Global Markets for In Vitro Toxicity Testing

• Publication date: September 2010

THIS REPORT CONTAINS An overview of the in-vitro toxicology testing market, explaining basic principles and practices, definitions, classes of tests, and different types of toxicology Analysis of trends in the global market, with data from 2009, estimates for 2010, and projections of compound annual growth rates (CAGRs) through 2015 A technical overview that describes toxicology testing strategies, various toxicology categor...

THIS REPORT CONTAINS

An overview of the in-vitro toxicology testing market, explaining basic principles and practices, definitions, classes of tests, and different types of toxicology
Analysis of trends in the global market, with data from 2009, estimates for 2010, and projections of compound annual growth rates (CAGRs) through 2015
A technical overview that describes toxicology testing strategies, various toxicology categories, and alternatives to standard toxicology methods
Information on technology in the markets, including revenues and developments
A thorough analysis of patents and comprehensive company profiles.
STUDY GOALS AND OBJECTIVES

BCC’s goal in conducting this study was to determine the current status of the global in vitro toxicity testing market and assess its growth potential over the 5-year period from 2010 to 2015. We were particularly interested in understanding the current market scenario for alternative measures to animal testing.

Predictive toxicology is often cross-referenced with in vitro methods. This report assesses the growth and market potential for these methods. In addition, we were interested in understanding the impact of these methods on different industry sectors.

One key objective was to present an analysis of the current in vitro toxicity testing market in major national markets and its future direction.

REASONS FOR DOING THE STUDY

Classical toxicology testing programs have been in place for many decades now. Over the past 2 decades, ongoing animal welfare activities have spurred the idea of pursuing alternative testing measures in toxicity with minimal pain and suffering to animals. This report aims to identify the key advances in different test categories and the extent of validation by the regulatory authorities. We also were interested in identifying the impact of new technology advancements with possible toxicology applications and also examining their growth potential.

There are different industries that require toxicity testing of their products. Previously, there was broad coverage of these applications. As this market relies strongly on both technology and regulatory forces, this study was aimed to identify the relevance of current developments on pharmaceuticals, chemicals, food additives, cosmetics, and household products.

SCOPE OF REPORT

The study encompasses the major types of traditional toxicity testing methods and the in vitro techniques that have been under review of the Interagency Coordinating Committee for Validation of Alternative Methods (ICCVAM) test methods for toxicity. BCC discusses the two major technology based approaches, mechanistic and nonmechanistic, and determines current market status; examines impact on future markets; and presents forecasts of growth over the next 5 years. Technological issues, including the latest trends, are discussed. Other influential factors such as validation of these alternative measures for toxicity and toxicity testing strategies for chemicals, pesticides, and food additives have also been included. BCC also examines the regulatory role and the different federal and international agencies that play an active role in in vitro toxicology research.

INTENDED AUDIENCE

This report is designed to satisfy the information needs of a wide variety of individuals involved in the toxicity marketplace, including company senior management executives seeking to base their strategic decisions on the latest insights into toxicology market forces and trends. It is also aimed at managers and executives in product research and development and particularly those responsible for bringing new products to market.

METHODOLOGY AND INFORMATION SOURCES

Both primary and secondary research methodologies were used in preparing this study. Primary research includes interviews with leading individuals in relevant companies and associations; primary sources of published data include research studies, company annual reports, and government publications. Secondary sources consist of literature searches, industry journals, and other commercial publications. Data for market estimates and forecasts are pooled from a range of sources, critically assessed by BCC.

ANALYST’s CREDENTIALS

Paul Evers has been involved in analyzing pharmaceutical markets for 20 years. He is the author of previous reports on leading-edge developments at the interface between Research and Development (R&D) and the marketplace. 

Global In Vitro Diagnostic Industry

Chapter- 1: INTRODUCTION -- Complimentary

STUDY GOALS AND OBJECTIVES 1
REASONS FOR DOING THE STUDY 1
SCOPE OF REPORT 1
INTENDED AUDIENCE 2
METHODOLOGY AND INFORMATION SOURCES 2
ANALYST’S CREDENTIALS 2
RELATED REPORTS 2
BCC ONLINE SERVICES 3
DISCLAIMER 3

Chapter-2: SUMMARY

SUMMARY 4
SUMMARY (CONTINUED) 5
SUMMARY TABLE GLOBAL IN VITRO TOXICOLOGY MARKET, THROUGH 2015 ($ MILLIONS) 6
SUMMARY FIGURE GLOBAL IN VITRO TOXICOLOGY MARKET, 2010 AND 2015 ($ MILLIONS) 6

