INDEX

Note: Italicized page locators indicate figures/photos; tables are noted with t.

AASLD. See American Association for molecular characteristics and ACE genotype, heart failure and, 486 the Study of Liver Diseases therapeutic use, 582t ACE genotype D, 486 AAV. See Adeno-associated virus other applications and additional ACE inhibitors. See Angiotensin- Abatacept (Orencia) information, 166 converting enzyme (ACE) clinical pharmacology, 164 pharmacokinetics, 165 inhibitors dosage form, 163 recommended dosage and Acel-Imune (diphtheria and tetanus dosage form, pharmacokinetics, and monitoring requirements, 165 toxoids and acellular pertussis disposition data, 556t role in therapy, 166 vaccine adsorbed) drug interactions, 164 route of administration, 165 dosage form, pharmacokinetics, and general description, 163 target, product type, indications, disposition data, 576t indications and use, 163 FDA approval year, 148t molecular characteristics and molecular characteristics and therapeutic response, 166 therapeutic use, 612t therapeutic use, 582t ABC transporters, protein, feature, and ACIP. See Advisory Committee for other applications, 165 total number of genes, 527t Immunization Practices pharmacokinetics, 164 Abelcet, 452 Acoustic filters, perfusion recommended dosing and Abilify, off-label promotion of, configurations and, 70 monitoring requirements, 163 settlement involving, 119t Acquired disorders, gene and cell role in therapy, 164 Abrin, construction of immunotoxins therapy and, 497, 497t route of administration, 163 and, 455, 455t ACR. See American College of target, product type, indications, Absorption, distribution, metabolism, Rheumatology FDA approval year, 148t and elimination Acromegaly therapeutic response, 164 new drugs and, 521 refractory, Somavert in treatment of, Abbott, revenue, market share, new molecular entities and, 14 348, 349 productivity, and research preclinical studies and, 108 Sandostatin in treatment for, 346 investments of, 5t Absorption, of recombinant protein Somatuline Depot in treatment of, Abbreviated new drug applications, pharmaceuticals, 85–86, 100 33, 340 111, 116–117 Absorption rate SST analogs and treatment of, 312 Abbreviations prescription drugs and, 80 Acrylated Fv products, recombinant, for common amino acids, COPYRIGHTEDsymbol, mathematical relationship, MATERIAL 458 623t–625t and physiological variables, 83 ACT. See Adoptive cell therapy explanation for, 626t–631t ACA. See Affordable Care Act Actemra (tocilizumab), 156 Abciximab (ReoPro), 147, 227 Academy of Managed Care Pharmacy, dosage form, 206 clinical pharmacology, 165 541 dosage form, pharmacokinetics, and dosage form, 165 Accelerated approval, 114 disposition data, 562t dosage form, pharmacokinetics, and Accelerated development and review indications and use, 206 disposition data, 556t process, use of, 107, 108 molecular characteristics and drug interactions, 165 Accupril (quinapril), restenosis after therapeutic use, 590t general description, 165 stent implantation and, 486 recommended dosage and indications and use, 165 ACE D allele, 486 monitoring requirements, 206

Biotechnology and Biopharmaceuticals: Transforming Proteins and Genes into Drugs, Second Edition. Rodney J. Y. Ho. © 2013 John Wiley & Sons, Inc. Published 2013 by John Wiley & Sons, Inc.

633

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 633 0002007355.INDD 633 8/20/2013 1:44:57 AM 634 index

Actemra (tocilizumab) (cont’d) molecular characteristics and for severe combined role in therapy, 206 therapeutic use, 591t immunodeficiency, 361 route of administration, 206 ADA gene, 361 ADH. See Antidiuretic hormone target, product type, indications, Adagen (PEG-ADA), 447 ADH1 gene, ADH isoenzymes FDA approval year, 149t Adagen (pegademase bovine) encoded by, 481 ACTH. See Adrenocorticotropic dosage form, 381 ADH2 gene, ADH isoenzymes hormone indications and use, 381 encoded by, 481 ActHIB (Haemophilus b conjugate role in therapy, 382 ADH3 gene, ADH isoenzymes vaccine, tetanus toxoid route of administration, 381 encoded by, 481 conjugate) Adalimumab (Humira) Adipocytes, 90, 213 dosage form, pharmacokinetics, and clinical pharmacology, 167 Adjuvants, vaccine, 398, 400, 405 disposition data, 577t dosage form, 167 Adjuvant systems, novel, and vaccine molecular characteristics and dosage form, pharmacokinetics, and delivery technologies, 400t therapeutic use, 613t disposition data, 556t ADME. See Absorption, distribution, Actimmune (interferon gamma 1b) drug interactions, 167 metabolism, and elimination dosage form, 300 general description, 166 Adoption of new therapies and dosage form, pharmacokinetics, and indications and use, 166 medicines, 536 disposition data, 574t molecular characteristics and Adoptive cell therapy, metastatic indications and use, 300 therapeutic use, 582t melanoma and, 505–506 molecular characteristics and other applications and additional Adrenocorticotropic hormone, sources therapeutic use, 608t information, 168 and clinical use of, 309t off-label promotion of, settlement pharmacokinetics, 167 Advanced Cell Technology, 510 involving, 118, 119t recommended dosage and Advate (antihemophilic factor recommended dosage and monitoring requirements, 167 (recombinant), plasma/albumin monitoring requirements, 300 role in therapy, 168 free) role in therapy, 301 route of administration, 167 dosage form, pharmacokinetics, and route of administration, 300 sponsors, indications, annual sales in disposition data, 565t Activase (alteplase), 33 millions, 6t molecular characteristics and clinical pharmacology, 374 target, product type, indications, therapeutic use, 594t dosage form, 373 FDA approval year, 148t Advate (antihemophilic factor VIII) dosage form, pharmacokinetics, and therapeutic response, 168 dosage form, 232 disposition data, 563t Adaptive immunity, 393 general description, 231–232 indications and use, 373 ADA-SCID, 506 indications and use, 232 molecular characteristics and ADCC. See Antibody-dependent pharmacokinetics, 233 therapeutic use, 592t cellular cytotoxicity recommended dosage and recommended dosage and monitoring Adcetris (brentuximab vedotin) monitoring requirements, requirements, 373–374 dosage form, 177 232–233 role in therapy, 374 dosage form, pharmacokinetics, and route of administration, 232 route of administration, 373 disposition data, 557t Adverse drug reactions, 96, 474 Activated V (Va) calcium, 225 drug interactions, 177 Advexin, 506 Activin A, 511, 511t indications and use, 176–177 Advisory Committee for Immunization Acute coronary syndrome molecular characteristics and Practices aptamer-based therapies and, 497 therapeutic use, 583t on bivalent HPV vaccine, 411 Integrilin in treatment of, 241 recommended dosage and on hepatitis B vaccine, 410 Acute lymphoblastic leukemia, monitoring requirements, 177 on quadrivalent HPV vaccine, 411 Leukine in treatment of, 249 role in therapy, 177 on varicella vaccine, 415 Acute myelogenous leukemia, Leukine route of administration, 177 on Zostavax, 416 in treatment of, 249 target, product type, indications, Affordable Care Act, biosimilars and, Acute myeloid leukemia, aptamer- FDA approval year, 149t 133, 134 based therapies and, 497 ADCs. see Antibody-drug conjugates Aflibercept (Eylea) Acute myocardial infarction Adefovir dipivoxil (Hepsera), 273 clinical pharmacology, 168–169 Activase in treatment of, 373, 374 Adeno-associated virus, 500 disposition, 169 Retavase in treatment of, 385, 386 as gene therapy for hemophilia, 503, dosage form, 168 TNKase in treatment of, 386, 387 504 dosage form, pharmacokinetics, and Acyclovir, 9, 9, 97 Adenosine deaminase (Adagen), 449, 506 disposition data, 556t Acylated insulin derivatives, 462 clearance and, 447 general description, 168 ADA. See Adenosine deaminase dosage form, pharmacokinetics, and indications and use, 168 Adagen (adenosine deaminase) disposition data, 562t molecular characteristics and dosage form, pharmacokinetics, and molecular characteristics and therapeutic use, 582t disposition data, 562t therapeutic use, 591t pharmacokinetics, 169

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 634 0002007355.INDD 634 8/20/2013 1:44:57 AM index 635

recommended dosage and dosage form, 288 target, product type, indications, monitoring requirements, 168 dosage form, pharmacokinetics, and FDA approval year, 148t role in therapy, 169 disposition data, 573t therapeutic response, 171 route of administration, 168 drug interactions, 289 Alendronate (Fosamax), 315 therapeutic response, 169 general description, 288 Alferon-N (interferon alfa-n3, human Africa, sub-Saharan, social indications and use, 288 leukocyte derived) entrepreneurs and conjugated molecular characteristics and dosage form, pharmacokinetics, and meningococcal vaccine for, 21 therapeutic use, 607t disposition data, 573t African American men, SRD5A2 and other applications and additional molecular characteristics and risk of prostate cancer in, 484 information, 289 therapeutic use, 608t African Americans, primaquine- pharmacokinetics, 289 Alglucerase (Ceradase) mediated hemolysis symptom recommended dosage and dosage form, pharmacokinetics, and and, 473 monitoring requirements, 289 disposition data, 562t Agalsidase, for Fabry’s disease, 363 role in therapy, 289 molecular characteristics and Agalsidase beta (Fabrazyme), 363 route of administration, 289 therapeutic use, 591t clinical pharmacology, 371 therapeutic response, 289 Alglucosidase, for Pompe’s disease, 363 dosage form, 370 Aldurazyme (laronidase), 364 Alglucosidase alfa (Myozyme, dosage form, pharmacokinetics, and dosage form, 380 Lumizyme), 363 disposition data, 562t dosage form, pharmacokinetics, and additional information, 373 general description, 370 disposition data, 563t clinical pharmacology, 372 indications and use, 370 indications and use, 380 dosage form, 372 molecular characteristics and molecular characteristics and dosage form, pharmacokinetics, and therapeutic use, 591t therapeutic use, 592t disposition data, 562t pharmacokinetics, 371 route of administration, 380 general description, 371 recommended dosage and Alefacept (Amevive), 151t indications and use, 372 monitoring requirements, clinical pharmacology, 169 molecular characteristics and 370–371 dosage form, 169 therapeutic use, 591t role in therapy, 371 dosage form, pharmacokinetics, and pharmacokinetics, 372 route of administration, 370 disposition data, 556t recommended dosage and therapeutic response, 371 drug interactions, 170 monitoring requirements, 372 Age-related macular degeneration, 423 general description, 169 role in therapy, 373 neovascular, Lucentis in treatment indications and use, 169 route of administration, 372 of, 202, 203 molecular characteristics and therapeutic response, 372–373 Aggregate mediators, 74 therapeutic use, 582t Alglucosidase alfa 2 (Lumizyme) aHUS. See atypical hemolytic uremic other applications, 170 dosage form, pharmacokinetics, and syndrome pharmacokinetics, 169–170 disposition data, 563t AIDS epidemic, parallel track recommended dosage and molecular characteristics and mechanism in response to, 108 monitoring requirements, 169 therapeutic use, 591t AIDSVAX, 402 role in therapy, 170 Alipogene tiparvovec, 507 AIDS wasting, Serostim in treatment route of administration, 169 ALK genetic markers, 489, 490 of, 351, 352 target, product type, indications, Alkyl-dihydroxyacetone phosphate AIN457, 150t FDA approval year, 148t (DHAP) synthase, therapeutic AJCC. See American Joint Committee therapeutic response, 170 potential with, 365t on Cancer Alemtuzumab (Campath) ALL. See Acute lymphoblastic Alanine, three- and one-letter code, clinical pharmacology, 170 leukemia linear formula, structure dosage form, 170 Allegra, 9 for, 623t dosage form, pharmacokinetics, and Allergic reactions, protein Alanine aminotransferase, 358 disposition data, 556t immunogenicity and, 92, 94 Albert, Adrien, 452 general description, 170 Allosteric interaction, 358 Albumin, expression in hepatocytes, 511 indications and use, 170 Allovectin, 508 Albumin vs. starch colloid, hypothesis- molecular characteristics and Alpha family, human chromosome, driven clinical trial and, 109, 110 therapeutic use, 582t number of genes, AA number, Alcohol addiction, vaccines against, 404 for multiple sclerosis, 279t, 280 homology, 256t Alcohol dehydrogenase other applications and additional Alpha feto-protein (AFP), 511 polymorphisms, modulating information, 171 Alpha-1-proteinase inhibitor (human), alcohol disposition and risk of pharmacokinetics, 170–171 alpha-1 antitrypsin (Prolastin) MI, 481 recommended dosage and dosage form, pharmacokinetics, and Aldesleukin (Proleukin), 253 monitoring requirements, 170 disposition data, 574t clinical pharmacology, 289 role in therapy, 171 molecular characteristics and disposition, 289 route of administration, 170 therapeutic use, 609t

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 635 0002007355.INDD 635 8/20/2013 1:44:57 AM 636 index

Alpha-1-proteinase inhibitor Amevive (alefacept) Analytical centrifugation, protein (Prolastin-C) dosage form, 169 characterization and stability clinical pharmacology, 418–419 dosage form, pharmacokinetics, and assessment with, 51t disposition, 419 disposition data, 556t ANDAs. See Abbreviated new drug dosage form, 418 indications and use, 169 applications general description, 418 molecular characteristics and Anemia, 212, 218, 430 indications and use, 418 therapeutic use, 582t anti-erythropoietin antibody- pharmcokinetics, 419 role in therapy, 170 associated, 115 recommended dosage and route of administration, G6PDH, Lapdap and exacerbation monitoring requirements, 418 recommended dosage and of, 490 role in therapy, 419 monitoring requirements, 169 Anges, 507, 508 route of administration, 418 target, product type, indications, Angina, refractory, gene therapy for, therapeutic response, 419 FDA approval year, 148t 502 ALT. See Alanine aminotransferase AMG 145, 151t Angiogenesis, defined, 262 Alteplase (Activase), 33, 81, 97, 365 AMG 479, 150t Angiogenesis inhibition, IFNs and, 262 clinical pharmacology, 374 AMG 827, 150t Angiomas, aptamer-based therapies disposition, 374 Amgen, 5, 28, 115, 116 and, 497 dosage form, 373 Immunex acquired by, 29 Angiomax (bivalirudin), 228 dosage form, pharmacokinetics, and revenue, market share, productivity, dosage form, 235 disposition data, 563t and research investments of, 5t dosage form, pharmacokinetics, and drug interactions, 374 roller bottle technology and, 68, 68 disposition data, 565t general description, 373 AMI. See Acute myocardial infarction indications and use, 235 indications and use, 373 Amino acids molecular characteristics and molecular characteristics and common, abbreviations for, 623t–625t therapeutic use, 596t therapeutic use, 592t degenerative base triplet on pharmacokinetics, 235 other applications and additional ribonucleotides coding for, 622t recommended dosage and information, 374 sequences of monitoring requirements, 235 pharmacokinetics, 374 immunogenicity of protein and role in therapy, 236 recommended dosage and alteration of, 93 route of administration, 235 monitoring requirement, somatostatin derivatives and, 312 Angiotensin-converting enzyme (ACE) 373–374 in somatostatin, 53 inhibitors, stent restenosis, role in therapy, 374 AML. See Acute myelogenous genetic polymorphism and, route of administration, 373 leukemia 486–487 therapeutic response, 374 Amoxicillin, 480 Anima, 458 Alu sequences, DNA fingerprinting Amphotec, 452 Animal cloning, 4, 495, 496, 497–499 and, 523 Amphotericin, particle size-dependent Dolly the sheep, 497, 498, 499 Alveolar surface, pulmonary delivery targeting of drugs and, 452 nuclear transfer technology in, 498, of drugs and, 434 Amphotericin B, 452 498 Alveoli, epithelial cells in lining of, 434 Amylase, 365 success in, 498 Alzheimer’s disease, 113, 434, 518 Amylin (Symlin), 313 Animal models, clinical studies for Ambisome, serious fungal infections Anakinra (Kineret), 163, 256 dose-response profiles and, 81 and, 452, 452t clinical pharmacology, 290 Animals AMCP. See Academy of Managed Care dosage form, 290 testing, preclinical studies and, 108 Pharmacy drug interactions, 290 therapeutic index for dose escalation AMD. See Age-related macular general description, 290 studies in, 429 degeneration indications and use, 290 Anistreplase, characteristics, American Association for the Study of molecular characteristics and pharmaceutical source, Liver Diseases, 296, 302, 304 therapeutic use, 607t mechanisms of action, 366t American Cancer Foundation, 552 other applications, 291 Ankle-brachial index, 508 American College of Gastroenterology, pharmacokinetics, 290 Ankylosing spondylitis 296, 302, 304 recommended dosage and Enbrel in treatment of, 185 American College of Rheumatology, monitoring requirements, 290 Humira in treatment of, 166, 167 290 role in therapy, 291 Remicade in treatment of, 190 American Foundation for AIDS route of administration, 290 Simponi in treatment of, 187, 188 Research, 552 therapeutic response, 290–291 Antagon (ganirelix acetate), 316 American Joint Committee on Cancer, Anakinra (Kineret solution), dosage dosage form, pharmacokinetics, and melanoma staging, 269 form, pharmacokinetics, and disposition data, 568t American Society of Clinical Oncology, disposition data, 573t molecular characteristics and 200 Analytical assay capabilities, new therapeutic use, 600t AME-133v, 150t molecular entities and, 14 Anterior chamber, eye, 433

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 636 0002007355.INDD 636 8/20/2013 1:44:57 AM index 637

Anterior pituitary, integrated hormone and physiological characteristics dosage form, pharmacokinetics, and release and regulation of, 310 of, 140–141, 143–144 disposition data, 564t Anthracyclines, enhancing delivery Antibody production, time course of, molecular characteristics and of, expressing transferrin on in serum of animals following therapeutic use, 594t liposomes and, 457 exposure to antigen, 143 Antihemophilic factor (recombinant), Anthrax, vaccines against, 404, 404t Antibody products, immunogenicity plasma/albumin free (Advate) Antibiotics, fermentation technology and, 93 dosage form, pharmacokinetics, and and, 8 Antibody-toxin conjugates, 454 disposition data, 565t Antibodies, 5, 140 Anticoagulation factors, therapeutic molecular characteristics and approved for human use organized use of, 225–228 therapeutic use, 594t according to approval date, Anticoagulation system, 212 Antihemophilic factor (recombinant 148t–149t Antidiuretic hormone, sources and plasma/albumin free) (Xyntha) binding-affinity optimization and, clinical use of, 309t dosage form, pharmacokinetics, and 158–159 Anti-EGFL-7, clinical leverage strategy disposition data, 565t biodistribution of, 151, 151 and, 32t molecular characteristics and biological properties and localization Antigen complex, 145 therapeutic use, 594t of, 141t Antigenome approaches, vaccines Antihemophilic factor VIII (ReFacto) CBER review of, 18 and, 403 dosage form, pharmacokinetics, and derivatives and, 147, 148t–149t, 149 Antigenomics disposition data, 565t in development, 158–159 new generation of vaccines and, 389 molecular characteristics and dosage form, pharmacokinetics, vaccine discovery and, 405 therapeutic use, 595t and disposition data, 556t–562t Antigen-presenting cells, 393, 398 Antihemophilic factor/von Willebrand molecular characteristics and Antigens factor complex (human)-factor enzymatic reactions for, 142 recombinant, enhanced antibody and VIII (Humate-P) molecular characteristics and cell-mediated immune response dosage form, pharmacokinetics, and therapeutic uses for, 582t–591t and particulate forms of, 451 disposition data, 565t monographs list, 162 time course of antibody protection molecular characteristics and in development, 158–159 in serum of animals following therapeutic use, 595t extravascular tissue penetration exposure to, 143 Antisense therapeutics, oligonucleotide and, 155 tumor-associated, 454 stability and, 496 humanization of, 158 tumor-specific, 454 Antithrombin (ATryn) in humans, physiological properties Antihemophiliac factor VIII (ReFacto), clinical pharmacology, 234 and disposition of, 143t 231–233 disposition, 234 humoral response and, 393 clinical pharmacology, 233 dosage form, 234 immune response and, 94–95 dosage form, 232 drug interactions, 234 improving function of, with Bi- and general description, 231–232 general description, 234 multi-functional antibodies, 159 indication and use, 232 indications and use, 234 molecular characteristics and other applications and additional pharmacokinetics, 234 therapeutic applications, 140– information, 233 recommended dosage and 141, 143–160 pharmacokinetics, 233 monitoring requirements, 234 monoclonal, naming conventions for, recommended dosage and monitoring role in therapy, 234 618–619 requirements, 232–233 route of administration, 234 monographs list, 162 role in therapy, 233 therapeutic response, 234 overview of, 140 route of administration, 232 Antithrombin (recombinant) (ATryn) relative plasma clearance and size therapeutic response, 233 dosage form, pharmacokinetics, and of, 155t Antihemophilic factor-human heavy disposition data, 565t review by CDER through BLA and light chains combination molecular characteristics and pathway, 104 (Recombinate) therapeutic use, 595t stability of, 144 dosage form, pharmacokinetics, and Antithrombin III (human) (Thrombate Antibody bioactivities, mechanisms disposition data, 565t III) of, 156 molecular characteristics and dosage form, pharmacokinetics, and Antibody-dependent cellular therapeutic use, 595t disposition data, 565t cytotoxicity, 156, 181, 262 Antihemophilic factor (human) molecular characteristics and Antibody-drug conjugates, 156–158, 176 (Koate-DVI or Koate-HP) therapeutic use, 596t Antibody engineering, 146, 158 dosage form, pharmacokinetics, and Antitoxin, 140 Antibody-mediated cytotoxicity, disposition data, 564t Antitrust laws, 131 enhancing, radiolabeled molecular characteristics and Antitumor effects antibody and, 157 therapeutic use, 594t in humans, overview, 262–264 Antibody molecules, discovery, Antihemophilic factor (Kogenate; of IFNs, 261 classification, biodistribution, Kogenate-FS) APCs. See Antigen-presenting cells

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 637 0002007355.INDD 637 8/20/2013 1:44:57 AM 638 index

Apidra (insulin glulisine) dosage form, pharmacokinetics, and Australia dosage form, 336 disposition data, 560t evidence and value data essential for dosage form, pharmacokinetics, and indications and use, 196 health care in, 542 disposition data, 569t molecular characteristics and health-care funding characteristics indications and use, 336 therapeutic use, 588t and HTA programs in U.S. vs., molecular characteristics and recommended dosage and 543t therapeutic use, 601t monitoring requirements, 196 Autoimmune diseases pharmacokinetic and route of administration, 196 immunogenicity and, 93 pharmacodynamics attributes, target, product type, indications, vaccines against, 404 461t FDA approval year, 149t Autoimmune response, 140 recommended dosage and AS. See Ankylosing spondylitis Autologous stem cell transplant, monitoring requirements, 336 ASCO. See American Society of Hodgkin lymphoma after failure role in therapy, 337 Clinical Oncology of, Adcetris and, 177 route of administration, 336 ASCT. See Autologous stem cell Automatic back-pressure regulator, Apolipoprotein E, liposome targeting transplant 30-L bench fermentor, 67 and, 457 Ashkenazi Jewish women, frequency of Autosomal chromosomes, human Applied research BRCA1 mutations in, 484 gene number identified to date capital intensiveness of, 24 Asia, new medicine development according to their distribution pharmaceutical drug discovery and in, 122 in, 519t development in, 25 AS P. See Aspartate aminotransferase Avastin (bevacizumab) Aptamer-based therapeutics, disease Asparaginase, 33 annual revenue for, 7 treatment and, 497 Asparagine antibody fragments, 497 Aptamers, 496–497 deamidation of, 89 dosage form, 175 Aranesp (darbepoetin alpha), 87, 220, three- and one-letter code, linear dosage form, pharmacokinetics, and 464 formula, structure for, 623t disposition data, 557t dosage form, 239 Aspartate aminotransferase, 358 indications and use, 175 dosage form, pharmacokinetics, and Aspartic acid, three- and one-letter molecular characteristics and disposition data, 565t code, linear formula, structure therapeutic use, 583t indications and use, 238–239 for, 623t route of administration, 175 molecular characteristics and Aspartylglucosaminadase, therapeutic sponsors, indications, annual sales in therapeutic use, 596t potential with, 365t millions, 6t recommended dosage and Aspirin, bioavailability of, 432 target, product type, indications, monitoring requirements, 239 Assisted reproductive technology FDA approval year, 148t role in therapy, 239 gonadotropins and, 316 Avonex (interferon beta-1a), 27, 28, 29 route of administration, 239 programs for dosage form, 296 sponsors, indications, annual sales in Follistim for ovulatory women dosage form, pharmacokinetics, and millions, 6t participating in, 326 disposition data, 573t Arbitragers, 132 Gonal-F for ovulatory women indications and use, 296 Arcalyst (rilonacept) participating in, 324 molecular characteristics and dosage form, pharmacokinetics, and Asthma, Xolair in treatment of, 197, 198 therapeutic use, 608t disposition data, 574t AstraZeneca, revenue, market share, for multiple sclerosis, 277, 278, 279t molecular characteristics and productivity, and research recommended dosage and therapeutic use, 609t investments of, 5t monitoring requirements, 296 Area under the curve, 153 ATP-binding cassette, protein, feature, role in therapy, 297, 298 IV dosing, symbol, mathematical and total number of genes, 527t route of administration, 296 relationship, and physiological ATryn (antithrombin) AVOREN trial, 176 variables, 83 dosage form, 234 Azathioprine therapy, pharmacogenetic Arginine, 89, 90 indications and use, 234 testing and, 490 three- and one-letter code, linear recommended dosage and formula, structure for, 623t monitoring requirements, 234 Baby hamster kidney (BHK) cells, 227 Argipressin, 318, 318t route of administration, 234 Bacille Calmette-Guérin Array technology, miniaturization and, therapeutic response, 234 SCID and, 361 520 ATryn (antithrombin, recombinant) vaccine against, 395 ART. See Assisted reproductive dosage form, pharmacokinetics, and Bacterial expression systems, vectors technology disposition data, 565t and, 48 Arthritis, 113 molecular characteristics and Basic research, pharmaceutical drug Arylamine N-acetyltransferase, genetic therapeutic use, 595t discovery and development variations found in, 478 Atypical hemolytic uremic syndrome, in, 25 Arzerra (ofatumumab) Soliris in treatment of, 184, 185 Basiliximab (Simulect), 151t, 256 dosage form, 196 AUC. See Area under the curve clinical pharmacology, 172

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 638 0002007355.INDD 638 8/20/2013 1:44:57 AM index 639

dosage form, 171 B-cell growth factor, cell source, role in therapy, 174 dosage form, pharmacokinetics, and functions, and molecular route of administration, 173 disposition data, 556t characteristics, 216t target, product type, indications, drug interactions, 172 B cells, 139, 141, 143, 144, 145 FDA approval year, 149t general description, 171 B-cell stimulatory factor II, cell source, therapeutic response, 173–174 indications and use, 171 functions, and molecular Belimumab (Benlysta) molecular characteristics and characteristics, 216t additional information, 175 therapeutic use, 582t BCG. See Bacille Calmette-Guérin clinical pharmacology, 174 other applications and additional BCG live (Pacis) dosage form, 174 information, 172 dosage form, pharmacokinetics, and dosage form, pharmacokinetics, and pharmacokinetics, 172 disposition data, 575t disposition data, 557t recommended dosage and molecular characteristics and general description, 174 monitoring requirements, therapeutic use, 611t indications and use, 174 171–172 BCG Live (TICE BCG, TICE strain, molecular characteristics and role in therapy, 172 TheraCys, Cannaught strain) therapeutic use, 583t route of administration, 171 dosage form, pharmacokinetics, and pharmacokinetics, 174 target, product type, indications, disposition data, 575t recommended dosage and FDA approval year, 148t molecular characteristics and monitoring requirements, 174 therapeutic response, 172 therapeutic use, 611t role in therapy, 175 Basophils, 140, 215 Bcl-families, BH domain signature route of administration, 174 Batch process, large-scale cultivation of found in, 526 therapeutic response, 174–175 host cells and, 68–69, 69 Bcr-Ab1 gene product, leukemia and, Bence Jones proteins, 145 Bayer, revenue, market share, 58 Bench-to-bedside flow, of biomedical productivity, and research bcr-abl-positive chronic myeloid science, 550 investments of, 5t leukemia, 263 Benefix (coagulation factor IX), 227 BayGam (human immune globulin) Bc12 protein, BRCA1 mutations and, dosage form, 236 dosage form, pharmacokinetics, and 484 indications and use, 236 disposition data, 558t Becaplermin (Regranex Gel) recommended dosage and molecular characteristics and additional information, 420 monitoring requirements, 236 therapeutic use, 585t clinical pharmacology, 420 role in therapy, 237 Bay HepB, therapeutic use for, 145t dosage form, 419 route of administration, 236 BayHep B (immune globulin against dosage form, pharmacokinetics, and Benefix (coagulation factor IX, human hepatitis B, human) disposition data, 575t recombinant) dosage form, pharmacokinetics, and general description, 419 dosage form, pharmacokinetics, and disposition data, 559t indications and use, 419 disposition data, 565t molecular characteristics and molecular characteristics and molecular characteristics and therapeutic use, 587t therapeutic use, 610t therapeutic use, 596t BayRab, therapeutic use for, 145t pharmacokinetics, 420 Benign prostatic hypertrophy, SRD5A2 BayRab (rabies immune globulin, recommended dosage and gene variants and, 484 human) monitoring requirements, 420 Benlimumab (Benlysta), target, dosage form, pharmacokinetics, and role in therapy, 420 product type, indications, FDA disposition data, 561t route of administration, 419 approval year, 149t molecular characteristics and therapeutic response, 420 Benlysta (belimumab) therapeutic use, 589t Beef insulin, 9, 32 dosage form, 174 BayRho-D, therapeutic use for, 145t Beer and wine fermentation dosage form, pharmacokinetics, and BayRho-D (immune globulin, human, technology, 7 disposition data, 557t against Rho-(D)) Belatacept (Nulojix) indications and use, 174 dosage form, pharmacokinetics, and additional information, 174 molecular characteristics and disposition data, 559t clinical pharmacology, 173 therapeutic use, 583t molecular characteristics and dosage form, 173 route of administration, 174 therapeutic use, 586t dosage form, pharmacokinetics, and target, product type, indications, BayTet, therapeutic use for, 145t disposition data, 557t FDA approval year, 149t Bay Tet (tetanus immune globulin, drug interactions, 173 Bergmena, Philip, 508 human), dosage form, general description, 173 Berofor, 258 pharmacokinetics, and indications and use, 173 Best Pharmaceuticals for Children Act disposition data, 561t molecular characteristics and (2002), 81, 103, 111, 113, 114, B-cell biology, advances in, 40 therapeutic use, 582t 114t B-cell chronic lymphocytic leukemia pharmacokinetics, 173 Beta-adrenergic receptor antagonists, (B-CLL), Campath in treatment recommended dosage and 486 of, 170, 171 monitoring requirements, 173 Beta-agalsidase (Fabrazyme), 454

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 639 0002007355.INDD 639 8/20/2013 1:44:57 AM 640 index

Beta-blocker therapy, ACE deletion Bile acid transporters, 530 Biologic response modifiers, delayed and, 486 Bill and Melinda Gates Foundation, 21 response and, 97 Beta-elimination, proteins and peptides Binding-site libraries, 159t Biologics potency assays, and, 98 Bioavailability, 82 characterization tests of proteins Beta family, human chromosome, for biotherapeutics, 100 and, 76 number of genes, AA number, parenteral routes and, 86t Biomarkers homology, 256t of recombinant protein drug development programs and, 524 Beta-glucuronidase (Ceredase), 362, 454 pharmaceuticals, 85–86 metabolites and, 528 Betaseron (interferon beta-1b), 27, 258 Biochemistry, biotechnology and, 7 metabolomics approach and, 520, 529 dosage form, 299 Biodegradable polymers, tested for validated, cost of drug development dosage form, pharmacokinetics, and sustained protein release, 440t and, 552 disposition data, 574t Bioengineering, 5, 7 Biomedical research and development, indications and use, 299 Bioequivalence public and private investment molecular characteristics and establishing of biosimilarity vs., 133 in, 550 therapeutic use, 608t generic drugs and, 117 Biomolecules, 1, 4, 41 for multiple sclerosis, 277, 278, 279t Biogen Idec, 6 as drug candidates, 549 orphan drug designation for, 28 revenue, market share, productivity, for rare or orphan diseases, 551 role in therapy, 300 and research investments of, 5t transformation into biotherapeutics, 5 route of administration, 299 Biographer, 459 Biopharmaceutical companies Bevacizumab (Avastin) Bioinformatics, in genomics, integrated drug development teams clinical pharmacology, 175 description of, 522t and, 549 dosage form, 175 Biological assay capabilities, new pharmacoeconomic strategies of, 542, dosage form, pharmacokinetics, and molecular entities and, 14 544–545 disposition data, 557t Biological macromolecules revenue, market share, productivity, drug interactions, 175–176 derivation of, 16 and research investments of, 5t general description, 175 manufacturing and assay costs for, 18 strategic acquisition of indications and use, 175 Biologic enzymes, regulation of, 358 biotechnology companies by, 35t molecular characteristics and Biologic License Application, 13, 14, 16, Biopharmaceutical development, therapeutic use, 583t 18, 22, 103, 104, 113, 123, 531, 550 expediting, 530 other applications, additional current Good Manufacturing Biopharmaceutical networks, information, 176 Practice guidelines and, 105 integrated, 36 pharmacokinetics, 175 drug approval process and, 114, 115, Biopharmaceuticals, 3 recommended dosage and 118 approved, average total cost per, 131 monitoring requirements, 175 drug development process and, 15 assessing value of, 126–128 role in therapy, 176 FDA, QA/QC standards and, 77 average cost outlays and duration route of administration, 175 IL-2 approval, 253 for, while progressing through sponsors, indications, annual sales in pharmacology and toxicology clinical trial phases, 130t millions, 6t assessment and, 81 business of, and economic impacts, target, product type, indications, for Rebif, 28 549 FDA approval year, 148t safety and efficacy data for, 14 CDER review and approval of, 18 therapeutic response, 176 vaccines and, 397 challenges facing the future of, 135 Bexxar (tositumomab I-131), 456 well-characterized characteristics of, 466 dosage form, 207 biopharmaceuticals and, 17 chemical drugs vs., 8–9 dosage form, pharmacokinetics, and Biologic license establishment, 104, 105 cost of developing, 128–131 disposition data, 562t Biologic Price Competition and cost of regulatory approval and indications and use, 207 Innovation Act of 2009, 117 marketing of, 24 molecular characteristics and Biologic products, 1, 4, 11, 41. See data exclusivity period for, 134 therapeutic use, 590t also Financing biologic drug derivation of, 1, 4 recommended dosage and development developing, translation of monitoring requirements, 207 classified as orphan drugs, 27 biotechnology for, 7 route of administration, 207 data exclusivity of, under BLAs, 117 dosage formulations and sites used target, product type, indications, development and approval of, 104 in administration of, 97t FDA approval year, 148t evaluating and developing, tools farming of, 498 BH domain of apoptosis regulator for, 40 genomic information and improved protein Bcl-2 family, protein, history of regulation governing in safety and production cost of, feature, and total number of U.S., 111 548–549 genes, 527t licensing of, 104–105, 107 graded response and, 95 Bias, preventing, in clinical trials, 113 understanding molecular influence of, on pharmaceutical BIC. See Biosimilar Implementation characteristics and mechanisms research and drug industry, Committee of, 80 549–550

