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Bioavailability Enhancement Technologies and Services Market, 2018-2030

Bioavailability Enhancement Technologies and Services Market, 2018-2030

INTRODUCTION
Low bioavailability is one of the primary concerns associated with marketed drugs; in fact, various studies indicate that around 40% of available drugs are poorly bioavailable / soluble. As the drug developers shift their focus towards development of lipophilic drug compounds, the issue with aqueous solubility / bioavailability of the drugs is likely to increase further. It is estimated that around 90% of NCEs belong to BCS class II and IV, which are known to be associated with low solubility / permeability. Given that a large number of drugs fail to reach the market due to poor bioavailability, the industry is looking for various tools / methods to mitigate this challenge. Moreover, as many companies seek to re-formulate existing product candidates that exhibit poor bioavailability (via the 505(b)(2) pathway), the demand for novel bioavailability enhancement methods has grown significantly.

To cater to this increasing demand, several contract manufacturers and technology providers have emerged in this domain. With more than 150 companies offering technologies / services for bioavailability enhancement, the market is highly fragmented; having said that, several mergers / acquisitions have also taken place as stakeholders strive to broaden their respective service portfolios. A number of players have developed novel, state-of-the art technologies to maintain a competitive edge in this rapidly emerging market. As drug developers continue to evaluate novel drug targets and classes, the bioavailability enhancement domain is expected to grow at a steady pace. In fact, since 2010, more than 4,000 articles, evaluating various bioavailability enhancement technologies have been published across several reputed journals. In addition, more than 6,000 patents have been filed post 2010, providing a significant scientific push to the development of novel approaches.

SCOPE OF THE REPORT
The ‘Bioavailability Enhancement Technologies and Services Market, 2018-2030’ report provides a comprehensive study on the current scenario of technologies and contract services related to bioavailability enhancement. The study features an elaborate discussion on the novel approaches adopted by different players offering solutions for altering the bioavailability of various drugs. Amongst other elements, the report features:

An overview of the current market landscape, featuring a comprehensive list of over 150 active contract services / technology providers, and a detailed analysis based on a number of parameters, such as geographical location of the company, approach adopted for bioavailability enhancement (size reduction, solid dispersion, lipid based methods and other novel approaches), type of dosage forms (solid, liquid, semi-solid, others), route of drug administration (oral, injectable, inhalation and topical).

Elaborate profiles of key players (identified on the basis of the breadth of their respective service portfolios) that are offering bioavailability enhancement services. Each profile features an overview of the company, its financial performance (if available), services portfolio, recent collaborations and the future outlook of the company.

An analysis of ongoing clinical studies evaluating the bioavailability of various drug compounds. The chapter features a comprehensive view on the focus areas of these clinical studies, highlighting the key players involved.

A review of the published scientific literature on bioavailability enhancement technologies, highlighting the heightened research activity and the focus areas of research groups across different types of bioavailability enhancement technologies.

A detailed analysis of over 6,000 patents that have been filed related to bioavailability enhancement technologies. The study presents a high-level view on the valuation of these patents and also highlights the emerging trends related to the innovation in this domain.

An analysis of the partnerships that have been established in the recent past, covering R&D collaborations, license agreements, mergers and acquisitions, co-service agreements, manufacturing and service agreements, and other relevant types of deals.

A comprehensive benchmark analysis, highlighting the key focus areas of small, mid-sized and large sized companies; the benchmark analysis provides a means to compare the existing capabilities within respective peer groups and help industry stakeholders identify ways to achieve a competitive edge over contemporary players.

A detailed estimation of the likely demand for bioavailability enhancement technologies / services. It provides a comprehensive view, in terms, of the annual number of projects, that are likely to require bioavailability enhancement over the period 2018-2030.

One of the key objectives of the report was to understand the primary growth drivers and estimate the future size of the market. Based on parameters, such as likely number of candidates in BCS II and IV, likely adoption rates of bioavailability enhancement approaches, expected trend in outsourcing and likely pricing, we have provided an informed estimate on the likely evolution of the market in the short to mid-term and long term, for the period 2018-2030. To account for the uncertainties associated with the expected future demand and to add robustness to our model, we have provided three forecast scenarios, portraying the conservative, base and optimistic tracks of the market’s evolution. All actual figures have been sourced and analyzed from publicly available information forums and primary research discussions. Financial figures mentioned in this report are in USD, unless otherwise specified.

EXAMPLE HIGHLIGHTS
1. We identified more than 155 players that are offering solutions / technologies for bioavailability enhancement of drugs. Of these, 17% are very large companies (more than 1,000 employees), 22% are large companies (201-1,000 employees), 21% are mid-sized companies (51-200 employees) and 40% are small sized players (less than 50 employees).
2. Around 80 companies are headquartered in the Americas (North America and South America), primarily in the US, of which, about 14% are based in New Jersey and 13% in California. Over 50 companies are headquartered in the European region, of which about 21% are based in Germany and 18% in the UK. In addition, around 20 companies are headquartered in the Asia Pacific region, with majority of the players (55%) based in India, followed by 14% companies in Israel and Japan.

3. Close to 55% of the companies have adopted size reduction-based approaches for bioavailability enhancement. The key size reduction technologies offered by these companies include (in order of popularity) nanoparticles (63), high pressure homogenization / micronization (40), milling (30), microfluidics (5), and bead layering (4).

4. Solid dispersion-based methods have been adopted by more than 50% of the technology / service providers; these include (in order of popularity) spray dried dispersion (45), hot melt extrusion (38), lyophilization (21), solvent evaporation (5), super critical fluids (4), agglomeration (3), and other polymer-based approaches (13).

5. We were also able to identify close to 50 companies that offer lipid-based approaches. The key technologies / services offered by these companies involve the use of (in order of popularity) liposomes (22), self-emulsifying drug delivery systems (14), nano-lipids (11), excipients (7), and other lipid-based systems (13). In addition, over 80 companies are presently offering services / technologies based on other novel approaches, such as co-use of cyclodextrin (16), use of micelles (8), and crystallization (5), for bioavailability enhancement.

6. Close to 80 partnerships have been inked in this domain in the last five years. The maximum number of partnerships (23) were inked in 2017, followed by 18 instances in 2016. More than 30% of the collaborations were focused on acquiring some or all the assets of a company. In addition, around 13% of the collaborations were service alliances, wherein, contract service / technology providers have combined their expertise to offer novel solutions for bioavailability enhancement to their clients.

