{"product_id":"nonclinical-safety-assessment-isbn-9780470745915","title":"Nonclinical Safety Assessment","description":"\u003cb\u003eNonclinical Safety Assessment\u003c\/b\u003e \u003cp\u003e\u003cb\u003eNonclinical Safety Assessment \u003c\/b\u003e \u003c\/p\u003e\u003cp\u003e\u003ci\u003eA Guide to International Pharmaceutical Regulations \u003c\/i\u003e  \u003c\/p\u003e\u003cp\u003eBringing a new drug to market is a costly time-consuming process. Increased regional and international regulation over the last twenty years, while necessary, has only served to amplify these costs. In response to this escalation, developmental strategies have shifted towards a more global approach. In order to create the most cost-effective and safe processes, it is critical for those bringing drugs to market to understand both the globally accepted regulations and the local variations. \u003ci\u003eNonclinical Safety Assessment: A Guide to International Pharmaceutical Regulations\u003c\/i\u003e provides a practical description of nonclinical drug development regulations and requirements in the major market regions.  \u003c\/p\u003e\u003cp\u003eIt includes:  \u003c\/p\u003e\u003cul\u003e\n\u003cli\u003eICH – the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use\u003c\/li\u003e \u003cli\u003eNational regulations, including US FDA, Canada, Mercosur and Brazil, South Africa, China, Japan, India and Australia\u003c\/li\u003e \u003cli\u003eRepeated dose toxicity studies\u003c\/li\u003e \u003cli\u003eCarcinogenicity; Genotoxicity; Developmental and reproductive toxicology; Immunotoxicology\u003c\/li\u003e \u003cli\u003eBiotechnology-derived pharmaceuticals\u003c\/li\u003e \u003cli\u003eVaccine development\u003c\/li\u003e \u003cli\u003ePhototoxicity and photocarcinogenicity\u003c\/li\u003e \u003cli\u003eDegradants, impurities, excipients and metabolites\u003c\/li\u003e\n\u003c\/ul\u003e \u003cp\u003e Primarily intended for those professionals actively involved in the nonclinical and clinical development of a pharmaceutical product, including toxicologists, pharmacologists, clinicians and project managers, this book provides a roadmap for successful new drug approval and marketing.  \u003c\/p\u003e\u003cp\u003eList of Contributors xvii\u003c\/p\u003e \u003cp\u003ePreface xix\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart I International Regulations and Nonclinical Studies for Pharmaceuticals 1\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e1 Introduction 3\u003c\/b\u003e\u003cbr\u003e \u003ci\u003eKathy M. McGown and William J. Brock\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e1.1 The Global Pharmaceutical Market 6\u003c\/p\u003e \u003cp\u003e1.2 Looking to the Future 9\u003c\/p\u003e \u003cp\u003e1.3 Legal and Regulatory Considerations in Drug Development 10\u003c\/p\u003e \u003cp\u003e1.4 The Drug Development Process – General Considerations 12\u003c\/p\u003e \u003cp\u003e\u003cb\u003e2 ICH: History and Nonclinical Guidances 17\u003c\/b\u003e\u003cbr\u003e \u003ci\u003eJan-Willem van der Laan and Kenneth L. Hastings\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e2.1 Introduction 17\u003c\/p\u003e \u003cp\u003e2.2 Organization of the ICH 19\u003c\/p\u003e \u003cp\u003e2.3 The ICH Process 20\u003c\/p\u003e \u003cp\u003e2.4 Animal Welfare and Alternative Methods 22\u003c\/p\u003e \u003cp\u003e2.5 ICH M3 23\u003c\/p\u003e \u003cp\u003e2.6 New Initiatives and Topics 24\u003c\/p\u003e \u003cp\u003e\u003cb\u003e3 Food and Drug Administration: Nonclinical Program and Pharmaceutical Approval 27\u003c\/b\u003e\u003cbr\u003e \u003ci\u003eWilliam J. Brock and Kenneth L. Hastings\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e3.1 Legislative Authority of the FDA 27\u003c\/p\u003e \u003cp\u003e3.2 Nonclinical Drug Development and the FDA 31\u003c\/p\u003e \u003cp\u003e3.3 Nonclinical Testing: General Conditions and Considerations 34\u003c\/p\u003e \u003cp\u003e3.4 Toxicity Testing: Small Molecules and Traditional Pharmaceuticals 34\u003c\/p\u003e \u003cp\u003e3.5 Toxicity Testing of Pharmaceuticals – The General Approach 35\u003c\/p\u003e \u003cp\u003e3.6 First-in-Human Dosing: Results from Nonclinical Studies 37\u003c\/p\u003e \u003cp\u003e\u003cb\u003e4 Nonclinical Pharmaceutical Development in MERCOSUR and Brazil 41\u003c\/b\u003e\u003cbr\u003e \u003ci\u003eCristiana Leslie Corr^ea, Giuliana Selmi, and Flavio Ailton Duque Zambrone\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e4.1 Introduction 41\u003c\/p\u003e \u003cp\u003e4.2 MERCOSUR 41\u003c\/p\u003e \u003cp\u003e4.3 Brazil 44\u003c\/p\u003e \u003cp\u003e\u003cb\u003e5 Nonclinical Safety Assessment: Canada 57\u003c\/b\u003e\u003cbr\u003e \u003ci\u003eJamie L. Doran and Mark T. Goldberg\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e5.1 Introduction 57\u003c\/p\u003e \u003cp\u003e5.2 Organization of Health Canada 58\u003c\/p\u003e \u003cp\u003e5.3 The Regulatory Framework for Drug Approval in Canada 60\u003c\/p\u003e \u003cp\u003e5.4 Nonclinical Assessment in Canada 64\u003c\/p\u003e \u003cp\u003e5.5 Clinical Trial Applications 70\u003c\/p\u003e \u003cp\u003e5.6 Special Regulatory Considerations 74\u003c\/p\u003e \u003cp\u003e\u003cb\u003e6 European Pharmaceutical Regulation – Nonclinical Testing Requirements 79\u003c\/b\u003e\u003cbr\u003e \u003ci\u003eAdam Woolley and Jan Willem van der Laan\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e6.1 Introduction 79\u003c\/p\u003e \u003cp\u003e6.2.1 Overview 82\u003c\/p\u003e \u003cp\u003e6.3 Nonclinical Testing in the Support of Clinical Trials 86\u003c\/p\u003e \u003cp\u003e6.4 Overview 96\u003c\/p\u003e \u003cp\u003e7 South Africa 99\u003cbr\u003e Fariza Feraoun and Malik Feraoun\u003c\/p\u003e \u003cp\u003e7.1 Introduction 99\u003c\/p\u003e \u003cp\u003e7.2 Country Information 100\u003c\/p\u003e \u003cp\u003e7.3 The Regulatory Aspects 101\u003c\/p\u003e \u003cp\u003e7.4 The Nonclinical Safety Assessment 109\u003c\/p\u003e \u003cp\u003e7.5 Conclusion 114\u003c\/p\u003e \u003cp\u003e\u003cb\u003e8 Asia Pacific: China 117\u003c\/b\u003e\u003cbr\u003e \u003ci\u003eLijie Fu and Qingli Wang\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e8.1 Introduction 117\u003c\/p\u003e \u003cp\u003e8.2 History of Drug Administration 118\u003c\/p\u003e \u003cp\u003e8.3 The Provisions for Drug Registration 122\u003c\/p\u003e \u003cp\u003e8.4 The SFDA 123\u003c\/p\u003e \u003cp\u003e8.5 The SFDA Affiliated