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 640 0002007355.INDD 640 8/20/2013 1:44:57 AM index 641

major costs of, reasons for, 552 influences on pharmacokinetics and hematopoietic growth factors and marketed, improving, 32–33 toxicity of, 530 distinct types of, 215 monographs list, 418 lengthy, expensive development life span of, 217 novel process for, 24 Blood clots advances in DNA cloning and manufacture of, issues related to, 64 formation of, 212 expression, 518 nomenclature of, 617–620 thrombolytic enzymes and cross developing, 33–34 antibodies (monoclonal), 618–619 section of blood vessel with, path to development of, 13 colony-stimulating factors, 620 359 in personalized medicine, 134t erythropoietins, 620 Blood-clotting factors, 225, 226 pharmacology and toxicology of, interferons, 619–620 Blood coagulation factors, 212 81–82 interleukins, 620 Blood growth factors, 212 pricing, 131–133 somatotropin growth hormones, Blood vessel, significant loss of blood unique, distinctive features of, 126 619 from, interactions between progress and benefits in transforming 25 top selling, annual sales in, 549 platelets and clotting cascades in proteins and genes into, 548 “well-characterized,” approval repair of, 225, 226 proving safety and effectiveness process for, 17 BL22, 455 of, 104 Biotechnology research B lymphocytes (B cells), 140, 215, 218, public health and, 551 government funding for, 25 393 public participation and high cost of, 7 Boceprevir (Victrelis), 274 development of, 551–552 Bioterrorism, vaccines and threat Boehringer Ingelheim, 112 routes of administration of, 428, 428 of, 404 Bone marrow transplant, autologous or synthesis of, 5 Biotherapeutics, 1, 4 allogenic, Leukine and, 249, 250 transition probabilities for clinical biomolecules transformed into, 5 Bone mass, low, Forteo in treatment of, phases for pharmaceuticals vs., 130 milestones and overall impact of, 4 353, 354 Biosimilar Implementation Committee, Birth defects, thalidomide and, 111 Bone metabolism, parathyroid 117 Bispecific antibodies hormone, peptide derivatives Biosimilar product development, draft antibody function improved with, and, 314 FDA guidance on, summary 159 Bone remodeling, osteoclasts and of, 116 in clinical trials, examples of, 159t osteoblasts in, 315 Biosimilars, 135, 225 Bivalirudin (Angiomax), 228 Bordetella pertussis, FDA-approved economics of, 133–134 clinical pharmacology, 235 subcellular vaccines against, 395 nonproprietary names and, 618 disposition, 235 Borrelia burgdorferi, FDA-approved Biosimilars: Questions and Answers dosage form, 235 subcellular vaccines against, 395 Regarding Implementation of dosage form, pharmacokinetics, and Botox, off-label promotion of, the Biologics Price Competition disposition data, 565t settlements and, 118, 119t and Innovation Act of 2009, 116 drug interactions, 235 Botox (onabotulinumtoxin A, Biotechnology, 8 general description, 234–235 neutrotoxin complex) broad definition of, 7 indications and use, 235 dosage form, pharmacokinetics, and drug development and, 549 molecular characteristics and disposition data, 575t history behind, 4 therapeutic use, 596t molecular characteristics and translation of, for developing pharmacokinetics, 235 therapeutic use, 611t biopharmaceuticals, 7 recommended dosage and Botox (onabotulinumtoxin A), for Biotechnology companies monitoring requirements, 235 blepharospasm, 422 financial viability of, 26, 26t role in therapy, 236 Botulinum toxin type a (Dysport) niche areas and, 27 route of administration, 235 dosage form, pharmacokinetics, and revenue, market share, productivity, therapeutic response, 235–236 disposition data, 575t and research investments of, BLA. See Biologic License Application molecular characteristics and 5–7, 5t Blackbox warnings, 27, 484 therapeutic use, 610t strategic acquisition of, 5–6 BLE. See Biologic license Bovine-extracted insulin, 308 strategic acquisition of, by integrated establishment Bovine somatotropin derivatives, biopharmaceutical companies, 35t Bleeding disorders, inherited, 225–226 suffixes for, 619 Biotechnology industry, novel Blepharospasm, Xeomin in treatment Bovine spongiform encephalopathy, 32 therapeutic agents and, 26 of, 421, 422 Bowman’s capsule, 91 Biotechnology medicines, top 25, based Blinatumomab (MT103), 159t BPCA. See Best Pharmaceuticals for on worldwide sales, 6t, 7, 10–11 Blinding, 113 Children Act Biotechnology products Blockbuster drugs, financial benefits BPD. See Bronchopulmonary dysplasia chemical products vs., 16–18 with, 34 Brambell receptor, 153, 154 identifying key in vitro correlates Blood, major role of, 218 BRCA1 mutations, altered response to predictive of in vivo responses Blood cells chemotherapy in women for, 531 hematopoietic development of, 213 with, 484

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 641 0002007355.INDD 641 8/20/2013 1:44:57 AM 642 index

Breast cancer dosage form, pharmacokinetics, and SNPs and predisposition to, 484 BRCA1 mutations and, 484 disposition data, 567t treatment of, biopharmaceuticals Herceptin in treatment of, 208, 209 molecular characteristics and and, 10 HER2-positive metastatic, Perjeta in therapeutic use, 599t vaccines for, 404, 405 treatment of, 201, 202 Campath (alemtuzumab) Cancer cells, liposomes and target- metastatic, Avastin in treatment dosage form, 170 selective delivery to, 450 of, 176 dosage form, pharmacokinetics, and Cancer therapy Breath samples, profiling engodenous disposition data, 556t IL-2 in, 253, 255 metabolites with, 528 indications and use, 170 interferon biology and, 256–271 Brentuximab vedotin (Adcetris) molecular characteristics and antitumor effects in humans, additional information, 177 therapeutic use, 582t overview, 262–264 clinical leverage strategy and, 31t for multiple sclerosis, 279t, 280 classification, pharmacology, and clinical pharmacology, 177 route of administration, 170 biological properties, 257–260 disposition, 177 target, product type, indications, clinical impact, 264–271 dosage form, 177 FDA approval year, 148t interferon proteins and genes, 257 dosage form, pharmacokinetics, and Canada mechanisms of IFN action, disposition data, 557t evidence and value data essential for 260–262 drug interactions, 177 health care in, 542 perspective on, 271 general description, 176 health-care expenditure growth rate Candida albicans, SCID and, 361 indications and use, 176–177 in, 536 Candidate gene association studies, 477 molecular characteristics and health-care funding characteristics and Capillary electrophoresis, protein therapeutic use, 583t HTA programs in U.S. vs., 543t characterization and stability pharmacokinetics, 177 infant mortality and life expectancy assessment, 51t recommended dosage and rankings in, 537t Capillary leak syndrome, 253, 255 monitoring requirements, 177 Canakinumab (Ilaris), 150t Capoxone (glatiramer acetate), dosage role in therapy, 177 clinical pharmacology, 178 form, pharmacokinetics, and route of administration, 177 dosage form, 178 disposition data, 575t target, product type, indications, dosage form, pharmacokinetics, and Capromab pendetide (ProstaScint) (In FDA approval year, 149t disposition data, 557t 111) therapeutic response, 177 drug interactions, 178–179 dosage form, pharmacokinetics, and Bristol Meyer Squibb, revenue, market general description, 178 disposition data, 557t share, productivity, and research indications and use, 178 molecular characteristics and investments of, 5t molecular characteristics and therapeutic use, 583t Bronchopulmonary dysplasia, 198 therapeutic use, 583t CAPS. See Cryopyrin-associated BsAbs. See Bispecific antibodies other applications, 179 periodic syndromes Buccal route of administration, pharmacokinetics, 178 Carboxylation, in small-molecule therapeutic proteins and, recommended dosage and drugs, 9 431–432 monitoring requirements, 178 Carboxypeptidase A, 431 Buerger disease, 508 role in therapy, 179 Carcino-embryonic antigen, 454 Byetta (exenatide), 435 route of administration, 178 Cardiolipin, 456 dosage form, 323 target, product type, indications, Cardiomyocytes, stem cell-derived, 510 dosage form, pharmacokinetics, and FDA approval year, 149t Cardiotoxicity screening, pluripotent disposition data, 568t therapeutic response, 179 stem cells in, 510 indications and use, 323 Canaliculi, 433 Cardiovascular disease, 227 molecular characteristics and Cancer, 4, 553 leeches and their proteins and, 228 therapeutic use, 599t ADCC function of therapeutic Carimune NF, 144t role in therapy, 324 antibodies against, 156 Carmustine, 481 route of administration, 324 biomolecules intended for, 549 Carnot, Paul, 218, 219 Bypass surgery, gene therapy for cellular transporters, drug resistance Catumaxomab (Removab), 159t preventing late graft failure and, 481 Caucasian men, SRD5A2 and risk of after, 502 chemotherapy, pharmacogenetics of, prostate cancer in, 484 480–481 CBA. See Cost-benefit analysis Caenorhabditis elegans development, estrogen resistance in, genes CBER. See Center for Biologics proteins implicated in, 524 identified for, 475 Evaluation and Research Caffeine, molecular structure of, 8 gene therapy strategies for, 33 CCA. See Cost-consequences analysis Calcitonin, 33 genetic variations in drug response CCDI. See Central cranial diabetes dosage configuration, device, and due to multifaceted genes and insipidus bioavailability, 460, 460t proteins, 474 C2C9 genotype parenteral formulations, uses for, 445 immunotoxin field and treatment dosing recommendation range Calcitonin salmon (Miacalcin) of, 455 according to, of individuals

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 642 0002007355.INDD 642 8/20/2013 1:44:57 AM index 643

on warfarin anticoagulation review of new biotechnology Cervical dystonia, Xeomin in treatment therapy, 483t products under, 18 of, 421, 422 warfarin response and, 483 well-characterized Cervical neoplasia and cancer, HPV, CDAI. See Crohn’s disease activity biopharmaceuticals and, 17 Cervarix in prevention of, 411 index Center for Tobacco Products, 112 Cetrorelix acetate (Cetrotide) CDC. See Centers for Disease Control Centers for Disease Control and clinical pharmacology, 321 and Prevention Prevention, 21, 390 dosage form, 321 CDER. See Center for Drug Central cranial diabetes insipidus, dosage form, pharmacokinetics, and Evaluation and Research 318 disposition data, 567t CD4, 464 Central nervous system, multiple general description, 320–321 CDMRP. See Congressionally Directed sclerosis and, 275 indications and use, 321 Medical Research Programs Central precocious puberty molecular characteristics and cDNA, defined, 43t Lupron in treatment of, 342 therapeutic use, 599t cDNA clone, defined, 43t Supprelin LA in treatment of, 330 other applications, 321 cDNA cloning, 44 Synarel in treatment of, 344, 345 pharmacokinetics, 321 cDNA sequence analysis, 523 Centrifugal forced-film evaporators, 73 recommended dosage and CDS. See Chemical-based delivery Centrifuges, large-capacity, for monitoring requirements, 321 system separating cell lysates role in therapy, 321 CD20Bi, 159t containing pharmaceutical route of administration, 321 CEA. See Carcino-embryonic antigen; products, 71, 72 therapeutic response, 321 Cost-effectiveness analysis CER. See Comparative effectiveness Cetrotide (cetrorelix acetate), 316 CEA studies, league table of: cost- research dosage form, 321 effectiveness ratio, 129t Ceredase (alglucerase), 362 dosage form, pharmacokinetics, and Cell cultures, batch size of, and molecular characteristics and disposition data, 567t estimated time required for therapeutic use, 591t indications and use, 321 fermentation, 67t Ceredase (beta-glucuronidase), 454 molecular characteristics and Cell-dependent mechanism, antibody Cerezyme (imiglucerase), 33, 362 therapeutic use, 599t bioactivities and, 156 dosage form, pharmacokinetics, and recommended dosage and Cell diameters, estimates of, solid- disposition data, 563t monitoring requirements, 321 liquid separation and, 71t molecular characteristics and role in therapy, 321 Cell disruption methods, 71t therapeutic use, 592t route of administration, 321 Cell expression systems, product yield Certolizumab pegol (Cimzia), 157 Cetus, 5 and, optimization of, 50 additional information, 180 Cetuximab (Erbitux) Cell-free mechanism, antibody clinical pharmacology, 179 clinical pharmacology, 181 bioactivities and, 156 dosage form, 179 dosage form, 181 Cell lysates, separation of, with large- dosage form, pharmacokinetics, and dosage form, pharmacokinetics, and capacity centrifuges, 72 disposition data, 557t disposition data, 557t Cell-mediated immune response, 395 drug interactions, 180 drug interactions, 182 induced by vaccination, 393 general description, 179 general description, 181 T lymphocytes and, 393 indications and use, 179 indications and use, 181 Cells, 4 molecular characteristics and molecular characteristics and Cell technologies, for large-scale therapeutic use, 584t therapeutic use, 584t protein production, 5 pharmacokinetics, 179–180 other applications and additional Cellular transporters, drug resistance recommended dosage and information, 182 and, 481–482 monitoring requirements, 179 pharmacogenetics and, 483 Center for Biologics Evaluation and role in therapy, 180 pharmacokinetics, 181–182 Research, 14, 18, 22, 29, 104, 617 route of administration, 179 recommended dosage and biopharmaceutical approval and, 17 target, product type, indications, monitoring requirements, 181 FDA review and approval process, 114 FDA approval year, 149t role in therapy, 182 guidelines for macromolecules, 16 therapeutic response, 180 route of administration, 181 vaccine regulation and, 18, 397 Cervarix (human papillomavirus target, product type, indications, Center for Drug Evaluation and bivalent vaccine, recombinant) FDA approval year, 148t Research, 14, 22, 104, 105, 114 dosage form, 411 therapeutic response, 182 development of chemicals and dosage form, pharmacokinetics, and CF. See Cystic fibrosis macromolecules into drugs and, disposition data, 579t CFUs. See Colony-forming units 17t drug interactions, 411 cGMP. See Current good development of meningococcal indications and use, 411 manufacturing practice vaccine and, 21 molecular characteristics and Characterization, data mining, FDA review and approval process therapeutic use, 615t molecular cloning and, 40–41, and, 114 route of administration, 411 43–50

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 643 0002007355.INDD 643 8/20/2013 1:44:58 AM 644 index

Chemical-based delivery systems, 453 clinical pharmacology, 322 target, product type, indications, Chemical biology, biotechnology and, 7 dosage form, 322 FDA approval year, 149t Chemical drugs dosage form, pharmacokinetics, and Circular dichroism, protein biopharmaceuticals vs., 8–9 disposition data, 568t characterization and stability general pharmacokinetic and general description, 322 assessment, 51t pharmacodynamic features of, indications and use, 322 Circulatory system, maintaining 85t molecular characteristics and integrity of, 229 Chemical instability mechanisms, of therapeutic use, 599t Cisplatin, 481 proteins and peptides, 98, 98 pharmacokinetics, 322 women with BRCA1 mutations and Chemical marking, protein recommended dosage and treatment with, 484 modifications and, 89–90 monitoring requirements, 322 CKD. See Chronic kidney disease Chemical modifications, molecular role in therapy, 322 Cladribine, for multiple sclerosis, 279t approaches vs., 460–461 route of administration, 322 Clarithromycin, 480 Chemical products, biotechnology therapeutic response, 322 Clearance, 84 products vs., 16–18 Christensen, James, 489 drug-drug interactions and, 92 Chemicals, development of into drugs, Christmas disease (hemophilia B), drug formulation and, 80 regulatory requirements for, 17t Benefix in treatment of, 236, 237 estimating, 85 Chemical stability, physical stability and, Chromatographic assays, hepatic, symbol, mathematical in protein pharmaceuticals, 98 characterization tests of proteins relationship, and physiological Chemistry, Manufacturing, and and, 76 variables, 83 Controls (CMC) guidelines, 105 Chromatography, 473 modulation of, 446–449, 466 Chemists, on FDA review team, 117 final protein purification and, 75 renal, symbol, mathematical Chemokines, 213, 252, 275, 393 intermediate protein purification relationship, and physiological Chemostat process, large-scale and, 74–75 variables, 83 cultivation of host cells and, 69, 69 Chromosomal translocation, 58 reticuloendothelial system and Chemotherapy, BRCA1 mutations and Chromosomes mononuclear phagocyte system altered response to, 484 locations of genes linked to medical in, 438 Chickenpox (varicella), 416 conditions and, 488 role of glycan on erythropoietin Varivax for, 415 mapping, 522t and, 87 Children, FDA requirements, clinical gene, 518–519 Clinical drug development testing and, 113, 114 Chronic kidney disease integrating pharmacoeconomic Chimeric antibodies, reducing anemia associated with, Aranesp in outcome research in, 538–539, immunogenicity of, 146 treatment of, 238–239 541 Chimeric Mab products, 158 anemia associated with, Epogen and interactions of pharmacoeconomic China Procrit in treatment of, 240, 241 model-building efforts and, 544 health-care expenditure growth rate Chronic lymphocytic leukemia, Arzerra Clinical hypothesis, 109 in, 536 in treatment of, 196 Clinical leverage strategy, 36 infant mortality and life expectancy Chronic myelogenous leukemia, IFN- in accelerating drug development, rankings in, 537t alpha in treatment of, 264–265 30–31 new medicine development in, 122 Chronic myeloid leukemia, 58, 256, 490 clinical trial success rates compared variolation in, 391 Chronic neutrophilic leukemia, 263 to, historical data on, 31t Chinese hamster ovary (CHO) cells, Chymotrypsin, 90, 431, 524 new drug candidates in human 219, 220, 258, 548 Ciliary body, 433 clinical trials using, examples of, Mab therapeutic molecule Cimvax (Haemophilus b conjugate 31t–32t production and, 147 and hepatitis B (recombinant) Clinical studies, 104, 109–110, 112–114 recombinant mammalian host cell vaccine) dose-response profiles and, 81 production and, 67, 68, 68 dosage form, pharmacokinetics, and drug development process and, 15 Chiron, 5 disposition data, 577t globalization and, 122 Chlamydia pneumoniae, developing molecular characteristics and interrelationship of preclinical vaccines against, 404 therapeutic use, 612t studies and, 109 Chlorproguanil (Lapudrine), malaria Cimzia (certolizumab pegol), 157 pharmacology, conducting, 80 control and dapsone combined dosage form, 179 Clinical testing with, 490 dosage form, pharmacokinetics, and cost and time required for, 530 CHMP. See Committee for Medicinal disposition data, 557t fast-track, 107, 108 Products for Human Use indications and use, 179 in Japan, 122 Cholera, vaccine, 395 molecular characteristics and public stock offerings and cash for Choridal neovascularization, aptamer- therapeutic use, 584t later stages of, 26 based therapies and, 497 recommended dosage and special populations and, 113 Choriogonadotropin alpha (Ovidrel), monitoring requirements, 179 of vaccines in human subjects, phases 315 route of administration, 179 of, 397

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 644 0002007355.INDD 644 8/20/2013 1:44:58 AM index 645

viable drug candidates in general description, 236 Colorectal cancer development pipeline and, 521 indications and use, 236 Erbitux in treatment of, 181, 182 Clinical translational research, 24 molecular characteristics and metastatic, Vectibix in treatment of, Clinical trials, 104 therapeutic use, 596t 199, 200 biopharmaceutical company pharmacokinetics, 236 metatstatic, Avastin in treatment of, strategies and, 542, 545 recommended dosage and 175, 176 bispecific antibodies in, examples, monitoring requirements, 236 Column chromatography techniques, 159t role in therapy, 237 71 drug failures and, 530 route of administration, 236 isolating proteins with, 49, 50 embryonic stem cell-based therapies, therapeutic response, 237 Combinatorial chemistry, 18, 521 510 Coagulation factors, 229 COMET. See Consortium for hypothesis-driven, 109, 110 disorders, 226–227 Metabolomic Toxicology interindividual variation and failure hematopoietic growth and, 212–215, Committee for Advanced Therapeutics of drug candidates in, 472 217–218 (CAT), 507 for new therapeutic antibodies, 139, monographs list, 231 Committee for Medicinal Products for 140 therapeutic use of, 225–228 Human Use, 507 phase I, 15–16, 110, 112, 112t Coagulation factor VIIa (human Comparative effectiveness research, phase II, 16, 112, 112t, 113 recombinant) (NovoSeven) 542 phase III, 16, 112t, 113 additional information, 238 Comparative gene mapping, 522t phase IV, 114 clinical pharmacology, 237 Compartmental mathematical model, registration of, 110 dosage form, 237 pharmacokinetic parameters success rates of, compared to clinical dosage form, pharmacokinetics, and and, 83 leverage strategy, 31t disposition data, 565t Complete molecular remission, 264–265 ClinicalTrials.gov, 110, 111, 118 drug interactions, 237–238 Computer-assisted drug design, 18 CLL. See Chronic lymphocytic general description, 237 Computing power, drug target numbers leukemia indications and use, 237 and, 7 Cloning, 8 molecular characteristics and Comvax (Haemophilus b conjugate animal, 496 therapeutic use, 596t and hepatitis B (recombinant) nuclear transfer technology in, pharmacokinetics, 237 vaccine) 498, 498 recommended dosage and dosage form, pharmacokinetics, and cDNA, 44 monitoring requirements, 237 disposition data, 577t genes, 44–47 role in therapy, 238 molecular characteristics and genomic, 46, 46–47 route of administration, 237 therapeutic use, 613t human, 496, 499 therapeutic response, 238 Concanavilin A (ConA), 252 of nuclei, 498 Coagulation system, 212 Concentration-effect relationship, 95 PCR, 44–46 COBAS AMPLICOR HCV Test, 302 Concentration-percent response, 96 Clopidogrel, CYP2C19 and, 490–492 Codeine, 97 Conformational integrity requirement, Closed formulary list, 538 Codon optimization, 503 428 Clostridium acetobutylicum, 8 Colchicine, 92 Congestive heart failure, ACE deletion Clotting cascade, 225 Cold ethanol precipitation procedures, and, 486 Clotting factor IX, 33 144 Congressionally Directed Medical Clotting factor VIIa, 33 Collagenase Clostridium histolyticum Research Programs, 552 Clotting factor VIII, 33 (Xiaflex) Conjugate vaccines, for immunizing CMA. See Cost-minimization analysis dosage form, pharmacokinetics, and young children, 395–396 CML. See Chronic myeloid leukemia disposition data, 563t Conjunctiva, 433 CMR. See Complete molecular molecular characteristics and Conjunctival sac, 433 remission therapeutic use, 592t Consortium for Metabolomic CMV infection. See Cytomegalovirus Collategene, 508 Toxicology, 529 infection Colony-forming units, 222 Contamination, improving marketed CMV retinitis, treating, 34 Colony-stimulating factor 1, cell biopharmaceuticals and c-Myc, 510 source, functions, and molecular concerns about, 32–33 CNS. See Central nervous system characteristics, 216t Contraceptive vaccines, 404 Coagulation cascade, in hemostatic Colony-stimulating factors, 214, 218, Control groups, in phase II trials, 113 system, 212 223 Controlled- and sustained-release Coagulation factor IX (human CBER review of, 18 strategies, 440–441, 443–444 recombinant) (Benefix) kidney metabolism and elimination lipid-membrane-based carriers, 441, clinical pharmacology, 236 of, 92 443–444 dosage form, 236 list of, according to effector cells and polymer-based drug carriers, 440–441 dosage form, pharmacokinetics, and clinical applications, 223t Controlled drug delivery, implanted disposition data, 565t naming conventions for, 619t, 620 devices for, 459

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 645 0002007355.INDD 645 8/20/2013 1:44:58 AM 646 index

Controlled-rate infusion devices, 458 Crixivan, development/approval of, debrisoquine metabolism by, Control release, 466 project-team approach and variations of, 474, 474 Copaxone (glatiramer acetate) accelerated timeline for, 19, 20 Cysteine, three- and one-letter code, dosage form, 420 Crizotinib (Xalkori), 489 linear formula, structure for, indications and use, 420 Crohn’s disease 623t molecular characteristics and Cinzia in treatment of, 179, 180 Cystic fibrosis, 57, 368 therapeutic use, 610t Humira in treatment of, 166, 167, 168 DNAse for, 366–367 for multiple sclerosis, 277 Remicade in treatment of, 190, 191 aerosolized, 460 role in therapy, 421 Tysabri in treatment of, 194, 195 genes identified for, 475 route of administration, 420 Crohn’s disease activity index, 179, 180 Pulmozyme in treatment of, 374, Copegus (ribavirin), in treatment of Cryopyrin-associated periodic 375 chronic hepatitis C, 301 syndromes, Ilaris in treatment Cytochrome P450, 510 Copolymer-1, 277 of, 178, 179 cloning of, 521 Copurification, 526t Cryptorchidism, 316 drug interactions and, 92 Corneal endothelium, 433 Crystallizability, 141 Cytochrome P450 3A genetics, in drug Corneal epithelium, 433 CSF-1, 222 metabolism, 479–480 Corneal stroma, 433 CSF-2, 222 CytoGam (hepatitis B immune Corticosteroids, for multiple sclerosis, CSF-3, 222 globulin, human), molecular 277 CSFs. See Colony-stimulating factors characteristics and therapeutic Cortrosyn (cosytntropin) C77T, 486 use, 585t dosage form, pharmacokinetics, and CTLA-4, Yervoy bound to, 505 CytoGam (human cytomegalovirus disposition data, 568t CTLs. See Cytotoxic T lymphocytes immune globulin), dosage molecular characteristics and CUA. See Cost-utility analysis form, pharmacokinetics, and therapeutic use, 599t Current Good Manufacturing Practice disposition data, 558t Corynebacterium diphtheriae, 455 guidelines CytoGram, therapeutic use for, 145t Cost-benefit analysis, 128, 128t description of FDA regulatory Cytokine erythopoietin, 219 Cost-consequences analysis, 128, 128t authority and, 77 Cytokines, 215 Cost-control measures FDA and compliance with, 76 dosage form, pharmacokinetics, and dilemmas tied to, 539 sections of, 105, 106 disposition data, 573t–574t quality-adjusted life year and, 540 Cyclic adenosine monophosphate hormones vs., 252 Cost-effectiveness analysis, 127–128, (cAMP) concentrations, PTH locally secreted, 252 128t and, 314 molecular characteristics, 252 demonstrating, health-care program Cyclic AMP receptor proteins, 526 molecular characteristics and adoption and, 539 Cyclic GMP receptor proteins, 526 therapeutic uses for, 607t–609t incremental cost effectiveness ratio Cyclic nucleotide-binding domain, monographs list, 288 and, 128 527t multiple sclerosis and, 275 quality-adjusted life year and, 540 Cyclophosphamide, 481 pleiotropic effects and, 501 Cost estimates, for biopharmaceuticals, Cyclosporine, 89, 445 proinflammatory, 393 129–131 Cyclosporine A, structure of, 446 review by CDER through BLA Cost management, formulary systems CYP, drug toxicities and role of, 510 pathway, 104 and, 538 CYP1A2, 476t, 479t therapeutic use of, 252 Cost-minimization analysis, 128t CYP3A, 479, 480 Cytomegalovirus (CMV) infection Cost-utility analysis, 128, 128t CYP3A4, 476t, 479, 480 adjuvanted pDNA therapy and, Cosytntropin (Cortrosyn) CYP3A5, 476t, 479 508–509 dosage form, pharmacokinetics, and CYP3A5*1, 480 immnoglobulin products and, 144 disposition data, 568t CYP3A5*3, 480 Cytomegalovirus (CMV) retinitis molecular characteristics and CYP3A7, 479 treating, 98 therapeutic use, 599t CYP3A43, 479 Vitravene (formiversen) for, 496 sources and clinical use of, 309t CYP activity data, 511–512, 513t Cytotoxic T lymphocytes, 393–394, 395 Cowpox, 391 CYP3A4 gene, 480 Cowpox vaccination, 140 CYP2C9, 476t, 479t Dabigatran (Pradexa), 483 CPI. See Critical Path Initiative CYP2C19, 476t, 479t, 480 Dacarbazine (DTIC), 508 CPP. See Central precocious puberty clopidogrel and, 490–492 Daclizumab (Zenapax) CP-690550, clinical leverage strategy warfarin anticoagulation effects, dosage form, pharmacokinetics, and and, 32t genetic variation in and vitamin disposition data, 557t Creatinine clearance, 85 K 2,3-epoxide reductase, molecular characteristics and Cremophor EL (POE-35 castor oil), 482–483 therapeutic use, 584t 446 CYP2C19 genetics, Helicobacter pylori role in therapy, 172 Creutzfeldt-Jakob disease, 33, 308, 353 infection and, 480 target, product type, indications, Critical Path Initiatives (2004), 112, 489 CYP2D6, 476t, 478, 479t FDA approval year, 148t

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 646 0002007355.INDD 646 8/20/2013 1:44:58 AM index 647

Dagarelix (Firmagon), molecular indications and use, 323 Designer protein therapeutics, 220 characteristics and therapeutic pharmacokinetics, 323 Desmopressin, 318t, 431, 432 use, 599t recommended dosage and bioavailability of, effects of Daltons, 8 monitoring requirements, 323 administration route and, 431t Dana Dibecare, 458 role in therapy, 323 schematic presentation of, 432 Dapsone-related hemolytic anemia, route of administration, 323 Desmopressin acetate, 318 lack of G6PDH and, 490 therapeutic response, 323 sources and clinical use of, 309t Daptacel (diphtheria and tetanus Degludec (insulin-degludec), 313, 462, Developmental project-team toxoids and acellular pertussis 463 strategies, in developing new vaccine adsorbed) pharmacokinetic and biopharmaceuticals, 520 dosage form, pharmacokinetics, and pharmacodynamics attributes, DHT. See Dihydrotestosterone disposition data, 576t 461t Diabetes, 4, 518 molecular characteristics and Demyelineated plaques, multiple glucose control for, Symlin in therapeutic use, 612t sclerosis and, 275 treatment of, 349, 350 Darbepoetin alpha (Aranesp), 220, 464 Denatured proteins, 87, 87 glycemic control for, long-acting, clinical pharmacology, 239 Dendritic cells, 140, 393 Levemir for, 334–335 dosage form, 239 Denileukin diftitox (Ontak), 455 glycemic control for, rapid-acting, dosage form, pharmacokinetics, and clinical pharmacology, 291 Apidra for, 336, 337 disposition data, 565t dosage form, 291 glycemic control for, rapid-acting, drug interactions, 239 dosage form, pharmacokinetics, and NovoLog for, 332–333 general description, 238 disposition data, 573t glycemic control in, Humulin and indications and use, 238–239 general description, 291 Novolin in treatment of, 331 molecular characteristics and molecular characteristics and glycemic control of, long-acting, therapeutic use, 596t therapeutic use, 607t Lantus for, 335, 336 other applications and additional other applications and additional glycemic control of, rapid-acting, information, 239 information, 292 Humalog for, 337, 338 pharmacokinetics, 239 pharmacokinetics, 291 treatment of, biopharmaceuticals recommended dosage and recommended dosage and and, 10 monitoring requirements, 239 monitoring requirements, 291 vaccines against, 404 role in therapy, 239 role in therapy, 292 Diabetes Control and Complications route of administration, 239 route of administration, 291 Trial, 332 therapeutic response, 239 therapeutic response, 291 Diabetes mellitus, 313 Data exclusivity clause, generic Denosumab (Prolia) Diabetic neuropathic ulcers, Regranex manufacturers and, 117 clinical leverage strategy and, 31t Gel in treatment of, 419, 420 Data exclusivity period, for clinical pharmacology, 183 Diarrhea in VIPomas, Sandostatin in biopharmaceuticals, 134 dosage form, 183 treatment for, 346, 347 Data mining, molecular cloning, dosage form, pharmacokinetics, and Differential scanning calorimetry, characterization and, 40–41, disposition data, 558t protein characterization and 43–50 general description, 182–183 stability assessment, 51t Daunorubicin, 456 indications and use, 183 Dihydropyrimidine dehydrogenase, 479t DDMAC. See Division of Drug molecular characteristics and gene coding for, degradation of Marketing, Advertising, and therapeutic use, 584t fluorouracil and, 481 Communications other applications, 183 genetic variations found in, 478 Deadweight loss, 131 pharmacokinetics, 183 Dihydrotestosterone, 484 Deamidation, proteins, peptides and, 98 recommended dosage and Dimethyl sulfoxide, 444, 511, 511t Debrisoquine metabolism, by CYP2D6, monitoring requirements, 183 Diphtheria, 156 variations of, 474, 474 role in therapy, 183 death rate of, progression in U.S., Decanter centrifuge, separation route of administration, 183 390, 390 of cell lysates containing therapeutic response, 183 Diphtheria, tetanus, and pertussis pharmaceutical products and, Denosumab (Prolia, Xgeva), target, vaccines. See Acel-Imune; 71, 72 product type, indications, FDA Daptacel; Infanrix; Pediarix; Deep vein thrombosis, Leiden approval year, 149t Tripedia mutation and, 477 Depakote, off-label promotion of, Diphtheria bacillus, isolation of, 140 Degarelix (Firmagon) settlements and, 118, 119t Diphtheria toxin, 464 clinical pharmacology, 323 Department of Defense, 552 construction of immunotoxins and, disposition, 323 Department of Health and Human 455t dosage form, 323 Services, 14, 104 Direct colony screening using protein dosage form, pharmacokinetics, and Department of Health Services, 81 blot, screening/verifying disposition data, 568t Department of Justice, 118 molecular clones from gene general description, 323 Desialylation, 86 expression system and, 49t