7. In the past few years, several advancements have taken place in the field, wherein industry stakeholders have tried to develop novel approaches for improving the solubility / bioavailability of drugs. We came across more than 11,500 patents, of which 53% were filed after 2010. A significant proportion (>35%) of the patents have been filed by companies that are based in China, followed by companies in the US and Japan.

8. We expect the bioavailability enhancement services market to grow at an annualized rate of ~14.6% between 2018 and 2030. Lipid-based and solid dispersion approaches for bioavailability enhancement occupy the biggest share of the current bioavailability enhancement services market. These techniques are likely to continue to occupy a larger share of the market in 2030 as well.

RESEARCH METHODOLOGY
The data presented in this report has been gathered via secondary and primary research. For all our projects, we conduct interviews with experts in the area (academia, industry, medical practice and other associations) to solicit their opinions on emerging trends in the market. This is primarily useful for us to draw out our own opinion on how the market will evolve across different regions and technology segments. Where possible, the available data has been checked for accuracy from multiple sources of information.

The secondary sources of information include
Annual reports
Investor presentations
SEC filings
Industry databases
News releases from company websites
Government policy documents
Industry analysts’ views

While the focus has been on forecasting the market till 2030, the report also provides our independent view on various trends emerging in the industry. This opinion is solely based on our knowledge, research and understanding of the relevant market gathered from various secondary and primary sources of information.

CHAPTER OUTLINES
Chapter 2 provides an executive summary of the insights captured in our research. It offers a high-level view on the likely evolution of the bioavailability enhancement technologies and services market in the short-mid and long term.

Chapter 3 is a general introduction to bioavailability. In this section, we have discussed, in detail, the concept of bioavailability and the current problems associated with bioavailability across various drug compounds. The chapter also features a detailed discussion on the current approaches being used for bioavailability enhancement.

Chapter 4 provides a comprehensive review of the global landscape of bioavailability enhancement technologies and service providers. It includes information related to over 150 companies that are currently operating in this domain. It features an in-depth market review, including a study of the regional distribution of players, analysis by company size and year of establishment, approach adopted for bioavailability enhancement, type of drug dosage form, route of administration, and the location of the company.

Chapter 5 features detailed profiles of some of the key players that are active in this domain and offer a wide range of services. Each profile presents an overview of the company, its financial information (if available), details related to its service(s) portfolio, recent developments (acquisitions / mergers, collaborations and expansions) and a comprehensive future outlook.

Chapter 6 presents a benchmark analysis of all the players engaged in this domain. It highlights the capabilities of these companies in terms of their expertise across bioavailability enhancement. The analysis allows companies to compare their existing capabilities within and beyond their peer groups and identify opportunities to become more competitive in the industry.

Chapter 7 features an elaborate discussion on the collaborations and partnerships that have been inked amongst players in this market. We have also discussed the various partnership models that have been implemented, highlighting the most common forms of deals / agreements prevalent in this domain. In addition, we have highlighted the key players, on the basis of the number of collaborations and also discussed the expansion of services (via acquisitions / mergers) by key players.

Chapter 8 provides a comprehensive publication analysis, highlighting the recent trends in published literature related to bioavailability enhancement technologies. It presents a relative comparison of key technologies, on the basis of the trend in number of publications (CAGR) and the impact factors of the journals wherein these articles were published.

Chapter 9 provides detailed analysis of the patents that have recently been filed related to bioavailability enhancement technologies. The study also highlights the upcoming trends in innovation in this domain. In addition, it presents a high-level view on the valuation of these patents

Chapter 10 features an overview of the various ongoing clinical studies that are evaluating the bioavailability of various drug candidates that are currently under development. The chapter features a comprehensive view on the focus areas of these clinical studies, highlighting the key players involved as well.

Chapter 11 presents a detailed estimation of the likely demand for bioavailability enhancement technologies / services. It provides a comprehensive view in terms of the annual number of projects that are likely to require bioavailability enhancement in the period 2018-2030.

Chapter 12 provides a comprehensive market forecast analysis, highlighting the future potential of contract services for bioavailability enhancement till the year 2030. It features the likely distribution of the market based on [A] approach used for bioavailability enhancement (solid dispersion, size reduction, lipid-based approaches, and other approaches), [B] region (North America, Europe, Asia-Pacific and rest of the world), and [C] opportunity from drugs across different BCS classifications (BCS II and BCS IV).

Chapter 13 is a summary of the overall report. In this chapter, we have provided a list of key takeaways from the report, and expressed our independent opinion related to the research and analysis described in the previous chapters. It also provides a brief overview of some of the upcoming future trends, which, we believe, are likely to influence the growth of this market in the foreseen future.

Chapter 14 is a collection of transcripts of the discussions by various stakeholders across the public domain.

Chapter 15 is an appendix, which provides tabulated data and numbers for all the figures provided in the report.

Chapter 16 is an appendix, which provides the list of companies and organizations mentioned in the report.

