Details

Biopharmaceuticals

Biochemistry and Biotechnology
2. Aufl.

von: Gary Walsh
103,95 €
Verlag:	Wiley-Blackwell
Format:	PDF
Veröffentl.:	08.02.2006
ISBN/EAN:	9780470868393
Sprache:	englisch
Anzahl Seiten:	576

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Beschreibungen

Titelbeschreibung

The latest edition of this highly acclaimed textbook, provides a comprehensive and up-to-date overview of the science and medical applications of biopharmaceutical products. Biopharmaceuticals refers to pharmaceutical substances derived from biological sources, and increasingly, it is synonymous with 'newer' pharmaceutical substances derived from genetic engineering or hybridoma technology. This superbly written review of the important areas of investigation in the field, covers drug production, plus the biochemical and molecular mechanisms of action together with the biotechnology of major biopharmaceutical types on the market or currently under development. There is also additional material reflecting both the technical advances in the area and detailed information on key topics such as the influence of genomics on drug discovery.

Inhaltsverzeichnis

Preface xvii Chapter 1 Pharmaceuticals, biologics and biopharmaceuticals 1 Introduction to pharmaceutical products 1 Biopharmaceuticals and pharmaceutical biotechnology 1 History of the pharmaceutical industry 3 The age of biopharmaceuticals 5 Biopharmaceuticals: current status and future prospects 8 Traditional pharmaceuticals of biological origin 12 Pharmaceuticals of animal origin 13 The sex hormones 14 The androgens 14 Oestrogens 15 Progesterone and progestogens 17 Corticosteroids 19 Catecholamines 21 Prostaglandins 23 Pharmaceutical substances of plant origin 27 Alkaloids 28 Atropine and scopalamine 28 Morphine and cocaine 29 Additional plant alkaloids 30 Ergot alkaloids 30 Flavonoids, xanthines and terpenoids 30 Cardiac glycosides and coumarins 33 Aspirin 33 Pharmaceutical substances of microbial origin 33 The macrolides and ansamycins 38 Peptide and other antibiotics 39 Conclusion 39 Further reading 40 Chapter 2 The drug development process 43 Drug discovery 44 The impact of genomics and related technologies upon drug discovery 45 Gene chips 47 Proteomics 49 Structural genomics 50 Pharmacogenetics 51 Plants as a source of drugs 52 Microbial drugs 53 Rational drug design 54 Combinatorial approaches to drug discovery 56 Initial product characterization 57 Patenting 57 What is a patent and what is patentable? 57 Patent types 62 The patent application 63 Patenting in biotechnology 64 Delivery of biopharmaceuticals 66 Oral delivery systems 66 Pulmonary delivery 67 Nasal, transmucosal and transdermal delivery systems 68 Pre-clinical trials 69 Pharmacokinetics and pharmacodynamics 69 Toxicity studies 71 Reproductive toxicity and teratogenicity 71 Mutagenicity, carcinogenicity and other tests 72 Clinical trials 73 Clinical trial design 75 Trial size and study population 75 Randomized control studies 76 Additional trial designs 76 The role and remit of regulatory authorities 78 The Food and Drug Administration 78 The investigational new drug application 80 The new drug application 82 European regulations 84 National regulatory authorities 84 The EMEA and the new EU drug approval systems 85 The centralized procedure 86 Mutual recognition 88 Drug registration in Japan 88 World harmonization of drug approvals 89 Conclusion 89 Further reading 89 Chapter 3 The drug manufacturing process 93 International pharmacopoeia 93 Martindale, the Extra Pharmacopoeia 94 Guides to good manufacturing practice 94 The manufacturing facility 97 Clean rooms 98 Cleaning, decontamination and sanitation (CDS) 101 CDS of the general manufacturing area 102 CDS of process equipment 102 Water for biopharmaceutical processing 104 Generation of purified water and water for injections (WFI) 105 Distribution system for WFI 107 Documentation 109 Specifications 110 Manufacturing formulae, processing and packaging instructions 110 Records 111 Generation of manufacturing records 111 Sources of biopharmaceuticals 112 E. coli as a source of recombinant, therapeutic proteins 112 Expression of recombinant proteins in animal cell culture systems 116 Additional production systems: yeasts 116 Fungal production systems 117 Transgenic animals 118 Transgenic plants 122 Insect cell-based systems 123 Production of final product 124 Cell banking systems 127 Upstream processing 128 Microbial cell fermentation 129 Mammalian cell culture systems 133 Downstream processing 134 Final product formulation 140 Some influences