Vaccines. From Concept To Clinic

Lawrence C. Paoletti, Pamela McInnes9780849311680, 0-8493-1168-3

Designed with academic vaccine researchers in mind, this book presents a road map of how a vaccine develops from an idea in a researcher’s imagination, to the lab bench, through preclinical evaluation, and into the clinic for safety and immunogenicity. The result of the editors’ own efforts to glean practical information on the steps necessary to manufacture, bottle, and test their vaccines for clinical trials, this book provides answers to researcher questions such as:oHow do I identify antigens that would produce effective vaccines?oCan I produce a clinical lot of vaccine in my laboratory?oHow should a vaccine be bottled?oWhich FDA expectations must I meet?oWhat is an IND application and how do I file it?oWhich CFRs apply to production of a vaccine?

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Table of contents :
Frontmatter……Page 2
About the Editors……Page 5
Foreword……Page 6
Preface……Page 9
Contributors……Page 11
Table of Contents……Page 13
IDENTIFICATION OF THE DISEASES FOR WHICH VACCINES ARE NEEDED……Page 14
Live Attenuated Vaccines……Page 15
Subunit Vaccines……Page 17
IDENTIFICATION AND SELECTION OF PROTECTIVE ANTIGENS……Page 19
ANIMAL MODELS AND VACCINE DELIVERY……Page 21
WHAT TYPE(S) OF IMMUNE RESPONSES?……Page 22
REFERENCES……Page 25
Animal Models and Animal Test Systems……Page 31
Selecting an Animal Species for Use……Page 33
Nonhuman Primates in Vaccine Development……Page 34
ANIMAL CARE CONSIDERATIONS……Page 35
USE OF RODENTS AS ANIMAL MODELS……Page 36
Infectious Challenge……Page 37
Immunologic Considerations……Page 38
NONHUMAN PRIMATE MODELS TO EVALUATE VACCINE IMMUNOGENICITY……Page 40
Considerations for Employing Primate Species……Page 41
Nonhuman Primates as Models for Infectious Diseases……Page 42
Comparative Immunology and Reproductive Physiology……Page 43
ENDOGENOUS AGENTS AS RISK FACTORS FOR ANIMAL MODELS……Page 45
OPTIMIZATION AND ALTERNATIVES TO THE USE OF ANIMALS……Page 46
REFERENCES……Page 48
PURPOSE OF ASSAY STANDARDIZATION AND VALIDATION……Page 55
SELECTION OF SEROLOGIC METHODS……Page 57
ASSAY DESIGN CONSIDERATIONS……Page 59
Antigens……Page 60
SERA……Page 63
Reference Standard Serum……Page 66
Quality Control Sera……Page 68
Subject Sera……Page 69
ASSAY CONDITIONS……Page 71
CORRELATIONS OF IMMUNOASSAYS TO FUNCTIONAL ASSAYS……Page 73
CONCLUSIONS……Page 75
REFERENCES……Page 76
INTRODUCTION……Page 88
GENERATING A LOT OF VACCINE FOR A PHASE 1 CLINICAL TRIAL……Page 89
Quantity……Page 91
Formulation……Page 92
Container Size/Doses……Page 93
Stability……Page 94
Vaccine Preparation……Page 95
SUMMARY AND SUBMISSION OF IND APPLICATION……Page 96
ACKNOWLEDGMENTS……Page 97
REFERENCES……Page 98
CLINICAL TRIAL DEFINITIONS……Page 99
PROCEDURES AND REQUIREMENTS FOR FILING AN IND APPLICATION……Page 100
SOURCES OF INFORMATION……Page 101
PREPARING THE IND APPLICATION……Page 102
INVESTIGATOR’S BROCHURE……Page 105