LIST OF COMPANIES AND ORGANIZATIONS

The following companies / institutes / government bodies and organizations have been mentioned in this report.
1. Abbott
2. AbbVie Contract Manufacturing
3. ABITEC
4. Accu-Break Pharmaceuticals
5. Aché Laboratórios Farmacêuticos
6. Acorn Biomedical
7. Actavis
8. Adare Pharmaceuticals
9. Admas Pharmaceuticals
10. Aegis Therapeutics
11. Aesica
12. Agere Pharmaceuticals
13. Aizant Drug Research Solutions
14. Ajinomoto
15. Alcami
16. Alexion Pharmaceuticals
17. Alkermes
18. Allergan
19. Alliance Contract Pharma
20. Almac Group
21. Althea Technologies
22. Altum Pharmaceuticals
23. Altus Formulation
24. Amatsigroup
25. AMRI
26. Applied Manufacturing Science
27. Aquestive Therapeutics
28. Arbro Pharmaceuticals
29. Arbutus Biopharma
30. Ardena Group
31. Ascendia Pharmaceuticals
32. Ashland
33. Athenex
34. Avara Pharmaceutical Services
35. Avro Pharma
36. Avomeen Analytical Services
37. BASF
38. Baxter International
39. BEC Chemicals
40. Bend Research
41. BioConnection
42. BioDuro
43. Bionpharma
44. Bio-serv
45. Bridgepoint Development Capital
46. Calando Pharmaceuticals
47. Calvert Laboratories
48. Camurus
49. Capsugel
50. Catalent
51. CEPiA Sanofi
52. Cerenis Therapeutics
53. ChemConnection
54. Chiasma Pharma
55. Co-Formulate
56. Colorcon
57. Continuous Technologies International
58. Corazon
59. COREALIS Pharma
60. CoreRx
61. Creative Biolabs
62. CritiTech
63. Croda International
64. Crystal Pharmatech
65. Crystallics
66. CrystecPharma
67. CuriRx
68. Cyclolab
69. Cyndea Pharma
70. Cytec
71. Dalton Pharma Services
72. Dauntless Pharmaceuticals
73. DisperSol Technologies
74. Dow Pharma Solutions
75. Eagle Pharmaceuticals
76. École Polytechnique Fédérale de Lausanne
77. Emisphere Technologies
78. Emmerson Resources
79. Entera Bio
80. Enteris BioPharma
81. Evonik Health Care
82. Evotec
83. ExxPharma Therapeutics
84. Ferring Pharmaceuticals
85. Forest Laboratories
86. Formac Pharmaceuticals
87. Formex
88. Foster Delivery Science
89. Friulchem
90. Fuji Chemical Industries
91. Gattefossé
92. Generex Biotechnology
93. GenPlus
94. Glatt Integrated Process Solutions
95. Glenmark Pharmaceuticals
96. GP Pharm
97. GVK Biosciences
98. Halo Pharma
99. Harvard University
100. Helix BioPharma
101. Hovione
102. IACTA Pharmaceuticals
103. iCeutica
104. IMCD
105. Indena
106. Industrias Biocontrolled
107. Instillo Group
108. Intas Pharmaceuticals
109. Intec Pharma
110. Jamia Hamdard University
111. Jetpharma
112. Jina Pharmaceuticals
113. Juniper Pharma Services
114. Keystone Nano
115. Kinex Pharmaceuticals
116. Kuecept
117. LATITUDE Pharmaceuticals
118. leon-nanodrugs
119. Lexaria Bioscience
120. Ligand Pharmaceuticals
121. Lipomize
122. Lonza
123. Losan Pharma
124. Lubrizol
125. Lypro Biosciences
126. Marinus Pharmaceuticals
127. Matinas BioPharma
128. Merrion Pharmaceuticals
129. Metrics Contract Services
130. MicroChem
131. Microfine Pharma
132. Micro-Macinazione
133. Micro-Sphere
134. Midas Pharma
135. MIKA PHARMACEUTICALS
136. Molecular Profiles
137. Monash University
138. Mutchler
139. Nanocopoeia
140. Nanomaterials
141. Nanomerics
142. Nanosphere Health Sciences
143. Natco Pharma
144. Nemus Bioscience
145. NETZSCH Premier Technologies
146. NeutriSci Internatinal
147. New York Center for Nanomedicine Research
148. Nippon Soda
149. Nisso America
150. NMT Pharmaceuticals
151. Nordic Bioscience
152. Novaliq
153. Novartis Pharmaceuticals
154. Novo Nordisk
155. Novozymes
156. Nuformix Technologies
157. Oasmia Pharmaceutical
158. Okklo Life Sciences
159. Opiant Pharmaceuticals
160. Pacira Pharmaceuticals
161. Particle Sciences
162. Patheon
163. Phares Drug Delivery
164. Pharmaceutics International
165. PharmaIN
166. PharmaSol
167. Pharmatek Laboratories
168. Pharmavize
169. Phasex
170. Phivida
171. Phosphorex
172. Pivot Pharmaceuticals
173. PixarBio
174. Planet Science
175. PolyPeptide Group
176. Porton Pharma Solutions
177. PowderSize
178. Prinova Group
179. PriviLS
180. ProCepT
181. ProJect Pharmaceutics
182. ProMed Pharma
183. Pulmatrix
184. PureTech Health
185. Quay Pharma Services
186. Quotient Sciences
187. Rani Therapeutics
188. Rhythm Pharmaceuticals
189. Rondol Industrie
190. Rottendorf Pharma
191. Rubicon Research
192. Samyang Biopharmaceuticals
193. Sancilio Pharmaceuticals Company
194. SARA Pharm Solutions
195. SciTech Development
196. SEPS Pharma
197. Shin-Etsu Chemical
198. Shionogi
199. Siegfried Holding
200. Singota Solutions
201. SiTec PharmaBio
202. SkyePharma
203. SolMic Research
204. SoluBest
205. Solvias
206. STA Pharmaceutical
207. Stanipharm
208. Supernus Pharmaceuticals
209. Tapemark
210. Tergus Pharma
211. Transgene Biotek
212. Univar
213. UPM Pharmaceuticals
214. Upperton Pharma Solutions
215. Variant Pharmaceuticals
216. Vectura
217. Veloxis Pharmaceuticals
218. Vesifact
219. Vitasome
220. VxP Pharma
221. W. R. Grace
222. WuXi AppTec
223. Xcelience
224. Xedev
225. XenoGesis
226. Xi'an Hongchang Pharmaceuticals
227. Xisle Pharma Ventures
228. Yale University