that can alter the biological activity of proteins 142 Proteolytic degradation 143 Protein deamidation 144 Oxidation and disulphide exchange 145 Alteration of glycoprotein glycosylation patterns 147 Stabilizing excipients used in final product formulations 150 Final product fill 153 Freeze-drying 155 Labelling and packing 158 Analysis of the final product 159 Protein-based contaminants 159 Removal of altered forms of the protein of interest from the product stream 160 Product potency 161 Determination of protein concentration 163 Detection of protein-based product impurities 164 Capillary electrophoresis 166 High-pressure liquid chromatography (HPLC) 167 Mass spectrometry 168 Immunological approaches to detection of contaminants 168 Amino acid analysis 169 Peptide mapping 170 N-terminal sequencing 171 Analysis of secondary and tertiary structure 173 Endotoxin and other pyrogenic contaminants 173 Endotoxin, the molecule 174 Pyrogen detection 176 Dna 179 Microbial and viral contaminants 180 Viral assays 181 Miscellaneous contaminants 182 Validation studies 183 Further reading 185 Chapter 4 The cytokines —the interferon family 189 Cytokines 189 Cytokine receptors 194 Cytokines as biopharmaceuticals 195 The interferons 196 The biochemistry of interferon-a 197 Interferon-b 198 Interferon-g 198 Interferon signal transduction 198 The interferon receptors 199 The JAK–STAT pathway 199 The interferon JAK–STAT pathway 202 The biological effects of interferons 203 The eIF-2a protein kinase system 207 Interferon biotechnology 207 Production and medical uses of IFN-a 210 Medical uses of IFN-b 213 Medical applications of IFN-g 214 Interferon toxicity 216 Additional interferons 218 Conclusion 219 Further reading 219 Chapter 5 Cytokines: interleukins and tumour necrosis factor 223 Interleukin-2 (IL-2) 225 IL-2 production 228 IL-2 and cancer treatment 228 IL-2 and infectious diseases 230 Safety issues 231 Inhibition of IL-2 activity 231 Interleukin-1 (IL-1) 232 The biological activities of IL- 1 233 IL-1 biotechnology 234 Interleukin-3: biochemistry and biotechnology 235 Interleukin- 4 236 Interleukin- 6 238 Interleukin- 11 240 Interleukin- 5 241 Interleukin- 12 244 Tumour necrosis factors (TNFs) 246 TNF biochemistry 246 Biological activities of TNF-a 247 Immunity and inflammation 248 TNF receptors 249 TNF: therapeutic aspects 250 Further reading 252 Chapter 6 Haemopoietic growth factors 255 The interleukins as haemopoietic growth factors 257 Granulocyte colony stimulating factor (G-CSF) 258 Macrophage colony-stimulating factor (M-CSF) 259 Granulocyte-macrophage colony stimulating factor (GM-CSF) 259 Clinical application of CSFs 261 Leukaemia inhibitory factor (LIF) 263 Erythropoietin (EPO) 264 The EPO receptor and signal transduction 267 Regulation of EPO production 267 Therapeutic applications of EPO 268 Chronic disease and cancer chemotherapy 271 Additional non-renal applications 272 Tolerability 273 Thrombopoietin 273 Further reading 275 Chapter 7 Growth factors 277 Growth factors and wound healing 277 Insulin-like growth factors (IGFs) 279 IGF biochemistry 280 IGF receptors 280 IGF-binding proteins 282 Biological effects 282 IGF and fetal development 283 IGFs and growth 283 Renal and reproductive effects 284 Neuronal and other effects 285 Epidermal growth factor (EGF) 285 The EGF receptor 286 Platelet-derived growth factor (PDGF) 287 The PDGF receptor and signal transduction 288 PDGF and wound healing 289 Fibroblast growth factors (FGFs) 289 Transforming growth factors (TGFs) 290 TGF-a 290 TGF-b 292 Neurotrophic factors 293 The neurotrophins 294 Neurotrophin receptors 296 The neurotrophin low-affinity receptor 297 Ciliary neurotrophic factor and glial cell line-derived neurotrophic factor 297 Neurotrophic factors and neurodegenerative disease 298 Amyotrophic lateral sclerosis (ALS) and peripheral neuropathy 298 Neurotrophic factors and neurodegenerative diseases of the brain 298 Further reading 300 Chapter 8 Hormones of therapeutic interest 303 Insulin 303 Diabetes mellitus 304 The insulin molecule 304 The insulin receptor and signal transduction 307 Insulin production 307 Enzymatic conversion of porcine insulin 311 Production of human insulin by recombinant DNA technology 312 Formulation of insulin products 314 Engineered insulins 317 Additional means of insulin administration 320 Treating diabetics with insulin-producing cells 321 Glucagon 321 Human growth hormone (hGH) 324 Growth hormone releasing factor (GHRF) and inhibitory factor (GHRIF) 325 The GH receptor 325 Biological effects of GH 327 Therapeutic uses of GH 