(a) Study Protocol……Page 106
(b) Investigator Data, (c) Facilities Data, and (d) Institutional Review Board Data……Page 109
CHEMISTRY, MANUFACTURING, AND CONTROL DATA……Page 113
PREVIOUS HUMAN EXPERIENCE AND ADDITIONAL INFORMATION……Page 115
COMPLETING THE IND FORM……Page 116
INTRODUCTION……Page 117
IND CONTENT AND FORMAT: ORIGINAL SUBMISSION……Page 118
Manufacturing Information……Page 121
2. General Safety……Page 122
Product Characterization……Page 123
Lot Release……Page 124
Safety and Toxicity Studies……Page 125
CLINICAL TRIALS……Page 126
Overview of the IND Process……Page 127
Clinical Hold……Page 128
Safety Reports……Page 129
Manufacturing……Page 130
Protocols……Page 131
Guidance Documents……Page 132
1. Pre-IND Meetings……Page 133
2. Other Meetings……Page 134
REFERENCES……Page 135
INTRODUCTION……Page 137
POLICIES AND LAWS AFFECTING TECHNOLOGY TRANSFER……Page 138
THE MECHANISMS OF TECHNOLOGY TRANSFER……Page 140
MATERIAL TRANSFER AGREEMENTS (MTAs)……Page 142
SPONSORED-RESEARCH AGREEMENT……Page 143
COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT (CRADA)……Page 145
INVENTIONS……Page 148
INVENTORSHIP……Page 149
PATENTS……Page 150
Enabling:……Page 152
THE PATENT PROCESS……Page 154
PROVISIONAL APPLICATION……Page 156
EFFECTS OF PUBLIC DISCLOSURES ON PATENTS……Page 157
RECORD KEEPING……Page 158
INVENTION RIGHTS……Page 159
LICENSING……Page 160
ROYALTY AND EQUITY……Page 163
FEDERAL TECHNOLOGY PROGRAMS……Page 164
TECHNOLOGY TRANSFER OFFICES……Page 165
CONCLUSION……Page 167
Appendix A: Technology Transfer Terminology……Page 168
Appendix B: Material Transfer Agreement (Provider)……Page 172
Materials Receipt Agreement……Page 175
Appendix C……Page 177
Appendix D: Small-Business Innovation Research (SBIR) Program……Page 179
Appendix E: Small Business Technology Transfer Research (STTR) Program……Page 181
REFERENCES……Page 182
IDENTIFICATION OF TRANSMISSION-BLOCKING TARGET ANTIGENS……Page 185
ISOLATION OF THE GENE ENCODING Pfs25……Page 186
INDUSTRIAL COLLABORATION……Page 187
Subunit Approaches……Page 188
Good Manufacturing Practices……Page 189
THE FUTURE: PRIME-BOOST AND FUSION PROTEINS……Page 190
REFERENCES……Page 191
Malignant Transformation of Cultured Cells with Human Adenovirus and Herpes Simplex Virus……Page 193
MOTIVATIONS FOR AND PROBLEMS IN THE DEVELOPMENT OF A LIVE VARICELLA VACCINE……Page 194
PRIMARY ISOLATION OF VACCINE VIRUS……Page 195
RATIONALE FOR AND DESIGN OF A LIVE VARICELLA VACCINE……Page 196
CLINICAL TRIALS WITH VACCINES PREPARED IN HUMAN DIPLOID CELLS……Page 197
VACCINATION OF CHILDREN WITH MALIGNANT DISEASES……Page 198
VIEWPOINTS REGARDING LIVE VARICELLA VACCINE AFTER INITIAL CLINICAL TRIALS……Page 199
CLINICAL VACCINE TRIALS IN THE UNITED STATES AND EUROPE……Page 200
DETECTION OF VIREMIA BEFORE AND AT THE ONSET OF CHICKENPOX: HERPES ZOSTER AND VARICELLA VACCINE……Page 201
FURTHER CLINICAL STUDIES IN THE UNITED STATES PARTICULARLY ON THE INCIDENCE OF ZOSTER AFTER VACCINATION……Page 203
REFERENCES……Page 204
Acronyms and Abbreviations……Page 209