1. PREFACE
1.1. Scope of the Report
1.2. Research Methodology
1.3. Chapter Outlines
2. EXECUTIVE SUMMARY
3. INTRODUCTION
3.1 An Overview of Drug Bioavailability
3.2 Need of Bioavailability Enhancement
3.3 Evolution of Bioavailability Enhancement Technologies
3.4 Studies for Assessment of Bioavailability
3.4.1 Study Design
3.4.1.1. Absolute Bioavailability
3.4.1.2. Relative Bioavailability
3.4.1.3. Single vs Multiple Dose Study
3.4.1.4. Healthy Subjects vs Patients
3.4.2. Assessment Methods
3.5. Factors Affecting Bioavailability
3.5.1. Drug Related Factors
3.5.2. Body Related Factors
3.6. Bioavailability Enhancement Technologies
3.6.1. Physical Technologies
3.6.1.1. Solid Dispersion
3.6.1.2. Nanosuspension Technology
3.6.2. Chemical Technologies
3.6.2.1. Lipid Based Formulations
3.6.2.2. Metal Based Drug Delivery System
3.6.2.3. Polymer Based Drug Delivery System
3.6.3. Biological Technologies
3.7. Trends in Bioavailability Enhancement
3.7.1. Need for Outsourcing Bioavailability Enhancement Requirements
4. MARKET OVERVIEW
4.1. Chapter Overview
4.2. Bioavailability Enhancement: List of Service Providers
4.2.1. Distribution by Company Portfolio
4.2.2. Distribution by Geographical Location
4.2.3. Distribution by Company Size
4.2.4. Distribution by Year of Establishment
4.2.5. Distribution by Bioavailability Enhancement Principle
4.2.6. Distribution by Bioavailability Enhancement Approach
4.2.6.1. Distribution by Lipid Based Approaches
4.2.6.2. Distribution by Size Reduction Approaches
4.2.6.3. Distribution by Solid Dispersion Approaches
4.2.6.4. Distribution by Other Approaches
4.2.7. Distribution by Dosage Form
4.2.8. Distribution by Route of Administration
4.2.9. Heat Map Analysis of Service Providers
4.2.10. Distribution by Leading Players
5. COMPANY PROFILES
5.1. Chapter Overview
5.2. Lonza
5.2.1. Company Overview
5.2.2. Financial Performance
5.2.3. Services Portfolio
5.2.4. Bioavailability Enhancement Services Portfolio
5.2.5. Recent Partnerships
5.2.6. Future Outlook
5.3. Catalent
5.3.1 Company Overview
5.3.2 Financial Performance
5.3.3 Services Portfolio
5.2.4. Bioavailability Enhancement Services Portfolio
5.2.5. Recent Partnerships
5.2.6. Future Outlook
5.4. Ascendia Pharmaceuticals
5.4.1. Company Overview
5.4.2. Services Portfolio
5.4.3. Bioavailability Enhancement Services Portfolio
5.4.4. Future Outlook
5.5. Particle Sciences (Acquired by Lubrizol)
5.4.1. Company Overview
5.4.2. Financial Performance
5.4.3. Services Portfolio
5.4.4. Bioavailability Enhancement Services Portfolio
5.4.5. Recent Partnerships
5.4.6. Future Outlook
5.6. Juniper Pharma Services
5.6.1. Company Overview
5.6.2. Financial Performance
5.6.3. Services Portfolio
5.6.4. Bioavailability Enhancement Services Portfolio
5.6.5. Recent Partnerships
5.6.6. Future Outlook
5.7. Phosphorex
5.7.1. Company Overview
5.7.2. Financial Performance
5.7.3. Services Portfolio
5.7.4. Bioavailability Enhancement Services Portfolio
5.7.5. Recent Partnerships
5.7.6. Future Outlook
5.8. Kuecept (Acquired by Aptuit / Evotec)
5.8.1. Company Overview
5.8.2. Financial Performance
5.8.3. Services Portfolio
5.8.4. Bioavailability Enhancement Services Portfolio
5.8.5. Recent Partnerships
5.8.6. Future Outlook
5.9. Creative Biolabs
5.9.1. Company Overview
5.9.2. Financial Performance
5.9.3. Services Portfolio
5.9.4. Bioavailability Enhancement Services Portfolio
5.9.5. Recent Partnerships
5.9.5. Future Outlook
5.10. WuXi AppTec
5.10.1. Company Overview
5.10.2. Financial Performance
5.10.3. Services Portfolio
5.10.4. Bioavailability Enhancement Services Portfolio
5.10.5. Recent Partnerships
5.10.6. Future Outlook
6. BENCHMARK ANALYSIS
6.1. Chapter Overview
6.2. Benchmark Analysis: Methodology
6.3. Benchmark Analysis: Peer Groups
6.3.1. Benchmark Analysis: North and South America, Peer Group I
6.3.2. Benchmark Analysis: North and South America, Peer Group II
6.3.3. Benchmark Analysis: North and South America, Peer Group III
6.3.4. Benchmark Analysis: Europe, Peer Group IV
6.3.5. Benchmark Analysis: Europe, Peer Group V
6.3.6. Benchmark Analysis: Asia-Pacific, Peer Group VI
6.3.7. Benchmark Analysis: Asia-Pacific, Peer Group VII
7. PARTNERSHIPS AND COLLABORATIONS
7.1. Chapter Overview
7.2. Types of Partnerships
7.3. Bioavailability Enhancement: Analysis of Partnerships
7.3.1. Distribution by Year of Partnerships
7.3.2. Distribution by Type of Partnerships
7.3.3. Distribution by Most Active Companies
7.3.4. Distribution by Leading Acquirers
8. PUBLICATION ANALYSIS
8.1. Chapter Overview
8.2. Bioavailability Enhancement: Analysis of Publications
8.2.1. Distribution by Year of Publications
8.2.2. Distribution by Key Journals
8.2.3. Emerging Areas: Word Clouds
8.2.4. Analysis be Key Approaches
8.2.4.1. Distribution by Number of Publications
8.2.4.2. Distribution by Year of Publications
8.2.4.3. Distribution by Growth Rate
8.2.4.4. Bubble Chart Analysis
8.2.5. Distribution by Leading Publications
9. PATENT ANALYSIS
9.1. Chapter Overview
9.2. Scope and Methodology
9.3. Bioavailability Enhancement: Analysis of Patents
9.3.1. Distribution by Publication Year
9.3.2. Distribution by Geographical Location
9.3.3. Distribution by CPC Classification
9.3.4. Emerging Areas: Word Cloud
9.3.5. Patent Valuation
9.3.6 Leading Citations
10. CLINICAL TRIALS ANALYSIS
10.1. Chapter Overview
10.2. Guidelines to Conduct Bioavailability Studies
10.3. Clinical Trials Analysis
10.3.1. Research Methodology
10.3.2. Distribution by Study Start Date
10.3.3. Distribution by Study Design
10.3.4. Distribution by Phase
10.3.5. Distribution by Trial Status
10.3.6. Distributions of Types of Molecules by Phase of Development
10.3.7. Distribution by Leading Players
10.3.8. Study Focus: Word Cloud
11. DEMAND ANALYSIS
11.1. Chapter Overview
11.2. Bioavailability Enhancement Opportunities
