGRAPHIC MARKET ANALYSIS 169 TABLE 54 GLOBAL ADVANCED ORTHOPEDIC PRODUCT REVENUE DISTRIBUTION BY REGION, 2014 ($ MILLIONS) FIGURE 31 GLOBAL ADVANCED ORTHOPEDIC PRODUCT REVENUE DISTRIBUTION BY REGION, 2014 ($ MILLIONS) INDUSTRY PARTICIPANTS 171 TABLE 55 ADVANCED ORTHOPEDIC TECHNOLOGY INDUSTRY PARTICIPANTS BY TYPE, TABLE 56 ADVANCED ORTHOPEDIC COMPETITORS' MARKET SHARE ESTIMATES, 2014 (%/$ BILLIONS) FIGURE 32 DISTRIBUTION OF SALES BY COMPETITOR, 2014 ($ BILLIONS) CHAPTER 10 COMPANY PROFILES 176 INTRODUCTION 176 ARTHREX INC. 176

11 ARTHROCARE CORP. 177 B. BRAUN MELSUNGEN AG 177 BIOMET INC. 178 CONMED CORP. 179 DEPUY SYNTHES COMPANIES 179 DJO FINANCE LLC 180 EXACTECH INC. 180 INTEGRA LIFE SCIENCES 181 MEDTRONIC INC. 181 NUVASIVE INC. 182 ORTHOFIX INTERNATIONAL N.V. 183 SANOFI 183 SMITH & NEPHEW PLC 184 STRYKER CORP. 185 TORNIER N.V. 185 WRIGHT MEDICAL GROUP INC. 186 ZIMMER HOLDINGS INC. 186 CHAPTER 11 APPENDIX: LEADING PRODUCT MANUFACTURERS 189 LEADING PRODUCT MANUFACTURERS 189

12 LIST OF TABLES TABLE HEADING SUMMARY TABLE GLOBAL MARKET FOR ADVANCED ORTHOPEDICS BY PRODUCT SEGMENT, THROUGH 2019 ($ MILLIONS) TABLE 1 PARTS OF 21 CFR 14 TABLE 2 LISTING OF ORTHOPEDIC-RELATED CDRH HUMANITARIAN DEVICE EXEMPTIONS, THROUGH MARCH 2014 TABLE 3 NUMBER OF MEDICAL DEVICES APPROVED WITH CLINICAL DATA REVIEW, TABLE 4 JAPANESE MEDICAL DEVICE NOMENCLATURE CODES FOR ORTHOPEDIC DEVICES TABLE 5 U.S. AMBULATORY VISITS ALL AGES BY FACILITY TYPE, TABLE 6 U.S. EMERGENCY ROOM VISITS BY INJURY LOCATION AND SPORT/ACTIVITY, 2008 DATA TABLE 7 U.S. EMERGENCY ROOM VISITS BY BODY SITE, 2010 DATA (THOUSANDS) 25 TABLE 8 ACTIVE U.S. PHYSICIANS BY SELECTED SPECIALTY, (THOUSANDS) TABLE 9 MEDICARE REIMBURSEMENT RATES FOR COMMON ORTHOPEDIC PROCEDURES, NATIONAL PAYMENT AMOUNT, 2009 AND 2014 (DOLLARS) TABLE 10 HEALTH EXPENDITURES AS PERCENTAGE OF GDP BY SELECT COUNTRY, (%) TABLE 11 ADVANCED ORTHOPEDIC MANUFACTURING AND SUPPLY FACILITIES 34 TABLE 12 ADVANCED ORTHOPEDIC SALES AND MARKETING EXPENDITURES BY MANUFACTURER FOR FISCAL YEAR ($ MILLIONS) TABLE 13 RESEARCH AND DEVELOPMENT EXPENDITURES FOR ADVANCED ORTHOPEDIC MANUFACTURERS AND SUPPLIERS, ($ MILLIONS) TABLE 14 EMPLOYEE DISTRIBUTION FOR ORTHOPEDIC MANUFACTURERS