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 647 0002007355.INDD 647 8/20/2013 1:44:58 AM 648 index

Direct injection, of protein advances in, 40, 47 Doxorubicin, 456 pharmaceuticals, 428 description of, 522t women with BRCA1 mutations and Discovery phase, in developing new Docetaxel (Taxotere), BRCA1 tumor treatment with, 484 biopharmaceuticals, 520 cell lines resistant to, 484 DPD. See Dihydropyrimidine Disease-modifying antirheumatic drugs DOJ. See Department of Justice dehydrogenase Actemra used in combination with, Dolly, cloned sheep, 497, 498, 499 Drotrecogin alfa (Xigris) 206 Domain modification, enhanced additional information, 377 Cimzia used in combination with, 180 pharmaceutical potential clinical pharmacology, 376 Humira used in combination with, 166 through, 56 dosage form, 376 Kineret used in combination with, 290 Dornase alpha (Pulmozyme), 33, 367 dosage form, pharmacokinetics, and Orencia used in combination with, 163 clinical pharmacology, 375 disposition data, 563t Simponi used in combination with, dosage form, 375 general description, 376 187, 188 drug interactions, 375 indications and use, 376 Diseases general description, 374 molecular characteristics and health-care expenditures and indications and use, 374–375 therapeutic use, 592t prevention of, 537 other applications and additional pharmacokinetics, 376 identifying specific genes associated information, 375 recommended dosage and with, 57 pharmacokinetics, 375 monitoring requirements, 376 immune system, vaccines and, recommended dosage and role in therapy, 376 393–394 monitoring requirements, 375 route of administration, 376 Disetronic, 458 role in therapy, 375 therapeutic response, 376 Disk stack centrifuge, separation route of administration, 375 Drug addiction, vaccines against, 404 of cell lysates containing therapeutic response, 375 Drug candidate selection, refining, 7 pharmaceutical products and, Dosage formulations Drug concentration, pharmacological 71, 72 in administration of and toxicological responses Distribution, of recombinant protein biopharmaceuticals, 97t and, 80 pharmaceuticals, 85–86 animal testing and, 108–109 Drug delivery Disulfide bridges, 141, 142 route of administration and, 98–99, advanced, 427–466 Disulfide exchange, 89–90, 98 100 approaches using devices, 458–460 Division of Drug Marketing, Dose concentration, pharmacological molecular approaches, 460–465 Advertising, and and toxicological responses physiological and mechanistic Communications, 118 and, 80 approaches, 436, 438–458 DMARDs. See Disease-modifying Dose-dependent effects, on volume of routes of therapeutic protein antirheumatic drugs distribution, 84t administration, 430–436 DMF. See N,N-dimethyl formamide Dose-effect relationship, knowledge flux and, 439 DMSO. See Dimethyl sulfoxide of, 95 goal of, 427 DNA Dose range, interindividual variation, reticuloendothelial system and PCR gene amplification and, 45 472 mononuclear phagocyte system of target genes, isolating, 44 Dose-response profiles in, 438 transcription of, to mRNA, 41 for drugs, 81 Drug development process DNA-based vaccines, 553 in a population, 96 accelerating, clinical leverage DNA-liposome complexes, 500 Dose-response relationship, knowledge strategy in, 30–31 DNA microarray technology, 525, 531 of, 95 collaborations involved in, 13 DNA plasmid products, well- Doses and dosing costs related to, 24 characterized, 17 for antibodies, 151–153 current trends in, 18–21 DNA replication technology, 7, 8 immunogenicity and, 93 project-team approach, 19–20 DNAse, aerosolized, 460 Double-blind studies, 113 social entrepreneurs, 20–21 DNAse (dornase alfa), for cystic Downregulation mechanism, drug incentives for, 133 fibrosis, 366–367, 434 interactions and, 92 increasing cost of, 18 DNAse (Pulmozyme) Downsizing, pharmaceutical companies integrating genomic, proteomic, dosage form, pharmacokinetics, and and, 34 and metabolomic tools for disposition data, 563t Downstream processing and acceleration of, 530–532 molecular characteristics and purification preclinical, 520 therapeutic use, 592t biotechnology products and, 70–71, product indications and therapeutic DNA sequences 73–75 target in, 27 in human genome, additional concentration of putative product schematic presentation of, 15 analysis of, 523 before purification, 71, 73–74 significant scientific and capital optimizing, to enhance protein further purification, 74–75 investments in, 24 expression, 48 objective in, 70 spending on, 14 DNA-sequencing technologies, 523 solid-liquid separation, 70–71 spiraling cost of, 530

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 648 0002007355.INDD 648 8/20/2013 1:44:58 AM index 649

success rate of, products of genomic Drug sponsors EDSS. See Expanded Disability Status and proteomic information pharmacoeconomic data collected Scale and, 524 by, 545 Efalizumab (Raptiva), target, product time and cost involved in, 16 phase II studies and, 16 type, indications, FDA approval transforming new molecules into Drug targets year, 148t drugs, 14–16 genetic variations in drug response Efficacy Drug discovery/development, proteins due to multifaceted genes and data for NDA or BLA, 14 and genes as targets for, 56–58 proteins, 474 globalization and, 122 Drug disposition, identifying proteins to sites of action, 449–450 interindividual variation and, 472 and processes central to, 531 validated, 33 pharmacogenetics and, historical Drug-drug interactions Drug therapeutic index, clinical impact perspective on, 473–475, 477 elderly patients and, 113 and, 429–430 Efficiency, drug pricing and mechanisms behind and concerns Durham-Humphrey Amendment assumptions tied to, 133 with, 92 (1951), 111 Efflux transporters, 445 Drug flux, across a barrier, schematic Durmowicz, Elizabeth, 114 EFPIA. See European Federation of representation of, 439, 439 Dynamic efficiency, drug development Pharmaceutical Industries and Drug formularies, 127, 545 and, 133 Associations biotechnology products and, 539 Dysport (botulinum toxin type a) EF2 regulatory protein, 156 overall impact on health care dosage form, pharmacokinetics, and EGFR. See Epidermal growth factor systems/patients and, 538 disposition data, 575t receptor Drug industry, influence of molecular characteristics and EG-IFN-alpha 2b (PEGintron-A), biopharmaceuticals on, 549–550 therapeutic use, 610t source, indication, comments, Drug interactions, FDA and In vitro 272t screening for, 530 Early-stage model, pricing estimates Egrifta (tesamorelin), 311 Drug-like characteristics, and, 542 dosage form, pharmacokinetics, and acceptable, evolution of, and Eastern Cooperative Oncology Group, disposition data, 572t pharmacokinetic properties, 521t melanoma studies, 268, 269, indications and use, 354 Drug-like properties, characterizing, 270 molecular characteristics and basis of, 449–450 Ebola, developing vaccines against, therapeutic use, 606t Drug Price Competition and Patent 404, 404t role in therapy, 355 Term Restoration Act of 1984, Ecallantide (Kalbitor) route of administration, 354 111, 133 dosage form, pharmacokinetics, and Ehrlich, Paul, 143, 145 Drug pricing. See Pricing for drugs disposition data, 575t ELA. See Establishment License Drugs molecular characteristics and Application absorbption of, permeation therapeutic use, 610t Elaprase (idursulfase), 364 enhancers and, 444–445 ECOG. See Eastern Cooperative dosage form, 378 administration of, systemic routes Oncology Group dosage form, pharmacokinetics, and for, 428 Economic good, value of, 126 disposition data, 563t approval of, risk-benefit assessment Economics, defined, 126 indications and use, 378 and, 81 Economic value, assigning, QALY and, molecular characteristics and evaluation of, by independent 538–539 therapeutic use, 592t experts, 14 Eculizumab (Soliris) role in therapy, 378–379 history of regulation governing in additional information, 185 route of administration, 378 U.S., 111 clinical pharmacology, 184 Elastase, 90 metabolism of, cytochrome P450 3A dosage form, 184 Elastic drug bellow, physically driven genetics in, 479–480 dosage form, pharmacokinetics, and portable infusion device and, potency of, 95 disposition data, 558t 458, 459 regulatory requirements for general description, 184 Elderly population development of chemicals and indications and use, 184 drug safety and efficacy data macromolecules into, 17t molecular characteristics and for, 81 resistance to, cellular transporters therapeutic use, 584t FDA requirements, clinical testing and, 481–482 pharmacokinetics, 184 and, 113 responses to recommended dosage and Electron paramagnetic resonance, genetic variations in, effects of, monitoring requirements, 184 protein characterization, 474, 474–475 role in therapy, 185 stability assessment and, 51t identifying interspecies differences route of administration, 184 Electroporation, vaccine delivery and, in, 81 target, product type, indications, 402 intersubject variation in, 472 FDA approval year, 148t Eli Lilly & Co., revenue, market share, Drug screening, combinatorial therapeutic response, 184 productivity, and research

chemistry merged with, 521 ED50, 96 investments of, 5t

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 649 0002007355.INDD 649 8/20/2013 1:44:58 AM 650 index

Elimination Endothelial cells, 90, 213 Eosinophil colony-stimulating factor, of biotherapeutics, 100 Endotoxin concentrations, removal of, cell source, functions, and drug-drug interactions and, 92 in protein purification, 74–75 molecular characteristics, 216t drug formulation and, 80 Endotoxin units, FDA requirements Eosinophil differentiation factor, cell of large molecules, 84 for, 98 source, functions, and molecular of recombinant protein Engerix-B (hepatitis B vaccine, characteristics, 216t pharmaceuticals, 86–87, 89–92 recombinant), 9, 10t Eosinophils, 215 of small molecules, 84 dosage form, 409–410 Epaxal (hepatitis A vaccine), 452 Elimination rate constant, 84 dosage form, pharmacokinetics, and Epidermal growth factor receptor, 181, symbol, mathematical relationship, disposition data, 578t 200 and physiological variables, 83 indications and use, 409 Epilepsy, cellular transporters, drug ELISA. See Enzyme-linked molecular characteristics and resistance and, 481 immunosorbent assay therapeutic use, 614t Epithelial cells, lining nose, Elitek (rasburicase), 367 route of administration, 410 gastrointestinal tract, and dosage form, 384 England, variolation in, 391 alveoli, 434 dosage form, pharmacokinetics, and Enkephalin, 452 Epitopes, 141, 145 disposition data, 563t enzyme-mediated targeting of, using Epivir (lamivudine or 3TC), 273 indications and use, 384 prodrug strategy, 453 EPO. See Erythropoietin molecular characteristics and Enkephalins, 54 Epoetin, 115, 116 therapeutic use, 593t Enzyme-based optimization, of IgG cell source, functions, and molecular route of administration, 384 antibody derivatives, 52 characteristics, 216t Elizabeth Taylor AIDS Foundation, 552 Enzyme-linked immunosorbent assays, 50 fully glycosylated vs. desialylated, 87 EMA. See European Medicines assessment of immunogenicity and, 93 naming conventions for, 620 Agency characterization tests of proteins roller bottle technology and Embedded controller, 30-L bench and, 76 production of, 68, 68 fermentor, 67 screening/verifying molecular clones Epoetin alfa (Epogen, Procrit) Embryonic cloning, 495, 496 from gene expression system clinical pharmacology, 240 EMEA. See European Agency for and, 49t disposition, 240 the Evaluation of Medicinal Enzyme replacement therapy, 359, dosage form, 240 Products 361–365 dosage form, pharmacokinetics, and Emphysema, Prolastin-C in treatment Enzymes, 3, 5, 473 disposition data, 565t of, 418, 419 defined, 357, 358 drug interactions, 240 Enbrel (etanercept), 57, 153, 464–465 dosage form, pharmacokinetics, and general description, 240 annual revenue for, 7 disposition data, 562t–564t indications and use, 240 dosage form, 185 fibrinolytic, 366 molecular characteristics and dosage form, pharmacokinetics, and future prospects for, 368 therapeutic use, 597t disposition data, 558t metabolic, polymorphically other applications and indications and use, 185 expressed, individualization of considerations, 241 molecular characteristics and drug regimens and, 476t pharmacokinetics, 240 therapeutic use, 584t molecular characteristics and recommended dosage and neutralization of TNF-alpha and, 156 therapeutic applications, monitoring requirements, 240 recommended dosage and 358–359, 361–368 role in therapy, 241 monitoring requirements, 185 molecular characteristics and route of administration, 240 route of administration, 185 therapeutic uses, 591t–594t therapeutic response, 240–241 sponsors, indications, annual sales in monographs list, 370 Epoetin alfa (Epogen; Procrit/Eprex), millions, 6t reported deficiencies in, and their sponsors, indications, annual target, product type, indications, clinical presentation, 360t sales in millions, 6t FDA approval year, 148t review by CDER through BLA Epoetin alfa (NeoRecormon), sponsors, Endocrine hormones, 308 pathway, 104 indications, annual sales in Endocytosis, of proteins, 91 role of genetic variation in, 475 millions, 6t Endoderm, 509 select, therapeutic potential use for, 365t Epogen (epoetin alfa), 28 Endogenous proteins, biologic drug as therapeutic agents, 365–368 dosage form, 240 candidates derived from, 40 DNAse enzyme for cystic fibrosis, dosage form, pharmacokinetics, and Endometriosis 366–367 disposition data, 565t Lupron in treatment of, 340, 342 oncolytic enzyme therapies, indications and use, 240 Synarel in treatment of, 344, 345 367–368 molecular characteristics and Endonucleases, defined, 43t thrombolytic, 365–366 therapeutic use, 597t Endopeptidases, 90 in vivo drug availability and, 530 role in therapy, 241 Endoplasmic reticulum, translation of “-zyme” suffix for, 357 sponsors, indications, annual sales in mRNA to protein in, 41 E1B-55 kDa, 501, 502 millions, 6t

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 650 0002007355.INDD 650 8/20/2013 1:44:58 AM index 651

EPO receptors, 222 life span of, 217 pharmacokinetics, 186 Epratuzumab, 150t origins of, 218 recommended dosage and Eprex (epoetin alfa) Erythropoiesis-stimulating agents, 219, monitoring requirements, 185 modification in production, and 221, 221t role in therapy, 186 significant consequences in Erythropoietin, 28, 33, 215, 219–222, route of administration, 185 erythropoietin immunogenicity, 229, 430, 501 sponsors, indications, annual sales in 115, 116 CBER review of, 18 millions, 6t sponsors, indications, annual sales in cell source, functions, and molecular target, product type, indications, millions, 6t characteristics, 216t FDA approval year, 148t Epstein-Barr virus, 275, 361 cell types increased/activated and therapeutic response, 186 Eptifibatide (Integrilin), 228 therapeutic uses for, 223t Ethnic variation, polymorphisms and, clinical pharmacology, 242 defective, RBC levels and, 94 482 disposition, 242 glycosylation and, 87, 462, 524 Ethylene-vinyl acetate copolymers, dosage form, 241 linkage to peptide backbone, 82t drug delivery and, 459 dosage form, pharmacokinetics, and with N-linked glycosyl group and Euglycemia, 313 disposition data, 565t terminal sialic acid cap, 88 Eukaryotes drug interactions, 242 molecular weight and volume of fermentation and, 67 general description, 241 distribution for, 84t identifying target genes in, gene- indications and use, 241 naming conventions for, 620 activation signals and tissue or molecular characteristics and Erythropoietin-alfa, 115 cell sources for, 43t therapeutic use, 597t Erythropoietin gene control, biology Eukaryotic cells other applications, 243 of, 221 choosing host cells for recombinant pharmacokinetics, 242 Erythropoietin immunogenicity, protein expression in recommended dosage and modification in production of pharmaceutical scale and, 65t monitoring requirements, Eprex, and consequences in, post-translational modification and, 64 241–242 115, 116 Eukaryotic hosts role in therapy, 243 Erythropoietin molecules, glycosylated, engineering expression system for route of administration, 241 molecular and biological proteins and, 47, 48 therapeutic response, 242 characteristics of, 464t production costs and erbA, 491 ESA APPRISE Oncology Program, biopharmaceuticals produced erbB, 491 239 in, 548 erbB-2, 490 ESAs. See Erythropoiesis-stimulating Europe, evidence and value data Erbitux (cetuximab), 552 agents essential for health care in, 542 approval of, 110 Escherichia coli, as prokaryotic host, 548 European Agency for the Evaluation dosage form, 181 Esoderm, 509 of Medicinal Products, 120t dosage form, pharmacokinetics, and Essential thrombocytosis, 263 European Federation of disposition data, 557t pegylated IFN-alpha, better platelet Pharmaceutical Industries and FDA’s refuse-to-file response letter control and, 266 Associations, 120t and, 109 Establishment License Application, European Medicines Agency (EMA), Imclone Systems and, 18 104, 105 115, 120, 507, 537 indications and use, 181 biopharmaceutical approval and, European Organization for Research molecular characteristics and 16, 17 and Treatment of Cancer, therapeutic use, 584t development of chemicals and melanoma studies, 268, 269 recommended dosage and macromolecules into drugs Evaporators, 73 monitoring requirements, 181 and, 17t EWGs. See Expert Working Groups route of administration, 181 Estrogen, 308 Excipients, for enhancing protein target, product type, indications, ESTs. See Expressed sequence tags stability in solution and FDA approval year, 148t ET. See Essential thrombocytosis lyophilized formulations, 99t Erely, Kark, 4 Etanercept (Enbrel), 464–465 Exenatide (Byetta) Ernst & Young, 26 clinical pharmacology, 185–186 additional information, 324 EROD assay, to assess CYP activity, dosage form, 185 clinical pharmacology, 324 511, 512 dosage form, pharmacokinetics, and disposition, 324 Erslev, Allan, 219 disposition data, 558t dosage form, 323 ERT. See Enzyme replacement therapy drug interactions, 186 dosage form, pharmacokinetics, and Ertumaxomab, 159t general description, 185 disposition data, 568t Erwinia caratovora, 367 indications and use, 185 drug interactions, 324 Erwinia chrysanthemi, 367 molecular characteristics and general description, 323 Erythroblasts, 213 therapeutic use, 584t indications and use, 323 Erythrocytes, 212 other applications and additional molecular characteristics and effect of high or low numbers of, 219t information, 186 therapeutic use, 599t

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 651 0002007355.INDD 651 8/20/2013 1:44:58 AM 652 index

Exenatide (Byetta) (cont’d) Factor IX, 225, 503, 504 Fentanyl skin patches, 435, 436 pharmacokinetics, 324 glycosylation linkage to peptide Fermentation recommended dosage and backbone, 82t of bacteria, yeast, and mammalian monitoring requirements, 324 Factor IXa, 225 cells, 7 role in therapy, 324 Factor VII, 225 batch size of cell cultures and route of administration, 324 glycosylation linkage to peptide estimated time required for, therapeutic response, 324 backbone, 82t 67t Exhaust condensor, 30-L bench Factor VIII, 225, 503, 504 Fermentation procedures fermentor, 67 glycosylation linkage to peptide for large-scale protein production, 5 Exhaust line, 30-L bench fermentor, 67 backbone, 82t systematic optimization of, in pilot Exocrine hormones, 308 Factor VIIIa, 225 plant, 66 Exon organization, analysis of, 523 Factor X, 225 Fermentation technology, 8 Exopeptidases, 90 glycosylation linkage to peptide Fermentors, 66 Expanded Disability Status Scale, 297 backbone, 82t 30-L bench, scaled for production of Expert Working Groups, 121 “Fail early-fail cheaply” notion, 530 recombinant proteins, 67 Expressed sequence tags, 58, 523 Falling-film evaporator, 73 Fexofenadine, 9, 108 Expression system, engineering for Familial cold autoinflammatory FGF-2 gene therapy, refractory angina respective proteins, 47–48 syndrome, Ilaris in treatment of, and, 502 Extavia (interferon beta-1b) 178, 179 FGI-101-1A6, 150t dosage form, 299 Family Smoking Prevention and Fibrin, 225, 227 dosage form, pharmacokinetics, and Tobacco Control Act (2009), 112 Fibrin degradation reactions, disposition data, 573t Fanolesomab (NeutroSpec), target, thrombolytic enzymes and, 359 indications and use, 299 product type, indications, FDA Fibrinogen, human and thrombin, molecular characteristics and approval year, 148t human (Tisseel kit) therapeutic use, 608t Fast-track clinical testing, 107, 108 dosage form, pharmacokinetics, and role in therapy, 300 FAST4WARD trial, 180 disposition data, 575t route of administration, 299 Fatty acyl groups, attributes of, 442t molecular characteristics and Extraction ratio, 85 Fatty alcohol: NAD+ oxidoreductase, therapeutic use, 610t Extramedullary hematopoiesis, 213 therapeutic potential with, 365t Fibrinolytic activity, therapeutic Exubera Fatty aldehyde dehydrogenase, enzymes and catalyzing of, bioavailability of, 434 therapeutic potential with, 365t mechanisms of action, 366t clinical success vs. commercial Fc, 141, 142 Fibrinolytic enzymes, 227, 366 success and, 435 FCAS. See Familial cold Fibroblast growth factor, 508 Eye, schematic representation of, 433 autoinflammatory syndrome Fibroblasts, 213 Eylea (aflibercept) Fc domain sequences, addition of, Field reviewers (FDA), 118 dosage form, 168 modulation of clearance of Filgrastim (Neupogen) dosage form, pharmacokinetics, and therapeutic protein by, 57 clinical pharmacology, 244 disposition data, 556t Fc receptor (FcRn), 153 dosage form, 243 indications and use, 168 fetal, role of, on human endothelial dosage form, pharmacokinetics, and molecular characteristics and cells in regulating human disposition data, 565t therapeutic use, 582t IgG concentration in blood drug interactions, 244 route of administration, 168 circulation, 154 general description, 243 FcRN, 86 indications and use, 243 Fab, 141, 142, 147 FDA. See Food and Drug molecular characteristics and

Fab2, 141, 142 Administration therapeutic use, 597t Fabrazyme (agalsidase beta), 363, 454 FDA Modernization Act (1997), 103, Orphan Drug Classification and dosage form, 370 105, 110, 111 impact of indications/timing dosage form, pharmacokinetics, and FDF. See Fibroblast growth factor of approval dates on revenues disposition data, 562t Febrile neutropenia for, 30t indications and use, 370 Neulasta in treatment of, 248 other applications and additional molecular characteristics and Neupogen in treatment of, 243, 244 information, 244 therapeutic use, 591t Fed-batch process, large-scale pharmacokinetics, 244 recommended dosage and cultivation of host cells and, recommended dosage and monitoring requirements, 370 69, 69 monitoring requirements, route of administration, 370 Federal Food, Drug, and Cosmetic Act 243–244 Fabry’s disease, 357 (1938), 111, 397 role in therapy, 244 Fabrazyme in treatment of, 363, Federal grants, for start-up route of administration, 243 370, 371 biotechnology companies, 26 sponsors, indications, annual sales in FACS. See Fluorescence-activated cell Feedback-regulated drug delivery millions, 6t sorter devices, 458 therapeutic response, 244

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 652 0002007355.INDD 652 8/20/2013 1:44:58 AM index 653

Filters Fluorescence-activated cell sorter, disposition, 326 in solid-liquid separation, 71 screening/verifying molecular dosage form, 326 30-L bench fermentor, 67 clones from gene expression dosage form, pharmacokinetics, and Filtration systems, protein system and, 49t disposition data, 568t concentration and, 74 Fluorescence-tagged antibody analysis, general description, 325–326 Final global payer model, 544 526 indications and use, 326 Financial crisis of 2007-2008, Fluorouracil, cetuximab used in molecular characteristics and biotechnology companies and, combination with, for carcinoma therapeutic use, 600t 26, 26t of the head and neck, 182 other applications, 327 Financing biologic drug development, Flux, estimating rate of drug moving pharmacokinetics, 326 23–36 across a barrier by, 439 recommended dosage and clinical leverage strategy and, 30–31 Fluzone Intradermal (influenza virus monitoring requirements, 326 evolving trends in, 34–36 vaccine) role in therapy, 326–327 overview of, 24–27 dosage form, 413 route of administration, 326 role of Orphan Drug Act and, 27–30 dosage form, pharmacokinetics, and therapeutic response, 326 therapeutic target considerations in, disposition data, 579t Follow-on biologics, 7, 224–225 32–34 indications and use, 413 Fomivirsen sodium (Vitravene), dosage developing novel molecular characteristics and form, pharmacokinetics, and biopharmaceuticals, 33–34 therapeutic use, 615t disposition data, 564t improving marketed role in therapy, 413 Fomivirsen (Vitravene), 34, 496 biopharmaceuticals, 32–33 route of administration, 413 dosage form, pharmacokinetics, and Finasteride (Proscar), 484 therapeutic response, 413 disposition data, 575t Fingolimod (Gilenya), for multiple FMCP. See Foundation of Managed molecular characteristics and sclerosis, 277, 279t Care Pharmacy therapeutic use, 610t Finnish Blood Bank, 271 fms-like tyrosine kinsase 3, cell source, Food and Drug Act (1906), 111 Firmagon (degarelix), 316 functions, and molecular Food and Drug Administration, 1, 14, dosage form, 323 characteristics, 216t 31, 103, 120t, 137, 536, 537, 544 dosage form, pharmacokinetics, and FOBs. See Follow-on biologics accelerated clinical evaluation and disposition data, 568t Folate, 484–485 drug approval by, 107 indications and use, 323 Folate metabolism, MTHFR in, 485– advancement of regulatory science molecular characteristics and 486 and, 550 therapeutic use, 599t Folic acid receptors, liposome targeting advisory panels, drug approval recommended dosage and and, 457 process, 114 monitoring requirements, 323 Folitropin-beta (Follistim), 315 biopharmaceutical approval process, route of administration, 323 Follicle-stimulating hormone, 308, 310, 16–18 First-in-human studies 315, 324, 325, 326 Category D classification, 265 design of, 112 Follistim (follitropin-beta), 315 consolidated review of new dose-escalation, 430 dosage form, pharmacokinetics, and biotechnology products by, 18 “First-to-market,” financial impact disposition data, 568t Critical Path Initiative, 489 of, 29 molecular characteristics and current Good Manufacturing Fixed cost, biopharmaceuticals and, 129 therapeutic use, 600t Practice guidelines and, 76, 77, Flebogamma, 144t Follitropin alfa (Gonal-F), 315 106 Flocculation method, for separating clinical pharmacology, 325 development of meningococcal solids and liquids, 71 disposition, 325 vaccine and, 21 FLT-3 ligand dosage form, 324 documentation of manufacturing cell source, functions, and molecular dosage form, pharmacokinetics, and process controls, 75 characteristics, 216t disposition data, 568t draft guidance on biosimilar product cell types increased/activated and general description, 324 development, 116 therapeutic uses for, 223t indications and use, 324 drug development and approval FluMist Quadrivalent (influenza virus molecular characteristics and process of, 14–16 vaccine, live, intranasal) therapeutic use, 599t endotoxin unit requirements of, 98 dosage form, 413 other applications, 325 Exubera marketing approval from, dosage form, pharmacokinetics, and pharmacokinetics, 325 435 disposition data, 579t recommended dosage and first interferon approved by, 256 indications and use, 413 monitoring requirements, 325 human testing of stem cell therapy molecular characteristics and role in therapy, 325 and, 214 therapeutic use, 615t route of administration, 325 increase in number of medicines route of administration, 413 therapeutic response, 325 approved by, 518 Fluorescence, protein characterization, Follitropin-beta (Follistim) insulin delivery devices approved stability assessment and, 51t clinical pharmacology, 326 by, 458

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 653 0002007355.INDD 653 8/20/2013 1:44:58 AM 654 index

Food and Drug Administration (cont’d) FSH. See Follicle-stimulating hormone Ganirelix acetate (Antagon) Investigational New Drug Functional genomics, description of, dosage form, pharmacokinetics, and applications and, 110 522t disposition data, 568t labeling approved by, 27, 118 Functional proteins, production of, molecular characteristics and licensing of biologic drug candidates genome sequences verified for, therapeutic use, 600t and, 13 519 Ganirelix acetate (Ganirelix acetate liposome-formulated drugs approved Fused gene analysis, 526, 526t injection) by, 443 Fusion proteins clinical pharmacology, 327 main goal of, 22 further refinement in design dosage form, 327 monoclonal antibodies approved of, 465 general description, 327 by, 33 target recognition domains and, 464 indications and use, 327 new drugs approved by, decline in, 34 Fv-toxin, 157 other applications, 327–328 nomenclature conventions and, 617, pharmacokinetics, 327 618 GAA deficiency (Pompe’s disease), recommended dosage and Office of Orphan Product Myozyme and Lumizyme in monitoring requirements, 327 Development, 29 treatment of, 371, 372, 373 role in therapy, 327 orphan designation from, 27 Gabiltril, off-label promotion of, route of administration, 327 Pediatric Rule promulgated by, 111 settlement involving, 119t therapeutic response, 327 pharmacogenetic information on GAG. See Glycosaminoglycans Ganitumab, 150t product labels and, 483 Galiximab, 150t GAO. See Government Accountability pharmacogenetics paradigm and, 492 Galsulfase (Naglazyme), 364 Office recombinant products as viewed clinical pharmacology, 377 Gardasil (human papillomavirus by, 105 dosage form, 377 quadrivalent vaccine), 8 review and approval process of, 104, dosage form, pharmacokinetics, and CBER review of, 18 114–118, 550 disposition data, 563t dosage form, 410 review team members, 117 general description, 377 dosage form, pharmacokinetics, and risk-benefit assessment and drug indications and use, 377 disposition data, 579t approval through, 81 molecular characteristics and drug interactions, 410 vaccines approved by, 397 therapeutic use, 592t indications and use, 410 Food and Drug Amendments Act, 110 for MPS VI Maroteaux-Lamy molecular characteristics and Forced-film evaporator, 73 syndrome, 364–365 therapeutic use, 615t Formulary committee, 127 pharmacokinetics, 377 route of administration, 410 Formulary systems, 538 recommended dosage and sponsors, indications, annual sales in Forteo (teriparatide), 314, 315 monitoring requirements, 377 millions, 6t dosage form, 353 role in therapy, 377 GASs. See Gamma-activated sites dosage form, pharmacokinetics, and route of administration, 377 Gastric cancer, Herceptin in treatment disposition data, 572t therapeutic response, 377 of, 208 indications and use, 353 Gamimmune N-10% & 5% (immune Gastrointestinal tract molecular characteristics and globulin intravenous, human) epithelial cells in lining of, 434 therapeutic use, 606t dosage form, pharmacokinetics, and molecular weight and bioavailability project-team approach in disposition data, 559t of protein, drug, and peptide development of, 19 molecular characteristics and absorbed from, 432t route of administration, 353 therapeutic use, 587t protein and peptide absorption from, sponsors, indications, annual sales in Gamma-activated sites, 261 factors tied to, 431t millions, 6t Gamma family, human chromosome, Gaucher, P.C.E., 362 Fosamax (alendronate), 315 number of genes, AA number, “Gaucher cells,” 388 Foundation of Managed Care homology, 256t Gaucher’s disease, 357, 368 Pharmacy, 541 Gammagard Liquid, 144t classification of, 362 Fraction excreted unchanged, symbol, Gammagard S/D, 144t glucocerebrosidase for, 362–363 mathematical relationship, and Gamma globulin, 144 type I, Cerezyme in treatment of, 379, physiological variables, 83 Gammaplex, 144t 380 Fragment of antigen binding. See Fab Gammar-PIV (immune globulin, Vpriv in treatment of, 387, 388 France, infant mortality and life human) GBA gene deficiency, Gaucher’s expectancy rankings in, 537t dosage form, pharmacokinetics, and disease and, 388 Freeze-dried protein formulations, disposition data, 559t GC-mass spectrometry, metabolomic improving stability of, 99 molecular characteristics and research and, 529t Fridericia correction method, 182 therapeutic use, 586t GC-SF. See Granulocyte colony- “From-gene-to screen” process, 57 Gamunex-C, 144t stimulating factor Fruit fly (Drosophila melanogaster), Ganciclovir, 9, 9 GDH-PQQ based glucose monitoring, 398, 523 Ganirelix, 33, 316 164

