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The area of drug discovery tools is one of the newest and most important sectors of pharmaceutical research and development. The term drug discovery tools usually refers to high-content screening (HCS) and analysis and is composed of those applications that require sufficient levels of sample throughput, whereby complex cellular events and phenotypes can be studied. Elements of drug performance like toxicity and specificity can be established simultaneously using mixed cell types--primary cells, cell lines, cell subpopulations. HCS seeks to assess the impact of phenotypic and cellular changes that are brought about by gene modification (such as with RNA interference (RNAi) approaches) and/or drug (or compound) treatment. The purpose of this examination by TriMark Publications is to describe the specific segments of the global drug discovery tools market. Within this area, the report covers those segments that are highly active in terms of innovation and growth. Specifically, this study examines the markets for small lab equipment all the way up to highly automated, large automated platforms, as well as accessory equipment such as reagents, supplies and manufacturers' original equipment manufacturer (OEM) additional equipment.
TABLE OF CONTENTS
1. Overview 4
1.1 Objectives of the Report 4
1.2 Methodology 5
1.3 Scope of the Report 6
1.4 Executive Summary 7
2. Technologies and Product Offering for High-Content Analysis 10
2.1 Definition of High-Content Analysis and Why It Is So Attractive a Discipline
11
2.2 Classes of Measurements Possible with High-Content Analysis Approaches and
Biological Functions Investigated 14
2.3 Instrumentation Platforms for High-Content Analysis 18
2.3.1 High-Content Screening Technology 18
2.3.2 High-Content Instruments 18
2.4 Reagent and Assay Platforms for High-Content Analysis 24
2.5 Cell-based Screening Technologies in Drug Development 29
2.5.1 Applications of Cell-based Assays 29
2.5.2 Pharma Drug Discovery Paradigm and Compound Screening 29
2.5.3 High-Content Analysis in the Biopharmaceutical Industry 30
3. Market Analysis of the High-Content Tools Space 32
3.1 High-Content Analysis Market Size and Growth 32
3.2 Market Survey to Assess Qualitative and Quantitative Parameters of the
High-Content Analysis Space 32
3.3 Experimental and Research Trends in High-Content Analysis 34
3.4 Challenges and Market Drivers in High-Content Analysis 39
3.4.1 Barriers to High-Content Analysis 41
3.4.2 Drivers of High-Content Analysis 42
3.5 High-Content Analysis in Combination with RNAi 42
3.6 Market Landscape of Instrumentation for High-Content Analysis 44
3.7 Reagent and Assay Usage in High-Content Analysis 48
3.8 Trends in the High-Content Analysis Assays/Reagents Space-Major Product
Vendors 51
3.9 Emerging Market Trends in High-Content Analysis 53
3.10 Market Forecasts for the High-Content Analysis Space 55
3.11 Use of HCS/HCA in Pharmaceutical Companies 57
3.12 Qualitative Opportunities and Challenges for Market Adoption 58
4. Strategic Analysis of the High-Content Tools Space 59
4.1 Analysis of the High-Content Market Structure 59
4.2 Description of the Drug Discovery Marketplace and Definition of the Field 59
4.3 Key Market Drivers and Challenges in the High-Content Analysis Space 60
4.4 Consolidated Picture of the High-Content Analysis Marketplace 64
4.5 High-Content Analysis Market Sectors and Growth Rate 65
4.6 Vendors of High-Content Analysis Technology 65
5. High-Content Analysis Technology Platforms 66
5.1 Methods of Digital Imaging 66
5.2 Fluorescence Microscopy 66
5.3 Major High-Content Analysis Instrumentation 67
5.3.1 High-Content Analysis Platforms to Support GPCR Screening 68
5.4 High-Content Analysis Reagents 68
5.5 Imaging Software 69
5.6 Enterprise-Level IT Solutions to Support High-Content Screening Experiments
69
5.6.1 Image Analysis Algorithms 70
5.7 Use of RNAi in High-Content Analysis 71
5.8 Industry Alliances to Leverage RNAi and High-Content Analysis 71
5.9 Emerging Trends in High-Content Analysis Technology Platforms 72
6. High-Content Analysis in Drug Selection, Screening and Biomarker Discovery 73
6.1 Stem Cells as Tools for Drug Discovery 74