AND SUPPLIERS, 2013 (NUMBER) TABLE 15 HIP REPLACEMENT: GLOBAL COST VARIATIONS, 2008 DATA ($ MILLIONS/NUMBER) TABLE 16 U.S. HEALTH INSURANCE COVERAGE BY AGE GROUP (%) 50 TABLE 17 WORLD HEALTH ORGANIZATION RANKING OF HEALTHCARE SYSTEMS, TOP 50, 2000 TABLE 18 ESTIMATED WORLD POPULATION BY SELECTED AGE GROUP AND SELECTED YEARS, THROUGH 2030 (MILLIONS) TABLE 19 GLOBAL POPULATION BY SELECTED COUNTRY, THROUGH 2015 (MILLIONS) 55 TABLE 20 U.S. POPULATION ESTIMATES AND PROJECTIONS BY AGE GROUP (THOUSANDS) TABLE 21 ESTIMATES OF EXPECTED U.S. LIFE EXPECTANCY AT BIRTH WITH PROJECTIONS BY GENDER, 2000 AND 2020 (YEARS) TABLE 22 GLOBAL LIFE EXPECTANCY AT BIRTH BY SELECTED COUNTRY, 1980 AND 2013 (YEARS) TABLE 23 ESTIMATED* PREVALENCE/INCIDENCE OF CONDITIONS AFFECTING THE GLOBAL ORTHOPEDIC INDUSTRY, AVERAGE FIGURE, (MILLIONS) TABLE 24 U.S. AGE-ADJUSTED PERCENT DISTRIBUTION OF BODY MASS INDEX (BMI) AMONG PERSONS, 18 YEARS AND OVER, BY SELECTED CHARACTERISTICS TABLE 25 PERCENT OF SMOKERS IN THE U.S. POPULATION, 18 AND OLDER, BY AGE AND GENDER, 2009 (%) TABLE 26 DAILY TOBACCO CONSUMPTION BY COUNTRY: 1990 COMPARED TO 2009* (TOTAL % SMOKERS) TABLE 27 PERCENT OF U.S. ADULTS ENGAGING IN PHYSICAL ACTIVITY AND FITNESS BY SELECTED CHARACTERISTICS, 2008 (%) TABLE 28 NUMBER OF ORTHOPEDIC PATENTS ISSUED BY YEAR, *

13 TABLE HEADING TABLE 29 ORTHOPEDIC PATENTS BY COUNTRY OF ORIGIN, * (NO. OF PATENTS) TABLE 30 ADVANCED ORTHOPEDIC PATENT INFORMATION BY ASSIGNEE 80 TABLE 31 BONE GRAFT PRODUCTS AND MATERIALS 97 TABLE 32 HUMAN BONE PRODUCTS AND COMPETITORS 98 TABLE 33 BONE-GROWTH STIMULATOR (BIOLOGICAL) PRODUCTS AND COMPETITORS TABLE 34 BONE-GROWTH STIMULATOR (ELECTRICAL/ULTRASOUND DEVICES) PRODUCTS AND COMPETITORS TABLE 35 SYNTHETIC BONE-REPLACEMENT PRODUCTS AND COMPETITORS 107 TABLE 36 BONE REPAIR AND REGENERATIVE PRODUCTS MARKET, THROUGH 2019 ($ MILLIONS) TABLE 37 REVENUE DISTRIBUTION FOR BONE REPAIR AND REGENERATIVE PRODUCTS BY PROCEDURE TYPE, 2014 ($ MILLIONS) TABLE 38 REVENUE DISTRIBUTION FOR BONE REPAIR AND REGENERATIVE PRODUCTS BY REGION, 2014 (%) TABLE 39 SUMMARY OF BONE REPAIR AND REGENERATIVE PRODUCTS BY COMPETITOR REVENUES, 2014 ($ MILLIONS) TABLE 40 FIXATION SYSTEMS AND OTHER SPECIALIZED