Chapter-3: OVERVIEW

BASICS OF TOXICOLOGY 7
TYPES AND APPLICATIONS 7
CONVENTIONAL (IN VIVO) TECHNIQUES 8
DEVELOPMENT OF IN VITRO TOXICOLOGY 8
Current Status 9
Current Uses of In Vitro Methods 9
INDUSTRY STRUCTURE 10

Chapter-4: TOXICOLOGY BACKGROUND

INTRODUCTION 11
TOXICITY TESTS 11
TOXICITY TESTS (CONTINUED) 12
ABOUT TOXICITY 13
ABOUT DOSES 14
DOSE 14
DOSE RESPONSE 14
THRESHOLD DOSE 14
ABOUT TOXIC SUBSTANCES 14
TOXICANT 14
TOXIN 15
ACUTE AND CHRONIC TOXICITY 15
TOXICOKINETICS 15
ABSORPTION 15
ORAL 15
INTRANASAL 16
INHALATION 16
DERMAL AND PARENTERAL ROUTES 16
DISTRIBUTION 17
METABOLISM 17
EXCRETION 18
TOXICITY TESTING: TRADITIONAL APPROACHES 18
FIGURE 1 STANDARD WHOLE ANIMAL TOXICITY TESTS 19
ACUTE TOXICITY 20
LD50 20
TABLE 1 APPROXIMATE RAT ORAL LD50 FOR VARIOUS CHEMICAL SUBSTANCES (MG/KG) 21
Range-finding Tests 22
Oral LD50 22
Dermal LD50 23
Inhalation LD50 23
DEVELOPMENTS IN ACUTE TOXICITY TESTING 24
SUBCHRONIC AND CHRONIC TOXICITY 24
Types of Tests 25
Frequency of Exposure 25
Chronic Toxicity Studies 26
Dosage Levels 27
Duration 27
Recovery 28
Analysis 28
TABLE 2 RISK ASSESSMENT BASED ON TOXICITY STUDIES 28
TABLE 2 (CONTINUED) 29
DERMAL AND OCULAR TOXICITY 29
Acute Dermal Toxicity 29
TABLE 3 DRAIZE TEST CLASSIFICATION OF DERMAL IRRITATION POTENTIAL 30
Study Design 31
Skin Sensitization 31
Study Design 32
Photoallergic and Phototoxic Reactions 33
Study Design 34
Acute Ocular Toxicity Tests 34
Eye Irritation and Corrosion Testing 34
Limitations of These Methods 35
TOXICITY TESTING FOR FERTILITY AND REPRODUCTION 35
History of Teratogenicity Testing 36
Teratogenic Agents 37
Animal Tests for Teratogenicity 38
Embryotoxicity 39
Male Reproductive Tests 39
Female Reproductive Tests 40
CARCINOGENICITY AND MUTAGENICITY TESTING 41
Carcinogenesis 41
In Vivo Carcinogenicity Testing 42
In Vivo Genotoxicity and Cytogenetic Tests 43