6.2 Cellular Systems Biology for Development of Toxicity Panels in Drug Safety
Testing 74
6.3 Drug Discovery Companies Marketing Cell-based Assays 75
6.4 Companies Using Cell-based Assays in Drug Discovery Programs 78
6.4.1 Phenotypic Drug Discovery (PDD) 78
6.4.2 Application of Quantitative High-Throughput Screening to HCA Cell-based
Assays 78
6.4.3 Application of High-Content Fingerprinting to Oncology Drug Discovery:
Focus on In Vitro and In Vivo Phenocopying and Cancer Stem Cell Analysis 79
6.5 Target Discovery and Validation by RNAi Screening 79
6.6 FLIM-FRET Methodology 79
6.7 Multidimensional Fluorescence Imaging (MDFI) Technology 79
7. Company Profiles 80
7.1 Acumen Pharmaceuticals, Inc. 80
7.2 Acumen Bioscience (division of TTP Group) 80
7.3 Applied Biosystems 80
7.4 BD Biosciences 82
7.5 DiscoveRX 82
7.6 Evotec Technologies (acquired by PerkinElmer) 82
7.7 Fisher BioImage 82
7.8 General Electric, GE Healthcare 83
7.9 Guava Technologies (now a division of Millipore) 83
7.10 Integral Molecular (Akceli Inc.) 84
7.11 LemnaTech GmbH 84
7.12 Millipore 84
7.13 Molecular Devices Corporation, now a division of MDS Analytical Techniques
86
7.14 NIH Chemical Genomics Center 88
7.15 PerkinElmer 89
7.16 Sangamo Biosciences, Inc. 91
7.17 Spotfire (acquired by TIBCO) 91
7.18 Thermo Scientific Cellomics 92
7.19 Translational Genomics Research Institute 92
7.20 Vala Sciences, Inc. 92
8. Glossary of Terms in the High-Content Analysis Space 93
LIST OF FIGURES
Figure 2.1: Scope of Biological Parameters Addressed Via a Typical High-Content
Analysis Experiment 13
Figure 2.2: Classes of Assays in Life Science Research and Drug Discovery
Illustrating the Relationship between Cell-based Assays and High-Content
Analysis 14
Figure 2.3: New Paradigm for Drug Discovery and Development Illustrating the
Central and Essential Role of Screening 16
Figure 2.4: Cumulative Known and New Drug Targets 31
Figure 3.1: Breakout of Market Survey Respondents by Geographical Location 32
Figure 3.2: Breakout of Market Survey Respondents by Affiliation-Academic,
Commercial, Vendor 32
Figure 3.3: Segmentation of Respondent Pool Based upon Usage of High-Content
Analysis in its Research Activities 33
Figure 3.4: Segmentation of the Survey Respondent Pool Based upon the Length of
Time they have been Using High-Content Analysis in Their Research Activities 33
Figure 3.5: Number of Parameters Studied Simultaneously in High-Content Analysis
Assays-Multivariate (Multi-Parameter) Analyses 35
Figure 3.6: Key Biological Processes Studied Utilizing High-Content Analysis
Tools 36
Figure 3.7: Breakout of High-Content Analysis Assays Currently Performed or
Expected to be Performed in the Future by Biological Pathway (or Target) 37
Figure 3.8: Breakout of High-Content Analysis Experiments Performed Per Week
(Distributed in our Respondent Pool) Across the Various Biological Pathways (and
Targets) 37
Figure 3.9: Which of the Biological Processes (Pathways/Targets) Addressed Using
High-Content Analysis-based Approaches are Growing in Importance and which are
Declining? 38
Figure 3.10: In Which Environment are High-Content Analysis Assays
Performed-Primary Screen, Secondary Screen, ADME/Tox Screen? 39
Figure 3.11: Key Challenges Faced by the Research Community in its Practice of
High-Content Analysis 40
Figure 3.12: Various Drivers Leading the Research Community to Perform
High-Content Analysis 41
Figure 3.13: HCA with RNAi-Current and Future Experimental Formats 43
Figure 3.14: HCA with RNAi-Number of Experiments Performed Per Month by the
Survey Respondent Pool 43
Figure 3.15: Growing and Steady Usage of Various Formats where RNAi is coupled
with HCA 44
Figure 3.16: Penetration of the Different High-Content Analysis Instrumentation
Platforms into the Marketplace 45
Figure 3.17: Instrumentation Platforms for High-Content Analysis Ranked by Top
Choice and Second Tier 46
Figure 3.18: High-Content Analysis Instrumentation and where they Lie on the
Throughput Curve 47
Figure 3.19: Top Instrumentation Value Drivers in the High-Content Analysis
Space 47
Figure 3.20: Important Sub-Cellular Features Studied via High-Content Analysis
Approaches 48
Figure 3.21: Breakout of End-Point Versus Kinetic Assays in the High-Content
