Vaccines : from concept to clinic : a guide to the development and clinical testing of vaccines for human use

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? 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 The identification of vaccine targets is a complex endeavor that requires a multidisciplinary approach that involves epidemiological analyses to identify the diseases for which vaccines are needed, a market analysis to verify whether the developed vaccines will be commercially viable, and a feasibility study to ascertain whether the vaccine development is feasible with the technologies and the knowledge available. Describes how a vaccine is taken from an idea in a researcher's imagination to the lab bench through preclinical evaluation, into the clinic for safety immunogenicity and efficacy, and ultimately to commercialization as a licensed product. For clinicians and researchers.