Chapter-5: IN VITRO TOXICOLOGY

WHY SEEK ALTERNATIVES TO ANIMAL TESTING? 44
LIMITATIONS OF TRADITIONAL TOXICITY TESTING 45
THE NONCONCORDANCE PROBLEM 45
TOXICITY TESTING OF PRODRUGS 46
HISTORY 47
TABLE 4 EVOLUTION OF IN VITRO TOXICOLOGY 48
TABLE 4 (CONTINUED) 49
TABLE 4 (CONTINUED) 50
TABLE 5 REGULATORY AND SCIENTIFIC ORGANISATIONS INVOLVED IN DEVELOPMENT OF ALTERNATIVE TESTING METHODS 50
TABLE 5 (CONTINUED) 51
THE THREE RS CONCEPT 51
The Three Rs Concept (Continued) 52
OFFICIAL RESPONSE IN U.S. AND EU 53
EVOLUTION OF IN VITRO TECHNOLOGY 54
CURRENT USES OF IN VITRO METHODS 54
APPLICATIONS OF IN VITRO METHODS 55
ACUTE SYSTEMIC TOXICITY 56
NRU Assay 56
MTT Assay 56
ACUTE ORAL TOXICITY (LD50) 57
LOCAL TOXICITY TESTING 57
Skin Toxicity 57
Murine Local Lymph Node Assay (LLNA) 58
Corrositex Assay 58
EpiDerm, EpiSkin, and TER 58
Photosensitization and Phototoxicity 59
Ocular Toxicity Testing 60
HET-CAM Test 61
Bovine Corneal Opacity and Permeability (BCOP) Assay 62
Isolated Chicken Eye (ICE) Test 63
Isolated Rabbit Eye (IRE) Test 64
EpiOcular Model 64
CHALLENGES 65
VALIDATION 65
Towards Validation 65
Towards Validation (Continued) 66
Towards Validation (Continued) 67
OECD Approach 68
ECVAM Approach 68
NICEATM-ICCVAM Approach 69
Other Countries and Regions 70
Industry Programs to Promote Validation 71
REGULATORY STATUS 71
INTERNATIONAL: THE OECD APPROACH 72
EUROPE: THE ECVAM APPROACH 72
U.S.: THE NICEATM-ICCVAM APPROACH 73
TABLE 6 VALIDATION AND REGULATORY ACCEPTANCE STATUS OF ALTERNATIVE TEST METHODS AND TESTING STRATEGIES 74
TABLE 6 (CONTINUED) 75
TABLE 6 (CONTINUED) 76
TABLE 6 (CONTINUED) 77
TABLE 6 (CONTINUED) 78
OTHER INTERNATIONAL ASPECTS 78
U.S. 78
Alternatives Research & Development Foundation 78
Institute for In Vitro Sciences, Inc. 79
International (Q)SAR Foundation to Reduce Animal Testing 80
Johns Hopkins Center for Alternatives to Animal Testing 81
Grants 81
Information 81
Workshops and Symposia 82
University of California at Davis Center for Animal Alternatives Information 82
EUROPE 83
ECVAM 83
JAPAN 84
Ministry of Health, Labour, and Welfare (MHLW) 84
National Institute of Health Sciences (NIHS) 84
JaCVAM 84
JaCVAM (Continued) 85
EUROPEAN BAN ON ANIMAL TESTING 86
PREDICTIVE TOXICOLOGY 87
TOXICOGENOMICS 87
MICROARRAYS 88
PROTEOMICS 88
METABOLOMICS 89
BIOINFORMATICS 89
COMPUTATIONAL TOXICOLOGY 90
Structure-Activity Relationships (SAR) 90
Physiologically Based Pharmacokinetic Models (PBPK) 91
Biologically Based Dose-Response (BBDR) Models 92
Computational Approaches to Predicting Metabolic Fate 92
Future Uses of Computational Toxicology 93
In Silico Modeling 94
TECHNOLOGY HURDLES 94
Standardization of Data Sets 95
Dynamic Complex Biological Processes 95
STATISTICAL TECHNIQUES FACE SOME IMPEDIMENTS 95
TOXICOGENOMICS TECHNIQUES FACE ECONOMIC REALITIES 96
IN VITRO TECHNOLOGY ADVANCES 96
ABSTRACTS 96
“Xenobiotic Metabolism Gene Expression in the EpiDerm In Citro 3-D Human Epidermis Model Compared to Human Skin” 96
“Altered Cytosolic Ca2+ Dynamics in Cultured Guinea pig Cardiomyocytes as an In Vitro Model to Identify Potential Cardiotoxicants” 97
“Cigarette Smoke Total Particulate Matter Increases Mucous Secreting Cell Numbers In Vitro: A Potential Model of Goblet Cell Hyperplasia” 98
“Validation of an In Vitro Screening Test for Predicting the Tumor-Promoting Potential of Chemicals Based on Gene Expression” 98
“An In Vitro Drug-Induced Hepatotoxicity Screening System Using CYP3A4-Expressing and ?-Glutamylcysteine Synthetase Knockdown Cells” 99
“In Vitro Assessment of Eye Irritancy Using the Reconstructed Human Corneal Epithelial SkinEthic HCE Model: Application to 435 Substances from Consumer Products Industry” 100
“Evaluation of EpiDerm Full Thickness-300 (EFT-300) as an In Vitro Model for Skin Irritation: Studies on Aliphatic Hydrocarbons” 101
“Novel Cultured Porcine Corneal Irritancy Assay with Reversibility Endpoint” 101
“Novel Cultured Porcine Corneal Irritancy Assay with Reversibility Endpoint” 102
“A Catch-Up Validation Study on Reconstructed Human Epidermis (SkinEthic RHE) for Full Replacement of the Draize Skin Irritation Test” 103
“Interlaboratory Evaluation of the Response of Primary Human Hepatocyte Cultures to Model CYP Inducers — A European Centre for Validation of Alternative Methods (ECVAM) — Funded Prevalidation Study” 104
“ECVAM’s Ongoing Activities in the Area of Acute Oral Toxicity” 105
“Genotoxicity Testing In Vitro — Development of a Higher-Throughput Analysis Method Based on the Comet Assay” 105
“Bringing Toxicology into the 21st Century: A Global Call to Action” 106
“Bringing Toxicology into (Continued) 107