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 654 0002007355.INDD 654 8/20/2013 1:44:58 AM index 655

GDP. See Gross domestic product cloning, 44–47 Genomic cloning, 46, 46–47 Gel electrophoresis, 76, 473 human chromosomes and locations Genomic DNA, defined, 43t Gelonin, construction of immunotoxins of, linked to medical conditions, Genomic information and, 455t 488 acquiring and analyzing, approaches Gemtuzumab ozogamicin (Mylotarg) human gene sequences with putative in, 522t dosage form, pharmacokinetics, and functions verified, 519t improved safety and production of disposition data, 558t identifying optimal source for biopharmaceuticals and, 548–549 target, product type, indications, isolation of, 43–44 Genomics, 18, 517, 518, 533 FDA approval year, 148t as targets for drug discovery and bioinformatics in, description of, 522t Genasense, 496 development, 56–58 comparative, 552 Gendicine, 507 transforming into as first link between sequences and Gene and cell therapy, 495–513 biopharmaceuticals, progress drug targets, 521–524 general strategies in, 499–501 and benefits in, 548 functional, description of, 522t cell therapy, 500–501 Gene therapeutics new generation of vaccines and, 389 gene therapy, 499–500 dosage form, pharmacokinetics, and structural, description of, 522t medical conditions and promise of, disposition data, 564t Genomic tools, accelerating drug 513 molecular characteristics and development with, 530–532 overview of, 496–497, 499 therapeutic uses for, 594t Genotropin (somatropin) in research, development, and Gene therapy, CBER evaluation of, 18 additional information, 353 clinical use, 506–509 Genetic biomarkers, list of drugs with, annual revenue for, 7 for select medical conditions, 501– that have been validated and dosage form, 351 506 provided in FDA-approved dosage form, pharmacokinetics, and head and neck cancer, 501–502 product label, 485t disposition data, 571t hemophilia, 502–503 Genetic constructs, yield optimization general description, 351 monogenic and acquired disorders, in, 65, 66 indications and use, 351 497t Genetic data, response to molecular characteristics and preventing late graft failure after chemotherapy and, 481 therapeutic use, 604t bypass surgery, 502 Genetic engineering, 40 off-label promotion of, settlements refractory angina, 502 Genetic information and, 118, 119t stem cell therapy to produce health insurance eligibility, pharmacokinetics, 352 insulin, 505 employment and, 489 route of administration, 351–352 stem cell therapy to repair heart transcription and translation of, 41 sponsors, indications, annual sales in attack damage, 503–505 Genetic Information millions, 6t T-cell therapy for metastatic skin Nondiscrimination Act, 489 therapeutic response, 352 cancer, 505–506 Genetic polymorphism, stent Genotypes, 477 stem cells in regenerative medicine restenosis, ACE inhibitors and, Genotyping, 472, 473 and diagnostics, 505–512 486–487 of drug disposition genes for dosing Genebank database, 523 Genetics decisions, 490 Gene cluster analysis, 526, 526t biotechnology and, 7 warfarin anticoagulation therapy Gene duplication, human genome and, modern, basis of, 8 and, 483 523 Genetics Institute, 28 Gentuzumab oxogamicin (Mylotarg), Gene expression systems Genetic variations molecular characteristics and features and requirements of, of drug effects, list of drugs with therapeutic use, 585t comparison, 47t genetic biomarkers, validated Genzyme, 6 screening and verifying molecular and provided in FDA-approved revenue, market share, productivity, clones from, methods for, 49t product label, 485t and research investments of, 5t Gene mapping in drug response, effects of, 474, Germany chromosome and comparative, 474–475 evidence and value data essential for description of, 522t in enzymes, role of, 475 health care in, 542 to chromosomes, 518–519 of metabolizing enzymes, list of health-care expenditure growth rate Gene modulation, IFNs and, 261 drugs validated as affecting in, 536 Genentech, 5, 57, 81, 491 pharmacokinetics and drug infant mortality and life expectancy Gene orthologs, 523 disposition, 479t rankings in, 537t Gene pair analysis, 526t mutations in genes coding for a Germline gene therapy, 499 Generic Drug Enforcement Act (1992), receptor and, 475, 477 Germ theory, 140 111 Genome-wide linkage analysis, 477 Geron Corporation, 510 Generic drugs, 538 Genomic analysis GFP. See Green fluorescent protein cost-effective development of, 117 addressing limitations of, 523 GH deficiency, 310 Hatch-Waxman Act and, 133 of yeast and human cells, 522 in children, 311 Genes Genomic clone, defined, 43t IGF-I and growth rates in, 309

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 655 0002007355.INDD 655 8/20/2013 1:44:59 AM 656 index

GHRH. See Growth hormone- Glucagon (glucagon recombinant) GMP. See Good Manufacturing releasing hormone dosage form, 328 Practice Gigantism, SST analogs and treatment indications and use, 328 GnRH. See Gonadotropin-releasing of, 312 pharmacokinetics, 328 hormone Gilenya (fingolimod), for multiple recommended dosage and GnRH decapeptide sequences, analogs sclerosis, 277, 279t monitoring requirements, 328 of, and therapeutic applications, GINA. See Genetic Information therapeutic response, 328 317t Nondiscrimination Act Glucagon-like peptide 1 (GLP-1) “Golden Age” of vaccine development, Glatiramer acetate (Copaxone) receptor, 435 396 clinical pharmacology, 420–421 Glucagon recombinant (GlucaGen, Goldwasser, Eugene, 219, 220 dosage form, 420 Glucagon) Golimumab (Simponi) dosage form, pharmacokinetics, and clinical pharmacology, 328 additional information, 188 disposition data, 575t disposition, 328 clinical leverage strategy and, 31t general description, 420 dosage form, 328 clinical pharmacology, 187 indications and use, 420 general description, 328 dosage form, 187 molecular characteristics and indications and use, 328 dosage form, pharmacokinetics, and therapeutic use, 610t other applications, 329 disposition data, 558t for multiple sclerosis, 277, 279t pharmacokinetics, 328 drug interactions, 187–188 pharmacokinetics, 421 recommended dosage and general description, 187 recommended dosage and monitoring requirements, 328 indications and use, 187 monitoring requirements, 420 role in therapy, 328–329 molecular characteristics and role in therapy, 421 route of administration, 328 therapeutic use, 585t route of administration, 420 therapeutic response, 328 pharmacokinetics, 187 therapeutic response, 421 Glucocerebrosidase, for Gaucher’s recommended dosage and GlaxoSmithKline, revenue, market disease, 362–363 monitoring requirements, 187 share, productivity, and research Glucocerebroside, 362 role in therapy, 188 investments of, 5t Glucose 6-phosphate dehydrogenase, route of administration, 187 Gleevec (imatinib), 58, 471, 490, 492 478, 479t target, product type, indications, Glioblastoma, Avastin in treatment of, Glutamic acid, three- and one-letter FDA approval year, 149t 175, 176 code, linear formula, structure therapeutic response, 188 Globalization for, 623t Gonadotropin-releasing hormone, 33, of clinical drug development and Glutamine 310, 316 marketing, 113 deamidation of, 89 Gonadotropins, 315 of drug approval, 118, 120–122 three- and one-letter code, linear pharmacokinetic parameters future of biopharmaceuticals and, 135 formula, structure for, 623t of, 316t of pharmaceutical research, 542 Glybera, 507 therapeutic application of, 315–316 pricing biopharmaceuticals and, Glycans, 87 Gonal-F (follitropin alfa), 315 131–132 Glycemic control, 313 dosage form, 324 GlucaGen (glucagon recombinant) Glycine, 90 dosage form, pharmacokinetics, and dosage form, 328 three- and one-letter code, linear disposition data, 568t dosage form, pharmacokinetics, and formula, structure for, 624t indications and use, 324 disposition data, 568t Glycoprotein (gp) IIb/IIIa, 227 Luveris (lutropin alfa) administered indications and use, 328 Glycoprotein hormones, 315 concomitantly with, 342, 343 pharmacokinetics, 328 properties and molecular molecular characteristics and recommended dosage and characteristics of, 311t therapeutic use, 599t monitoring requirements, 328 Glycoprotein IIb/IIIa inhibitor, role in therapy, 325 Glucagon, 33, 307, 308, 505 bivalirudin and provisional use route of administration, 325 sources and clinical use of, 309t of, 234, 235 Good Manufacturing Practice, Glucagon, recombinant (Glucagon for Glycoproteins, 87 77, 105 injection/GlucaGen) Glycosaminoglycans, 363 Goserelin, 33 dosage form, pharmacokinetics, and Glycosylation, 64, 548 Goserelin acetate (Zoladex) disposition data, 568t effects of, on plasma concentration clinical pharmacology, 329 molecular characteristics and of GM-CSF, 82 disposition, 329 therapeutic use, 600t erythropoietin and, 462 dosage form, 329 Glucagon for injection/GlucaGen of IgG, 89, 153 dosage form, pharmacokinetics, and (glucagon, recombinant) of protein pharmaceuticals, disposition data, 568t dosage form, pharmacokinetics, and variations in, 82 general description, 329 disposition data, 568t protein stability and, 87, 89 indications and use, 329 molecular characteristics and GM-CSF. See Granulocyte-macrophage molecular characteristics and therapeutic use, 600t colony-stimulating factor therapeutic use, 600t

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 656 0002007355.INDD 656 8/20/2013 1:44:59 AM index 657

other applications, 330 Growth hormones, 3, 104, 307, elimination, symbol, mathematical pharmacokinetics, 329 308, 310 relationship, and physiological recommended dosage and G6PD. See Glucose 6-phosphate variables, 83 monitoring requirements, 329 dehydrogenase Haptens, 92 role in therapy, 330 G6PDH, dapsone-related hemolytic Harmonization guidelines, global drug route of administration, 329 anemia and lack of, 490 development and, 120–121 therapeutic response, 329–330 GSK249320, 150t Hatch-Waxman Act, 133 Gout, uric acid in, Krystexxa in “Guidance for Industry,” FDA, QA/QC Havrix (hepatitis A vaccine, treatment of, 383, 384 standards and, 77 inactivated) Government Gurdon, John, 510 dosage form, pharmacokinetics, and funding for biopharmaceutical drug GUSTO, 366 disposition data, 578t development and, 25, 36 molecular characteristics and pharmaceutical drug discovery and Haemophilus b conjugate and hepatitis therapeutic use, 613t development and, 25 B (recombinant) vaccine HBV. See Hepatitis B virus Government Accountability Office (Cimvax) HBV surface “s” antigen, 272 (GAO), 118, 536 dosage form, pharmacokinetics, and HCC. See Hepatocellular carcinoma GPIIb/IIIa inhibitors, 33 disposition data, 577t hCG. See Human chorionic Graft failure after bypass surgery, gene molecular characteristics and gonadotropin therapy for, 502 therapeutic use, 612t HCV. See Hepatitis C virus Graft-versus-host reactions, 140 Haemophilus b conjugate and hepatitis Head and neck cancer Granulocyte colony-stimulating factor, B (recombinant) vaccine Erbitux in treatment of, 181, 182 29, 33, 215, 222–223, 229, 501 (Comvax) gene therapy to augment cell source, functions, and molecular dosage form, pharmacokinetics, and chemotherapy for, 501–502 characteristics, 216t disposition data, 577t Headplate ports, 30-L bench fermentor, cell types increased/activated and molecular characteristics and 67 therapeutic uses for, 223t therapeutic use, 613t Health authority bodies, 541 glycosylation linkage to peptide Haemophilus b conjugate vaccine, Health care backbone, 82t tetanus toxoid conjugate pharmacoeconomics and rising cost roller bottle technology and (ActHIB, OmniHIB) of, 126 production of, 68, 68 dosage form, pharmacokinetics, and regional differences in type of Granulocyte-macrophage colony- disposition data, 577t evidence and value data stimulating factor, 33, 222 molecular characteristics and essential for, 541–542 cell source, functions, and molecular therapeutic use, 613t Health-care decisions, health outcomes characteristics, 216t Haemophilus b (conjugate vaccine, and, 536–538 effects of glycosylation on plasma meningococcal protein Health-care expenditures concentration of, 82 conjugate) (PedvaxHIB) comparison of growth rate among formulation of, in liposomes, 443 dosage form, pharmacokinetics, and select nations, 536 glycosylation linkage to peptide disposition data, 577t outcome comparison with rankings backbone, 82t molecular characteristics and for select countries, 537t naming conventions for, 619t therapeutic use, 613t Health economics, 126 Granulocyte-monocyte colony- Haemophilus b conjugate vaccine Health insurance eligibility, genetic stimulating factor, 29 (diphtheria CRM 197-protein information and, 489 cell types increased/activated and conjugate) (HibTITER) Health Insurance Portability and therapeutic uses for, 223t dosage form, pharmacokinetics, and Accountability Act, 489 Granulocytopenia, 217 disposition data, 577t Health plans, cost of new medicines Granulomatous disease, chronic, molecular characteristics and and, 127–128 Actimmune in treatment of, 300, therapeutic use, 613t Health technology assessment (HTA) 301 Haemophilus influenzae, FDA- models, 127, 535, 539, 541, 544– Green fluorescent protein, 525 approved subcellular vaccines 545, 549, 551 Gross domestic product, health-care against, 395 Heart and Estrogen/Progestin expenditures and, 536 Hairy cell leukemia Replacement Study, 487 Growth factor fusion toxin, 455 BL22 (RFB4-PE38) and, 455 Heart attacks, stem cell therapy for Growth factors, 229 Intron A in treatment of, 294 repairing damage from, 503–505 Growth failure, somatropin in Roferon A in treatment of, Heart disease, vaccines against, 404 treatment of, 351, 352, 353 292, 293 Heart failure, angiotensin-converting Growth hormone analogs, naming type B-cell, malignant, interferon enzyme genotype and, 486 conventions for, 619 treatments for, 256 Heat-assisted evaporation strategies, 73 Growth hormone-releasing hormone Hale, Victoria, 20, 21 Heavy (H) chains, 141, 141t, 142 derivatives, therapeutic Half-life Helicobacter pylori infection, CYP2C19 application of, 311–312 defined, 84 genetics and, 480

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 657 0002007355.INDD 657 8/20/2013 1:44:59 AM 658 index

Helixate FS (antihemophilic factor) Heparin-induced thrombocytopenia molecular characteristics and dosage form, pharmacokinetics, and bivalirudin and, 234, 235 therapeutic use, 614t disposition data, 564t Refludan in treatment of, 244, 245 Hepatitis B vaccine (recombinant) molecular characteristics and Heparin-induced thrombocytopenia (Recombivax) therapeutic use, 594t and thrombosis syndrome, dosage form, pharmacokinetics, and Hemagglutinin A, 400 bivalirudin and, 234, 235 disposition data, 578t Hematological system, divisions within, Hepatic clearance, of protein and molecular characteristics and 212 nucleic acid drugs, PEG therapeutic use, 614t Hematologic and coagulation factors modification and, 449t Hepatitis B virus dosage form, pharmacokinetics, and Hepatitis, immnoglobulin products Engerix-B and Recombivax HB in disposition data, 564t–567t and, 144 treatment of, 409, 410 molecular characteristics and Hepatitis A inactivated and hepatitis B global infection with, CDC estimates, therapeutic uses for, 594t–599t (recombinant) vaccine (Twinrix) 272 Hematology research, 212 dosage form, pharmacokinetics, and interferon treatment for, 272–273, 280 Hematopoiesis, 212, 217, 500 disposition data, 578t Intron A in treatment of, 294 Hematopoietic cell types, effect of high molecular characteristics and Hepatitis C virus or low numbers of, 219t therapeutic use, 613t, 614t Copegus in treatment of, 301 Hematopoietic control, 218 Hepatitis A vaccine, inactivated global infection with, CDC estimates, Hematopoietic cytokines, extensive (Havrix) 273 study of, 224 dosage form, pharmacokinetics, and Infergen in treatment of, 295, 296 Hematopoietic growth, coagulation disposition data, 578t interferon in treatment of, 273–274, 280 factors and, 212–215, 217–218 molecular characteristics and Intron A in treatment of, 294 Hematopoietic growth factors, 214–215, therapeutic use, 613t Pegasys in treatment of, 301, 302 223 Hepatitis A vaccine, inactivated PegIntron in treatment of, 302, 303 cell source, functions, and molecular (Vaqta) Rebetol in treatment of, 302, 303 characteristics, 216t dosage form, pharmacokinetics, and Roferon A in treatment of, 292, 293 list of, according to effector cells and disposition data, 578t Hepatocellular carcinoma, 273 clinical applications, 223t molecular characteristics and Hepatocyte differentiation, human monographs list, 231 therapeutic use, 614t stem cell lines available for, 511t therapeutic use of, 218–225 Hepatitis A vaccine (Epaxal), 452 Hepatocyte growth factor, 511, 511t erythropoietin, 219–222 Hepatitis B antigen, HLA types B46 Hepatocyte growth factors follow-on biologics and prospects, and B15 and, 93 developing, high cost of, 224 224–225 Hepatitis B immune globulin (human) Hepatocytes GM-CSF, M-CSF, and CSF, 223 (CytoGam), molecular derived from stem cells and their granulocyte colony-stimulating characteristics and therapeutic metabolic functions, summary factor, 222–223 use, 585t of, 513t other HGFs, 224 Hepatitis B immune globulin from pluripotent stem cells, 510–512 thrombopoietin, 223–224 (human) (Nabi-HB), dosage proteolysis and, 90 Hematopoietic proteins, 212 form, pharmacokinetics, and stem cell-derived, evaluating, 511 Hematopoietic stem cells, 140, 213, 214 disposition data, 558t Hepatocyte stimulatory factor, cell Hemophilia, 225–226 Hepatitis B vaccine, 3, 9, 11 source, functions, and molecular Hemophilia, gene therapy for, 502–503, history behind, 8 characteristics, 216t 504 inactivated, 33 Hepatosplenic T-cell lymphoma, 168 Hemophilia A, 226 recombinant, comparison of dose HepG2 cells, 512 IV formulation of desmopressin and recommendations, 10t Hepsera (adefovir dipivoxil), 273 treatment of, 318 Hepatitis B vaccine (Engerix-B, HER2, 152, 200 NovoSeven in treatment of, 237 Recombivax HB) HER3, 200 ReFacto in treatment of, 231, 232, 233 clinical pharmacology, 410 HER4, 200 Hemophilia B, 226, 227, 503 dosage form, 409–410 HER2 antigen expression, levels of, Benefix in treatment of, 236, 237 general description, 409 and overall response rate to NovoSeven in treatment of, 237, 238 indications and use, 409 Herceptin, 491t Hemorrhage recommended dosage and Herceptin (trastuzumab), 134, 471, 490, hemostasis and, 225 monitoring requirements, 410 492, 552 ReFacto in treatment of, 231, 232, 233 role in therapy, 410 annual revenue for, 7 Hemostasis, 212 route of administration, 410 dosage form, 208 defined, 225 therapeutic response, 410 dosage form, pharmacokinetics, and maintaining, 365, 366 Hepatitis B vaccine (recombinant) disposition data, 562t platelets and fibrin working (Engerix-B) dose-dependent nonlinearity in together in response to blood dosage form, pharmacokinetics, and clearance and plasma half-life vessel leakage, 213 disposition data, 578t of, 152t

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 658 0002007355.INDD 658 8/20/2013 1:44:59 AM index 659

dose-dependent pharmacokinetics High-throughput gene sequencing, Hodgkin lymphoma, Adcetris in of, 152, 152 advent of, 56 treatment of, 177 FDA approval of as therapy, HER2 High-throughput screening, 18 Hollow fiber culture system, 70, 71 expression test on tumor tissues High throughput technologies, 4 Hollywood studios, “blockbuster” and, 491 HIPAA. See Health Insurance concept and, 34 indications and use, 208 Portability and Accountability H1N1 generic vaccine (influenza A individualized drug therapy and, 490 Act (H1N1) 2009 monovalent levels of HER2 antigen expression Hirudin, 228 vaccine), 412 and overall response rate to, Hirudo medicinalis (medical leeches), Hormone replacement therapy, 491t 228 prothrombotic mutations, risk of molecular characteristics and Hispanic men, SRD5A2 and risk of MI and, 487 therapeutic use, 591t prostate cancer in, 484 Hormones nonproprietary USANC assigned Histidine, 89 cytokines vs., 252 name, 618 three- and one-letter code, linear dosage form, pharmacokinetics, and recommended dosage and formula, structure for, 624t disposition data, 568t–572t monitoring requirements, 208 Histrelin acetate (Supprelin LA, integrated release of, 310 role in therapy, 208 Vantas) molecular characteristics and route of administration, 208 clinical pharmacology, 330 therapeutic uses for, 308, sponsors, indications, annual sales in dosage form, 330 599t–607t millions, 6t dosage form, pharmacokinetics, and monographs list, 320 target, product type, indications, disposition data, 568t new, approval of, 33 FDA approval year, 148t general description, 330 potency of, 308 Herd immunization, 395 indications and use, 330 recombinant, 307 Heredity, Mendelian principles of, 8, molecular characteristics and recombinant and synthetic, 473 therapeutic use, 600t therapeutic application of, Herpes infection, acyclovir for, 9 other applications, 331 309–318 Herpes simplex virus, size-dependent pharmacokinetics, 330 gonadotropin-releasing hormone, targeting to lymphoid tissue recommended dosage and 316 and, 451 monitoring requirements, 330 gonadotropins, 315–316 Herpes zoster (shingles), Zostavax for role in therapy, 331 growth hormone-releasing prevention of, 416 route of administration, 330 hormone derivatives, 311–312 HER2/neu, 490 therapeutic response, 330–331 human growth hormone, 310 hESC. See Human embryonic stem HIT. See Heparin-induced insulin and derivatives, 313–314 cells thrombocytopenia keratinocyte growth factor, HESs. See Hydroxyethyl starches HITTS. See Heparin-induced 312–313 Heterogeneity, pharmacology and, thrombocytopenia and oxytocin, 316–317 81–82 thrombosis syndrome parathyroid hormone, 314–315 Hexameric insulin, 313 HIV/AIDS, 553 somatostatin derivatives, 312 HGFs. See Hematopoietic growth biomulecules intended for, 549 vasopressin derivatives, 317–318 factors Crixivan for, 19 Host-against-mouse allergic (HAMA) HGS. See Human Genome Sciences developing vaccines against, 404, reactions, 143 HHS. See Department of Health and 404t, 405 Host cells Human Services prime-boost immunization and large-scale cultivation of, methods HibTITER (Haemophilus b conjugate vaccines against, 402–403 for, 66–70 vaccine, diphtheria CRM HIV/AIDS foundations, 552 batch process, 68–69, 69 197-protein conjugate) HIV/AIDS vaccine, challenges in chemostat process, 69, 69 dosage form, pharmacokinetics, and development of, 402 fed-batch process, 69, 69 disposition data, 577t HIV drugs, small or peptide-based, perfusion configuration, 69, 69–70 molecular characteristics and 551 yield optimization in, 65, 66 therapeutic use, 613t HIV gag, processing, role of protease HPLC. See High-pressure liquid High, Katherine, 503, 504 in, 54 chromatography High-molecular-weight HIV protease substrates and inhibitors, HPLC-ion exchange, protein biopharmaceuticals, 1 55, 56 characterization, stability High-performance chromatography, HIV proteins, recombinant, 551 assessment and, 51t 528 HIV resistance, genes identified for, HPLC-reversed phase, protein High-pressure liquid chromatography, 475 characterization, stability dosage formulations for Hizentra, 144t assessment and, 51t biopharmaceuticals and, 98 hMG. See Human menopausal HPLC-size exclusion, protein High-throughput assays, proteomics gonadotropin characterization, stability and, 525 HMRbase, 308 assessment and, 51t

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 659 0002007355.INDD 659 8/20/2013 1:44:59 AM 660 index

HPV diseases and cancer, Gardasil in molecular characteristics and role in therapy, 332 prevention of, 410 therapeutic use, 601t route of administration, 331 HRT. See Hormone replacement Human chorionic gonadotropin therapeutic response, 332 therapy (Profasi) Humanized Mab products, 158 HSA. See Human serum albumin dosage form, pharmacokinetics, and Human menopausal gonadotropin, HSCs. See Hematopoietic stem cells disposition data, 569t sources and clinical use of, 309t HSTCL. See Hepatosplenic T-cell molecular characteristics and Human Metabolome database, 529 lymphoma therapeutic use, 601t Human monoclonal antibody, HTA models. See Health technology Human clinical efficacy trials, molecular weight and volume of assessment models integrating pharmacoeconomic distribution for, 84t Humalog (insulin lispro), 462, 463 studies with, 540 Human papillomavirus bivalent dosage form, 337–338 Human clinical trials, of drug vaccine (Cervarix) dosage form, pharmacokinetics, and candidates, progression in, 112t dosage form, 411 disposition data, 569t Human cloning, 496, 499 dosage form, pharmacokinetics, and indications and use, 337 Human cytomegalovirus immune disposition data, 579t molecular characteristics and globulin (CytoGam), dosage drug interactions, 411 therapeutic use, 601t form, pharmacokinetics, and general description, 411 other applications, 338–339 disposition data, 558t indications and use, 411 pharmacokinetic and Human efficacy drug testing, 539 molecular characteristics and pharmacodynamics attributes, Human embryonic kidney (HEK) cells, therapeutic use, 615t 461t 548 route of administration, 411 recommended dosage and Human embryonic stem cells, 505, 509, Human papillomavirus quadrivalent monitoring requirements, 338 509 vaccine (Gardasil) role in therapy, 338 Human EPO, 220 clinical pharmacology, 410 route of administration, 338 Human gene count, recent estimates dosage form, 410 sponsors, indications, annual sales in of, 548 dosage form, pharmacokinetics, and millions, 6t Human genes, identification of, disposition data, 579t Humalog Mix 50/50 genomic information and, 523 drug interactions, 410 dosage form, 338 Human gene sequences, with putative general description, 410 pharmacokinetics, 338 functions verified, 519t indications and use, 410 route of administration, 338 Human genome mapping, 4, 523 molecular characteristics and Humalog Mix 70/30 Human genome project, 40, 518, 548 therapeutic use, 615t dosage form, 337–338 Human Genome Sciences, 58 pharmacokinetics, 410 pharmacokinetics, 338 Human GH (hGH), delineation of, as recommended dosage and route of administration, 338 soma-trem vs. soma-tropin, 309 monitoring requirements, 410 Humalog Mix 75/25 Human growth hormone, 28, 252 role in therapy, 411 dosage form, 337 concentration in plasma, effects of route of administration, 410 pharmacokinetics, 338 route and sustained release therapeutic response, 410–411 route of administration, 338 formulation in time course of, Human recombinant DNAse, dose- Human Ab technologies, 4 441 dependent effects on volume of Human-against-mouse allergic PLG-formulated, 441 distribution for, 84, 84t reactions, 146 therapeutic application of, 310 Human recombinant erythropoietin, Human-based recombinant proteins, Human IFN molecules, family of, 256t dose-dependent effects on immune responses and, 92 Human immune globulin (BayGam) volume of distribution for, 84t Human cells dosage form, pharmacokinetics, and Human recombinant tumor necrosis genomic analysis of, 522 disposition data, 558t factor-alpha, dose-dependent number of unique gene transcripts molecular characteristics and effects on volume of distribution in, 523 therapeutic use, 585t for, 84, 84t Human chorionic gonadotropin, 308, Human insulin (Humulin, Novolin) Humans, gene therapy in, ex vivo and 309t, 315 clinical pharmacology, 332 in vivo approaches, 499–500 Human chorionic gonadotropin dosage form, 331 Human serum albumin, physiological (Novarel) drug interactions, 332 properties and disposition of, in dosage form, pharmacokinetics, and general description, 331 humans, 143t disposition data, 568t indications and use, 331 Human Stem Cell Institute, Moscow, molecular characteristics and other applications and additional 507 therapeutic use, 600t information, 332 Human studies, Investigational New Human chorionic gonadotropin pharmacokinetics, 332 Drug applications and, 110 (Pregnyl) recommended dosage and Humate-P (antihemophilic factor/ dosage form, pharmacokinetics, and monitoring requirements, von Willebrand factor complex disposition data, 568t 331–332 (human)-factor VIII)

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 660 0002007355.INDD 660 8/20/2013 1:44:59 AM index 661

dosage form, pharmacokinetics, and Hunter syndrome, 364 ICS. See Inhaled corticosteroids disposition data, 565t Elaprase in treatment of, 378 ID disease genes, 4 molecular characteristics and Hurler-Scheie syndrome, 363, 364, 380 Iduronate-2-sulfatase, for MPS II therapeutic use, 595t Hurler syndrome, 363, 380 Hunter syndrome, 364 Humatrope (somatropin) Hybridomas, 8, 145, 146, 158 Idursulfase (Elaprase), 364 additional information, 353 Hybridoma technology, development additional information, 379 dosage form, 351 of, 145–146 clinical pharmacology, 378 general description, 351 Hydrogen-bonding activity, 521 dosage form, 378 indications and use, 351 Hydrolysis, proteins, peptides and, 98 dosage form, pharmacokinetics, and molecular characteristics and Hydrophilic drugs, hydrophobic drugs disposition data, 563t therapeutic use, 604t vs., 453 general description, 378 pharmacokinetics, 352 Hydrophobic drugs, hydrophilic drugs indications and use, 378 route of administration, 351 vs., 453 molecular characteristics and therapeutic response, 352 Hydrophobicity, 83, 521 therapeutic use, 592t Humegon (menotropins) Hydroxyethyl starches, 109, 110 pharmacokinetics, 378 dosage form, pharmacokinetics, and Hydroxylation, in small-molecule recommended dosage and disposition data, 570t drugs, 9 monitoring requirements, 378 molecular characteristics and Hyperimmune gamma globulins, 139 role in therapy, 378–379 therapeutic use, 603t Hyperimmune globulins route of administration, 378 Humira (adalimumab), 531, 552 production of, 144 therapeutic response, 378 annual revenue for, 7 therapeutic use for, 145t IFN-alfa family, 258 dosage form, pharmacokinetics, and Hypocalcemia, 314 IFN-alpha, 257, 259 disposition data, 556t Hypoglycemia, 313 alone or in combination, preclinical indications and use, 166 Hypoglycemic reactions, GlycaGen and rationale for, in MPN, 263–264 injectable, 167 Glucogon in treatment of, 328, antiproliferative and apoptotic molecular characteristics and 329 effects of, 261–262 therapeutic use, 582t Hypoparathyroidism, 314 for myeloproliferative neoplasms, neutralization of TNF-alpha and, 156 Hypothalamus, integrated hormone 263 route of administration, 167 release and regulation of, 310 proteins induced in humans by, 261t sponsors, indications, annual sales in Hypothesis-driven clinical trial, what is IFN-alpha1, 258 millions, 6t missing in, 110 IFN-alpha2, 258, 262 target, product type, indications, HZ. See Herpes zoster B-cell lymphomas and, 263 FDA approval year, 148t for chronic myelogenous leukemia Humoral immune response, 395 IAET. See International Association of treatment, 265 antibodies and, 393 Enterostomal Therapy for melanoma, 267–270 induced by vaccination, 393 Ibritumomab tiuxetan (Zevalin) polycythemia vera and molecular- Humulin (insulin) clinical pharmacology, 189 response benefits of, 265 dosage form, 331 dosage form, 188 side effects of, 269, 270–271 dosage form, pharmacokinetics, and dosage form, pharmacokinetics, and IFN-alpha2a (Roferon A), 258 disposition data, 569t disposition data, 559t source, indication, comments, 272t general description, 331 general description, 188 IFN-alpha2b (Intron A), 258 molecular characteristics and indications and use, 188 for melanoma, 268 therapeutic use, 601t molecular characteristics and source, indication, comments, 272t role in therapy, 332 therapeutic use, 586t IFN-alpha-con1 (Infergen), source, route of administration, 331 other applications and additional indication, comments, 272t Humulin N information, 189–190 IFN-alpha-n (Welferon), source, dosage form, 331 pharmacokinetics, 189 indication, comments, 272t route of administration, 331 recommended dosage and IFNAR-1, 260 Humulin R monitoring requirements, IFNAR-2, 260 dosage form, 331 188–189 IFN-beta, 257, 258–259, 261–262 route of administration, 331 role in therapy, 189 IFN-beta 1a, for melanoma, 267 Humulin (rh-Insulin), sponsors, route of administration, 188 IFN-beta1b (Betaseron), 258 indications, annual sales in target, product type, indications, IFNGR-1, 260 millions, 6t FDA approval year, 148t IFNGR-2, 260 Humulin R (U-500) therapeutic response, 189 IFN-kappa, 259 dosage form, 331 IBS. See Irritable bowel syndrome IFN-lambda, 259 route of administration, 331 ICER. See Incremental cost- IFN-lambda Type III IFNs, 259–260 Humulin 70/30 effectiveness ratio IFN-omega, 259 dosage form, 331 ICH. See International Conference on IFNs. See Interferons route of administration, 331 Harmonization IFN-stimulated genes, 256

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 661 0002007355.INDD 661 8/20/2013 1:44:59 AM 662 index