Analysis Space 49
Figure 3.22: Types of Cellular Targets Studied Using High-Content Analysis
Approaches 49
Figure 3.23: Top-most Target Class Studied Utilizing High-Content Analysis
Approaches 50
Figure 3.24: Distribution of High-Content Analysis Experiments across the
Respondent Pool-Number of Experiments Performed Per Week 50
Figure 3.25: Average Reagent/Assay Costs Per High-Content Analysis Experiment 51
Figure 3.26: Stratification of Reagent/Assay Suppliers into the High-Content
Analysis Space 52
Figure 3.27: Monthly Reagent/Assay Purchases for High-Content Analysis by the
End-user Community from Various Vendors 52
Figure 3.28: Growth or Decline in Importance of the Various High-Content
Analysis Vendors to the End-user Community 53
Figure 3.29: Percentage of High-Content Analysis Experiments that Involve GFP
Across the Market Landscape 54
Figure 3.30: Breakout of High-Content Analysis Reagents Marketplace:
Made-in-House Versus Off-the-Shelf 55
Figure 3.31: Breakout of Spending on Various Components of the High-Content
Analysis Discipline 55
Figure 3.32: Historic/Forecast Growth of the Total Screening Space, Broken-out
by Primary Screening, Secondary Screening (including High-Content Analysis as a
Subset) and ADME/Tox, for 2004-2016 56
Figure 3.33: Historic/Forecast Growth of the Screening Space-Broken-out by
Cell-based Assays and Biochemical Assays, 2004-2016 57
Figure 4.1: Drug Discovery and Development Ensemble and the Position of the
Various Segments of High-Content Analysis in the Space 62
Figure 4.2: Relative Size and Position of the High-Content Analysis Space in the
Overall Scheme of the Life Science Tools Marketplace 65
Figure 5.1: High-Content Analysis-Positional Biosensors Using Caspases and
Monitoring the Translocation of a Tagged Protein from the Cytoplasm to the
Nucleus 70
Figure 6.1: HCA Target Classes: Breakout of Current Drug Targets into Their
Constituent Classes 73
Figure 6.2: GPCR Assay Technologies 74
LIST OF TABLES
Table 2.1: Comparison of the Key Features of High-Content Analysis and
High-Throughput Screening 11
Table 2.2: Impact of High-Content Analysis on Drug Discovery-Impact of Several
Drivers 12
Table 2.3: Biological Application Areas Associated with High-Content Analysis 13
Table 2.4: Classes of Measurements and Targets Identified Using Phenotypic
Screening (High-Content Analysis) 14
Table 2.5: Classes of Cellular Measurements Possible with Fluorescent Protein
Biosensors 16
Table 2.6: Multi-Parameter High-Content Analysis Assays to Study Biological
Systems in Life Science Research and Drug Discovery, Demonstrating the Breadth
and Scalability of the High-Content Analysis Approach 17
Table 2.7: Companies Offering Systems for High-Throughput Imaging 19
Table 2.8: Comparison of the Major Instrumentation Platforms and Their
Associated Specifications for High-Content Analysis-I 20
Table 2.9: Comparison of the Major Instrumentation Platforms and Their
Associated Specifications for High-Content Analysis-II 20
Table 2.10: Price Points and Target Markets of the Various High-Content Analysis
Instrument Platforms 21
Table 2.11: Companies Offering Flow Cytometry Products and Services 21
Table 2.12: Integrated Product Platforms Offered by the Different High-Content
Analysis Vendors 23
Table 2.13: High-Content Analysis Assays Developed by Thermo Scientific
Cellomics 25
Table 2.14: Thermo Scientific Cellomics HCS Reagent Kits (formerly called "HitKits")
and Their Therapeutic Areas of Application 26
Table 2.15: Millipore's HCA Assay/Reagent Portfolio 27
Table 2.16: Cell Lines for GPCR High-Content Analysis that can be Deployed onto
the BD Biosciences/Atto Pathway HT Instrument Platform 28
Table 2.17: Examples of High-Content Screens 30
Table 3.1: What Fraction of High-Content Analysis Assays are Cell-based Versus
Biochemical-based 34
Table 4.1: Comparison of the Key Features of High-Content Analysis and
High-Content Screening 60
Table 4.2: Snapshot of the Various HCA Assays, Demonstrating the Scalability of
this Discipline 63
Table 5.1: Modes of Digital Imaging 66
Table 5.2: Modes of Fluorescence Microscopy 66
Table 5.3: Major High-Content Analysis Instrumentation 67
Table 5.4: Image Analysis Algorithms 70