11.3. Research Methodology
11.4. Demand Analysis: New Chemical Entities (NCEs)
11.5. Demand Analysis: Generics
12. MARKET FORECAST
12.1. Chapter Overview
12.2. Forecast Methodology
12.3. Overall Bioavailability Enhancement Market, 2018-2030
12.4. Bioavailability Enhancement Market: Distribution by BCS Classification
12.4.1. Bioavailability Enhancement Market by BCS II Drugs
12.4.2. Bioavailability Enhancement Market by BCS IV Drugs
12.5. Bioavailability Enhancement Market: Distribution by Type of Bioavailability Enhancement Approach
12.5.1. Bioavailability Enhancement Market by Lipid Based Approaches
12.5.2. Bioavailability Enhancement Market by Size Reduction Based Approaches
12.5.3. Bioavailability Enhancement Market by Solid Dispersion Based Approaches
12.5.4. Bioavailability Enhancement Market by Other Bioavailability Enhancement Approaches
12.6. Bioavailability Enhancement Market: Distribution by Geographical Location
12.6.1. Bioavailability Enhancement Market in the Americas (North America / South America)
12.6.2. Bioavailability Enhancement Market in Europe
12.6.3. Bioavailability Enhancement Market in Asia-Pacific
12.6.4. Bioavailability Enhancement Market in Rest of the World
13. CONCLUSION
13.1. Challenges Associated with Low Solubility and Permeability of Drugs Has Led to Increasing Demand for Bioavailability Enhancement
13.2. The Market is Characterized by The Presence of Several Established Players, As Well As Small and Mid-Sized Companies in Different Geographies
13.3. Size Reduction, Solid Dispersion and Lipid Based Methods are Offered by Several Technology / Service Providers; Players Offering Other Approaches are Also Emerging
13.4. The Field Has Witnessed Increasing Partnership Activity As Multiple Players are Collaborating for Expanding Capabilities
13.5. Ongoing Advances Have Led to Rapid Innovation and Increase in Patent Filling Activity
13.6. The Rising Number of BCS II and BCS IV Drugs and Increasing Adoption of Different Approaches for Enhancement of Drug Bioavailability is Likely to Foster the Long-Term Growth
14. TRANSCRIPTS OF PUBLIC DISCUSSIONS
14.1. Chapter Overview
14.2. David Vodak, Vice President of Chemistry, Bend Research
14.3. John K Tilloston, Pharmaceutical and Nutritional Technical Business Director, ABITEC
14.4. Kaspar van den Dries, Senior Director Formulation Sciences and Martin Piest, Senior Formulation Scientist, Patheon
14.5. Anonymous, MilliporeSigma Process Solutions
14.6. Brent Moody, Principal Scientist, Science and Technology, Catalent Pharma Solutions
14.7. Anonymous, Sancilio Pharmaceuticals
14.8. Frank Romanski, BASF Pharma Solutions
14.9. Karl Kolter, BASF Pharma Solutions
15. APPENDIX 1: TABULAR DATA
16. APPENDIX 2: LIST OF COMPANIES
LIST OF FIGURES
Figure 3.1 Biopharmaceutical Classification System
Figure 3.2 Biopharmaceutical Classification System: Change in Trends
Figure 3.3 Bioavailability Enhancement Technologies: Evolutionary Timeline
Figure 3.4 Different Designs to Study Drug Bioavailability
Figure 3.5 Single Dose Study to Evaluate Bioavailability
Figure 3.6 Multiple Dose Study to Evaluate Bioavailability
Figure 3.7 Bioavailability Assessment: Methodologies
Figure 3.8 Bioavailability Assessment: Factors Affecting Bioavailability
Figure 3.9 Solid Dispersion: Classifications
Figure 3.10 Solid Dispersion: Preparation Methodologies
Figure 3.11 Solid Dispersion: List of Drugs Prepared by Hot Melt Extrusion
Figure 3.12 Solid Dispersion: List of Drugs Prepared by Melting / Fusion
Figure 3.13 Solid Dispersion: List of Drugs Prepared by Solvent Evaporation
Figure 3.14 Solid Dispersion: List of Drugs Prepared by Spray-Dried Dispersion
Figure 3.15 Solid Dispersion: Melt Agglomeration Technique
Figure 3.16 Nanosuspension: Preparation Methodologies
Figure 3.17 Lipid Based Formulations: Classification
Figure 3.18 Biological Formulation Technologies
Figure 4.1 Bioavailability Enhancement Service Providers: Distribution by Bioavailability Enhancement Approach and Geography
Figure 4.2 Bioavailability Enhancement Service Providers: Geographical Landscape
Figure 4.3 Bioavailability Enhancement Service Providers: Distribution by Company Size
Figure 4.4 Bioavailability Enhancement Service Providers: Cumulative Distribution by Year of Establishment
Figure 4.5 Bioavailability Enhancement Service Providers: Distribution by Bioavailability Enhancement Principle
Figure 4.6 Bioavailability Enhancement Service Providers: Distribution by Bioavailability Enhancement Approach
Figure 4.7 Bioavailability Enhancement Service Providers: Distribution by Lipid Based Approaches
Figure 4.8 Bioavailability Enhancement Service Providers: Distribution by Size Reduction Approaches
Figure 4.9 Bioavailability Enhancement Service Providers: Distribution by Solid Dispersion Based Approaches
Figure 4.10 Bioavailability Enhancement Service Providers: Distribution by Other Formulation Approaches
Figure 4.11 Bioavailability Enhancement Service Providers: Distribution by Dosage Form
Figure 4.12 Bioavailability Enhancement Service Providers: Distribution by Route of Administration
Figure 4.13 Bioavailability Enhancement Service Providers: Heat Map Analysis by Dosage Form and Bioavailability Enhancement Approaches
Figure 4.14 Bioavailability Enhancement Service Providers: Leading Players
Figure 4.15 Bioavailability Enhancement Service Providers: Dosage Form Wise Global Distribution of Leading Players
Figure 5.1 Lonza: Annual Revenues, 2013-2017 (CHF Billion)
Figure 5.2 Lonza: Custom Contract Manufacturing Services
Figure 5.3 Lonza: Bioavailability Enhancement Services Portfolio
Figure 5.4 Catalent: Annual Revenues, 2013– 2017 (USD Billion)
Figure 5.5 Catalent: Revenues by Product Types, 2017 (USD Million)
Figure 5.6 Catalent: Services Portfolio