IFN-stimulated response element, 261 route of administration, 178 Immune globulin against D (RH1), IFN-tau, 259 target, product type, indications, human (RhoGam Rho (D), IgA, 141 FDA approval year, 149t MICRhoGAM Rho D) biological properties and localization IL-1beta dosage form, pharmacokinetics, and of, 141, 141t immune-stimulatory, elucidation of disposition data, 559t physiological properties and short peptide for, 56t molecular characteristics and disposition of, in humans, 143t reduction of domain contributing to therapeutic use, 587t IgD, 141 adverse response of, 57 Immune globulin against hepatitis B biological properties and localization Ilectin (insulin), molecular (human) (BayHep B) of, 141, 141t characteristics and therapeutic dosage form, pharmacokinetics, and physiological properties and use, 601t disposition data, 559t disposition of, in humans, 143t Illectin II (insulin), dosage form, molecular characteristics and IgE, 141 pharmacokinetics, and therapeutic use, 587t biological properties and localization disposition data, 569t Immune globulin (human) against Rho of, 141, 141t Imatinib (Gleevec), 58, 262, 490 (D) (BayRho-D full and mini physiological properties and Imatinib mesylate, for chronic dose) disposition of, in humans, 143t myelogenous leukemia dosage form, pharmacokinetics, and IGF-I. See Insulin-like growth factor-I treatment, 263, 265 disposition data, 559t IgG, 141 IMC-A12 cixutumumab, 150t molecular characteristics and biological properties and localization Imciromab pentetate (Myoscint, In therapeutic use, 586t of, 141, 141t 111) Immune globulin (human) carbohydrate moiety of, 87, 89 dosage form, pharmacokinetics, and (Sandoglobulin) classes 1, 2, and 4, 143 disposition data, 559t dosage form, pharmacokinetics, and deamidation of amino acids and, 89 molecular characteristics and disposition data, 559t disposition of, 89 therapeutic use, 586t molecular characteristics and Fc domain of, 464 Imclone Systems, Erbitux and, 18, therapeutic use, 587t glycosylated, 89 109–110 Immune globulin intravenous (human) glycosylation linkage to peptide Imiglucerase (Cerezyme), 33 (Gamimmune N-10% & 5%) backbone, 82t clinical pharmacology, 379 dosage form, pharmacokinetics, and glycosylation on, degree of, 153 dosage form, 379 disposition data, 559t human, mouse, chimeric, and dosage form, pharmacokinetics, and molecular characteristics and humanized antibodies in disposition data, 563t therapeutic use, 587t comparison to, 147, 147t general description, 379 Immune-IFN, 257 physiological properties and indications and use, 379 Immune responses, 92–95 disposition of, in humans, 143t molecular characteristics and assessment of immunogenicity, 93–94 safe and effective drug development therapeutic use, 592t factors modulating immunogenicity, and, 552 pharmacokinetics, 379 93 stability of, 144 recommended dosage and impacts of antibody and other IgG molecules monitoring requirements, 379 immune responses, 94–95 extravascular tissue penetration and, role in therapy, 380 Immune system, 140, 393–394 155 route of administration, 379 Immunex, 5, 29, 57 nonspecific tissue distribution and therapeutic response, 379 Immunity carbohydrate portion of, 86 Immortalized hybrid cells, monoclonal adaptive, 393 used for therapeutic purposes, 153 antibody production and, 146 innate, 393 IgM, 141 Immune cell transplantation, 501 Immuno-affinity column biological properties and localization Immune disorders, biopharmaceuticals chromatography, purification of of, 141, 141t and treatment of, 10 proteins and, 49 physiological properties and Immune effector cells, IFNs and, 262 Immunoassays, dosage formulations for disposition of, in humans, 143t Immune globulin, human, against Rho biopharmaceuticals and, 98 IHA. See Intrahepatic artery (D) (WinRho SDF) Immunoblot analysis, characterization administration dosage form, pharmacokinetics, and tests of proteins and, 76 Ilaris (canakinumab) disposition data, 559t Immunofluorescence, screening/ dosage form, 178 molecular characteristics and verifying molecular clones from dosage form, pharmacokinetics, and therapeutic use, 587t gene expression system and, 49t disposition data, 557t Immune globulin, human (Gammar- Immunogenicity, safety-related, indications and use, 178 PIV) glycosylation and, 548 molecular characteristics and dosage form, pharmacokinetics, and Immunogenicity assays, development therapeutic use, 583t disposition data, 559t of, 93 recommended dosage and molecular characteristics and Immunoglobin purification technology, monitoring requirements, 178 therapeutic use, 586t 144

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 662 0002007355.INDD 662 8/20/2013 1:44:59 AM index 663

Immunoglobulin class G, monoclonal other applications and additional molecular characteristics and antibodies derived from, 139 information, 422 therapeutic use, 607t Immunoglobulin G (IgG) antibody pharmacokinetics, 422 recommended dosage and derivatives, enzyme-based recommended dosage and monitoring requirements, 295 optimization of, 52 monitoring requirements, route of administration, 295 Immunoglobulin molecule, schematic 421–422 source, indication, comments, 272t presentation of, 142 role in therapy, 422 Infertile women Immunoglobulin products, intravenous, route of administration, 421 anovulatory, Follistim in treatment approved indications, therapeutic response, 422 of, 325, 326 characteristics, and formulations, Increlex (mecasermin) anovulatory, Gonal-F in treatment 144t dosage form, 344 of, 324, 325 Immunoglobulins, 140, 141 dosage form, pharmacokinetics, and Ovidrel and final follicular discovery of, in blood, 159 disposition data, 570t maturation and early overview of, 140 indications and use, 343 luteinization in, 322 Immunology, vaccination and concept molecular characteristics and Infixes of, 392 therapeutic use, 602t for antibodies Immunomodulating agents, 252 role in therapy, 344 representing antibody source, Immunoprecipitation, screening/ route of administration, 344 618–619 verifying molecular clones from Incremental cost-effectiveness ratio, representing target or disease, 618, gene expression system and, 49t 125, 128, 131 619t Immunotherapeutics, interleukins as, India, variolation in, 391 naming conventions and, 617, 618, 618 252–253, 255–256 Indications, product labels for drugs Infliximab (Remicade), 35, 151t, 166 Immunotoxins, 156, 454 and, 122 annual revenue for, 7 cancer cells in bone marrow aspirate Indinavir, development/approval of, clinical pharmacology, 190 and, 157 project-team approach and dosage form, 190 construction of, properties of toxins accelerated timeline for, 19, 20 dosage form, pharmacokinetics, and used in, 455t Individual dose response, 95 disposition data, 560t recombinant, 455 Individualization of drug regimens, drug interactions, 190–191 Imogam Rabies-HT, therapeutic use polymorphically expressed general description, 190 for, 145t metabolic enzymes and indications and use, 190 Imogam Rabies-HT (rabies immune transporters and, 476t molecular characteristics and globulin, human) Individualized gene-based medicine, as therapeutic use, 588t dosage form, pharmacokinetics, and mixed blessing, 487, 489 other applications and additional disposition data, 561t INDs. See Investigational New Drug information, 191 molecular characteristics and (IND) applications pharmacokinetics, 190 therapeutic use, 589t Induced pluripotent stem cells, 501, recommended dosage and Imovax (rabies vaccine) 509–510 monitoring requirements, 190 dosage form, pharmacokinetics, and Infanrix (diphtheria and tetanus role in therapy, 191 disposition data, 580t toxoids and acellular pertussis route of administration, 190 molecular characteristics and vaccine) sponsors, indications, annual sales in therapeutic use, 616t dosage form, pharmacokinetics, and millions, 6t Implants, drug delivery systems and, 459 disposition data, 576t target, product type, indications, In-111, 455, 456 molecular characteristics and FDA approval year, 148t Inactivated polio vaccine, 395 therapeutic use, 612t therapeutic response, 191 Incentives Infant mortality Influenza, 113 with biopharmaceuticals, 135 ranking of, for select countries, Influenza A/H1N1, Fluzone in drug development, 133 537t Intradermal in treatment of, 413, in pricing biopharmaceuticals, 131, ranking of, in United States, 536 414 132, 133 Infections Influenza A/H3N2, Fluzone Incivek (telaprevir), 274 immune system and, 140 Intradermal in treatment Incobotulinumtoxin-A (Xeomin) treatment of, biopharmaceuticals of, 413 clinical pharmacology, 422 and, 10 Influenza A (H1N1) 2009 monovalent dosage form, 421 vaccines and, 393, 394 vaccine dosage form, pharmacokinetics, and Infectious Diseases Society of America, clinical pharmacology, 412 disposition data, 575t 296, 302, 304 dosage form, 412 drug interactions, 422 Infergen (interferon alfacon-1) dosage form, pharmacokinetics, and general description, 421 dosage form, 295 disposition data, 579t indications and use, 421 dosage form, pharmacokinetics, and drug interactions, 412 molecular characteristics and disposition data, 573t general description, 412 therapeutic use, 611t indications and use, 295 indications and use, 412

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 663 0002007355.INDD 663 8/20/2013 1:44:59 AM 664 index

Influenza A (H1N1) 2009 monovalent Injection-site reactions, 94 pharmacokinetic and vaccine (cont’d) Innate immunity, 393 pharmacodynamics attributes, molecular characteristics and “Innovation or Stagnation?--Challenge 461t therapeutic use, 615t and Opportunity on the Critical pharmacokinetics, 333 recommended dosage and Path to New Medical Products” recommended dosage and monitoring requirements, 412 (FDA), 112 monitoring requirements, 333 role in therapy, 412 Innovators, pricing biopharmaceuticals role in therapy, 333 route of administration, 412 and, 131, 133 route of administration, 333 therapeutic response, 412 INNP. See International sponsors, indications, annual sales in Influenza B/Texas, Fluzone Intradermal Nonproprietary Names millions, 6t in treatment of, 413 Committee therapeutic response, 333 Influenza virus vaccine, 395 INR. See International normalized Insulin B chain, 10 Influenza virus vaccine, live, intranasal ratio Insulin-degludec (Degludec), 462, 463 (FluMist Quadrivalent) Insomnia, 113 pharmacokinetic and clinical pharmacology, 413 Institute for Genomic Research, pharmacodynamics attributes, dosage form, 413 The, 58 461t dosage form, pharmacokinetics, and Institutional review board, 110 Insulin delivery devices, improvements disposition data, 579t Insulin, 3, 11, 252, 307, 308, 309, 331, 524 in, 458–459 drug interactions, 413 aerosolized, intranasal route and Insulin delivery services, sensor- general description, 412–413 Alzheimer’s patients, 434 augmented insulin pump indications and use, 413 cloning of, from cDNA isolated from therapy, 459 molecular characteristics and pancreas, 44 Insulin derivatives, pharmacological therapeutic use, 615t deamidation of amino acids and, 89 attributes of, 314t pharmacokinetics, 413 derivatives and, therapeutic Insulin detemir (Levemir), 313, 462, recommended dosage and application of, 313–314 463 monitoring requirements, 413 developing alternative noninjectable clinical pharmacology, 334 role in therapy, 413 forms of, 435 dosage form, 334 route of administration, 413 dosage configuration, device, and dosage form, pharmacokinetics, and therapeutic response, 413 bioavailability, 460, 460t disposition data, 569t Influenza virus vaccine (Fluzone human, amino acid sequence of, 10 drug interactions, 334 Intradermal) for human administration, sequence general description, 334 clinical pharmacology, 414 variation between, 10t molecular characteristics and dosage form, 413 infants, toddlers and use of, 313 therapeutic use, 601t dosage form, pharmacokinetics, and molecularly engineered derivatives, other applications, 335 disposition data, 579t 461–462, 463 pharmacokinetic and general description, 413 producing, stem cell therapy pharmacodynamics attributes, indications and use, 413 for, 505 461t molecular characteristics and pulmonary delivery of, 434 pharmacokinetics, 334 therapeutic use, 615t short- and long-acting, recommended dosage and recommended dosage and molecular derivatives of monitoring requirements, 334 monitoring requirements, 414 with pharmacokinetic and role in therapy, 334–335 role in therapy, 414 pharmacodynamics attributes, route of administration, 334 route of administration, 413 461t therapeutic response, 334 therapeutic response, 414 sources and clinical use of, 309t Insulin glargine (Lantus), 9, 313, 462, Infrared spectroscopy, protein STDHF and intranasal delivery of, 463 characterization, stability 445 clinical pharmacology, 335 assessment and, 51t variants for, 9, 461 disposition, 336 Infusion device, physically driven Insulin A chain, 10 dosage form, 335 portable, 458, 459 Insulin aspart (NovoLog), 9, 462, 463 dosage form, pharmacokinetics, and Infusion pumps, highly compact clinical pharmacology, 333 disposition data, 569t computer-controlled, 458 dosage form, 333 drug interactions, 336 Inhalation devices, portable, 460 dosage form, pharmacokinetics, and general description, 335 Inhaled corticosteroids, 198 disposition data, 569t indications and use, 335 Inhale Therapeutic Systems, 435 drug interactions, 333 molecular characteristics and Injections general description, 332 therapeutic use, 601t disposition of therapeutic proteins indications and use, 332–333 other applications and additional after, 429 molecular characteristics and information, 336 drug delivery systems and, 458–459, therapeutic use, 601t pharmacokinetic and 459 other applications and additional pharmacodynamics attributes, of protein pharmaceuticals, 428 information, 334 461t

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 664 0002007355.INDD 664 8/20/2013 1:44:59 AM index 665

pharmacokinetics, 335 recommended dosage and other applications and recommended dosage and monitoring requirements, 338 considerations, 293 monitoring requirements, 335 role in therapy, 338 pharmacokinetics, 292–293 role in therapy, 336 route of administration, 338 recommended dosage and route of administration, 335 sponsors, indications, annual sales in monitoring requirements, 292 sponsors, indications, annual sales in millions, 6t role in therapy, 293 millions, 6t therapeutic response, 338 route of administration, 292 therapeutic response, 336 Insulin probes, implantable, therapeutic response, 293 Insulin glulisine (Apidra), 9 engineering challenges with, Interferon alfa 2b (Intron A) clinical pharmacology, 337 458–459 clinical pharmacology, 294 dosage form, 336 Insulin receptor resistance, genes disposition, 294 dosage form, pharmacokinetics, and identified for, 475 dosage form, 294 disposition data, 569t Insulin recombinant (Novolin) dosage form, pharmacokinetics, and drug interactions, 337 dosage form, pharmacokinetics, and disposition data, 573t general description, 336 disposition data, 569t drug interactions, 294 indications and use, 336 molecular characteristics and general description, 293 molecular characteristics and therapeutic use, 601t indications and use, 294 therapeutic use, 601t Insulin (Velosulin BR) molecular characteristics and other applications, 337 dosage form, pharmacokinetics, and therapeutic use, 607t pharmacokinetic and disposition data, 569t other applications and pharmacodynamics attributes, molecular characteristics and considerations, 295 461t therapeutic use, 601t pharmacokinetics, 294 pharmacokinetics, 337 Insurance companies, genetic recommended dosage and recommended dosage and information and, 489 monitoring requirements, 294 monitoring requirements, 336 Insurance premiums, price of drugs role in therapy, 294 role in therapy, 337 and, 127 route of administration, 294 route of administration, 336 Integrated biopharmaceutical therapeutic response, 294 therapeutic response, 337 companies, 7 Interferon alfacon-1 (Infergen) Insulin (Humulin) Integrated translational research, 4 additional information, 296 dosage form, pharmacokinetics, and Integrilin (eptifibatide), 228 clinical pharmacology, 295 disposition data, 569t dosage form, 241 dosage form, 295 molecular characteristics and dosage form, pharmacokinetics, and dosage form, pharmacokinetics, and therapeutic use, 601t disposition data, 565t disposition data, 573t Insulin (Ilectin II) indications and use, 241 drug interactions, 296 dosage form, pharmacokinetics, and molecular characteristics and general description, 295 disposition data, 569t therapeutic use, 597t indications and use, 295 molecular characteristics and recommended dosage and molecular characteristics and therapeutic use, 601t monitoring requirements, therapeutic use, 607t Insulin-like growth factor, 86 241–242 pharmacokinetics, 295 Insulin-like growth factor-1, 309 role in therapy, 243 recommended dosage and deficiency, severe primary, Increlex in route of administration, 241 monitoring requirements, 295 treatment of, 343, 344 Intellectual property of medicines, role in therapy, 296 Insulin lispro (Humalog), 9, 462, granting of, to innovators, 131 route of administration, 295 463 Interferon alfa therapeutic response, 296 additional information, 339 glycosylation linkage to peptide Interferon alfa-n1 (Welferon) clinical pharmacology, 338 backbone, 82t dosage form, pharmacokinetics, and disposition, 338 naming conventions and, 619 disposition data, 573t dosage form, 337–338 rectally absorbed, 444–445 molecular characteristics and dosage form, pharmacokinetics, and Interferon alfa 2a (Roferon A) therapeutic use, 608t disposition data, 569t clinical pharmacology, 292 Interferon alfa-n3 (human leukocyte drug interactions, 338 disposition, 293 derived) (Alferon-N) general description, 337 dosage form, 292 dosage form, pharmacokinetics, and indications and use, 337 dosage form, pharmacokinetics, and disposition data, 573t molecular characteristics and disposition data, 573t molecular characteristics and therapeutic use, 601t drug interactions, 293 therapeutic use, 608t other applications, 338–339 general description, 292 ask alfa vs. Interferon beta pharmacokinetic and alpha glycosylation linkage to peptide pharmacodynamics attributes, indications and use, 292 backbone, 82t 461t molecular characteristics and naming conventions and, 619 pharmacokinetics, 338 therapeutic use, 607t rectally absorbed, 444–445

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 665 0002007355.INDD 665 8/20/2013 1:44:59 AM 666 index

Interferon beta-1a (Avonex) antitumor effects in humans, products and antiviral indications, clinical pharmacology, 297 overview, 262–264 272t dosage form, 296 classification, pharmacology, and review by CDER through BLA dosage form, pharmacokinetics, and biological properties, 257–260 pathway, 104 disposition data, 573t clinical impact, 264–271 side effects with, 272 drug interactions, 297 interferon proteins and genes, 257 therapeutic use of, 252 FDA approval for marketing, 29 mechanisms of IFN action, 260– in viral hepatitis, 271–272 general description, 296 262 Interferon signaling pathways, types I indications and use, 296 perspective on, 271 and II, 260 molecular characteristics and Interferon gamma Interindividual variation, 472–473 therapeutic use, 608t glycosylation linkage to peptide Interleukin 1alpha, cell source, for multiple sclerosis, 277, 279t backbone, 82t functions, and molecular other applications, 297 naming conventions and, 619 characteristics, 216t pharmacokinetics, 297 Interferon gamma-1b (Actimmune) Interleukin 1beta, cell source, functions, recommended dosage and clinical pharmacology, 300 and molecular characteristics, monitoring requirements, 296 dosage form, 300 216t role in therapy, 297 dosage form, pharmacokinetics, and Interleukin-1 (IL-1), 253 route of administration, 296 disposition data, 574t formulation of, in liposomes, 443 therapeutic response, 297 drug interactions, 301 specific protein member, 255t Interferon beta-1a (Rebif) general description, 300 Interleukin-2 (IL-2), 253, 255 additional information, 298–299 indications and use, 300 cell types increased/activated and clinical pharmacology, 298 molecular characteristics and therapeutic uses for, 223t dosage form, 298 therapeutic use, 608t effective size of, conjugated to PEG dosage form, pharmacokinetics, and other applications and additional and IL-2 clearance in rats, 448t disposition data, 574t information, 301 formulation of, in liposomes, 443 drug interactions, 298 pharmacokinetics, 300–301 glycosylation linkage to peptide general description, 297 recommended dosage and backbone, 82t indications and use, 297 monitoring requirements, 300 indications, clinical studies, clinical molecular characteristics and role in therapy, 301 progress, 255t therapeutic use, 608t route of administration, 300 LAK cells and, 97 other applications, 298 therapeutic response, 301 path to approval for, 253 pharmacokinetics, 298 Interferon Nomenclature Committee, specific protein member, 255t recommended dosage and 619 Interleukin-4 (IL-4), 255, 460, 460t monitoring requirements, 298 Interferon proteins and genes, 257 indications, clinical studies, clinical role in therapy, 298 Interferons, 26, 33, 252 progress, 255t route of administration, 298 CBER review of, 18 Interleukin-6 (IL-6), 252, 443 therapeutic response, 298 for chronic hepatitis B, 272–273, 280 Interleukin-7 (IL-7), 255 Interferon beta-1b (Betaseron, for chronic hepatitis C, 273–274, 280 formulation of, in liposomes, 443 Extavia), 27 discovery of, 271 indications, clinical studies, clinical clinical pharmacology, 299 dosage form, pharmacokinetics, and progress, 255t disposition, 299 disposition data, 573t–574t subcutaneous, pharmacokinetic dosage form, 299 human, commercially available parameters of, in liposome and dosage form, pharmacokinetics, and preparations, 262t soluble forms, 443t disposition data, 573t, 574t intracellular pathway of signal Interleukin-8 (IL-8), angiogenesis general description, 299 transduction by, 260 inhibition and, 262 indications and use, 299 kidney metabolism and elimination Interleukin-10 (IL-10), 253, 255 molecular characteristics and of, 92 indications, clinical studies, clinical therapeutic use, 608t mechanisms of action, 260–262 progress, 255t for multiple sclerosis, 27, 28, 277, angiogenesis inhibition, 262 specific protein member, 255t 279t antiproliferative and apoptotic Interleukin-11 (IL-11), 227, 255 other applications and additional effects, 261–262 cell types increased/activated and information, 300 gene modulation, 261 therapeutic uses for, 223t pharmacokinetics, 299 immune effector cells, 262 indications, clinical studies, clinical recommended dosage and receptors, 260–262 progress, 255t monitoring requirements, 299 signal transduction, 261 Interleukin-12 (IL-12), 255 role in therapy, 300 molecular characteristics and indications, clinical studies, clinical route of administration, 299 therapeutic uses for, 607t–609t progress, 255t therapeutic response, 299 monographs list, 288 Interleukin-15 (IL-15), 255 Interferon biology in multiple sclerosis, 275, 277, 279–280 indications, clinical studies, clinical cancer therapy and, 256–271 naming conventions for, 619–620 progress, 255t

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 666 0002007355.INDD 666 8/20/2013 1:44:59 AM index 667

Interleukin receptor derivatives, 256 bioavailability, biologic response, and route of administration, 192 Interleukins, 215, 252 ease of use with, 86t target, product type, indications, cell source, target cell receptor, and immunogenicity, 93 FDA approval year, 149t proposed major functions, 254t Intravitreal route of administration, therapeutic response, 192 in clinical trials, 255t 428 Iplex (mecasermin rinfabate) discovery of, 252, 253 Intron A (interferon alfa-2b), 258 dosage form, pharmacokinetics, and families and specific protein member, dosage form, 294 disposition data, 570t 255t dosage form, pharmacokinetics, and molecular characteristics and as immunotherapeutics, 252–253, disposition data, 573t therapeutic use, 602t 255–256 indications and use, 294 iPSCs. See Induced pluripotent stem kidney metabolism and elimination molecular characteristics and cells of, 92 therapeutic use, 607t IPV. See Inactivated polio vaccine naming conventions for, 620, 620t off-label promotion of, settlements IRB. See Institutional review board Interleukin-28A (IL-28A), 259 and, 118, 119t Iris, 433 Interleukin-28B (IL-28B), 259 recommended dosage and Irritable bowel syndrome, 528 Interleukin-29 (IL-29), 259 monitoring requirements, 294 Ischemic stroke, acute, Activase in Intermediate purification, for role in therapy, 294 treatment of, 373, 374 recombinant protein in route of administration, 294 ISGs. See IFN-stimulated genes concentrated solution, 74–75 source, indication, comments, 272t Isoelectric focusing, dosage International Association of Investigational New Drug (IND) formulations for Enterostomal Therapy, guide to applications, 26–27, 32, 113 biopharmaceuticals and, 98 chronic wound staging, 420 clinical vaccine development and, Isoleucine, three- and one-letter code, International Conference on 397 linear formula, structure for, Harmonization, 14 drug development process and, 15 624t establishment of, 118 information in, 110 ISRE. See IFN-stimulated response Expert Working Groups and five- Investigational New Drug petition, element step process of, 121 components of, 15 IVIG. See Intravenous immunoglobulin member organizations of, role and Investments, by biopharmaceutical products relation to, 120t companies, 5, 5t, 6, 7 mission of, 120 in vitro enzyme synthesis, 4 Jacobsen, Leon, 219 safety and efficacy guidelines of, in vitro optimization, interrelationship JAK-1, 261 121–122 between in vivo animal testing JAK-2, 261 International Network of Agencies for and, 109 JAK inhibitor, clinical leverage strategy Health Technology Assessment, in vitro PCR techniques, 44, 45 and, 32t 541 in vitro therapeutic index, 429 JAK-2 inhibitors, 263 International Nonproprietary Names in vivo animal testing, interrelationship Janus kinase 2, 263 Committee (WHO), 617, 620 between in vitro optimization Januvia, 435 International normalized ratio, 482 and, 109 Japan International reference pricing, 132 in vivo therapeutic index, 429 health-care expenditure growth rate Intra-arterial (IA) route of I131 isotope, 456 in, 536 administration, 428 Iontophoresis infant mortality and life expectancy Intradermal (ID) route of defined, 459 rankings in, 537t administration, 428 limitations with, 460 new medicine development in, 122 Intrahepatic artery administration, 507 Iontophoretic drug sensor, 459 Japanese encephalitis virus, vaccine Intramuscular (IM) administration, Ipilimumab (Yervoy), 505 for, 395 85, 428 additional information, 192–193 Japan Pharmaceutical Manufacturers bioavailability, biologic response, and clinical pharmacology, 192 Association, 12ot ease of use with, 86t dosage form, 192 Jenner, Edward, 140, 390, 391, 395 bioavailability of drug and, 82 dosage form, pharmacokinetics, and Jesty, Benjamin, 391 immunogenicity, 93 disposition data, 560t JIA. See Juvenile idiopathic arthritis Intravenous immunoglobulin products, drug interactions, 192 Johnson & Johnson, 115 144 general description, 192 revenue, market share, productivity, according to approved indications, indications and use, 192 and research investments characteristics, and formulations, molecular characteristics and of, 5t 144t therapeutic use, 588t JPMA. See Japan Pharmaceutical Intravenous infusion, eliminating pharmacokinetics, 192 Manufacturers Association high peak plasma drug levels recommended dosage and Juvenile idiopathic arthritis, abatacept and, 458 monitoring requirements, in treatment of, 164 Intravenous (IV) administration, 192 Juvenile rheumatoid arthritis, Enbrel in 85, 428 role in therapy, 192 treatment of, 185, 186

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 667 0002007355.INDD 667 8/20/2013 1:45:00 AM 668 index

Kala-azar, vaccine against, 20 Kogenate, 226 other applications, 340 Kalbitor (ecallantide) Kogenate; Kogenate-FS (antihemophilic pharmacokinetics, 339 dosage form, pharmacokinetics, and factor) recommended dosage and disposition data, 575t dosage form, pharmacokinetics, and monitoring requirements, 339 molecular characteristics and disposition data, 564t role in therapy, 340 therapeutic use, 610t molecular characteristics and route of administration, 339 Kaposi’s sarcoma therapeutic use, 594t therapeutic response, 340 AIDS-related, Intron A in treatment Kogenate-FS (antihemophilic factor VIII) Lansoprazole, 480 of, 294 dosage form, 232 Lantus (insulin glargine), 462, 463 AIDS-related, Roferon A in general description, 231–232 additional information, 335 treatment of, 293 indications and use, 232 clinical pharmacology, 335 IFN-alpha2 treatment and, 263 pharmacokinetics, 233 dosage form, 335 PEG-modified doxorubicin recommended dosage and dosage form, pharmacokinetics, and liposomes and, 456 monitoring requirements, disposition data, 569t Kappa family, human chromosome, 232–233 indications and use, 335 number of genes, AA number, route of administration, 232 molecular characteristics and homology, 256t therapeutic response, 233 therapeutic use, 601t Karl Fischer technique, protein Kohler, Georges, 145 pharmacokinetic and characterization, stability KRAS mutations, metastatic colorectal pharmacodynamics attributes, assessment and, 51t carcinoma and, 200 461t Kay, Mark, 504 Krystexxa (pegloticase), 367 recommended dosage and Kefauver-Harris Drug Amendments dosage form, 383 monitoring requirements, 335 (1962), 77, 111 dosage form, pharmacokinetics, and route of administration, 335 Kepivance (palifermin), 312, 313 disposition data, 563t sponsors, indications, annual sales in dosage form, 247 indications and use, 383 millions, 6t dosage form, pharmacokinetics, and molecular characteristics and Lapdap, 490 disposition data, 567t therapeutic use, 593t Lapudrine (chlorproguanil), malaria indications and use, 247 route of administration, 383 control and dapsone combined molecular characteristics and Kupffer cells, 84, 86 with, 490 therapeutic use, 598t IgG molecules and, 153 Large molecules pharmacokinetics, 247 proteolysis and, 90 elimination of, 84 route of administration, 247 volume of distribution and, 84 Keratinocyte growth factor (KGF), 247, Labels and labeling, 81 Laronidase (Aldurazyme) 312–313 “Clinical Studies” section in, 81 additional information, 381 Kidney disease, immunogenicity and, 93 development of chemicals and clinical pharmacology, 380 Kidneys macromolecules into drugs and, dosage form, 380 drug clearance and, 446 17t, 18 dosage form, pharmacokinetics, and erythropoietin production and, 220 FDA approval of, 118 disposition data, 563t filtration and metabolism of “Overview and General Introduction general description, 380 therapeutic proteins in, 91 to Clinical Pharmacology” indications and use, 380 protein and peptide filtration and, 91 section in, 81 molecular characteristics and Kineret (anakinra), 256 of prescription drugs, FDA and, 104 therapeutic use, 592t dosage form, 290 subjects in, 27 for mucopolysaccharidosis I, 363–364 indications and use, 290 Labor induction, Pitocin for, 347, 348 pharmacokinetics, 380 molecular characteristics and LaForce, Marc, 21 recommended dosage and therapeutic use, 607t LAK cells, IL-2 and, 253 monitoring requirements, 380 recommended dosage and Lamivudine (Epivir), 273 role in therapy, 381 monitoring requirements, 290 Langerhans cells, 140 route of administration, 380 role in therapy, 291 Lanreotide, 312 therapeutic response, 380–381 route of administration, 290 Lanreotide acetate (Somatuline Depot) L-asparaginase Kineret solution (anakinra), dosage clinical pharmacology, 339 derivatives and, 367 form, pharmacokinetics, and disposition, 340 plasma half-life comparisons for, 367t disposition data, 573t dosage form, 339 LC-mass spectrometry, metabolomic Klf4, 510 dosage form, pharmacokinetics, and research and, 529t

Koate-DVI or Koate-HP disposition data, 570t LD50, 96 (antihemophilic factor, human) drug interactions, 340 Leber congenital amaurosis (LCA2), dosage form, pharmacokinetics, and general description, 339 507 disposition data, 564t indications and use, 339 Leeches (Hirudo medicinalis), 228 molecular characteristics and molecular characteristics and Leiden mutation, 477 therapeutic use, 594t therapeutic use, 602t Leishmaniasis

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 668 0002007355.INDD 668 8/20/2013 1:45:00 AM index 669

amphotericin B and, 452 role in therapy, 342 Lipopolypeptides, 458 vaccine against, 20 route of administration, 340–341 Liposome drug delivery systems, Lens, eye, 433 therapeutic response, 341–342 target-specific, 456 Lepirudin (Refludan), 228 Leuprolide acetate (Lupron, Lupron Liposomes clinical pharmacology, 245 Depot) defined, 443 disposition, 245 dosage form, pharmacokinetics, and target-directed, 500 dosage form, 245 disposition data, 570t targeting of, based on ligand- dosage form, pharmacokinetics, and molecular characteristics and receptor interactions, 456–458 disposition data, 565t therapeutic use, 602t target-selective delivery to cancer drug interactions, 245 Levemir (insulin-detemir), 313, 462, 463 cells, 450 general description, 244 dosage form, 334 Liposome targeting agents, ligands and indications and use, 244 dosage form, pharmacokinetics, and receptors tested as, 457t molecular characteristics and disposition data, 569t Liquid chromatography/mass therapeutic use, 597t indications and use, 334 sepctrometry (LC/MS), CYP other applications, 245 molecular characteristics and activity assessment and, 511, 512 pharmacokinetics, 245 therapeutic use, 601t Live attenuated vaccines, 389, 394–395, recommended dosage and pharmacokinetic and 405 monitoring requirements, 245 pharmacodynamics attributes, Liver role in therapy, 245 461t drug clearance and, 446 route of administration, 245 role in therapy, 334–335 proteolysis and, 90 therapeutic response, 245 route of administration, 334 Liver disease, immunogenicity and, 93 Leucine LH. See Luteinizing hormone Liver transplantation, MDR1 protein metabolism and, 90 Library, defined, 43t expression and outcome of, 482 three- and one-letter code, linear Licensing LMB-2, 455 formula, structure for, 624t of biologic products and drugs, 14, Long interspersed nuclear elements, Leu-enkaphalin prodrug, modified, 453 104–105, 107 523 Leukemia, 58, 213, 214 globalization and, 122 Lot release, development of chemicals Leukemia inhibitory factor, cell for vaccines, 392t, 397 and macromolecules into drugs source, functions, and molecular Lidocaine, oral vs. rectal routes of and, 17t, 18 characteristics, 216t administration for, 432 Lovonorgestrel (Norplant system), 459 Leukine (sargramostim), 29 LIF. See Leukemia inhibitory factor Low-molecular-weight drugs, dosage form, 249–250 Life expectancy chemically based analogs and, dosage form, pharmacokinetics, and biotherapeutic products and, 548 530 disposition data, 567t drug safety and rise in, 113 Lucentis antibody fragments, 497 indications and use, 249 ranking of, for select countries, 537t Lucentis (ranibizumab) molecular characteristics and ranking of, in United States, 536 dosage form, 202 therapeutic use, 598t vaccines and increase in, 389, 390, dosage form, pharmacokinetics, and Orphan Drug Classification and impact 405 disposition data, 561t of indications/timing of approval Ligand receptor-based targeting, 454 indications and use, 202 dates on revenues for, 30t Ligand-receptor interactions, targeting molecular characteristics and recommended dosage and of liposomes and, 456–458 therapeutic use, 589t monitoring requirements, 250 Light/fill port combination, 30-L bench recommended dosage and role in therapy, 250 fermentor, 67 monitoring requirements, 202 route of administration, 250 Light (L) chains, 141, 141t, 142 role in therapy, 203 Leukocytes, 140, 212 Light scattering, protein route of administration, 202 effect of high or low numbers of, 219t characterization, stability sponsors, indications, annual sales in origins of, 218 assessment and, 51t millions, 6t Leukocytosis, 212 Lin, Fu-Kuen, 219, 220 target, product type, indications, Leukopenia, 217, 270 Linear pharmacokinetic profile, FDA approval year, 148t Leuprolide, 33, 459 therapeutic use of antibodies LUMIZYME ACE program, 373 Leuprolide acetate (Lupron) and, 153 Lumizyme (alglucosidase alfa) clinical pharmacology, 341 LINEs. See Long interspersed nuclear dosage form, 372 dosage form, 340 elements general description, 371 general description, 340 Linkage disequilibrium, 477 indications and use, 372 indications and use, 340 Lipase, 365 pharmacokinetics, 372 other applications and additional Lipid-membrane-based carriers, 441, recommended dosage and information, 342 443–444 monitoring requirements, 372 pharmacokinetics, 341 Lipitor, 489 role in therapy, 373 recommended dosage and Lipodystrophy, HIV-associated, Egrifta route of administration, 372 monitoring requirements, 341 in treatment of, 354, 355 therapeutic response, 373