DEVICES AND MARKETERS 121 TABLE 41 CARTILAGE AND SOFT TISSUE BIOLOGICS AND BIOMATERIALS SEGMENT 126 TABLE 42 CARTILAGE AND OTHER SOFT TISSUE REPAIR AND REGENERATIVE PRODUCTS MARKET, THROUGH 2019 ($ MILLIONS) TABLE 43 GLOBAL DISTRIBUTION OF REVENUES FROM CARTILAGE AND OTHER SOFT TISSUE REPAIR AND REGENERATIVE PRODUCTS BY REGION, 2014 (%/$ MILLIONS) TABLE 44 SUMMARY OF CARTILAGE AND OTHER SOFT TISSUE REPAIR AND REGENERATIVE PRODUCTS BY COMPETITOR REVENUES, 2014 (%/$ MILLIONS) TABLE 45 HIP REPLACEMENT PRODUCT SUPPLIERS 138 TABLE 46 KNEE REPLACEMENT PRODUCT SUPPLIERS 143 TABLE 47 SPINE REPLACEMENT/FIXATION PRODUCT SUPPLIERS 146 TABLE 48 OTHER EXTREMITY REPLACEMENTS, JOINT PRODUCT SUPPLIERS 153 TABLE 49 BIOLOGICAL JOINT PRODUCTS AND OTHER RELATED DEVICES 157 TABLE 50 JOINT REPLACEMENT, IMPLANT AND REGENERATIVE PRODUCT MARKETS, THROUGH 2019 ($ MILLIONS) TABLE 51 GLOBAL REVENUE DISTRIBUTION FOR JOINT REPLACEMENTS, IMPLANTS AND REGENERATIVE PRODUCTS, 2014 (%/$ MILLIONS) TABLE 52 SUMMARY OF JOINT REPLACEMENTS, IMPLANTS AND REGENERATIVE PRODUCTS BY COMPETITOR REVENUES, 2014 (%/$ MILLIONS) TABLE 53 GLOBAL MARKET FOR ADVANCED ORTHOPEDICS BY PRODUCT SEGMENT, THROUGH 2019 ($ MILLIONS) TABLE 54 GLOBAL ADVANCED ORTHOPEDIC PRODUCT REVENUE DISTRIBUTION BY REGION, 2014 ($ MILLIONS) TABLE 55 ADVANCED ORTHOPEDIC TECHNOLOGY INDUSTRY PARTICIPANTS BY TYPE, TABLE 56 ADVANCED ORTHOPEDIC COMPETITORS' MARKET SHARE ESTIMATES, 2014 (%/$ BILLIONS)

14 LIST OF FIGURES FIGURE TITLE SUMMARY FIGURE ADVANCED ORTHOPEDIC TECHNOLOGY, IMPLANTS AND REGENERATIVE PRODUCTS, ($ MILLIONS) FIGURE 1 HEALTH EXPENDITURES AS PERCENT OF GDP BY COUNTRY: (%) 31 FIGURE 2 ADVANCED ORTHOPEDIC SALES, MARKETING AND ADMINISTRATIVE EXPENDITURES BY MANUFACTURER FOR FISCAL YEAR ($ MILLIONS) FIGURE 3 RESEARCH AND DEVELOPMENT EXPENDITURES FOR ADVANCED ORTHOPEDIC MANUFACTURERS AND SUPPLIERS, ($ MILLIONS) FIGURE 4 HIP REPLACEMENT: GLOBAL COST VARIATIONS ($ MILLIONS/NUMBER) 49 FIGURE 5 U.S. HEALTH INSURANCE COVERAGE BY AGE GROUP (%) 51 FIGURE 6 ESTIMATED WORLD POPULATION BY SELECTED AGE GROUP AND SELECTED YEARS, ($ MILLIONS) FIGURE 7 GLOBAL POPULATION BY SELECTED COUNTRY, 2010 AND PROJECTED 2015 (MILLIONS) FIGURE 8 U.S. POPULATION