Enhanced descriptions from Syndetics:

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.

Table of contents provided by Syndetics

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

Author notes provided by Syndetics

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.