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 669 0002007355.INDD 669 8/20/2013 1:45:00 AM 670 index

Lumizyme (alglucosidase alfa 2) recommended dosage and Macrophage colony-stimulating factor, dosage form, pharmacokinetics, and monitoring requirements, 343 215, 223, 501 disposition data, 563t role in therapy, 343 cell source, functions, and molecular molecular characteristics and route of administration, 342 characteristics, 216t therapeutic use, 591t therapeutic response, 343 Macrophage-CSF, 222 Lung cancer drug development, Luveris (lutropin alfa), 315 naming conventions for, 619t Xalkori for, 524 dosage form, 342 Macrophages, 140, 213, 393 Lupron Depot (leuprolide acetate) dosage form, pharmacokinetics, and Macugen (pegatanib sodium), 449, 497 dosage form, 340 disposition data, 570t dosage form, 422 dosage form, pharmacokinetics, and indications and use, 342 dosage form, pharmacokinetics, and disposition data, 570t molecular characteristics and disposition data, 575t indications and use, 340 therapeutic use, 602t indications and use, 422 molecular characteristics and role in therapy, 344 molecular characteristics and therapeutic use, 602t route of administration, 342 therapeutic use, 611t route of administration, 340–341 Lyme disease, FDA-approved role in therapy, 423 Lupron Depot-3 Month 11.25 mg, subcellular vaccines against, 395 route of administration, 422 pharmacokinetics, 341 Lyme disease vaccine (recombinant Macular degeneration, 510 Lupron Depot-4 Month 30 mg, OspA), acrylated (LYMErix) Macugen (pegatanib) for treatment pharmacokinetics, 341 dosage form, pharmacokinetics, and of, 422, 423, 497 Lupron Depot-PED disposition data, 579t Mad cow disease, 32, 308 dosage form, 340 molecular characteristics and “Magic bullet” theory, 143, 145 indications and use, 340 therapeutic use, 615t Magnetic resonance imaging, multiple recommended dosage and LYMErix (withdrawn) (Lyme disease sclerosis and, 275, 276 monitoring requirements, 341 vaccine, recombinant OspA, Maitland, Charles, 391 therapeutic response, 342 acrylated) Maitland, Peter, 228 Lupron Injection dosage form, pharmacokinetics, and Major histocompatibility complex class dosage form, 340 disposition data, 579t I, 393 recommended dosage and molecular characteristics and Major histocompatibility complex class monitoring requirements, 341 therapeutic use, 615t II, 393 route of administration, 340 Lymphoblasts, 213 Major molecular response, 265 Lupron (leuprolide acetate), 316 Lymphocyte leukemia, chronic, Malaria additional information, 342 Genasense for, 496 developing vaccines against, 404, 404t dosage form, 340 Lymphocytes, 140, 213, 393 Lapdap and control of, 490 dosage form, pharmacokinetics, and Lymphoid tissues, size-dependent Mammalian IFNs disposition data, 570t targeting to, 450–452 classification of, 257–260 indications and use, 340 Lymphokine activated killer (LAK) type I IFNs, 257–259 molecular characteristics and cells, IL-2 and, 97 type II IFNs, 259 therapeutic use, 602t Lymphokines, 252 type III IFNs, 259–260 recommended dosage and Lymphoma, Ontak (denileukin Mannose-6-phosphate (Man6P) monitoring requirements, 341 diftitox) in treatment of, 455 receptor, 359 route of administration, 340–341 Lymphopoeitin 1, cell source, functions, Manufacturing facilities, Good Luteinizing hormone, 308, 310, 315 and molecular characteristics, Manufacturing Practice deficiency, Luveris in treatment of, 216t guidelines and, 105 342, 343 Lyophilization, protein, 99 Manufacturing guidelines, surges during ovarian Lyophilized formulations, enhancing, biopharmaceutical dosage forms hyperstimulation, Ganerelix for excipients used for, 99t and, 97 prevention of, 327 Lysine, 89 Manufacturing process controls, FDA Luteinizing hormone-releasing protein metabolism and, 90 and documentation of, 75 hormone, 33 three- and one-letter code, linear Manufacturing process modification, Lutropin alfa (Luveris), 315 formula, structure for, 624t development of chemicals and clinical pharmacology, 343 Lysosomes, 359 macromolecules into drugs and, dosage form, 342 17t, 18 dosage form, pharmacokinetics, and Mabs. See Monoclonal antibodies Mapping disposition data, 570t Macroeconomics, 126 gene, 47t, 49t drug interactions, 343 Macromolecules, 1, 4, 7, 41 of single nucleotide polymorphisms, general description, 342 clearance of, 92 477 indications and use, 342 drug development and, regulatory MAPPIT, 526t molecular characteristics and requirements for, 17t March of Dimes, 20 therapeutic use, 602t optimization of, with desired Marginal cost, biopharmaceuticals pharmacokinetics, 343 pharmaceutical properties, 53t and, 129

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 670 0002007355.INDD 670 8/20/2013 1:45:00 AM index 671

Market exclusivity provision, 36 therapeutic response, 344 dosage form, pharmacokinetics, and for drugs with orphan designation, Mecasermin rinfabate (Iplex) disposition data, 570t nonexclusive possibility and, dosage form, pharmacokinetics, and molecular characteristics and 28–29 disposition data, 570t therapeutic use, 603t new drug candidates and, 27 molecular characteristics and Menotropins (Repronex) Orphan Drug Act and, controversy therapeutic use, 602t dosage form, pharmacokinetics, and over, 28 MEDI-545, 150t disposition data, 570t Marketing of drug products, MEDI-551, 150t molecular characteristics and globalization and, 118, 120–122 Medicaid, 27, 114, 487, 536 therapeutic use, 603t Maroteaux-Lamy syndrome, Medical technologies, economists and Mepolizumab, 150t Naglazyme in treatment of, 377 view of, 126 Merck & Co., revenue, market share, Mass spectrometry Medicare, 27, 114, 487, 536 productivity, and research characterization of protein fragments Medications, safe and effective use investments of, 5t and, 50 of, 80 Mergers and acquisitions, dosage formulations for Medicine biopharmaceutical companies biopharmaceuticals and, 98 assessing economic and health and, 34, 35t, 549 metabolomic research and, 528, 529t impact of, 126 Merial, 508 protein characterization, stability personalized, economic impact of, Mesoderm, 509 assessment and, 51t 134–135 Messenger RNA for protein identification, 520 Medullary hematopoiesis, 213 transcription of DNA to, 41 Mast cell growth factor II, cell source, Megakaryocyte growth and Messenger RNA, encoding of target functions, and molecular development factor, cell source, protein and, 43 characteristics, 216t functions, and molecular Metabolic/transport susceptibility, 521 Mast cells, 140 characteristics, 216t Metabolism Master cell bank, optimization of Megakaryocytes, 213 of biotherapeutics, 100 product yield and, 66 Melanoma drug formulation and, 80 Maternity patients, drug safety and IFN-alpha2 for, 267–270 of proteins in eliminating organs, efficacy data for, 81 immune cell therapy and, 501 90–92 Matrix metalloproteinases, 502 metastatic, IL-2 therapy and, 255 of recombinant protein MBL-HCV1, 150t metastatic, interferon treatment for, pharmaceuticals, 86–87, 89–92 MBP. See Myelin-basic protein 256 Metabolite signatures, biomarkers of M-CSF. See Macrophage colony- pDNA-based therapy and, 508 drug effects and, 529 stimulating factor Sylatron in treatment of, 304, 305 Metabolome, 528 MDP, 400 T-cell therapy and, 505–506 Metabolomic analysis, success of, 528 MDR1, drug resistance and, 481, 482 Membrane permeability, 521 Metabolomic research, analytical MDR1 expression, outcome of liver Membrane permeability coefficient, of technologies used for, 529t transplantation and, 482 solutes, 442 Metabolomics, 517, 533, 552 MDX-447, 159t Membrane separation, for protein accelerating drug development with, Mean residence time, symbol, concentration, 74 530–532 mathematical relationship, and Membrane support fabrication, solid- biomarker identification and, 520 physiological variables, 83 liquid separation and, 71 defined, 528 Measles, 389, 405 Mendel, Gregor, 473 metabolic profile education, 528–530 death rate tied to, progression in Mendelian genetics, 4, 8 Methionine, 90 U.S., 390, 390 Meningitis A vaccine, “virtual drug residues, oxidation of, 89 Measles/mumps/rubella (MMR) development” model and, 36 three- and one-letter code, linear vaccine, 395 Meningitis Vaccine Program, 21, 21, 36 formula, structure for, 624t Mecasermin (Increlex) Meningococcal vaccine Methotrexate, Humira used in clinical pharmacology, 344 collaborative/virtual approach to combination with, 166, 167 dosage form, 344 development of, 21 Methotrexate toxicity, dosage form, pharmacokinetics, and human self-antigen and, 403 pharmacogenetics and, 484–486 disposition data, 570t social entrepreneurs and Methoxy polyethylene glycol-epoetin general description, 343 development of, 21 beta (Mircera) indications and use, 343 Meningococcus, FDA-approved dosage form, pharmacokinetics, and molecular characteristics and subcellular vaccines against, 395 disposition data, 567t therapeutic use, 602t Menotropins (FSH; LH) (Pergonal) molecular characteristics and pharmacokinetics, 344 dosage form, pharmacokinetics, and therapeutic use, 598t recommended dosage and disposition data, 570t Methylation, in small-molecule drugs, 9 monitoring requirements, 344 molecular characteristics and Methylenetetrahydrofolate reductase, role in therapy, 344 therapeutic use, 603t 485–486 route of administration, 344 Menotropins (Humegon) MF. See Myelofibrosis

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 671 0002007355.INDD 671 8/20/2013 1:45:00 AM 672 index

M5A, 150t MMR. See Major molecular response role of, in drug delivery and MGDF. See Megakaryocyte growth and Modeccin, construction of clearance, 438 development factor immunotoxins and, 455, 455t Monophosphoryl lipid A, 452 MHC I. See Major histocompatibility Molecular adjuvants, 400 Monospecific polyclonal antibodies, complex class I Molecular approaches in drug delivery, 145 MHC II. See Major histocompatibility 460–462, 464–465 Montagu, Mary Wortley, 391 complex class II Molecular biology, 18 Morphine, 434 Miacalcin (calcitonin salmon) Molecular characteristics, therapeutic Motor, 30-L bench fermentor, 67 dosage form, pharmacokinetics, and applications and, 212–229 Mouse/human chimeric antibodies, 146 disposition data, 567t Molecular clones and cloning Mouse monoclonal antibodies molecular characteristics and data mining, characterization and, for human therapeutic use, 145–146 therapeutic use, 599t 40–41, 43–50 reducing immunogenicity of, 146 Micelles, permeation enhancers and, from gene expression system, MPD Research Consortium Clinical 444, 445 screening/verifying, 49t Trial Group, 267 MICRhoGAM Rho (D) immune Molecular cloning tools, MPIF-1, 58 globulin against D (RH1), standardization of, 48 MPN. See Myeloproliferative human) Molecular engineering, drug safety and, neoplasms dosage form, pharmacokinetics, and 552 MPS. See Mononuclear phagocyte disposition data, 559t Molecular optimization, 51–54, 56, 466 system molecular characteristics and drug development process and, 15 MPS cells, clearance and, 446 therapeutic use, 587t increasing tissue and target MPS II. See Mucopolysaccharidosis II Microarray technology, 531, 532, 532 penetration by reducing size of MPS II Hunter syndrome, iduronate-2- Microbiologists, on FDA review team, macromolecule, 52 sulfatase for, 364 117 rational design of minimum binding MPS pathways, IgG and, 153 Microbiology, biotechnology and, 7 domain, 52–54, 56 MPS VI. See Mucopolysaccharidosis Microeconomics, 126 Molecular target information, type VI Micro infusion pumps, microprocessor- knowledge critical to selection MPS VI Maroteaux-Lamy syndrome, controlled, 459 of, 40 galsulfase for, 364–365 Micromedex, 137 Molecular weight mRNA. See Messenger RNA Micro-RNA (miRNA), 496 distribution of proteins to tissues MRPs. See Multi-drug-resistant Mid-pre-payer model, 544 and, 86 associated protein isoforms Milatuxumab, 150t elimination of recombinant protein MS. See Mass spectrometry; Multiple Milstein, Cesar, 145 pharmaceuticals and, 86 sclerosis Miniaturization Monoclonal antibodies, 3, 8, 454 MT110, 159t array technology and, 520 developing, 33 MT103 (blinatumomab), 159t of infusion pumps, 459 in development, partial list of, MTHFR. See of micro-processor-controlled 150t–151t Methylenetetrahydrofolate programmable devices, 465 distribution and, 85–86 reductase Mini infusion pumps, microprocessor- growth in, 139 MTHFR gene, 486 controlled, 459 immunogenicity and, 93 MTP, 400 Minimed, 458, 459 from mouse, mouse-human MTP-PE, 400 Ministry of Health, Labor and Welfare, chimeric, humanized, to human Muckle-Wells syndrome, Ilaris in Japan, 120t monoclonal antibodies, 145–147 treatment of, 178, 179 Mircera (methoxy polyethylene glycol- naming conventions for, 618–619, Mucopolysaccharidosis I. See also epoetin beta), 220 619t Hurler-Scheie syndrome; Hurler dosage form, pharmacokinetics, and therapeutic, impacts on disease syndrome; Scheie syndrome disposition data, 567t outcome and, 160 Aldurazyme (laronidase) in molecular characteristics and Monoclonal antibody technologies, 5 treatment of, 380, 381 therapeutic use, 598t Monoclonal hybridoma Ab, 4 laronidase for, 363–364 Mistletoe lectin, construction of Monocyte colony-stimulating factor, Mucopolysaccharidosis II, Elaprase in immunotoxins and, 455, 455t cell types increased/activated treatment of, 378 Mitogen-activated protein (MAP) and therapeutic uses for, 223t Mucopolysaccharidosis VI, Naglazyme kinase cascade, 261 Monocytes, 140, 215 in treatment of, 377 Mitoxantrone (Novantrone), for Monogenic disorders, gene and cell Mucosa, licensed vaccines designed multiple sclerosis, 277 therapy and, 497, 497t for pathogens infecting humans MK-6072, 150t Monomeric insulin, 313 through, 402t MK-3415A, 150t Mononuclear phagocyte system Multi-chamber centrifuge, separation MM-111, 159t effect of particle size and increase of cell lysates containing MMAE, 176, 177 in potential for phagocytic pharmaceutical products and, MMPs. See Matrix metalloproteinases recognition by cells of, 450, 451 71, 72

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 672 0002007355.INDD 672 8/20/2013 1:45:00 AM index 673

Multicolony-stimulating factor, cell Myeloma, immortal B-cells and, 145, general description, 344 source, functions, and molecular 146, 146 indications and use, 344 characteristics, 216t Myeloproliferative neoplasms molecular characteristics and Multi-drug-resistant associated protein IFN-alpha for, 263 therapeutic use, 603t isoforms, 445 preclinical rationale for IFN-alpha other applications and additional Multi-functional antibodies, antibody alone or in combination for, information, 345 function improved with, 159 263–264 pharmacokinetics, 345 Multimeric insulins, 462 Mylotarg (gemtuzumab ozogamicin) recommended dosage and Multiple sclerosis, 113 dosage form, pharmacokinetics, and monitoring requirements, 345 Avonex in treatment of, 296, 297 disposition data, 558t role in therapy, 345 Betaseron and Extavia in treatment molecular characteristics and route of administration, 344 of, 299, 300 therapeutic use, 585t Naglazyme (galsulfase), 364 disease presentation and location of target, product type, indications, dosage form, 377 CNS lesions, 277t FDA approval year, 148t indications and use, 377 interferons in, 27, 28, 275, 277, 279– Myocardial infarction, 368. See also molecular characteristics and 280 Acute myocardial infarction therapeutic use, 592t pathology and proposed mechanisms alcohol dehydrogenase role in therapy, 377 of therapeutic interventions, 278 polymorphisms and risk of, 481 route of administration, 377 pathology signatures of, MRI prothrombotic mutations, women Naming conventions, 215. See also analyses, 276 taking HRT and risk of, 487 Nomenclature for biotechnology Rebif in treatment of, 297, 298 stem cell therapy and, 503–505 products relapsing-remitting, Copaxone in Myoscint (In 111) (imciromab Nanoparticle drug delivery, small treatment of, 420, 421 pentetate), 158 liposomes and, 443 two year outcomes for biologics and dosage form, pharmacokinetics, and Nanoparticles, drug safety and, 552 chemical based therapeutics for, disposition data, 559t Nasal route of administration, 279t molecular characteristics and therapeutic proteins and, Tysabri in treatment of, 194, 195 therapeutic use, 586t 433–434 Mumps, 389, 405 Myozyme (alglucosidase alfa), 363 NAT: NAT2, 479t death rate tied to, progression in dosage form, 372 Natalizumab (Tysabri), 156 U.S., 390, 390 dosage form, pharmacokinetics, and clinical pharmacology, 195 Muramyl tripeptidyl- disposition data, 562t dosage form, 194 phosphatidylethanolamine, 452 general description, 371 dosage form, pharmacokinetics, and Muromonab, 8 indications and use, 372 disposition data, 560t Muromonab-CD3 (Orthoclone/OKT3), molecular characteristics and drug interactions, 195 146 therapeutic use, 591t general description, 194 clinical pharmacology, 193 pharmacokinetics, 372 indications and use, 194 dosage form, 193 recommended dosage and molecular characteristics and dosage form, pharmacokinetics, and monitoring requirements, 372 therapeutic use, 588t disposition data, 560t role in therapy, 373 for multiple sclerosis, 279 drug interactions, 193 route of administration, 372 other applications and additional general description, 193 therapeutic response, 372 information, 195–196 indications and use, 193 pharmacokinetics, 195 molecular characteristics and Nabi-HB, therapeutic use for, 145t recommended dosage and therapeutic use, 588t Nabi-HB (hepatitis B immune monitoring requirements, 194 pharmacokinetics, 193 globulin, human), dosage role in therapy, 195 recommended dosage and form, pharmacokinetics, and route of administration, 194 monitoring requirements, 193 disposition data, 558t target, product type, indications, role in therapy, 193–194 N-acetylgalactosamine, 87 FDA approval year, 148t route of administration, 193 N-acetylglucosamine, 87 therapeutic response, 195 target, product type, indications, N-acetylneuraminic acid (sialic acid), 87 NAT 1 and 2. See Arylamine FDA approval year, 148t NAEPP. See National Asthma N-acetyltransferase therapeutic response, 193 Education and Prevention National Asthma Education and Muscle tone, abnormal, Xeomin in Program Prevention Program, 198 treatment of, 421, 422 Nafarelin, 33 National Cancer Institute, 506 Mustard plant, estimated gene count Nafarelin acetate (Synarel) National Center for Advancing for, 523 clinical pharmacology, 345 Translation Sciences, 512, 550 MVP. See Meningitis Vaccine Program dosage form, 344 National Center for Toxicogenomics, MWS. See Muckle-Wells syndrome dosage form, pharmacokinetics, and 531 Myelin-basic protein, 275 disposition data, 570t National Heart, Lung, Blood Institute, Myelofibrosis, 263 drug interactions, 345 198

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 673 0002007355.INDD 673 8/20/2013 1:45:00 AM 674 index

National Institute for Health and route of administration, 246 assessing effectiveness of, 112–113 Clinical Excellence (UK), 128 Neumega (recombinant interleukin-11), completion of phase II clinical trials National Institute of Biological 224, 227 and, 113 Standards and Control, 76 Neupogen (filgrastim) testing and evaluation of, 80–81 National Institute of Environmental dosage form, 243 New drugs Health Sciences, 531 dosage form, pharmacokinetics, and discovery and development of, National Institutes of Health, 14, 25, 81, disposition data, 565t 520–521 110, 198, 512, 549, 550 indications and use, 243 launching, costs related to, 518 National Library of Medicine, 110 marketing exclusivity awarded to, 29 pharmacokinetics and development National Multiple Sclerosis Society, 277 molecular characteristics and of, 521 “Native” enzymes, 357, 368 therapeutic use, 597t New molecular entities, 25 Native proteins, unfolding of, 87, 87 Orphan Drug Classification and approval process for, 14, 15 NAT2, 476t impact of indications/timing of costs related to marketing approval Natural killer cells, 140, 253, 262, 393 approval dates on revenues for, of, 24 Natural killer cell stimulating factor, 30t current trends in drug development cell source, functions, and recommended dosage and and, 18 molecular characteristics, 216t monitoring requirements, drug development process and, NBE. See New biological entity 243–244 15, 27 NCATS. See National Center for role in therapy, 244 IND petition and, 15 Advancing Translational Science route of administration, 243 R&D costs for, 129–130 NDA. See New Drug Application sponsors, indications, annual sales in safety and efficacy of, preclinical NDC. See New drug candidate millions, 6t and clinical evaluation for, 107, Neglected diseases, cost of drug Neurontin, off-label promotion of, 107 development for, 18 settlement involving, 119t NHL. See Non-Hodgkin’s lymphoma Nektor Therapeutics, 435 Neutralizing antibodies, immune NHLBI. See National Heart, Lung, Neoral, 446 response and, 94 Blood Institute NeoRecormon (epoetin alfa), 115 Neutropenia, 217, 222 NICE. See National Institute for annual revenue for, 7 IFNs and, 270 Health and Clinical Excellence sponsors, indications, annual sales in inducing, drugs tied to, 217t NIEHS. See National Institute of millions, 6t Neutrophils, 213, 215, 217, 229, 393 Environmental Health Sciences Neovasculogen, 507, 508 NeutroSpec (technetium (99m Tc) NIH. See National Institutes of Health NESP. See Novel erythropoiesis fanolesomab) NMEs. See New molecular entities stimulating protein dosage form, 205 NMR. See Nuclear magnetic resonance Netherlands dosage form, pharmacokinetics, and spectrometry evidence and value data essential for disposition data, 561t NMR spectroscopy, protein health care in, 542 indications and use, 205 characterization, stability health-care funding characteristics and molecular characteristics and assessment and, 51t HTA programs in U.S. vs., 543t therapeutic use, 590t N,N-dimethyl formamide, permeation Neulasta (pegfilgrastim), 449 recommended dosage and enhancement and, 444 dosage form, 248 monitoring requirements, 205 Nocturnal hypoglycemia, 462 dosage form, pharmacokinetics, and role in therapy, 205 Nofetumomab (Verluma, technetium disposition data, 567t route of administration, 205 Tc 99m) indications and use, 248 target, product type, indications, dosage form, pharmacokinetics, and molecular characteristics and FDA approval year, 148t disposition data, 560t therapeutic use, 598t New biological entity, 80 molecular characteristics and recommended dosage and New Drug Application, 16, 22, 103, 104, therapeutic use, 588t monitoring requirements, 248 115, 531, 550 Nomenclature of biotechnology role in therapy, 248 current Good Manufacturing products route of administration, 248 Practice guidelines and, 105 antibodies, as in monoclonal sponsors, indications, annual sales in development of chemicals and antibodies, 618–619 millions, 6t macromolecules into drugs and, colony-stimulating factors, 620 Neumega (oprelvekin), 255 17t erythropoietins, 620 dosage form, 246 FDA review and approval process interferons, 619–620 dosage form, pharmacokinetics, and and, 115, 116, 118 interleukins, 620 disposition data, 567t FDA’s reemphasis on safety and, 552 overview, 617 indications and use, 246 pharmacology and toxicology somatotropin growth hormones, molecular characteristics and assessment and, 81 619 therapeutic use, 598t safety and efficacy data for, 14 Noncompartmental mathematical recommended dosage and treatment hypotheses and, 32 model, pharmacokinetic monitoring requirements, 246 New drug candidates parameters and, 83

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 674 0002007355.INDD 674 8/20/2013 1:45:00 AM index 675

Non-Hodgkin’s lymphoma revenue, market share, productivity, sponsors, indications, annual sales in Bexxar in treatment of, 207, 208 and research investments of, 5t millions, 6t efficacy of radiolabeled Zevalin vs. Novartis Aqua Health, 508 NovoSeven RT, 227 Rituxan for treatment of, 158, Novel biopharmaceuticals, developing, Nplate (romiplostim), 224 158t 33–34 molecular characteristics and Intron A in treatment of, 294 Novel drug candidates, business therapeutic use, 590t myeloid recovery with, Leukine in strategy behind, 35 NSO cells, murine myeloma-derived, treatment of, 249 Novel drug delivery strategies, 548 Riguxan in treatment of, 203, 204 categories of, 440 Nuclear magnetic resonance transformed B-cell, radiolabeled Novel erythropoiesis stimulating spectrometry, metabolomic anti-CD20 antibody and, 456 protein, 462, 464, 464t research and, 528, 529t Zevalin in treatment of, 188, 189 Novel therapeutic agents, Nuclear transfer technology, in animal Non-linear dose-dependent biotechnology industry and, 26 cloning, 498, 498 pharmacokinetics, therapeutic Novolin (human insulin) Nucleic acid drugs, effects of PEG use of antibodies and, 153 dosage form, 331 modification on reduction of Non-neutralizing antibodies, immune general description, 331 renal or hepatic clearance of, 449t response and, 94 route of administration, 331 Nucleic acids, inhibited gene expression Nonpeptide hormones, 308 Novolin (insulin recombinant) and, 495, 496 Nonprofit organizations, social dosage form, pharmacokinetics, and Nucleotide-binding domain, protein, entrepreneurs strategically disposition data, 569t feature, and total number of aligned with, 20–21 molecular characteristics and genes, 527t Nonproprietary names, for drugs, 618 therapeutic use, 601t Nulojix (belatacept) Nonretroviral viral vectors, gene Novolin (rh-Insulin), sponsors, dosage form, pharmacokinetics, and delivery and, 500 indications, annual sales in disposition data, 557t Non-small cell lung cancer, aptamer- millions, 6t dosage forms, 173 based therapies and, 497 Novolin 70/30, dosage form, 331 indications and use, 173 Non-squamous non-small cell lung NovoLog (insulin-aspart), 462, 463 molecular characteristics and cancer, Avastin in treatment of, additional information, 334 therapeutic use, 582t 175, 176 dosage form, 333 route of administration, 173 Nonviral systems, gene delivery and, dosage form, pharmacokinetics, and target, product type, indications, 500 disposition data, 569t FDA approval year, 149t Noonan syndrome, Norditropin in indications and use, 332–333 Nutropin Depot (somatropin) treatment of, 351 molecular characteristics and discontinuance of, 441 Norditropin (somatropin) therapeutic use, 601t dosage form, 351 additional information, 353 pharmacokinetic and dosage form, pharmacokinetics, and annual revenue for, 7 pharmacodynamics attributes, disposition data, 571t dosage form, pharmacokinetics, and 461t general description, 351 disposition data, 571t pharmacokinetics, 333 indications and use, 351 general description, 351 recommended dosage and molecular characteristics and indications and use, 351 monitoring requirements, 333 therapeutic use, 605t molecular characteristics and route of administration, 333 route of administration, 352 therapeutic use, 605t sponsors, indications, annual sales in Nutropin (somatropin) pharmacokinetics, 352 millions, 6t additional information, 353 route of administration, 351 NovoLog PenFill cartridges, 333 dosage form, 351 sponsors, indications, annual sales in Novo Nordisk, revenue, market share, dosage form, pharmacokinetics, and millions, 6t productivity, and research disposition data, 571t Norplant system (lovonorgestrel), investments of, 5t general description, 351 459 NovoSeven (coagulation factor VIIa) indications and use, 351 Nose, epithelial cells in lining of, 434 dosage form, 237 molecular characteristics and Novantrone (IV), for multiple sclerosis, dosage form, pharmacokinetics, and therapeutic use, 605t 277 disposition data, 565t pharmacokinetics, 352 Novantrone (mitoxantrone), for indications and use, 237 routes of administration, 351 multiple sclerosis, 277 molecular characteristics and Novarel (human chorionic therapeutic use, 596t Oct4, 510 gonadotropin) off-label promotion of, settlements Octagam, 144t dosage form, pharmacokinetics, and and, 118, 119t Octapeptide (Sandostatin) disposition data, 568t recommended dosage and dosage form, pharmacokinetics, and molecular characteristics and monitoring requirements, 237 disposition data, 570t therapeutic use, 600t role in therapy, 238 molecular characteristics and Novartis, 58 route of administration, 237 therapeutic use, 603t

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 675 0002007355.INDD 675 8/20/2013 1:45:00 AM 676 index

Octreotide acetate (Sandostatin, Oligomerization states, of some protein molecular characteristics and Sandostatin LAR Depot), 52, 312 enzymes, and their therapeutic therapeutic use, 593t clinical pharmacology, 346 applications, 358, 358t ONCEPT, 508 disposition, 347 Oligonucleotide stability, antisense Oncology drugs, annual costs related dosage form, 346 therapeutics and, 496 to, 131 dosage form, pharmacokinetics, and Omalizumab (Xolair) Oncolytic enzyme therapies, 367 disposition data, 570t clinical pharmacology, 197 L-asparaginase and derivatives, 367 general description, 346 disposition, 197 urate-oxidase and derivatives, indications and use, 346 dosage form, 197 367–368 molecular characteristics and dosage form, pharmacokinetics, and Oncostatin M (OSM), 511, 511t therapeutic use, 603t disposition data, 560t One World Health, 20 other applications and additional general description, 197 Online Mendelian Inheritance in Man information, 347 indications and use, 197 database, 495, 497, 518 pharmacokinetics, 346–347 molecular characteristics and Ontak (denileukin diftitox), 455, 464 recommended dosage and therapeutic use, 589t dosage form, 291 monitoring requirements, 346 other applications and additional dosage form, pharmacokinetics, and role in therapy, 347 information, 198 disposition data, 573t route of administration, 346 pharmacokinetics, 197 indications and use, 291 sponsors, indications, annual sales in recommended dosage and molecular characteristics and millions, 6t monitoring requirements, 197 therapeutic use, 607t therapeutic response, 347 role in therapy, 197–198 recommended dosage and Ocular route of administration, route of administration, 197 monitoring requirements, 291 therapeutic proteins and, target, product type, indications, role in therapy, 291 432–433 FDA approval year, 148t route of administration, 291 OECD countries, pharmacoeconomic therapeutic response, 197 Onyx-O15, 501, 502 data and forecast models used Omega family, human chromosome, OOPD. See Office of Orphan Product in, 536, 545 number of genes, AA number, Development Ofatumumab (Arzerra), 150t homology, 256t Open frame piping, 30-L bench clinical pharmacology, 196 Omeprazole, 480 fermentor, 67 disposition, 196 “-omic” technologies Open-preferred formulary, 538 dosage form, 196 metabolomics as, capabilities Ophthalmic drug administration, dosage form, pharmacokinetics, and of, 528 anatomical barriers from site disposition data, 560t validated biomarkers, cost of drug of, 432 general description, 196 development and, 552 Ophthalmic therapies, candidate indications and use, 196 OMIM. See Online Mendelian proteins and peptides for, 433t molecular characteristics and Inheritance in Man database Oprelvekin (Neumega), 255 therapeutic use, 588t Ommaya reservoir, 459 additional information, 247 pharmacokinetics, 196 OmniHIB (Haemophilus b conjugate clinical pharmacology, 246 recommended dosage and vaccine, tetanus toxoid disposition, 246 monitoring requirements, 196 conjugate) dosage form, 246 role in therapy, 196–197 dosage form, pharmacokinetics, and dosage form, pharmacokinetics, and route of administration, 196 disposition data, 577t disposition data, 567t target, product type, indications, molecular characteristics and drug interactions, 246 FDA approval year, 149t therapeutic use, 613t general description, 245–246 therapeutic response, 196 Omnitrope (somatropin) indications and use, 246 Office of Orphan Product dosage form, 351 molecular characteristics and Development, 551 dosage form, pharmacokinetics, and therapeutic use, 598t Office of Technology Assessment, 24, disposition data, 572t pharmacokinetics, 246 539, 541 general description, 351 recommended dosage and Off-label promotions indications and use, 351 monitoring requirements, 246 prosecution of drug sponsors for, 123 route of administration, 351 role in therapy, 246–247 settlements involving, 118, 119t Omontys, 221 route of administration, 246 OHSS. See Ovarian hyperstimulation Onabotulinumtoxin A, neutrotoxin therapeutic response, 246 syndrome complex (Botox) Optic nerve, 433 OKT3 (Orthoclone), 33 for blepharospasm, 422 Optimization ADCC function of, 157 dosage form, pharmacokinetics, and of macromolecules with desired kidney transplantation and, 156 disposition data, 575t pharmaceutical properties, 53t Oligodendrocyte progenitor cells, molecular characteristics and molecular, 51–54, 56 spinal-cord injury treatment therapeutic use, 611t Oral mucositis, severe, Kepivance in and, 510 Oncaspar (pegaspargase), 367, 449 treatment of, 247, 248