ESTIMATES AND PROJECTIONS BY AGE GROUP, (THOUSANDS) FIGURE 9 ESTIMATES OF EXPECTED U.S. LIFE EXPECTANCY AT BIRTH WITH PROJECTIONS BY GENDER, 2000 AND 2020 (YEARS) FIGURE 10 GLOBAL LIFE EXPECTANCY AT BIRTH BY SELECTED COUNTRY, 1980 AND 2013 (YEARS) FIGURE 11 ESTIMATED* PREVALENCE/INCIDENCE OF CONDITIONS AFFECTING THE GLOBAL ORTHOPEDIC INDUSTRY, AVERAGE FIGURE, (MILLIONS) FIGURE 12 NUMBER OF U.S. HIP REPLACEMENT PROCEDURES, (NUMBER) 63 FIGURE 13 NUMBER OF U.S. KNEE REPLACEMENT PROCEDURES, (NUMBER) FIGURE 14 NUMBER OF U.S. SPINAL FUSION PROCEDURES, (NUMBER) 65 FIGURE 15 NUMBER OF U.S. PHYSICIAN VISITS FOR ROTATOR CUFF PROBLEMS, (MILLIONS) FIGURE 16 OBESITY BY COUNTRY (%) 67 FIGURE 17 DAILY TOBACCO CONSUMPTION BY COUNTRY: 1990 COMPARED TO 2009* (TOTAL % SMOKERS) FIGURE 18 NUMBER OF ORTHOPEDIC PATENTS ISSUED BY YEAR, * 77 FIGURE 19 ORTHOPEDIC PATENTS BY COUNTRY OF ORIGIN, * (NO. OF PATENTS) FIGURE 20 BONE REPAIR AND REGENERATIVE PRODUCTS MARKET ($ MILLIONS) FIGURE 21 REVENUE DISTRIBUTION FOR BONE REPAIR AND REGENERATIVE PRODUCTS BY PROCEDURE TYPE, 2014 ($ MILLIONS) FIGURE 22 REVENUE DISTRIBUTION FOR BONE REPAIR AND REGENERATIVE PRODUCTS BY REGION, 2014 (%) FIGURE 23 SUMMARY OF BONE REPAIR AND REGENERATIVE PRODUCTS BY COMPETITOR REVENUES, 2014 ($ MILLIONS) FIGURE 24 CARTILAGE AND OTHER SOFT TISSUE REPAIR AND REGENERATIVE PRODUCTS MARKET, ($ MILLIONS) FIGURE 25 GLOBAL DISTRIBUTION OF REVENUES FROM CARTILAGE AND OTHER SOFT TISSUE REPAIR AND REGENERATIVE PRODUCTS BY REGION, 2014 (%) FIGURE 26 SUMMARY OF CARTILAGE AND OTHER SOFT TISSUE REPAIR AND REGENERATIVE PRODUCTS BY COMPETITOR REVENUES, 2014 ($ MILLIONS) FIGURE 27 JOINT REPLACEMENT, IMPLANT AND REGENERATIVE PRODUCT MARKETS, ($ MILLIONS) FIGURE 28 GLOBAL REVENUE DISTRIBUTION FOR JOINT REPLACEMENTS, IMPLANTS AND REGENERATIVE PRODUCTS, 2014 (%)

15 FIGURE TITLE FIGURE 29 SUMMARY OF JOINT REPLACEMENTS, IMPLANTS AND REGENERATIVE PRODUCTS BY COMPETITOR REVENUES, 2014 ($ MILLIONS) FIGURE 30 GLOBAL MARKET FOR ADVANCED ORTHOPEDICS BY PRODUCT SEGMENT, THROUGH 2019 ($ MILLIONS) FIGURE 31 GLOBAL ADVANCED ORTHOPEDIC PRODUCT REVENUE DISTRIBUTION BY REGION, 2014 ($ MILLIONS) FIGURE 32 DISTRIBUTION OF SALES BY COMPETITOR, 2014 ($ BILLIONS)