Organizations 123\u003c\/p\u003e \u003cp\u003e8.6 General Registration Procedures 125\u003c\/p\u003e \u003cp\u003e8.7 Pharmaceutical Application 125\u003c\/p\u003e \u003cp\u003e8.8 Import Drug Application 127\u003c\/p\u003e \u003cp\u003e8.9 Testing Guidelines and Safety Evaluation 129\u003c\/p\u003e \u003cp\u003e8.10 GLP Compliance in China 131\u003c\/p\u003e \u003cp\u003e8.11 Animal Welfare Requirements 133\u003c\/p\u003e \u003cp\u003e\u003cb\u003e9 Pharmaceutical Regulations for Nonclinical Safety Assessment in Japan 135\u003c\/b\u003e\u003cbr\u003e \u003ci\u003eKazuichi Nakamura and Osamu Fueki\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e9.1 History of Regulation for Nonclinical Safety Assessment in Japan 135\u003c\/p\u003e \u003cp\u003e9.2 Approval Application of New Drugs in Japan 136\u003c\/p\u003e \u003cp\u003e9.3 Current Nonclinical Safety Guidelines Available in Japan 139\u003c\/p\u003e \u003cp\u003e9.4 Current Trends of Conduct of Nonclinical Safety Evaluation in Japan 139\u003c\/p\u003e \u003cp\u003e9.5 Safety Assessment of Unapproved Drugs 142\u003c\/p\u003e \u003cp\u003e9.6 Necessity of 3Rs (Reduction\/Refinement\/Replacement) of Animal Studies 142\u003c\/p\u003e \u003cp\u003e9.7 Attitude of Japanese Pharmaceutical Companies and the Regulatory Agency toward Nonclinical Safety Assessment 142\u003c\/p\u003e \u003cp\u003e\u003cb\u003e10 Indian Regulatory Process for Nonclinical Drug Development 145\u003c\/b\u003e\u003cbr\u003e \u003ci\u003eK.S. Rao and S. Natesan\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e10.1 Introduction 145\u003c\/p\u003e \u003cp\u003e10.2 Drug Development 146\u003c\/p\u003e \u003cp\u003e10.3 Quality Systems 147\u003c\/p\u003e \u003cp\u003e10.4 Nonclinical Drug Development – Key Regulatory Requirements 148\u003c\/p\u003e \u003cp\u003e10.5 Nonclinical Safety Assessment – Key Approval Requirements 149\u003c\/p\u003e \u003cp\u003e10.6 Data Required for Clinical Study Approval 151\u003c\/p\u003e \u003cp\u003e10.7 Animal Toxicology 154\u003c\/p\u003e \u003cp\u003e10.8 Animal Pharmacology 166\u003c\/p\u003e \u003cp\u003e10.9 Safety Assessment Requirements: Indian Schedule Yand International Guidelines 168\u003c\/p\u003e \u003cp\u003e10.10 Good Laboratory Practice Quality System in India 168\u003c\/p\u003e \u003cp\u003e10.11 Safety Assessment Test Facilities in India 171\u003c\/p\u003e \u003cp\u003e10.12 Investigational New Drug Application for Undertaking Clinical Trials 173\u003c\/p\u003e \u003cp\u003e\u003cb\u003e11 Asia Pacific: Australia 175\u003c\/b\u003e\u003cbr\u003e \u003ci\u003eDouglas Francis\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e11.1 Introduction 175\u003c\/p\u003e \u003cp\u003e11.2 Australian Therapeutic Goods Administration (TGA) 176\u003c\/p\u003e \u003cp\u003e11.3 Clinical Trials in Australia 183\u003c\/p\u003e \u003cp\u003e11.4 Nonclinical Data to Support the Conduct of Clinical Trials in Australia and Marketing Application to the TGA 188\u003c\/p\u003e \u003cp\u003ePart II Toxicology Studies Supporting Clinical Development 197\u003c\/p\u003e \u003cp\u003e12 Repeated-Dose Toxicity Studies in Nonclinical Drug Development 199\u003cbr\u003e Shana Azri-Meehan and Louise Latriano\u003c\/p\u003e \u003cp\u003e12.1 Introduction 199\u003c\/p\u003e \u003cp\u003e12.2 General Considerations 200\u003c\/p\u003e \u003cp\u003e12.3 Study Design Considerations 205\u003c\/p\u003e \u003cp\u003e12.4 Study Observations and Assessments 211\u003c\/p\u003e \u003cp\u003e\u003cb\u003e13 Evaluation of Potential Carcinogenicity 219\u003c\/b\u003e\u003cbr\u003e \u003ci\u003eJames A. Popp and Matthew S. Bogdanffy\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e13.1 Introduction 219\u003c\/p\u003e \u003cp\u003e13.2 Preparation for the Carcinogenicity Study 223\u003c\/p\u003e \u003cp\u003e13.3 Elements of the Protocol\/Study Plan 228\u003c\/p\u003e \u003cp\u003e13.4 Study Performance 241\u003c\/p\u003e \u003cp\u003e13.5 Alternative Models to Evaluate Potential Carcinogenicity in Lieu of a 2-Year Mouse Study 244\u003c\/p\u003e \u003cp\u003e13.6 Special Consideration for Carcinogenicity Evaluation of Biotherapeutics 247\u003c\/p\u003e \u003cp\u003e13.7 Regulatory Implications of a Study Identifying an Animal Carcinogenic Response 248\u003c\/p\u003e \u003cp\u003e13.8 Interpreting the Relevance of Positive Results for Human Safety 249\u003c\/p\u003e \u003cp\u003e13.9 Communicating the Results in the Product Label 251\u003c\/p\u003e \u003cp\u003e\u003cb\u003e14 Genetic Toxicology 255\u003c\/b\u003e\u003cbr\u003e \u003ci\u003eMark W. Powley\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e14.1 Background 255\u003c\/p\u003e \u003cp\u003e14.2 Regulations Guiding Drug Development 256\u003c\/p\u003e \u003cp\u003e14.3 Genotoxic Impurities 261\u003c\/p\u003e \u003cp\u003e14.4 Regulatory Decision Making 263\u003c\/p\u003e \u003cp\u003e\u003cb\u003e15 Developmental and Reproductive Toxicology 265\u003c\/b\u003e\u003cbr\u003e \u003ci\u003eRobert M. Parker and Raymond G. York\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e15.1 Introduction 265\u003c\/p\u003e \u003cp\u003e15.2 Standard Reproduction and Developmental Toxicity Study Designs 266\u003c\/p\u003e \u003cp\u003e15.3 Timing of Preclinical Developmental and Reproductive Toxicity Studies 273\u003c\/p\u003e \u003cp\u003e15.4 Based on Disease Indication 275\u003c\/p\u003e \u003cp\u003e15.5 Based on Pharmaceutical Characteristic 279\u003c\/p\u003e \u003cp\u003e15.6 Other Reasons to Conduct Preclinical Reproductive and Developmental Toxicity Studies 291\u003c\/p\u003e \u003cp\u003e15.7 Excipients 293\u003c\/p\u003e \u003cp\u003e15.8 Conclusion 293\u003c\/p\u003e \u003cp\u003e\u003cb\u003e16 Juvenile Animal Toxicity Studies: Regulatory Expectations, Decision Strategies and Role in Paediatric Drug Development 297\u003c\/b\u003e\u003cbr\u003e \u003ci\u003eMelissa S. Tassinari, Luc M. De Schaepdrijver, and Mark E. Hurtt\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e16.1 Introduction 297\u003c\/p\u003e \u003cp\u003e16.2 Regulatory Environment 298\u003c\/p\u003e \u003cp\u003e16.3 Relevance and Place in Drug Development 302\u003c\/p\u003e \u003cp\u003e16.4 Strategies for Decision Making: When are Studies Needed and Appropriate? 