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 676 0002007355.INDD 676 8/20/2013 1:45:00 AM index 677

Oral polio vaccine, 395 Ovarian cancer, BRCA1 mutations and, recommended dosage and Oral route of administration 484 monitoring requirements, 247 bioavailability of drug and, 82 Ovarian hyperstimulation syndrome, 327 role in therapy, 248 therapeutic proteins and, 430–431 Ovarian stimulation, controlled, route of administration, 247 Orencia (abatacept), 153 Cetrotide and, 321 therapeutic response, 248 dosage form, pharmacokinetics, and Ovidrel (choriogonadotropin alpha), 315 Palivizumab (Synagis) disposition data, 556t dosage form, 322 clinical pharmacology, 198 dosage forms for, 163 dosage form, pharmacokinetics, and dosage form, 198 indications and use of, 163 disposition data, 568t dosage form, pharmacokinetics, and molecular characteristics and indications and use, 322 disposition data, 560t therapeutic use, 582t molecular characteristics and drug interactions, 199 target, product type, indications, therapeutic use, 599t general description, 198 FDA approval year, 148t route of administration, 322 indications and use, 198 Organ perfusion, drug clearance and, 85 therapeutic response, 322 molecular characteristics and Organ rejection Ovulation, Ovidrel and induction of, 322 therapeutic use, 589t acute, Simulect and prophylaxis for, Oxidation, proteins, peptides and, 98 other applications and additional 171 OxyContin, off-label promotion of, information, 199 in kidney transplant patients, Nulojix settlement involving, 119t pharmacokinetics, 198–199 and, 173, 174 Oxytocin (Pitocin), 33, 308 recommended dosage and Orphan diseases, biomolecules for, 551 additional information, 348 monitoring requirements, 198 Orphan Drug Act (1983), 23, 36, 111 amino acid sequence and cyclic role in therapy, 199 market exclusivity provision and, structure, 317t route of administration, 198 27, 28 clinical pharmacology, 348 sponsors, indications, annual sales in reaping financial benefits of, 30 disposition, 348 millions, 6t role of, 27, 29–30 dosage form, 348 target, product type, indications, Orphan Drug Classification, impact of dosage form, pharmacokinetics, and FDA approval year, 148t indications/timing of approval disposition data, 570t PAMPs. See Pathogen-associated dates on revenues of Neupogen drug interactions, 348 molecular patterns and Leukine under, 30t general description, 347 Pancreas, cloning of insulin from cDNA Orphan drugs indications and use, 347–348 isolated from, 44 defined, 111 molecular characteristics and Pancreatic enzymes, for steatorrhea, regulations for, 28–29 therapeutic use, 603t 365 Orthoclone/OKT3 (muromonab-CD3), pharmacokinetics, 348 Pandemic flu vaccines, CBER and 8, 33, 146 recommended dosage and regulation of, 18 ADCC function of, 157 monitoring requirements, 348 Panitumumab (Vectibix) dosage form, 193 role in therapy, 348 additional information, 201 dosage form, pharmacokinetics, and route of administration, 348 clinical pharmacology, 200 disposition data, 560t therapeutic application of, 316–317 dosage form, 199 indications and use, 193 therapeutic response, 348 dosage form, pharmacokinetics, and kidney transplantation and, 156 disposition data, 561t molecular characteristics and PA. See Psoriatic arthritis dose-dependent nonlinearity in therapeutic use, 588t Pacis (BCG live) clearance and plasma half-life recommended dosage and dosage form, pharmacokinetics, and of, 152t monitoring requirements, 193 disposition data, 575t dose-dependent pharmacokinetics role in therapy, 193–194 molecular characteristics and of, 152 route of administration, 193 therapeutic use, 611t general description, 199 target, product type, indications, Paclitaxel (Taxol), BRCA1 tumor cell indications and use, 199 FDA approval year, 148t lines resistant to, 484 molecular characteristics and Osteoblasts, in bone remodeling, 315, Palifermin (Kepivance), 312 therapeutic use, 589t 315 clinical pharmacology, 247 other applications, 200 Osteoclasts, in bone remodeling, 315 dosage form, 247 pharmacogenetics and, 483 Osteopetrosis, malignant, Actimmune dosage form, pharmacokinetics, and pharmacokinetics, 200 in treatment of, 300 disposition data, 567t recommended dosage and Osteoporosis drug interactions, 247–248 monitoring requirements, drug delivery and, 428 general description, 247 199–200 Forteo in treatment of, 19, 353, 354 indications and use, 247 role in therapy, 200 parathyroid hormone and, 315, 315 molecular characteristics and route of administration, 199 Prolia in treatment of, 183 therapeutic use, 598t target, product type, indications, OTA. See Office of Technology other applications, 248 FDA approval year, 148t Assessment pharmacokinetics, 247 therapeutic response, 200

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 677 0002007355.INDD 677 8/20/2013 1:45:00 AM 678 index

PA P. See Pokeweed antiviral protein PedavaxHIB (Haemophilus dosage form, 301 Papain, 52, 141, 147 b conjugate vaccine, dosage form, pharmacokinetics, and PAP-GM-CSF, 404 meningococcal protein disposition data, 574t Papilloma viral vaccines, CBER review conjugate), molecular indications and use, 301 of, 18 characteristics and therapeutic molecular characteristics and Parallel track, 108 use, 613t therapeutic use, 609t Parallel trade, 132, 133 Pediarix (diphtheria and tetanus recommended dosage and Parathyroid hormone, 252, 307, 308 toxoids, hepatitis B, inactivated monitoring requirements, 301 sources and clinical use of, 309t poliovirus combined) route of administration, 301 therapeutic application of, 314–315 dosage form, pharmacokinetics, and source, indication, comments, 272t Paraxel International, 112 disposition data, 576t sponsors, indications, annual sales in Parenteral formulations, 428 molecular characteristics and millions, 6t Parenteral routes of administration therapeutic use, 611t Pegfilgrastim (Neulasta) bioavailability and, 86t Pediatric patients, drug safety and clinical pharmacology, 248 biopharmaceuticals and, 97–98, 97t efficacy data for, 81 dosage form, 248 therapeutic proteins and, 430 Pediatric population, defined, 114 dosage form, pharmacokinetics, and Parkinson’s disease, 57, 501, 510, 518, Pediatric Research Equity Act (2003), disposition data, 567t 529 81, 103, 112, 113, 114, 114t general description, 248 Paromycin, 20, 21 Pediatric Review Committee, 114 indications and use, 248 Paroxysmal nocturnal hemoglobinuria, Pediatric Rule, 111 molecular characteristics and Soliris in treatment of, 184, 185 PEF-IFN-alpha2a (Pegasys), source, therapeutic use, 598t Passive immunity, antitoxin and, 140 indication, comments, 272t other applications and additional Pasteur, Louis, 140 PEG. See Polyethylene glycol information, 249 Patents PEG-ADA (Adagen), 447 pharmacokinetics, 248 generic drugs and, 133 Pegademase bovine (Adagen) recommended dosage and pricing biopharmaceuticals and, 131 additional information, 382 monitoring requirements, 248 therapeutic targets and, 32 clinical pharmacology, 381 role in therapy, 249 PATH. See Performance Appropriate dosage form, 381 route of administration, 248 Technology for Health drug interactions, 381–382 therapeutic response, 249 Pathogen-associated molecular general description, 381 PEG-IFN-alpha2, for melanoma, 270 patterns, 398, 399 indications and use, 381 PEG-IFN-alpha2b, for melanoma, 269 Pathogens, genetic variations in drug pharmacokinetics, 381 PEG-IL-2, 255 response due to multifaceted recommended dosage and indications, clinical studies, clinical genes and proteins monitoring requirements, 381 progress, 255t in human interactions with, 474 role in therapy, 382 Peginterferon alfa-2a (Pegasys) Patient-Centered Outcomes Research, route of administration, 381 additional information, 302 540 therapeutic response, 382 clinical pharmacology, 301–302 Patient perspective, in Pegaptanib sodium (Macugen), 497 disposition, 302 pharmacoeconomics, 127 clinical pharmacology, 422–423 dosage form, 301 Patient Protection and Affordable Care disposition, 423 dosage form, pharmacokinetics, and Act, 117, 540, 551 dosage form, 422 disposition data, 574t Pattern-recognition receptors, 398 dosage form, pharmacokinetics, and drug interactions, 302 Patton, John S., 435 disposition data, 575t general description, 301 Pauling, Linus, 528 general description, 422 indications and use, 301 Payer perspective, in indications and use, 422 molecular characteristics and pharmacoeconomics, 127 molecular characteristics and therapeutic use, 609t PBSC. See Peripheral blood stem therapeutic use, 611t pharmacokinetics, 302 cells other applications, 423 recommended dosage and PCI. See Percutaneous coronary pharmacokinetics, 423 monitoring requirements, 301 intervention recommended dosage and role in therapy, 302 PCOR. See Patient-Centered monitoring requirements, 422 route of administration, 301 Outcomes Research role in therapy, 423 sponsors, indications, annual sales in PCR. See Polymerase chain reaction route of administration, 422 millions, 6t PCR cloning, 44–46 therapeutic response, 423 therapeutic response, 302 PCR technique, 4 Pegaspargase (Oncaspar), 367 Peginterferon alfa-2b (PegIntron) PDL. See Protein Design Laboratory dosage form, pharmacokinetics, and clinical pharmacology, 303 pDNA-based gene therapy, 507–509 disposition data, 563t dosage form, 303 PDUFA. See Prescription Drug User molecular characteristics and dosage form, pharmacokinetics, and Fee Act therapeutic use, 593t disposition data, 574t PE. See Pseudomonas exotoxin Pegasys (peginterferon alfa-2a), 449 drug interactions, 303–304

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 678 0002007355.INDD 678 8/20/2013 1:45:00 AM index 679

general description, 302 role in therapy, 384 cyclic, 431 indications and use, 302–303 route of administration, 383 iontophoresis and delivery of, molecular characteristics and therapeutic response, 384 459–460 therapeutic use, 609t PEG modification, reduction of renal new, introduction of, 33 other applications and additional and hepatic clearance of protein production of, development of information, 304 and nucleic acid drugs, 449t molecular tools and, 24 pharmacokinetics, 303 Pegvisomant (Somavert), 310 Peptide-sequencing techniques, recommended dosage and clinical pharmacology, 349 advances in, 40 monitoring requirements, 303 dosage form, 348 Peptide solutions/suspensions, role in therapy, 304 dosage form, pharmacokinetics, and formulation of, 430 route of administration, 303 disposition data, 570t Peptide transporters, 530 therapeutic response, 304 drug interactions, 349 PeRC. See Pediatric Review Committee Peginterferon alfa-2b (Sylatron) general description, 348 Percutaneous coronary intervention clinical pharmacology, 304 indications and use, 348 bivalirudin and, 234, 235 disposition, 305 molecular characteristics and Integrilin and, 241 dosage form, 304 therapeutic use, 603t Percutaneous transluminal coronary dosage form, pharmacokinetics, and pharmacokinetics, 349 angioplasty, bivalirudin and, 234, disposition data, 574t recommended dosage and 235 drug interactions, 305 monitoring requirements, 349 Performance Appropriate Technology general description, 304 role in therapy, 349 for Health, 21 indications and use, 304 route of administration, 349 Perfusion configuration, large-scale molecular characteristics and therapeutic response, 349 cultivation of host cells and, 69, therapeutic use, 609t Pegylated ADA therapy, for SCID 69–70 other applications and additional patients, 361 Pergonal (menotropins, FSH; LH) information, 305 Pegylated IFN-alpha, essential dosage form, pharmacokinetics, and pharmacokinetics, 305 thrombocytosis, better platelet disposition data, 570t recommended dosage and control and, 266 molecular characteristics and monitoring requirements, 304 Pegylated IFN-beta 2, 258 therapeutic use, 603t role in therapy, 305 PEGylated IL-2 derivatives, effect of Peripheral arterial disease (PAD), 507 route of administration, 304 molecular size on clearance and Peripheral blood stem cells, Neupogen therapeutic response, 305 half-life of PEGylated product and mobilization of, 244 PEGintron-A (EG-IFN-alpha 2b), demonstrated with, 448 Perjeta (pertuzumab) source, indication, comments, Pegylated interferons, chronic hepatitis dosage form, 201 272t C and, 274 dosage form, pharmacokinetics, and PegIntron (peginterferon alfa-2b), 449 Pegylation, 220 disposition data, 561t dosage form, 303 ADA, clearance and, 447 indications and use, 201 dosage form, pharmacokinetics, and reduction in renal clearance and, 449 molecular characteristics and disposition data, 574t Pepsin, 52, 90, 141, 147, 431 therapeutic use, 589t indications and use, 302–303 PEPT1, 530 recommended dosage and molecular characteristics and PEPT2, 530 monitoring requirements, 201 therapeutic use, 609t Peptibodies, 224 role in therapy, 202 recommended dosage and Peptide conformational equilibrium, route of administration, 201 monitoring requirements, 303 modulation of, achieving, 54 target, product type, indications, route of administration, 303 Peptide hormones, 308 FDA approval year, 149t PEG length, target binding by clinical significance of, 308–309 Permeability coefficients, rates of immunoliposomes and, 456 extracted synthetic, historically passage measured by, 441 Pegloticase (Krystexxa), 367 used for clinical diagnosis and Permeation enhancement, 444–446, 466 additional information, 384 treatment, 309t Permeation enhancers clinical pharmacology, 383 properties and molecular drug absorbption and, 444–445 dosage form, 383 characteristics of, 311t flux and, 439 dosage form, pharmacokinetics, and Peptide pharmaceuticals, quality general classification of, 444, 445t disposition data, 563t control and assurance of, 76 major, representation and summary drug interactions, 383 Peptide prodrugs, tissue targeting with, of, and their functional general description, 383 452–453 attributes, 444 indications and use, 383 Peptides, 3 Personalized medicine, 135, 524, 552 molecular characteristics and aerosolized, tested in humans with advances in, 417–492 therapeutic use, 593t portable devices for pulmonary current and future prospects of pharmacokinetics, 383 delivery, 46, 460t pharmacogenetics, 490–492 recommended dosage and biopharmaceuticals and, 8 individualized gene-based monitoring requirements, 383 chemical degradation of, 87 medicine, 487, 489

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 679 0002007355.INDD 679 8/20/2013 1:45:01 AM 680 index

Personalized medicine (cont’d) Hollywood studios and, 34 Pharmacoeconomics, 125 interindividual variation, pharmacogenetic approach and, 489 maturity of, 551 introduction to, 472–473 settlements against, 118, 119t overview of, 126 pharmacogenetics in Pharmaceutical drugs, discovery and personalized medicine and, 134t drug disposition and development of, schematic perspectives in, 127 pharmacokinetics, 478–483 presentation, 25 Pharmacoeconomic studies pharmacogenetics in drug effects Pharmaceutical industry integrating with human clinical and pharmacodynamics, 483–487 biotechnology drugs and success of, 7 efficacy trials, 540 pharmacogenetics in drug safety pharmacogenetics not widely uses for, 539 and efficacy, 473–475, 477 embraced by, 492 Pharmacogenetic approach, biopharmaceuticals and other Pharmaceutical Manufacturers pharmaceutical companies and, examples in, 134t Association, 14, 518 489 economic impact of, 134–135 Pharmaceutical networks, integrated, Pharmacogenetic evaluations evolution of, 492 efficiencies in drug development defined, 473 Perspective, defined, 127 and, 19–20 history behind, 473 Pertussis Pharmaceutical potential, enhanced, Pharmacogenetics, 134, 472, 552 death rate tied to, progression in through domain modification, 56 of cancer chemotherapy, 480–481 U.S., 390, 390 Pharmaceutical products, FDA current and future prospects of, vaccine, 395 approval of marketing licenses 490–492 Pertuzumab (Perjeta) for, 14–16 in drug safety and efficacy, historical additional information, 202 Pharmaceutical profile evaluations, of perspective on, 473–475, 477 clinical leverage strategy and, 32t new molecular entities, 14 methotrexate toxicity and, 484–486 clinical pharmacology, 201 Pharmaceutical research pharmacogenomics vs., 473 dosage form, 201 biopharmaceuticals and, 549–550 Pharmacogenetics in drug disposition dosage form, pharmacokinetics, and spending on, 14 and pharmacokinetics, 478–483 disposition data, 561t Pharmaceutical Research and alcohol dehydrogenase general description, 201 Manufacturer Association, 549 polymorphisms, 481 indications and use, 201 Pharmaceutical Research and cancer chemotherapy, 480–481 molecular characteristics and Manufacturers of America, cellular transporters and drug therapeutic use, 589t 120t resistance, 481–482 pharmacokinetics, 201 Pharmaceuticals CYP2C19 genetics and Helicobacter recommended dosage and new, art and science in pricing of, pylori infection, 480 monitoring requirements, 201 132–133 cytochrome P450 3A genetics in drug role in therapy, 202 physicochemical properties of, 83 metabolism, 479–480 route of administration, 201 transition probabilities for clinical MDR1 expression and outcome of target, product type, indications, phases for biopharmaceuticals liver transplantation, 482 FDA approval year, 149t vs., 130 warfarin anticoagulation effects and therapeutic response, 201 Pharmacists, 81 genetic variation in CYP2C19, PF00547659, 150t Pharmacodynamics, 430, 471 482–483 PF04236921, 150t defined, 477 Pharmacogenomics p53 protein, 506 of drugs, 95 description of, 522t Pfizer, 28, 435, 489 genetic makeup and, integrating pharmacogenetics vs., 473 revenue, market share, productivity, clinically observed phenotype toxicology and, 521 and research investments of, 5t and genetic information, 478 Pharmacogenomic studies, 531 P450 genes, significant functional pharmacokinetics in drug effects and, Pharmacokinetic behavior, genetic impacts of, 476t, 479 483–487 makeup and, integrating P-glycoprotein, 445, 446 variations in drug response and, 472 clinically observed phenotype Pgp, 476t, 481, 482 Pharmacoeconomic analysis, 128t, 133 and genetic information, 478 PHA. See Phytohemagglutinin Pharmacoeconomic data Pharmacokinetic data, 95 Phages, 158 customization of, 546 Pharmacokineticists, on FDA review Phagocytes, 87, 438 drug sponsors and, 545 team, 117 Phagocytic cells, with mannose Pharmacoeconomic forecast models, Pharmacokinetic parameters, symbol, receptors, clearance and, 86 535 mathematical relationship, and Phagocytosis, 86, 438 Pharmacoeconomic model-building physiological variables, 83 Pharmaceutical biotechnology, efforts, interactions of clinical Pharmacokinetic principles, 82–85 historical perspective on, 8 drug development programs Pharmacokinetic profiles, 7, 466 Pharmaceutical companies and, 544 Pharmacokinetic properties, evolution global presence and alliance of, Pharmacoeconomic outcome research, of acceptable predictor of 35–36 integrating in clinical drug drug-like characteristics and, historic mergers and, 34, 35t development, 538–539, 541 521t

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 680 0002007355.INDD 680 8/20/2013 1:45:01 AM index 681

Pharmacokinetics, 430, 471 IFN-alpha’s clinical utility in, 265 Plasmid vectors, developing/optimizing, defined, 477 Philadelphia chromosome-positive being first to market and, 64 dose-dependent, of panitumumab chronic myelogenous leukemia, Plate evaporator, 73 and trastuzumab, 152, 152 Roferon A in treatment of, 292 Platelets, 212, 215, 227, 229 in drug effects and Phospholipids, commonly used, 442 effect of high or low numbers of, 219t pharmacodynamics, 483–487 PhRMA. See Pharmaceutical Research origins of, 218 altered response to chemotherapy and Manufacturer Association Platform technology development, in women with BRCA1 PHS. See Public Health Services public participation and funding mutations, 484 Phylogenic profiling, 526, 526t of, 552 angiotensin-converting enzyme Physical stability, chemical Pleiotropic-CSF, naming conventions genotype and heart failure, 486 stability and, in protein for, 619t pharmacogenetics and pharmaceuticals, 98 Pleiotropic cytokines, interferons as, methotrexate toxicity, 484–486 Physicians, on FDA review team, 117 256 prothrombotic mutations, and risk Physicochemical properties, 450 Pleiotropic effects, cytokines and, 501 of acute MI in women taking Phytohemagglutinin, 252 Pleiotropic hematopoietic growth HRT, 487 Pichia pastoris strain, transgenic glycol- factors, 215 SNPs predispose to cancer and engineered, 548 Pleiotropic proteins, cytokines as, 252 alter therapy response, 484 PIGF. See Placental growth factor PLG. See Polyactide cofabricated with stent restenosis, ACE inhibitors, PI-3K, 261 glycolide and genetic polymorphism, Pilarino, Giacomo, 391 Pluripotent stem cells, 213, 214, 497 486–487 Pitocin (oxytocin), 33 hematopoietic growth factors drug formulation and, 80 dosage form, 348 required by, in bone marrow to glycosylation and, 548 indications and use, 347–348 develop into distinct types of new drug development and, 521 molecular characteristics and blood cells, 215 pharmacogenetics in drug disposition therapeutic use, 603t induced, 501, 509–510 and, 478–483 role in therapy, 348 PMDA, Japan, 120 variations in drug response and, 472 route of administration, 348 PML. See Progressive multifocal Pharmacological assessments, of Pixar, 34 leukoencephalopathy biopharmaceuticals, 99 PLA, 22 Pneumococcal vaccine, polyvalent-23 Pharmacological responses, preclinical development of chemicals and types of S. pneumoniae (PNU- studies on, 14 macromolecules into drugs and, Immune-23) Pharmacologists, on FDA review team, 17t dosage form, pharmacokinetics, and 117 drug approval process and, 114 disposition data, 579t Pharmacology Placebo, defined, 113 molecular characteristics and health science practitioners and, 80 Placental growth factor, aflibercept therapeutic use, 616t toxicology and, 81–82 and, 168, 169 Pneumococcal vaccine, polyvalent-23 Pharming, 498 Plague, vaccine for, 395 pneumococcal isolates Phase I clinical studies, new molecular Plaque psoriasis (Pneumovax 23) entities and, 15–16 Amevive in treatment of, 169, 170 dosage form, pharmacokinetics, and Phase II clinical studies, evaluating Remicade in treatment of, 190 disposition data, 580t efficacy of new drug candidates Stelara in treatment of, 210 molecular characteristics and in, 16 Plasma, 218 therapeutic use, 616t Phase III clinical studies, purpose Plasma cells, 141 Pneumococcal 7-valent conjugate of, 16 Plasma clearance, antibody size and, vaccine (Prevnar) Phenotypes, 477, 478 155t dosage form, pharmacokinetics, and Phenotypic data, response to Plasmacytoma stimulating factor, cell disposition data, 579t chemotherapy and, 481 source, functions, and molecular molecular characteristics and Phenotyping, 472, 473 characteristics, 216t therapeutic use, 615t Phenylalanine, 90 Plasma drug concentration, therapeutic Pneumococcus, FDA-approved three- and one-letter code, linear index and time course of, 436 subcellular vaccines against, formula, structure for, 624t Plasma drug levels, controlled- and 395 Phenylalanine ammonia-lyase, sustained-release strategies and, Pneumocystis carinii pneumonia therapeutic potential with, 365t 440 in AIDS patients, G6PDH biomarker Phenylthiourea, heredity and inability Plasma extracts, review with PLA by and, 490 to perceive bitterness after CBER, 104 SCID and, 361 tasting, 473 Plasmid expression systems, gene Pneumovax 23 (pneumococcal vaccine, Philadelphia chromosome, 58, 473, 490 cloning and, 48 polyvalent-23 pneumococcal Philadelphia chromosome-negative Plasmids isolates), molecular MPN defined, 43t characteristics and therapeutic IFN-alpha in treatment of, 263 genomic cloning and, 46 use, 616t

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 681 0002007355.INDD 681 8/20/2013 1:45:01 AM 682 index

PNH. See Paroxysmal nocturnal Pore sizes Pregnyl (human chorionic hemoglobinuria of filter, protein concentration and, gonadotropin) PNU-Immune-23 (pneumococcal 74 dosage form, pharmacokinetics, and vaccine, polyvalent, 23 types of solid-liquid separation and, 71 disposition data, 568t S. pneumoniae) Pork insulin, 9, 32 molecular characteristics and dosage form, pharmacokinetics, and Porter, Rodney R., 141 therapeutic use, 601t disposition data, 579t Ports, 30-L bench fermentor, 67 Prescription drugs molecular characteristics and Posterior chamber, eye, 433 pharmacological and toxicological therapeutic use, 616t Postmarketing studies, 15, 114 assessments of, 80 POE-35 castor oil (Cremophor EL), Postpartum bleeding, Pitocin in product labels for, 27, 81 446 treatment of, 348 risk-benefit assessment and, 81 Pokeweed antiviral protein, PPIs. See Proton pump inhibitors Prescription Drug User Fee Act construction of immunotoxins PPMS. See Primary progressive (1992), 16 and, 455t multiple sclerosis version V renewed for 2013, 111 Poliomyelitis Prader-Willi syndrome, 310, 352, 353 Prescriptive authority, 81 death rate tied to, progression in Pradexa (dabigatran), 483 Prevnar (pneumococcal 7-valent U.S., 390, 390 Pramlintide acetate (Symlin) conjugate vaccine) near global eradication of, 389, 390, additional information, 350 dosage form, pharmacokinetics, and 405 clinical pharmacology, 350 disposition data, 579t Polio vaccine, 20 disposition, 350 molecular characteristics and Polishing step, in protein purification, 75 dosage form, 349 therapeutic use, 615t Polyactate-glycolate (PLG) polymer, dosage form, pharmacokinetics, and Price and pricing, 114 rhGH encapsulated in, 310 disposition data, 571t of biopharmaceuticals, 131–133 Polyactide cofabricated with glycolide, drug interactions, 350 cost vs., 128–129 440 general description, 349 of biosimilars, 133–134 Polyactide implantable materials, 459 indications and use, 349 follow-on biologics and, 224 Polyclonal antibodies, 159, 160 molecular characteristics and of new drugs, inputs into global naming conventions for, 618–619 therapeutic use, 604t pricing strategies for, 132 Polyclonal IgG, 139 pharmacokinetics, 350 pharmacoeconomic analysis behind, Polycythemia vera, 263 recommended dosage and 127–128 cytoreductive therapies in, treatment monitoring requirements, 350 target product profiles and, 542 algorithm, 266 role in therapy, 350 Primaquine-mediated hemolysis IFN-alpha2 and, 265 route of administration, 350 symptom, African Americans Polyethylene glycol, 359 therapeutic response, 350 and, 473 chemical conjugation of, 462 PREA. See Pediatric Research Equity Primary progressive multiple sclerosis, drug clearance and, 446–447 Act 275 Polyethylene glycol derivatives, Precipitation, 526t “Prime-boost” approach, vaccine schematic of, used for pegylation Precipitation reagents, protein delivery and, 402 of proteins, 447 purification and, 73–74 Prime-boost immunization, vaccines Polyhistidine, purification of proteins Preclinical drug development, 520 against HIV/AIDS and, and, 49 Preclinical studies, 104, 107, 108–109 402–403 Polymerase chain reaction, conceptual drug development process and, 15 Prion protein, 308 presentation of, 45 interrelationship of clinical studies Private funding Polymerase pol, processing, role of and, 109 pharmaceutical drug discovery, protease in, 54 new molecular entities and, 14 development and, 25 Polymer-based drug carriers, 440–441 Preclinical testing, viable drug for start-up biotechnology Polymeric membrane-based candidates in development companies, 26 implantable drug delivery pipeline and, 521 Privigen, 144t systems, 459 Preclinical translational research, 24 PRO140, 150t Polymers, biodegradable, testing for Prefixes Process-stream procedures, for sustained protein release, 440t for antibodies, monoclonal, 618 purification of recombinant Polypeptides, short, large-scale naming conventions and, 617, 618, 618 proteins, 70 purification methods for, 70 for somatotropin growth hormones, Procrit (epoetin alfa) Pompe’s disease 619 dosage form, 240 alglucosidase for, 363 Pregnancy dosage form, pharmacokinetics, and Myozyme and Lumizyme in Category D classification and CML disposition data, 565t treatment of, 371, 372, 373 treatment during, 265 indications and use, 240 Porcine-extracted insulin, 308 Ovidrel and induction of, 322 molecular characteristics and Porcine somatotropin derivatives, prevention of, lovonorgestrel therapeutic use, 597t suffixes for, 619 (Norplant system) for, 459 role in therapy, 241

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 682 0002007355.INDD 682 8/20/2013 1:45:01 AM index 683

sponsors, indications, annual sales in role in therapy, 419 role of, in processing HIV gag and millions, 6t route of administration, 418 polymerse pol, 54 Prodrugs, defined, 452 ProLease, 440 ubiquity of, 90 Product indications, in drug Proleukin (aldesleukin), 253 Protein characterization and stability development process, 27 dosage form, 288 assessment, analytical Productivity, cost of drug development dosage form, pharmacokinetics, and techniques used in, 51t and, 530 disposition data, 573t Protein chemistry, advances in, reasons Product labels. See Labels and indications and use, 288 for, 524 labeling molecular characteristics and Protein clearance mechanisms, novel Product launch, pharmacoeconomic therapeutic use, 607t delivery strategies and, 438 data and, 539 recommended dosage and Protein Design Laboratory, 147 Product License Application, 13, 16, monitoring requirements, 289 Protein disposition mechanisms, 103, 104, 105 role in therapy, 289 size-dependent, schematic Product yield optimization, ultimate route of administration, 289 representation of, 437 goal of, 65 Prolia (denosumab), 552 Protein drugs Profasi (human chorionic dosage form, 183 general pharmacokinetic and gonadotropin) dosage form, pharmacokinetics, and pharmacodynamic features of, 85t dosage form, pharmacokinetics, and disposition data, 558t molecular characteristics and disposition data, 569t indications and use, 183 disposition of, 437t molecular characteristics and molecular characteristics and Protein enzymes, oligomerization states therapeutic use, 601t therapeutic use, 584t of, and therapeutic applications, Profit margins recommended dosage and 358t of marketed therapeutic protein monitoring requirements, 183 Protein expression, enhancing, product, determinants of, 64 role in therapy, 183 optimizing DNA sequences optimization of recombinant route of administration, 183 and, 48 expression systems and, 50 target, product type, indications, Protein folding, chemical and physical product yield optimization and, 65 FDA approval year, 149t stability and, 98 Progesterone, 308 Proline, 89 Protein function, predicting, computer Progressive multifocal three- and one-letter code, linear algorithms for, 526 leukoencephalopathy, 279 formula, structure for, 625t Protein glycosylation, 41 Proinflammatory cytokines, 253, 393 Pro-opiomelanocortin (POMC)- as part of post-translational Proinflammatory process, interleukins derived hormones, properties modification, 42 and, 253 and molecular characteristics Protein hormones, 308 Project-team approach of, 311t extracted synthetic, historically in developing new Proscar (finasteride), 484 used for clinical diagnosis and biopharmaceuticals, 520 ProstaScint (In 111) (capromab treatment, 309t drug development and, 19–20, 20, 22 pendetide), 158 Protein lyophilization, 99 Prokaryotes, fermentation and, 67 dosage form, pharmacokinetics, and Protein molecules, biopharmaceutical Prokaryotic cells disposition data, 557t development and, 552 choosing host cells for recombinant molecular characteristics and Protein pharmaceuticals protein expression in therapeutic use, 583t chemical and physical instability and, pharmaceutical scale and, 65t Prostate cancer possible mechanisms of, 98, 98 recombinant protein production and, advanced, Firmagon in treatment of, direct injection of, 428 64–65 323 immunogenicity of, and clinical Prokaryotic hosts advanced, Trelstar in treatment of, consequences, 94t engineering expression system for 355, 356 production of, using roller bottles, 68 proteins and, 47, 48 advanced, Vantas in treatment quality control and assurance of, 76 production costs and of, 330 type of glycosylation--N or O-- biopharmaceuticals produced BRCA1 mutations and, 484 linkage on, produced in in, 548 leuprolide for treatment of, 459 mammalian cells, 82t Prolastin (alpha-1-proteinase inhibitor Lupron in treatment of, 340 Protein polymorphism, 474 (human), alpha-1 antitrypsin) Provenge in treatment of, 414, 415 Protein precipitation, 73 dosage form, pharmacokinetics, and SRD5A2 gene variants and, 484 Protein precipitation agents, disposition data, 574t vaccine, 404 mechanisms of actions for, 74t molecular characteristics and Zoladex in treatment of, 329, 330 Protein product libraries, 523 therapeutic use, 609t Prostate Cancer Foundation, 552 Protein products, new, evaluating Prolastin-C (alpha-1-proteinase Prostate Cancer Prevention Trial, 484 immunogenicity of, 94 inhibitor) Protease inhibitors, 54 Protein-protein interaction studies, dosage form, 418 Proteases, 365 yeast two-hybrid systems and, indications and use, 418 protein metabolism by, 90 525, 525