Figure 5.7 Catalent: Bioavailability Enhancement Services Portfolio
Figure 5.8 Ascendia Pharmaceuticals: Services Portfolio
Figure 5.9 Ascendia Pharmaceuticals: Bioavailability Enhancement Services Portfolio
Figure 5.10 Particle Sciences: Services Portfolio
Figure 5.11 Particle Sciences: Bioavailability Enhancement Services Portfolio
Figure 5.12 Juniper Pharmaceuticals: Annual Revenues, 2013–2017 (USD Million)
Figure 5.13 Juniper Pharma Services: Services Portfolio
Figure 5.14 Juniper Pharma Services: Bioavailability Enhancement Services Portfolio
Figure 5.15 Phosphorex: Polymeric Nanoparticles Applications
Figure 5.16 Phosphorex: Bioavailability Enhancement Services Portfolio
Figure 5.17 Kuecept: Services Portfolio
Figure 5.18 Kuecept: Bioavailability Enhancement Services Portfolio
Figure 5.19 Creative Biolabs: Services Portfolio
Figure 5.20 Creative Biolabs: Bioavailability Enhancement Services Portfolio
Figure 5.21 WuXi AppTec: Annual Revenues, 2010–Q3 2015 (USD Million)
Figure 5.22 WuXi AppTec: Services Portfolio
Figure 5.23 WuXi AppTec: Bioavailability Enhancement Services Portfolio
Figure 6.1 Benchmark Analysis: Distribution of Industry Players by Year of Establishment and Geographical Location
Figure 6.2 Benchmark Analysis: American Companies, Peer Group I
Figure 6.3 Benchmark Analysis: American Companies, Peer Group II
Figure 6.4 Benchmark Analysis: American Companies, Peer Group III
Figure 6.5 Benchmark Analysis: European Companies, Peer Group IV
Figure 6.6 Benchmark Analysis: European Companies, Peer Group V
Figure 6.7 Benchmark Analysis: European Companies, Peer Group VI
Figure 6.8 Benchmark Analysis: Asian Companies, Peer Group VII
Figure 6.9 Benchmark Analysis: Asian Companies, Peer Group VIII
Figure 7.1 Bioavailability Enhancement Partnerships: Cumulative Year-wise Trend
Figure 7.2 Bioavailability Enhancement Partnerships: Distribution by Type of Collaboration
Figure 7.3 Bioavailability Enhancement Partnerships: Yearly Distribution by Type of Collaboration
Figure 7.4 Bioavailability Enhancement Partnerships: Distribution by Most Active Players
Figure 7.5 Bioavailability Enhancement Partnerships: Distribution by Key Acquirers
Figure 7.6 Bioavailability Enhancement Partnerships: Distribution by Key Acquirers
and Year of Acquisitions
Figure 8.1 Bioavailability Enhancement Publications: Cumulative Year-Wise Trend
Figure 8.2 Bioavailability Enhancement Publications: Top 15 Journals
Figure 8.3 Bioavailability Enhancement Publications: Emerging Areas
Figure 8.4 Bioavailability Enhancement Publications: Distribution of Approaches by Number of Publications
Figure 8.5 Bioavailability Enhancement Publications: Distribution of Approaches by Year of Publication
Figure 8.6 Bioavailability Enhancement Publications: Distribution of Approaches by CAGR (2008-2017)
Figure 8.7 Bioavailability Enhancement Publications: Technology Wise Bubble Chart Analysis
Figure 9.1 Bioavailability Enhancement Patents: Distribution by Type of Patent
Figure 9.2 Bioavailability Enhancement Patents: Distribution by Type of Technology
Figure 9.3 Bioavailability Enhancement Patents: Cumulative Distribution by Year and Bioavailability Enhancement Approach
Figure 9.4 Bioavailability Enhancement Patents: Distribution by Patent CAGR and Bioavailability Enhancement Approach
Figure 9.5 Bioavailability Enhancement Patents: Distribution by Publication Year
Figure 9.6 Bioavailability Enhancement Patents: Year-wise Regional Distribution
Figure 9.7 Bioavailability Enhancement Patents: Cumulative Distribution by CPC Classification Symbol
Figure 9.8 Bioavailability Enhancement Patents: Emerging Areas
Figure 9.10 Bioavailability Enhancement Patents: Age of Patent
Figure 9.11 Bioavailability Enhancement Patents: Patent Valuation
Figure 9.12 Bioavailability Enhancement Patents: Geographical Patent Valuation
Figure 9.13 Bioavailability Enhancement Patents: Leading Players
Figure 10.1 Bioavailability Studies: Cumulative Year Wise Trend
Figure 10.2 Bioavailability Studies: Study Design
Figure 10.3 Bioavailability Studies: Clinical Trial Distribution
Figure 10.4 Bioavailability Studies: Trial Status Wise Distribution
Figure 10.5 Bioavailability Studies: Distribution of Molecules by Phase of Development
Figure 10.6 Bioavailability Studies: Leading Players
Figure 10.7 Bioavailability Studies: Study Focus
Figure 11.1 Demand Analysis: Enhanced Formulation Drug Approvals (2010-2015)
Figure 11.2 Demand Analysis: Likelihood of Approval
Figure 11.3 Demand Analysis: Distribution by Dosage Forms
Figure 11.4 Demand Analysis: Distribution of Types of Molecule by Phase of Development
Figure 11.5 Demand Analysis: Expected Phase wise BCS Distribution of Drugs (2030)
Figure 11.6 Demand Analysis: Expected Demand (NCEs)
Figure 11.7 Demand Analysis: Expected Demand (NCEs), Opportunity Segmentation by Technology (2025-2030)
Figure 11.8 Demand Analysis: Expected Demand (Generics)
Figure 11.9 Demand Analysis: Expected Demand (Generics), Opportunity Segmentation by Technology (2025-2030)
Figure 12.1 Bioavailability Enhancement Market: Cost of Bioavailability Enhancement,
Figure 12.2 Bioavailability Enhancement Market: Trends in Out-Sourcing
Figure 12.3 Overall Bioavailability Enhancement Market, 2018-2030: Base Scenario (USD Billion)
Figure 12.4 Bioavailability Enhancement Market: Segmentation by BCS Classification, 2018-2030: Base Scenario (USD Billion)
Figure 12.5 Bioavailability Enhancement Market: Market Shares of Formulation Approaches, (2018, 2025, 2030)
Figure 12.6 Bioavailability Enhancement Market: Segmentation by Formulation Approaches, 2018-2030: Base Scenario (USD Billion)
Figure 12.7 Bioavailability Enhancement Market: Segmentation by Geographical Location, 2018-2030: Base Scenario (USD Billion)
LIST OF TABLES