328 Recombinant hGH (rhGH) and pituitary dwarfism 328 Idiopathic short stature and Turner’s syndrome 330 Metabolic effects of hGH 330 GH, lactation and ovulation 331 The gonadotrophins 331 Follicle stimulating hormone (FSH), luteinizing hormone (LH) and human chorionic gonadotrophin (hCG) 331 Pregnant mare serum gonadotrophin (PMSG) 335 The inhibins and activins 337 LHRH and regulation of gonadotrophin production 338 Medical and veterinary applications of gonadotrophins 339 Sources and medical uses of FSH, LHand hCG 340 Recombinant gonadotrophins 342 Veterinary uses of gonadotrophins 344 Gonadotrophin releasing hormone (GnRH) 345 Additional recombinant hormones now approved 345 Conclusions 348 Further reading 348 Chapter 9 Blood products and therapeutic enzymes 351 Disease transmission 351 Whole blood 353 Platelets and red blood cells 353 Blood substitutes 353 Dextrans 354 Albumin 355 Gelatin 357 Oxygen-carrying blood substitutes 357 Haemostasis 358 The coagulation pathway 358 Terminal steps of coagulation pathway 361 Clotting disorders 365 Factor VIII and haemophilia 366 Production of Factor VIII 368 Factors IX, VII a and XIII 371 Anticoagulants 372 Heparin 372 Vitamin Kantimetabolites 375 Hirudin 375 Antithrombin 379 Thrombolytic agents 380 Tissue plasminogen activator (tPA) 381 First-generation tPA 383 Engineered tPA 383 Streptokinase 385 Urokinase 386 Staphylokinase 386 a1 -Antitrypsin 388 Enzymes of therapeutic value 389 Asparaginase 390 DNase 392 Glucocerebrosidase 393 a-Galactosidase and urate oxidase 395 Superoxide dismutase 397 Debriding agents 397 Digestive aids 398 Lactase 400 Further reading 400 Chapter 10 Antibodies, vaccines and adjuvants 403 Polyclonal antibody preparations 403 Anti-D immunoglobulin 406 Normal immunoglobulins 407 Hepatitis Band tetanus immunoglobulin 407 Snake and spider antivenins 408 Monoclonal antibodies 409 Production of monoclonals via hybridoma technology 411 Antibody screening: phage display technology 412 Therapeutic application of monoclonal antibodies 414 Tumour immunology 415 Antibody-based strategies for tumour detection/destruction 417 Drug-based tumour immunotherapy 424 First-generation anti-tumour antibodies: clinical disappointment 426 Tumour-associated antigens 426 Antigenicity of murine monoclonals 428 Chimaeric and humanized antibodies 429 Antibody fragments 432 Additional therapeutic applications of monoclonal antibodies 433 Cardiovascular and related disease 433 Infectious diseases 433 Autoimmune disease 434 Transplantation 434 Vaccine technology 435 Traditional vaccine preparations 436 Attenuated, dead or inactivated bacteria 438 Attenuated and inactivated viral vaccines 439 Toxoids, antigen-based and other vaccine preparations 440 The impact of genetic engineering on vaccine technology 441 Peptide vaccines 444 Vaccine vectors 445 Development of an AIDS vaccine 447 Difficulties associated with vaccine development 450 AIDS vaccines in clinical trials 450 Cancer vaccines 452 Recombinant veterinary vaccines 452 Adjuvant technology 453 Adjuvant mode of action 455 Mineral-based adjuvants 455 Oil-based emulsion adjuvants 455 Bacteria/bacterial products as adjuvants 457 Additional adjuvants 458 Further reading 460 Chapter 11 Nucleic acid therapeutics 463 Gene therapy 463 Basic approach to gene therapy 464 Some additional questions 467 Vectors used in gene therapy 468 Retroviral vectors 468 Additional viral-based vectors 472 Manufacture of viral vectors 474 Non-viral vectors 476 Manufacture of plasmid DNA 480 Gene therapy and genetic disease 482 Gene therapy and cancer 485 Gene therapy and AIDS 486 Gene-based vaccines 488 Gene therapy: some additional considerations 488 Anti-sense technology 488 Anti-sense oligonucleotides 490 Uses, advantages and disadvantages of ‘oligos’ 491 Delivery and cellular uptake of oligonucleotides 493 Manufacture of oligonucleotides 493 Vitravene, an approved antisense agent 494 Antigene sequences and ribozymes 494 Conclusion 495 Further reading 496 Appendix 1 Biopharmaceuticals thus far approved in the USA or European Union 499 Appendix 2 Some Internet addresses relevant to the biopharmaceutical sector 509 Appendix 3 Two selected monographs reproduced from the European Pharmacopoeia with permission from the European Commission: I. Products of recombinant DNA technology 515 II. Interferon a-2 concentrated solution 520 Appendix 4 Manufacture of biological medicinal products for human use. (Annex 2 from The Rules Governing Medicinal Products in the European Community, Vol. 4, Good Manufacturing Practice for Medicinal Products) 527 Index 533