304\u003c\/p\u003e \u003cp\u003e16.5 Case Studies: Application of Data Review and Decision Making 307\u003c\/p\u003e \u003cp\u003e16.6 Summary 309\u003c\/p\u003e \u003cp\u003e\u003cb\u003e17 Immunotoxicology 313\u003c\/b\u003e\u003cbr\u003e \u003ci\u003eLeigh Ann Burns-Naas and Marc J. Pallardy\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e17.1 Introduction 313\u003c\/p\u003e \u003cp\u003e17.2 Regulatory Expectations for the Immunotoxicology Evaluation of Pharmaceuticals 314\u003c\/p\u003e \u003cp\u003e17.3 Special Considerations 335\u003c\/p\u003e \u003cp\u003e17.4 Summary 342\u003c\/p\u003e \u003cp\u003eReferences 342\u003c\/p\u003e \u003cp\u003e\u003cb\u003e18 Nonclinical Safety Assessment: Biotechnology-Derived Pharmaceuticals 347\u003c\/b\u003e\u003cbr\u003e \u003ci\u003eChristopher E. Ellis, Melanie T. Hartsough, Martin D. Green, and Hanan Ghantous\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e18.1 Introduction 347\u003c\/p\u003e \u003cp\u003e18.2 Unique Characteristics of Biopharmaceuticals 348\u003c\/p\u003e \u003cp\u003e18.3 Species Selection 349\u003c\/p\u003e \u003cp\u003e18.4 Immunogenicity 356\u003c\/p\u003e \u003cp\u003e18.5 Biological Activity\/Pharmacodynamics 358\u003c\/p\u003e \u003cp\u003e18.6 Pharmacokinetics\/Toxicokinetics 359\u003c\/p\u003e \u003cp\u003e18.7 Nonclinical Safety Assessment 362\u003c\/p\u003e \u003cp\u003e18.8 Tissue Cross-Reactivity (TCR) 371\u003c\/p\u003e \u003cp\u003e18.9 Clinical Starting Dose Selection for Biopharmaceuticals 373\u003c\/p\u003e \u003cp\u003e18.10 Comparability 375\u003c\/p\u003e \u003cp\u003e\u003cb\u003e19 International Safety Regulations for Vaccine Development 381\u003c\/b\u003e\u003cbr\u003e \u003ci\u003eRobert V. House\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e19.1 Introduction 381\u003c\/p\u003e \u003cp\u003e19.2 What \"Toxicities\" have been Attributed to Vaccination? 381\u003c\/p\u003e \u003cp\u003e19.3 How Vaccines are (Slightly) Different from Other Biopharmaceuticals 383\u003c\/p\u003e \u003cp\u003e19.4 Regulatory Framework for Assessing Safety of Vaccines 383\u003c\/p\u003e \u003cp\u003e19.5 Parameters Monitored 387\u003c\/p\u003e \u003cp\u003e19.6 Clinical Safety Assessment of Vaccines 389\u003c\/p\u003e \u003cp\u003e19.7 Summary 390\u003c\/p\u003e \u003cp\u003e\u003cb\u003e20 Phototoxicity and Photocarcinogenicity 393\u003c\/b\u003e\u003cbr\u003e \u003ci\u003eRobert E. Osterberg, Christopher P. Sambuco, and Paul Donald Forbes\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e20.1 History of Phototoxicity, Photocarcinogenicity and Photogenotoxicity Testing at the US Food and Drug Administration (FDA) 393\u003c\/p\u003e \u003cp\u003e20.2 FDA Photosafety Testing Guidance 397\u003c\/p\u003e \u003cp\u003e20.3 Status of In Vivo Testing for Photocarcinogenesis 417\u003c\/p\u003e \u003cp\u003e20.4 Photocarcinogenesis Study Designs 418\u003c\/p\u003e \u003cp\u003e20.5 Photo Co-Carcinogenesis 418\u003c\/p\u003e \u003cp\u003e20.6 Future Testing Concepts, with Emphasis on Biomarkers 423\u003c\/p\u003e \u003cp\u003e\u003cb\u003e21 Degradants, Impurities, Excipients and Metabolites 431\u003c\/b\u003e\u003cbr\u003e \u003ci\u003eRobert E. Osterberg and Mark W. Powley\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e21.1 Degradants, Impurities, and Excipients 431\u003c\/p\u003e \u003cp\u003e21.2 Metabolites 442\u003c\/p\u003e \u003cp\u003eReferences 446\u003c\/p\u003e \u003cp\u003eIndex 449\u003c\/p\u003e  \u003cp\u003e“As a toxicologist with a quarter-century of experience in pharmaceutical drug development, I found the reading of this book thoroughly enjoyable and useful.”  (\u003ci\u003eBritish Toxicology Society Newsletter\u003c\/i\u003e, 1 October 2013)\u003c\/p\u003e \u003cp\u003e\u003cb\u003eEditors \u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e William J. Brock \u003ci\u003eBrock Scientific Consulting, Montgomery Village, USA \u003c\/i\u003e \u003c\/p\u003e\u003cp\u003e\u003cb\u003eKenneth L. Hastings\u003c\/b\u003e \u003ci\u003eSanofi, Bethesda, USA \u003c\/i\u003e \u003c\/p\u003e\u003cp\u003e\u003cb\u003eKathy M. McGown\u003c\/b\u003e \u003ci\u003eFoxKiser, USA\u003c\/i\u003e  \u003c\/p\u003e\u003cp\u003e\u003cb\u003eNonclinical Safety Assessment \u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003ci\u003eA Guide to International Pharmaceutical Regulations \u003c\/i\u003e  \u003c\/p\u003e\u003cp\u003eBringing a new drug to market is a costly time-consuming process. Increased regional and international regulation over the last twenty years, while necessary, has only served to amplify these costs. In response to this escalation, developmental strategies have shifted towards a more global approach. In order to create the most cost-effective and safe processes, it is critical for those bringing drugs to market to understand both the globally accepted regulations and the local variations. \u003ci\u003eNonclinical Safety Assessment: A Guide to International Pharmaceutical Regulations\u003c\/i\u003e provides a practical description of nonclinical drug development regulations and requirements in the major market regions.  \u003c\/p\u003e\u003cp\u003eIt includes:  \u003c\/p\u003e\u003cul\u003e\n\u003cli\u003eICH – the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use\u003c\/li\u003e \u003cli\u003eNational regulations, including US FDA, Canada, Mercosur and Brazil, South Africa, China, Japan, India and Australia\u003c\/li\u003e \u003cli\u003eRepeated dose toxicity studies\u003c\/li\u003e \u003cli\u003eCarcinogenicity; Genotoxicity; Developmental and reproductive toxicology; Immunotoxicology\u003c\/li\u003e \u003cli\u003eBiotechnology-derived pharmaceuticals\u003c\/li\u003e \u003cli\u003eVaccine development\u003c\/li\u003e \u003cli\u003ePhototoxicity and photocarcinogenicity\u003c\/li\u003e \u003cli\u003eDegradants, impurities, excipients and metabolites\u003c\/li\u003e\n\u003c\/ul\u003e \u003cp\u003e Primarily intended for those professionals actively involved in the nonclinical and clinical development of a pharmaceutical product, including toxicologists, pharmacologists, clinicians and project managers, this book provides a roadmap for successful new drug approval and marketing.\u003c\/p\u003e","brand":"Wiley","offers":[{"title":"Default Title","offer_id":47989694824677,"sku":"NP9780470745915","price":186.95,"currency_code":"USD","in_stock":false}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/1842\/7735\/files\/9780470745915.jpg?v=1761785134","url":"https:\/\/k12savings.com\/products\/nonclinical-safety-assessment-isbn-9780470745915","provider":"K12savings","version":"1.0","type":"link"}