Table 3.1 Solid Dispersion Method: List of Drugs
Table 3.2 Nanoparticles: List of Drugs
Table 3.3 Nanosuspensions: List of Drugs
Table 3.4 Liposome Based Formulations: List of Drugs
Table 3.5 Micelles Based Formulations: List of Drugs
Table 3.6 Micro-Emulsion Based Parenteral Formulations: List of Drugs
Table 3.7 Micro-Emulsion Based Oral Formulations: List of Drugs
Table 3.8 Lipid Based Oral Formulations: List of Drugs
Table 3.9 Metal Based Drug Delivery Approaches: List of Drugs
Table 3.10 Polymer Based Drug Delivery Approaches: List of Drugs
Table 3.11 Biological Formulation Technologies: List of Drugs
Table 4.1 Bioavailability Enhancement Service Providers: Information on Company Portfolio
Table 4.2 Bioavailability Enhancement Service Providers: Information on Bioavailability Enhancement Approaches
Table 4.3 Bioavailability Enhancement Service Providers: Information on Lipid Based Approaches
Table 4.4 Bioavailability Enhancement Service Providers: Information on Size Reduction Approaches
Table 4.5 Bioavailability Enhancement Service Providers: Information on Solid Dispersion Based Approaches
Table 4.6 Bioavailability Enhancement Service Providers: Information on Other Approaches
Table 5.1 Lonza: Future Outlook
Table 5.2 Catalent: Future Outlook
Table 5.3 Catalent: List of Upcoming Conferences
Table 5.4 Ascendia Pharmaceuticals: Future Outlook
Table 5.5 Particle Sciences: Future Outlook
Table 5.6 Juniper Pharma Services: Future Outlook
Table 5.7 Phosphorex: Future Outlook
Table 5.8 Creative Biolabs: Future Outlook
Table 5.9 WuXi AppTec: Future Outlook
Table 6.1 Benchmark Analysis: Peer Groups
Table 7.1 Bioavailability Enhancement: Partnerships, 2013-2018
Table 8.1 Bioavailability Enhancement: Leading Publications
Table 9.1 Bioavailability Enhancement Patents: Most Popular CPC Symbols
Table 9.2 Bioavailability Enhancement Patents: List of Top CPC Classifications
Table 9.3 Bioavailability Enhancement Patents: List of Top Leading Patents
Table 10.1 Bioavailability Studies: Regulatory Guidelines and Methodologies
Table 14. 1 Technology Selection for Enhancing Bioavailability
Table 15.1 Bioavailability Enhancement Service Providers: Distribution by Type of Bioavailability Approach and Geography
Table 15.2 Bioavailability Enhancement Service Providers: Distribution by Company Size
Table 15.3 Bioavailability Enhancement Service Providers: Cumulative Distribution by Year of Establishment
Table 15.4 Bioavailability Enhancement Service Providers: Distribution by Bioavailability Enhancement Principle
Table 15.5 Bioavailability Enhancement Service Providers: Distribution by the Type of Approach
Table 15.6 Bioavailability Enhancement Service Providers: Distribution by Lipid Based Approaches
Table 15.7 Bioavailability Enhancement Service Providers: Distribution by Size Reduction Approaches
Table 15.8 Bioavailability Enhancement Service Providers: Distribution by Solid Dispersion Based Approaches
Table 15.9 Bioavailability Enhancement Service Providers: Distribution by Other Formulation Approaches
Table 15.10 Bioavailability Enhancement Service Providers: Distribution by Dosage Form
Table 15.11 Bioavailability Enhancement Service Providers: Distribution by Route of Administration
Table 15.12 Bioavailability Enhancement Service Providers: Heat Map Analysis by Dosage Form and Bioavailability Enhancement Approaches
Table 15.13 Lonza: Annual Revenues, 2013-2017 (CHF Billion)
Table 15.14 Catalent: Annual Revenues, 2013– 2017 (USD Billion)
Table 15.15 Catalent: Revenues by Product Types, 2017 (USD Million)
Table 15.16 Juniper Pharmaceuticals: Annual Revenues, 2013–2017 (USD Million)
Table 15.17 WuXi AppTec: Annual Revenues, 2010–Q3 2015 (USD Million)
Table 15.18 Benchmark Analysis: Distribution of Industry Players by Year of Establishment and Geographical Location
Table 15.19 Benchmark Analysis, Peer Group I: Distribution by Bioavailability Enhancement Principle
Table 15.20 Benchmark Analysis, Peer Group I: Distribution by Type of Bioavailability Approach
Table 15.21 Benchmark Analysis, Peer Group I: Distribution by Dosage Form
Table 15.22 Benchmark Analysis, Peer Group I: Distribution by Route of Administration
Table 15.23 Benchmark Analysis, Peer Group II: Distribution by Bioavailability Enhancement Principle
Table 15.24 Benchmark Analysis, Peer Group II: Distribution by Bioavailability Enhancement Approach
Table 15.25 Benchmark Analysis, Peer Group II: Distribution by Dosage Form
Table 15.26 Benchmark Analysis, Peer Group II: Distribution by Route of Administration
Table 15.27 Benchmark Analysis, Peer Group III: Distribution by Bioavailability Enhancement Principle
Table 15.28 Benchmark Analysis, Peer Group III: Distribution by Bioavailability Enhancement Approach
Table 15.29 Benchmark Analysis, Peer Group III: Distribution by Dosage Form
Table 15.30 Benchmark Analysis, Peer Group III: Distribution by Route of Administration
Table 15.31 Benchmark Analysis, Peer Group IV: Distribution by Bioavailability Enhancement Principle
Table 15.32 Benchmark Analysis, Peer Group IV: Distribution by Bioavailability Enhancement Approach
Table 15.33 Benchmark Analysis, Peer Group IV: Distribution by Dosage Form
Table 15.34 Benchmark Analysis, Peer Group IV: Distribution by Route of Administration
Table 15.35 Benchmark Analysis, Peer Group V: Distribution by Bioavailability Enhancement Approach
Table 15.36 Benchmark Analysis, Peer Group V: Distribution by Approach Type
Table 15.37 Benchmark Analysis, Peer Group V: Distribution by Dosage Form
Table 15.38 Benchmark Analysis, Peer Group V: Distribution by Route of Administration
Table 15.39 Benchmark Analysis, Peer Group VI: Distribution by Bioavailability Enhancement Principle
Table 15.40 Benchmark Analysis, Peer Group VI: Distribution by Bioavailability Enhancement Approach