Chapter-6: COMMERCIAL ASPECTS

MARKETS BY END USER 108
COSMETICS AND HOUSEHOLD PRODUCTS 109
PHARMACEUTICAL INDUSTRY 110
FOOD INDUSTRY 111
CHEMICALS INDUSTRY 112
TABLE 7 IN VITRO TOXICITY TESTING MARKET BY INDUSTRY SECTOR, THROUGH 2015 ($ MILLIONS) 113
MARKETS BY TECHNOLOGY 113
MARKETS BY TECHNOLOGY (CONTINUED) 114
MARKETS BY TECHNOLOGY (CONTINUED) 115
TABLE 8 WORLD IN VITRO TOXICOLOGY MARKET, THROUGH 2015 ($ MILLIONS) 116
MARKET BY COUNTRY 116
U.S. 116
TABLE 9 U.S. IN VITRO TOXICOLOGY MARKET, THROUGH 2015 ($ MILLIONS) 116
TABLE 10 COMPANIES IN THE U.S. IN VITRO TOXICITY MARKETPLACE 117
EUROPE 117
Germany 118
TABLE 11 GERMAN IN VITRO TOXICOLOGY MARKET, THROUGH 2015 ($ MILLIONS) 118
United Kingdom 118
TABLE 12 U.K. IN VITRO TOXICOLOGY MARKET, THROUGH 2015 ($ MILLIONS) 118
France 119
TABLE 13 FRENCH IN VITRO TOXICOLOGY MARKET, THROUGH 2015 ($ MILLIONS) 119
Italy 119
TABLE 14 ITALIAN IN VITRO TOXICOLOGY MARKET, THROUGH 2015 ($ MILLIONS) 120
Spain 120
TABLE 15 SPANISH IN VITRO TOXICOLOGY MARKET, THROUGH 2015 ($ MILLIONS) 120
JAPAN 120
TABLE 16 JAPANESE IN VITRO TOXICOLOGY MARKET, THROUGH 2015 ($ MILLIONS) 121
INDIA 121
TABLE 17 INDIAN IN VITRO TOXICOLOGY MARKET, THROUGH 2015 ($ MILLIONS) 121
CHINA 121
TABLE 18 CHINESE IN VITRO TOXICOLOGY MARKET, THROUGH 2015 ($ MILLIONS) 122
REST OF WORLD 122
TABLE 19 REST-OF-WORLD IN VITRO TOXICOLOGY MARKET, THROUGH 2015 ($ MILLIONS) 122
PATENT ASPECTS 123
TABLE 20 U.S. PATENTS ISSUED FOR IN VITRO TOXICITY RESEARCH 123
TABLE 20 (CONTINUED) 124
TABLE 20 (CONTINUED) 125
RECENT PATENT ACTIVITY 125
TABLE 21 RECENTLY ISSUED PATENTS 126

Chapter-7: THE TOXICOLOGY INDUSTRY

STRUCTURE 127
CROS 127
TABLE 22 COMPANIES OFFERING IN VITRO TOXICITY TESTING SERVICES 128
TABLE 22 (CONTINUED) 129
TABLE 22 (CONTINUED) 130
TABLE 22 (CONTINUED) 131
COMPANY PROFILES 131
ACCELRYS SOFTWARE, INC. 131
APREDICA 132
BIO-RAD LABORATORIES 133
BIORELIANCE INVITROGEN BIOSERVICES 133
CEETOX, INC. 134
CELSIS INTERNATIONAL, LTD. 134
CHARLES RIVER LABORATORIES INTERNATIONAL, INC. 135
COVANCE, INC. 136
ENTELOS, INC. 136
TOXICOGENOMICS 137
EPITHELIX SÀRL 137
FLUOFARMA 138
GENEGO, INC. 138
GENE LOGIC, INC. 139
HTG, INC. 140
ICONIX BIOSCIENCES, INC. 141
INTERTEK INTERNATINAL, LTD. 141
INVITROGEN 142
IN VITRO INTERNATIONAL 143
IN VITRO TECHNOLOGIES 143
MATTEK CORPORATION 144
MOLECULAR TOXICOLOGY, INC. 145
MB RESEARCH LABORATORIES 146
RTI HEALTH SOLUTIONS 146
SBW, LTD. 147
SMITHERS GROUP 148
STRATICELL 149
TECAN GROUP AG 150
XENOBIOTIC DETECTION SYSTEMS (XDS) 151
XENOMETRIX 152

Chapter-8: APPENDIX

APPENDIX 153
GLOSSARY 153