Rezension

"…contains just about everything that anyone would want to know about the subject…It's all here in this easy-to-read textbook.” (Biochemistry and Molecular Education, March/April 2004) "...well written… (and) copiously illustrated..." (Chemistry & Industry, 17th January 2005) “This book should be recommended reading for all under-graduate course in pharmacy and the pharmaceutical sciences …”. (Cell Biochemistry & Function, March-April 2005)

Autorenportrait

Gary Walsh is a senior lecturer in industrial biochemistry at the University of Limerick, Ireland. He combines industrial experience within the pharmaceutical industry with an extensive teaching and academic research background in pharmaceutical biotechnology. He has published half a dozen highly acclaimed books on various aspects of protein biotechnology. He is on the editorial board of several biopharmaceutical journals and is closely affiliated with the European Association of Pharma Biotechnology, serving as its scientific secretary.

Back cover copy

Biopharmaceuticals: Biochemistry and Biotechnology, Second Edition, provides a comprehensive, up-to-date overview of the science and medical applications of biopharmaceutical products. Extensively revised and updated, the Second Edition of this highly successful textbook discusses the latest developments in the field, providing a greater focus on actual commercial products and how they are manufactured. Substantial new sections on detailing biopharmaceutical drug delivery and how advances in genomics and proteomics will impact upon (bio)pharmaceutical drug development are also included. <ul> <li>Provides a balanced overview of the biopharmaceutical industry, including material on key developments in the field.</li> <li>Each chapter supplemented with an extensive further reading section</li> <li>Aimed at students taking courses in biotechnology, pharmaceutical science, biochemistry, microbiology or medicine</li> <li>An ideal reference for those already employed in the (bio)pharmaceutical sector wishing to gain a better overview of the industry.</li> </ul> Reviews of Biopharmace u ticals: "Biopharmaceuticals: Biochemistry and Biotechnology contain(s) some very useful information and ultimately serves as a comprehensive introduction to both the biopharmaceutical industry and its role within the larger arena of pharmaceuticals. For those new to, or keen to be involved with biopharmaceuticals, the book will undoubtedly provide a solid grounding of not just the technology, but of the industry as a whole." —Pharmaceutical Technology Europe "This great compliment of scientific literature, is easy-to-read and understand, up-to-date as well as comprehensive." —Bioseparation "Biopharmaceuticals…is well written and provides an excellent overview of the biotechnology industry…. This book is an excellent and balanced source of information about the biotechnology industry." —FEBS Letters