Table 15.41 Benchmark Analysis, Peer Group VI: Distribution by Dosage Form
Table 15.42 Benchmark Analysis, Peer Group VI: Distribution by Route of Administration
Table 15.43 Benchmark Analysis, Peer Group VII: Bioavailability Enhancement Principle
Table 15.44 Benchmark Analysis, Peer Group VII: Distribution by Bioavailability Enhancement Approach
Table 15.45 Benchmark Analysis, Peer Group VII: Distribution by Dosage Form
Table 15.46 Benchmark Analysis, Peer Group VII: Distribution by Route of Administration
Table 15.47 Benchmark Analysis, Peer Group VIII: Distribution by Bioavailability Enhancement Principle
Table 15.48 Benchmark Analysis, Peer Group VIII: Distribution by Bioavailability Enhancement Approach
Table 15.49 Benchmark Analysis, Peer Group VIII: Distribution by Dosage Form
Table 15.50 Benchmark Analysis, Peer Group VIII: Distribution by Route of Administration
Table 15.51 Bioavailability Enhancement Partnerships: Cumulative Year-wise Trend
Table 15.52 Bioavailability Enhancement Partnerships: Distribution by Type of Collaboration
Table 15.53 Bioavailability Enhancement Partnerships: Distribution by Most Active Players
Table 15.54 Bioavailability Enhancement Partnerships: Distribution by Leading Acquirers
Table 15.55 Bioavailability Enhancement Publications: Cumulative Year-Wise Trend
Table 15.56 Bioavailability Enhancement Publications: Top 15 Journals
Table 15.57 Bioavailability Enhancement Publications: Distribution of Approaches by Number of Publications
Table 15.58 Bioavailability Enhancement Publications: Year-Wise Technology Distribution
Table 15.59 Bioavailability Enhancement Publications: Distribution of Approaches by CAGR (2008-2017)
Table 15.60 Bioavailability Enhancement Publications: Bubble Analysis
Table 15.61 Bioavailability Enhancement Publications: Distributions of Top Publications by Technology
Table 15.62 Bioavailability Enhancement Patents: Distribution by Type of Patent
Table 15.63 Bioavailability Enhancement Patents: Distribution by Type of Approach
Table 15.64 Bioavailability Enhancement Patents: Cumulative Distribution by Publication Years for Bioavailability Enhancement Approaches
Table 15.65 Bioavailability Enhancement Patents: Distribution by Bioavailability Enhancement Approach and Patent CAGR
Table 15.66 Bioavailability Enhancement Patents: Distribution by Publication Year
Table 15.67 Bioavailability Enhancement Patents: Year-Wise Regional Distribution
Table 15.68 Bioavailability Enhancement Patents: Age of Patent
Table 15.69 Bioavailability Enhancement Patents: Patent Valuation
Table 15.70 Bioavailability Studies: Cumulative Year Wise Trend
Table 15.71 Bioavailability Studies: Intervention of Study
Table 15.72 Bioavailability Studies: Purpose of Study
Table 15.73 Bioavailability Studies: Allocation of Study
Table 15.74 Bioavailability Studies: Masking of Study
Table 15.75 Bioavailability Studies: Clinical Trials Distribution
Table 15.76 Bioavailability Studies: Trial Status Wise Distribution
Table 15.77 Bioavailability Studies: Distribution of Types of Molecule by Phase of Development
Table 15.78 Bioavailability Studies: Leading Players
Table 15.79 Demand Analysis: Enhanced Formulation Drug Approvals (2010-2015)
Table 15.80 Demand Analysis: Likelihood of Approval
Table 15.81 Demand Analysis: Distribution by Dosage Forms
Table 15.82 Demand Analysis: Phase wise BCS Distribution of Drugs (2018)
Table 15.83 Demand Analysis: Expected Phase wise BCS Distribution of Drugs (2030)
Table 15.84 Demand Analysis: Expected Demand (NCEs)
Table 15.85 Demand Analysis: Expected Demand (NCEs), Opportunity Segmentation by Technology (2025-2030)
Table 15.86 Demand Analysis: BCS for Generic Drugs, 2013 Scenario
Table 15.87 Demand Analysis: BCS for Generic Drugs, 2018 Scenario
Table 15.88 Demand Analysis: BCS for Generic Drugs, 2030 Scenario
Table 15.89 Demand Analysis: Expected Demand (Generic Drugs)
Table 15.90 Bioavailability Enhancement Market: Trends in Bioavailability Enhancement Cost, 2018-2030 (USD Million)
Table 15.91 Bioavailability Enhancement Market: Drugs Adopting Out-Licensing Approach for Bioavailability Enhancement
Table 15.92 Overall Bioavailability Enhancement Market, 2018-2030: Conservative Scenario (USD Billion)
Table 15.93 Overall Bioavailability Enhancement Market, 2018-2030: Base Scenario (USD Billion)
Table 15.94 Overall Bioavailability Enhancement Market, 2018-2030: Optimistic Scenario (USD Billion)
Table 15.95 Bioavailability Enhancement Market: Segmentation by BCS Classification, 2018-2030: Conservative Scenario (USD Billion)
Table 15.96 Bioavailability Enhancement Market: Segmentation by BCS Classification, 2018-2030: Base Scenario (USD Billion)
Table 15.97 Bioavailability Enhancement Market: Segmentation by BCS Classification, 2018-2030: Optimistic Scenario (USD Billion)
Table 15.98 Bioavailability Enhancement Market: Market Shares of Formulation Approaches, (2018, 2025, 2030)
Table 15.99 Bioavailability Enhancement Market: Segmentation by Formulation Approaches, 2018-2030: Conservative Scenario (USD Billion)
Table 15.100 Bioavailability Enhancement Market: Segmentation by Formulation Approaches, 2018-2030: Base Scenario (USD Billion)
Table 15.101 Bioavailability Enhancement Market: Segmentation by Formulation Approaches, 2018-2030: Optimistic Scenario (USD Billion)
Table 15.102 Bioavailability Enhancement Market: Segmentation by Geographical Location, 2018-2030: Conservative Scenario (USD Billion)
Table 15.103 Bioavailability Enhancement Market: Segmentation by Geographical Location, 2018-2030: Base Scenario (USD Billion)
Table 15.104 Bioavailability Enhancement Market: Segmentation by Geographical Location, 2018-2030: Optimistic Scenario (USD Billion)

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