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 683 0002007355.INDD 683 8/20/2013 1:45:01 AM 684 index

Protein purification, functional groups recombinant, 30-L bench fermentor dosage form, 414 attached to column matrices scaled for production of, 67 dosage form, pharmacokinetics, and for, 75t recombinant, optimizing production disposition data, 580t Protein purification chromatography, of, 50 indications and use, 414 industrial-scale, matrices used review by CDER through BLA molecular characteristics and for, 75t pathway, 104 therapeutic use, 616t Proteins, 3, 4, 5, 41 schematic of polyethylene glycol role in therapy, 415 aerosolized, tested in humans with derivatives used for pegylation Provider perspective, in portable devices for pulmonary of, 447 pharmacoeconomics, 127 delivery, 46, 460t in solution, hydrodynamic size of, 450 Provigil, offf-label promotion of, biopharmaceuticals and, 8 targeting of, to target tissues and settlement involving, 119t biotransformation of, 84 cells, 450 PROWESS-SHOCK trial, Xigris and, chemical and physical degradation as targets for drug discovery and 377 in, mechanisms of, 87 development, 56–58 PRR. See Pattern-recognition receptors chemical marking and modifications transforming into PSC833, 446 in, 89–90 biopharmaceuticals, progress Pseudomonas endotoxin, 464 chemical modifications vs. molecular and benefits in, 548 Pseudomonas exotoxin, 455 approaches and, 460–461 unfolded, 87 Pseudomonas exotoxin A, construction clearance of, 92 unknown, computational approaches of immunotoxins and, 455, 455t with common structure and used to predict functions of, 526t Psoriasis, drug delivery and, 428 functional domains, 527t Protein stability in solution, enhancing, Psoriatic arthritis degradation of, bioavailability of excipients used for, 99t Enbrel in treatment of, 185 protein pharmaceuticals Protein synthesis, 7 Humira in treatment of, 166, 167, 168 and, 85 Protein synthesis and stability Remicade in treatment of, 190 effects of PEG modification on regulation of, 524 Simponi in treatment of, 187, 188 reduction of renal or hepatic schematic representation of, 41 PTCA. See Percutaneous transluminal clearance of, 449t Protein therapeutics, 1, 4 coronary angioplasty endocytosis of, 91 Proteolysis, defined, 90 PTH. See Parathyroid hormone engineering expression system for, Proteolytic products, elimination of, 91 Public access, biopharmaceutical 47–48 Proteomic data, derivation of, 523 development and, 551–552 excretion of, outside of cells, 50 Proteomics, 18, 461, 517, 533, 552 Public health expressed recombinant, verifying new drug targets and promise of, biopharmaceuticals and, 551 molecular and functional 519–520 biotherapeutic products and, 548 characteristics of, 48–49 new generation of vaccines and, 389 progress in, over past century, 389 functional, large-scale manufacturing procedures encompassed within, 520 Public Health Service Act, 116, 397 of, 40 from sequences to functions, 524– Public Health Services, 14 fusion, 464 526, 528 Public-private partnership, improving glycosylation and stability of, 87, 89 vaccine discovery and, 405 translational success and, hematopoietic, 212 Proteomic tools, accelerating drug 550–551 inactivation of, from native to development with, 530–532 Public stock offerings, cash for later various denaturation states, 87 Prothrombin, conversion of, to active stages of clinical testing and, 26 iontophoresis and delivery of, form thrombin, 225 Pulmonary embolism, acute massive, 459–460 Prothrombotic mutations, risk of acute Activase in treatment of, 373, 374 liposome-encapsulated, 443, 444 MI in women taking HRT and, Pulmonary route of administration, metabolism of, 87 487 therapeutic proteins and, 434 in eliminating organs, 90–92 Protirelin (Thyrel TRH), 33 Pulmozyme (DNAse) by proteases found at cell dosage form, pharmacokinetics, and dosage form, pharmacokinetics, and surface and internal cellular disposition data, 571t disposition data, 563t organelles, 90 molecular characteristics and molecular characteristics and new, introduction of, 33 therapeutic use, 604t therapeutic use, 592t pegylated, 258 Proton pump inhibitors, 480 Pulmozyme (dornase alfa), 33, 367 phosphorylated, 90 Protropin (somatrem) dosage form, 375 physical and chemical integrity of, dosage form, pharmacokinetics, and drug interactions, 375 86–87 disposition data, 571t indications and use, 374 precipitation and extraction of, in molecular characteristics and recommended dosage and stainless stir-tanks, 74 therapeutic use, 604t monitoring requirements, 375 processing, 7 Prourokinase, characteristics, role in therapy, 375 production of, development of pharmaceutical source, route of administration, 375 molecular tools and, 24 mechanisms of action, 366t Pure red-cell aplasia, 115 purification procedures for, 49–50, 50 Provenge (sipuelucel-T), 404 Purification

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 684 0002007355.INDD 684 8/20/2013 1:45:01 AM index 685

concentration of putative product Rabies immune globulin (human) Rare diseases before, 71, 73–74 (Imogam Rabies-HT) biomolecules for, 551 downstream processing and, for dosage form, pharmacokinetics, and Orphan Drug Act and, 28 recombinant products, 70–71, disposition data, 561t Rasburicase (Elitek), 367, 368 73–75 molecular characteristics and additional information, 385 intermediate, for recombinant therapeutic use, 589t clinical pharmacology, 384 protein in concentrated solution, Rabies vaccine (Imovax) dosage form, 384 74–75 dosage form, pharmacokinetics, and dosage form, pharmacokinetics, and for protein products, 49–50, 50 disposition data, 580t disposition data, 563t of recombinant factor VIII products, molecular characteristics and drug interactions, 384–385 226–227 therapeutic use, 616t general description, 384 Purine metabolism, ADA deficiency Rabies vaccine (RabAvert) indications and use, 384 and, 447 dosage form, pharmacokinetics, and molecular characteristics and Purity of products disposition data, 580t therapeutic use, 593t immunogenicity and, 93 molecular characteristics and pharmacokinetics, 384 improving marketed therapeutic use, 616t recommended dosage and biopharmaceuticals and, 32–33 RAC. See Recombinant DNA Advisory monitoring requirements, 384 PV. See Polycythemia vera Committee role in therapy, 385 Racemization, proteins, peptides route of administration, 384 Quadrivalent rHPV vaccine (Gardasil), and, 98 therapeutic response, 385 sponsors, indications, annual Radioimmunoconjugates Rational drug design, overall goal of, 52 sales in millions, 6t effective killing radius of, 157 RBCs. See Red blood cells Quality-adjusted life year (QALY), used for tumor and myocardial RCC. See Renal cell carcinoma 128, 134, 540 imaging, 158 Rebetol (ribavirin), in treatment of Quality Considerations in Radiolabeled antibody, 157 chronic hepatitis C, 302, 303 Demonstrating Biosimilarity to Radionuclides, therapeutic response of Rebif (interferon beta-1a), 27, 28 a Reference Protein Product, antibodies and, 455–456 dosage form, 298 116 Raman spectroscopy, protein dosage form, pharmacokinetics, and Quality control characterization, stability disposition data, 574t biopharmaceutical dosage forms assessment and, 51t indications and use, 297 and, 97 Ramucirumab, clinical leverage molecular characteristics and development of chemicals and strategy and, 31t therapeutic use, 608t macromolecules into drugs and, Randomized, double-blind placebo- for multiple sclerosis, 277, 278, 279t 17t, 18 controlled clinical trials, 113 role in therapy, 298 for recombinant proteins, 75–77 Randomized, placebo-controlled route of administration, 298 Quality of life clinical trials, 113 study design of, 29 biotherapeutic products and, 548 Ranibizumab (Lucentis) therapeutic response, 298 health-related, 538 clinical pharmacology, 202 Receptor downregulation, antibodies Quantal concentration-effect analysis, 96 dosage form, 202 and, 156 Quantal concentration-effect curve, 96 dosage form, pharmacokinetics, and Receptor-ligand interactions, at cell Quantal dose response, 95 disposition data, 561t surfaces, 7 Quinapril (Accupril), restenosis after drug interactions, 202 Recombinant clotting factors, 226–227, stent implantation and, 486 general description, 202 229 indications and use, 202 Recombinant DNA, terminology used RA. See Rheumatoid arthritis molecular characteristics and in research, 43t RabAvert (rabies vaccine) therapeutic use, 589t Recombinant DNA Advisory dosage form, pharmacokinetics, and other applications, 203 Committee, 504 disposition data, 580t pharmacokinetics, 202 Recombinant DNase, delivery of, 98 molecular characteristics and recommended dosage and Recombinant DNA technology, 1, 5, therapeutic use, 616t monitoring requirements, 202 8, 40 Rabies role in therapy, 203 Recombinant enzymes, 357 hyperimmune globulin products and, route of administration, 202 Recombinant factor VIIa, 227 145 sponsors, indications, annual sales in Recombinant factor VIII products, immnoglobulin products and, 144 millions, 6t purification of, 226–227 Rabies immune globulin (human) target, product type, indications, Recombinant hormones, therapeutic (BayRab) FDA approval year, 148t application of, 309–318 dosage form, pharmacokinetics, and therapeutic response, 202–203 Recombinant human erythropoietin, disposition data, 561t Raptiva (efalizumab), target, product 220, 222 molecular characteristics and type, indications, FDA approval Recombinant human GH, 310 therapeutic use, 589t year, 148t Recombinant human insulin, 4, 32

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 685 0002007355.INDD 685 8/20/2013 1:45:01 AM 686 index

Recombinant IFNs, 256, 257 recommended dosage and Regranex Gel (becaplermin) Recombinant immunotoxins, 455 monitoring requirements, dosage form, 419 Recombinant interleukin-11 232–233 dosage form, pharmacokinetics, and (Neumega), 227 route of administration, 232 disposition data, 575t Recombinant protein expression, therapeutic response, 233 indications and use, 419 choosing host cells for, in Recombivax HB (hepatitis B vaccine), molecular characteristics and pharmaceutical scale, 65t 9, 10t therapeutic use, 610t Recombinant protein pharmaceuticals dosage form, 409–410 recommended dosage and absorption, distribution, and dosage form, pharmacokinetics, and monitoring requirements, 420 availability of, 85–86 disposition data, 578t role in therapy, 420 disposition of, 85–87, 89–92 indications and use, 409 route of administration, 419 elimination and metabolism of, molecular characteristics and Regulation 86–87, 89–92 therapeutic use, 614t of biotechnology product chemical “marking” modifications, route of administration, 410 manufacturing, 105 89–90 Recothrom (thrombin, topical, current Good Manufacturing glycosylation and protein stability, recombinant) Practice, 105, 106 87, 89 dosage form, pharmacokinetics, and of development of chemicals and mechanisms of chemical and disposition data, 567t macromolecules into drugs, 17t physical degradation of molecular characteristics and of drug development process, 14–16, 15 proteins, 87 therapeutic use, 599t drug-drug interactions and, 92 molecular weight, 86 Rectal route of administration, of drug product label, 27 physical and chemical integrity of therapeutic proteins and, 432 of drug review and approval, 104 proteins, 86–87 Red blood cell count, 218 of drugs and biologics in U.S., history protein metabolism in eliminating Red blood cells, 212, 215, 229 of, 111 organs, 90–92 erythropoietin-alfa and, 115 of orphan drugs, 28–29 proteolysis, 90 identification of, 218 of protein synthesis and stability, 524 Recombinant protein production, FDA life span of, 220 of vaccines, 397 and review of, 104, 105 ReFacto (antihemophilic factor VIII) Regulatory agencies, globalization and, Recombinant proteins dosage form, 232 120 immunogenicity and design of, 93 dosage form, pharmacokinetics, and Reimbursement decisions, regional large-scale production of, 63–77 disposition data, 565t differences in type of evidence optimizing production of, 50 general description, 231–232 and value data essential for, properties and molecular indications and use, 232 541–542 characteristics of, 311t molecular characteristics and Relapsing-remitting multiple sclerosis, purification of, process stream therapeutic use, 595t 275 in, 71 recommended dosage and Relationship integration studies, quality assurance and quality control monitoring requirements, phenotype and genetic for, 75–77 232–233 information in, 478 in sterile pharmaceutical products, route of administration, 232 Remicade (infliximab), 35 process controls for, 76 therapeutic response, 233 annual revenue for, 7 30-L bench fermentor scaled for Reference product, 116 dosage form, 190 production of, 67 Refludan (lepirudin), 228 dosage form, pharmacokinetics, and validation of purification process dosage form, 245 disposition data, 560t for, 76 indications and use, 244 indications and use, 190 Recombinant protein solutions, recommended dosage and molecular characteristics and reducing volume of, 73–74 monitoring requirements, 245 therapeutic use, 588t Recombinant vaccines, 389, 392, 396, role in therapy, 245 neutralization of TNF-alpha and, 156 405 route of administration, 245 recommended dosage and Recombinate (antihemophilic factor- Refludan (lepirudin-thrombin monitoring requirements, 190 human recombinant heavy and inhibitor) role in therapy, 191 light chains combination) dosage form, pharmacokinetics, and route of administration, 190 dosage form, pharmacokinetics, and disposition data, 565t sponsors, indications, annual sales in disposition data, 565t molecular characteristics and millions, 6t molecular characteristics and therapeutic use, 597t target, product type, indications, therapeutic use, 595t Refractometry, protein FDA approval year, 148t Recombinate (antihemophilic factor characterization, stability Removab (catumaxomab), 159t VIII), 226 assessment and, 51t Renal cell carcinoma dosage form, 232 Refractory angina, gene therapy for, 502 aptamer-based therapies and, 497 general description, 231–232 Regenerative medicine, pluripotent metastatic, Avastin in treatment of, pharmacokinetics, 233 stem cells in, 510 175, 176

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 686 0002007355.INDD 686 8/20/2013 1:45:01 AM index 687

metastatic, Proleukin in treatment of, Restriction endonuclease fragment rh-Factor VIIa (NovoSeven), sponsors, 288, 289 analysis, 47 indications, annual sales in Renal clearance, of protein and nucleic Restriction enzymes, defined, 43t millions, 6t acid drugs, PEG modification Retavase (reteplase) rhGH. See Recombinant human GH and, 449t dosage form, 385 rh-Insulin (Humulin), sponsors, Renal elimination, drug clearance and, dosage form, pharmacokinetics, and indications, annual sales in 446 disposition data, 564t millions, 6t Renal transplant patients, acute indications and use, 385 RhoGam Rho, therapeutic use for, 145t allograft rejection in, Orthoclone molecular characteristics and RhoGamRho (D) (immune globulin OKT3 in treatment for, 193 therapeutic use, 593t against D (RH1), human) ReoPro (abciximab), 52, 147, 227, 552 pharmacokinetics, 385 dosage form, pharmacokinetics, and dosage form, pharmacokinetics, and recommended dosage and disposition data, 559t disposition data, 556t monitoring requirements, 385 molecular characteristics and dosage form, route of administration, role in therapy, 386 therapeutic use, 587t monitoring requirements, 165 route of administration, 385 rhTPO side effect, endogenous form indications and use, 165 Reteplase (Retavase), 33 of TPO hematopoietic cytokine molecular characteristics and clinical pharmacology, 385 and, 224 therapeutic use, 582t disposition, 386 Ribavirin (Copegus), in treatment of role in therapy, 166 dosage form, 385 chronic hepatitis C, 301, 302 target, product type, indications, dosage form, pharmacokinetics, and Ribavirin (Rebetol), in treatment of FDA approval year, 148t disposition data, 564t chronic hepatitis C, 302, 303 Reproducibility, pharmaceutical drug interactions, 386 Ribonucleic acid, 44, 358 products and, 548 general description, 385 Ribonucleotides, degenerative base Repronex (menotropins) indications and use, 385 triplet on, that codes for specific dosage form, pharmacokinetics, and molecular characteristics and amino acids, 622t disposition data, 570t therapeutic use, 593t Ricin, 156, 455, 455t molecular characteristics and other applications, 386 Rilonacept (Arcalyst) therapeutic use, 603t pharmacokinetics, 385–386 dosage form, pharmacokinetics, and RES. See Reticuloendothelial system recommended dosage and disposition data, 574t Research and development (R&D) monitoring requirements, 385 molecular characteristics and expenditures, by biotechnology and role in therapy, 386 therapeutic use, 609t biopharmaceutical companies, route of administration, 385 Rituxan (rituximab), 35, 456 5t, 6, 7 therapeutic response, 386 annual revenue for, 7 increased expenditures in, 549, 550 Reticuloendothelial system, drug dosage form, 203 Reslizumab, 150t delivery and clearance and, 438 dosage form, pharmacokinetics, and Respigam (respiratory syncytial virus Retina, 433 disposition data, 561t immune globulin, human) Retinal vein occlusion, macular edema indications and use, 203 dosage form, pharmacokinetics, and after, Lucentis in treatment of, molecular characteristics and disposition data, 561t 202, 203 therapeutic use, 590t molecular characteristics and Retrotransposition, 523 for multiple sclerosis, 280 therapeutic use, 589t Retroviral translocation, 510 non-Hodgkin’s lymphoma and Respiratory syncytial virus, Synagis in Retroviruses, recombinant, gene Zevalin vs., 158, 158t treatment of, 198 transfer and, 500 recommended dosage and Respiratory syncytial virus immune Return on investment, integrated monitoring requirements, globulin (human) (Respigam) biopharmaceutical networks 203–204 dosage form, pharmacokinetics, and and, 36 role in therapy, 204 disposition data, 561t Reverse vaccinology, 403, 405 route of administration, 203 molecular characteristics and RG1273, clinical leverage strategy and, sponsors, indications, annual sales in therapeutic use, 589t 32t millions, 6t Responsible Head rhEPO. See Recombinant human target, product type, indications, biopharmaceutical approval and, 16, 17 erythropoietin FDA approval year, 148t development of chemicals and Rheumatoid arthritis Rituximab (Rituxan), 151t, 262 macromolecules into drugs Cimzia in treatment of, 179, 180 clinical pharmacology, 204 and, 17t Enbrel in treatment of, 57 disposition, 204 Resterilizable harvest/drain valve, 30-L Kineret in treatment of, 290, 291 dosage form, 203 bench fermentor, 67 Orencia in treatment of, 163, 164 dosage form, pharmacokinetics, and Resterilizable inoculation/addition Remicade in treatment of, 190, 191 disposition data, 561t valves, 30-L bench fermentor, 67 Simponi in treatment of, 187 drug interactions, 204 Resterilizable sample, 30-L bench TNF-alpha-receptor-Fc fusion general description, 203 fermentor, 67 protein and, 465 indications and use, 203

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 687 0002007355.INDD 687 8/20/2013 1:45:01 AM 688 index

Rituximab (Rituxan) (cont’d) nasal, 433–434 Sandostatin (octreotide, somatostatin, molecular characteristics and ocular, 432–433 octatpeptide) therapeutic use, 590t oral, 430–431 dosage form, pharmacokinetics, and for multiple sclerosis, 280 parenteral, 430 disposition data, 570t other applications and additional pulmonary, 434 molecular characteristics and information, 204 rectal and vaginal, 432 therapeutic use, 603t pharmacokinetics, 204 transdermal and topical, 435–436 Sandostatin (octreotide acetate), 52 recommended dosage and RPE65 gene, 507 additional information, 347 monitoring requirements, RRMS. See Relapsing-remitting dosage form, 346 203–204 multiple sclerosis indications and use, 346 role in therapy, 204 RSV. See Respiratory syncytial virus recommended dosage and route of administration, 203 Rubella, 389, 405 monitoring requirements, 346 sponsors, indications, annual sales in death ratetied to, progression in U.S., role in therapy, 347 millions, 6t 390, 390 route of administration, 346 target, product type, indications, Rule of five, drug-like properties and, sponsors, indications, annual sales in FDA approval year, 148t 449 millions, 6t therapeutic response, 204 Rupture disk safety device, 30-L bench Sangstat (thymoglobulin) Rivaroxaban (Xarelto), 483 fermentor, 67 dosage form, pharmacokinetics, and rM28, 159t disposition data, 561t RNA. See Ribonucleic acid Sabin, Albert, 390 molecular characteristics and RNA-inhibitor (RNAi), 496 Saccharomyces cerevisiae (yeast), as therapeutic use, 590t RNA screening, screening/verifying eukaryotic host, 548 Sanofi-Aventis, 435, 507, 508 molecular clones from gene S-adenosylhomocysteine (SAH) revenue, market share, productivity, expression system and, 49t hydrolase, 361 and research investments of, 5t RO4905417, 150t Safety Sanstat, therapeutic use for, 145t Robotics, 18 interindividual variation and, 472 Saporin, construction of immunotoxins Roche, revenue, market share, pharmacogenetics and, historical and, 455t productivity, and research perspective on, 473–475, 477 Sargramostim (Leukine) investments of, 5t public demands and, 552 clinical pharmacology, 250 Roferon A (interferon alfa-2a), 258 Safety and efficacy data dosage form, 249–250 dosage form, 292 globalization and, 122 dosage form, pharmacokinetics, and dosage form, pharmacokinetics, and for NDA or BLA, 14 disposition data, 567t disposition data, 573t SAGE. See Serial analysis of gene drug interactions, 250 indications and use, 292 expression general description, 249 molecular characteristics and Saizen (somatropin) indications and use, 249 therapeutic use, 607t additional information, 353 molecular characteristics and role in therapy, 293 dosage form, 351 therapeutic use, 598t route of administration, 292 dosage form, pharmacokinetics, and Orphan Drug Classification and source, indication, comments, 272t disposition data, 572t impact of indications/timing Roller bottles, protein pharmaceutical general description, 351 of approval dates on revenues production and use of, 68, 68 indications and use, 351 for, 30t Romiplostim (Nplate), 224 molecular characteristics and other applications and additional dosage form, pharmacokinetics, and therapeutic use, 605t information, 250 disposition data, 561t route of administration, 351 pharmacokinetics, 250 molecular characteristics and Sales, worldwide, top 25 biotechnology recommended dosage and therapeutic use, 590t medicines, 6t, 7, 10–11 monitoring requirements, 250 Rotary Foundations, 20 Salk, Jonas, 390 role in therapy, 250 Roundworms, estimated gene count Samulski, Jude, 503 route of administration, 250 for, 523 Sandoglobulin (immune globulin, therapeutic response, 250 Routes of administration, 97–98 human) (IGIV) Scale, 548 bioavailability of drug and, 82 dosage form, pharmacokinetics, and Scale-up, 70, 129 chemical and physical stability disposition data, 559t Scarcity, 126 and, 98 molecular characteristics and SCF. See Stem cell factor dosage formulations and, 98–99, 100 therapeutic use, 587t Scheie syndrome, 363, 364, 380 immunogenicity and, 93 Sandostatin LAR Depot (octreotide SCID. See Severe combined modification of, and improving acetate) immunodeficiency therapeutic index, 430 dosage form, 346 SCID-X1, 506 systemic, types of, 428, 428 recommended dosage and Scientific Considerations in therapeutic protein monitoring requirements, 346 Demonstrating Biosimilarity to buccal, 431–432 route of administration, 346 a Reference product, 116

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 688 0002007355.INDD 688 8/20/2013 1:45:01 AM index 689

Sclera, 433 SFDA, China, 120 dosage form, pharmacokinetics, and SCNT. See Somatic cell nuclear transfer Shingles (herpes zoster), Zostavax for disposition data, 580t Scopolamine skin patches, 435, 436 prevention of, 416 general description, 414 Scotland, health-care funding Short bowel syndrome, Zorbtive in indications and use, 414 characteristics and HTA treatment of, 351 molecular characteristics and programs in U.S. vs., 543t Short inhibitory RNA (siRNA), 496 therapeutic use, 616t Scroll centrifuge, separation of Short interspersed nuclear elements, 523 recommended dosage and cell lysates containing Short stature homeobox-containing monitoring requirements, 414 pharmaceutical products and, gene (SHOX) deficiency, role in therapy, 415 71, 72 Humatrope in treatment of, 351 route of administration, 414 SDS-PAGE Sialic acid, 87 therapeutic response, 414–415 characterization tests of proteins Sialic tubes, implantable drug delivery Sites of action, targeting to, 449–450 and, 76 systems and, 459 Size-dependent targeting, to lymphoid dosage formulations for Sialylation, prolonged half-life of IgG tissues, 450–452 biopharmaceuticals and, 98 and, 153 SJIA. See Systemic juvenile idiopathic Seasonal flu vaccines, CBER and Sickle cell disease, 473 arthritis regulation of, 18 Sickle cell trait, 473 Skin cancer, metastatic, T-cell therapy Segmental duplication, 523 Side chain modifications, new chemical for, 505–506 Seldane, 9 entities and, 9, 11 Skin Cancer Foundation, 552 SELEX, 496 Signal transduction SLE. See Systemic lupus erythematosus Sensor-augmented insulin pump antibodies and, 156 Small molecular weight drugs, therapy, 459 IFNs and, 261 development of, 25 Sentinel lymph node (SNL) biopsies, Simponi (golimumab) Small-molecule drugs, 1, 3, 8, 11, 444 melanoma and, 269 dosage form, 187 Small molecules Sepsis, Xigris in treatment of, 376 dosage form, pharmacokinetics, and elimination of, 84 Serial analysis of gene expression, 523, disposition data, 558t large-scale purification methods for, 525 indications and use, 187 70 Serine, three- and one-letter code, molecular characteristics and volume of distribution and, 84 linear formula, structure for, therapeutic use, 585t Smallpox, 140 625t recommended dosage and eradication of, 389, 390, 391, 405 Serine protease, protein, feature, and monitoring requirements, 187 vaccine, 404 total number of genes, 527t role in therapy, 188 development of, 395 Serine residues, phosphorylation of, 90 route of administration, 187 variolation and vaccination against, Serono, 28, 29 target, product type, indications, brief history of, 391 Seroquel, off-label promotion of, FDA approval year, 149t SNPs. See Single nucleotide settlement involving, 119t Simulect (basiliximab), 256 polymorphisms Serostim (somatropin) dosage form, 171 Social entrepreneurs, drug and vaccine additional information, 353 dosage form, pharmacokinetics, and development and, 19, 20–21 dosage form, 351 disposition data, 556t Societal perspective, in dosage form, pharmacokinetics, and indications and use, 171 pharmacoeconomics, 127 disposition data, 572t molecular characteristics and Sodium butyrate, 511, 511t general description, 351 therapeutic use, 582t Solid-liquid separation indications and use, 351 recommended dosage and on industrial scale, 73 molecular characteristics and monitoring requirements, recombinant products and, 70–71 therapeutic use, 605t 171–172 Soliris (eculizumab) off-label promotion of, settlement role in therapy, 172 dosage form, 184 involving, 119t route of administration, 171 dosage form, pharmacokinetics, and route of administration, 351 target, product type, indications, disposition data, 558t Serum albumin, 144 FDA approval year, 148t indications and use, 184 Serum Institute of India, development SINEs. See Short interspersed nuclear molecular characteristics and of meningococcal vaccine elements therapeutic use, 584t and, 21 Single-blind studies, 113 recommended dosage and Settlements, involving off-label Single nucleotide polymorphisms, 480 monitoring requirements, 184 promotion, 118, 119t fine-mapping, 480 route of administration, 184 Severe combined immunodeficiency genome-wide map of, 477 target, product type, indications, syndrome, 361, 506 predisposition to cancer and altered FDA approval year, 148t ADA deficiency in, Adagen in response to therapy, 484 Solutes, membrane permeability treatment of, 381, 382 Sipuelucel-T (Provenge), 404 coefficient of, 442 adenosine deaminase for, 361–362 clinical pharmacology, 414 Somatic cell nuclear transfer, 497, 498 PEG-ADA for, 447, 448 dosage form, 414 Somatic gene therapy, 499

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 689 0002007355.INDD 689 8/20/2013 1:45:01 AM 690 index

Somatostatin, 33, 52, 308, 310, 505 molecular characteristics and Spot blot, screening/verifying amino acids in, 53 therapeutic use, 605t molecular clones from gene derivatives Somatropin (Nutropin Depot) expression system and, 49t amino acid sequences compared dosage form, pharmacokinetics, and SPS trial, 416 to endogenous somatostatin, 312 disposition data, 571t SRD5A2 gene variants, DHT, BPH, therapeutic application of, 312 molecular characteristics and prostate cancer and, 484 Somatostatin (Sandostatin) therapeutic use, 605t ST1571, 58 dosage form, pharmacokinetics, and Somatropin (Omnitrope) Stability, of biopharmaceutical disposition data, 570t dosage form, pharmacokinetics, and formulations, 99 molecular characteristics and disposition data, 572t Standard Metabolic Reporting therapeutic use, 603t molecular characteristics and Structures, 528 Somatotropic hormones, properties therapeutic use, 605t Staphylococcus aureus, drug-resistant, and molecular characteristics Somatropin (Saizen) developing vaccines against, 404 of, 311t dosage form, pharmacokinetics, and Stargardt’s macular dystrophy, 510 Somatotropin growth hormones, disposition data, 572t Start-up companies, biopharmaceutical naming conventions for, 619 molecular characteristics and and biotechnology, 7 Somatotropin (STT), 33, 308 therapeutic use, 605t evolving trends in, 34 deamidation of amino acids and, 89 Somatropin (Serostim) funding for, 26 sources and clinical use of, 309t dosage form, pharmacokinetics, and objectives of, 23 Somatrem (Protropin), 310 disposition data, 572t STAT family of proteins, type III IFNs dosage form, pharmacokinetics, and molecular characteristics and and, 259 disposition data, 571t therapeutic use, 605t Statisticians, on FDA review team, 117 molecular characteristics and Somatropin (Tev-Tropin) STAT1, 259 therapeutic use, 604t dosage form, pharmacokinetics, and STDHF, calcitonin bioavailability after Somatropin, 449 disposition data, 572t intranasal administration with, Somatropin (Genotropin) molecular characteristics and 445 clinical pharmacology, 352 therapeutic use, 605t Steady state plasma concentration, IV disposition, 352 Somatropin (Valtropin) dosing, symbol, mathematical dosage form, 351 dosage form, pharmacokinetics, and relationship, and physiological dosage form, pharmacokinetics, and disposition data, 572t variables, 83 disposition data, 571t molecular characteristics and Steam traps, 30-L bench fermentor, 67 drug interactions, 352 therapeutic use, 606t Steatorrhea, pancreatic enzymes for, general description, 351 Somatropin (Zorbitive) 365 indications and use, 351 dosage form, pharmacokinetics, and Stelara (ustekinumab) molecular characteristics and disposition data, 572t dosage form, 210 therapeutic use, 604t molecular characteristics and dosage form, pharmacokinetics, and other applications and additional therapeutic use, 606t disposition data, 562t information, 353 Somatuline Depot (lanreotide indications and use, 210 pharmacokinetics, 352 acetate) molecular characteristics and role in therapy, 352–353 dosage form, 339 therapeutic use, 591t route of administration, 351–352 dosage form, pharmacokinetics, and recommended dosage and sponsors, indications, annual sales in disposition data, 570t monitoring requirements, 210 millions, 6t indications and use, 339 role in therapy, 210 therapeutic response, 352 molecular characteristics and route of administration, 210 trade names, 350 therapeutic use, 602t target, product type, indications, Somatropin (Humatrope) role in therapy, 340 FDA approval year, 149t dosage form, pharmacokinetics, and route of administration, 339 Stem cell evaluation criteria and disposition data, 571t Somavert (pegvisomant), 310 markers, published, summary molecular characteristics and dosage form, pharmacokinetics, and of, 512t therapeutic use, 604t disposition data, 570t Stem cell factor, 219 Somatropin (Norditropin) molecular characteristics and cell source, functions, and molecular dosage form, pharmacokinetics, and therapeutic use, 603t characteristics, 216t disposition data, 571t Sox2, 510 cell types increased/activated and molecular characteristics and Spinal-cord injury, stem cell therapy therapeutic uses for, 223t therapeutic use, 605t and, 501, 510 Stem cell lines, for hepatocyte sponsors, indications, annual sales in Spin filter, perfusion configurations differentiation, 511t millions, 6t and, 70 Stem cell research, hematopoietic stem Somatropin (Nutropin) Sp/O cells, murine myeloma-derived, cells and, 214 dosage form, pharmacokinetics, and 548 Stem cells disposition data, 571t Spongiform virus, 308 high self-renewal capability of, 510

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 690 0002007355.INDD 690 8/20/2013 1:45:01 AM index 691

published hepatocytes derived bioavailability of drug and, 82 Synagis (palivizumab) from and metabolic functions, of biopharmaceuticals, 98 dosage form, 198 summary of, 513t immunogenicity and, 93 dosage form, pharmacokinetics, and Stem cells in regenerative medicine Subcutaneous infusion, 458 disposition data, 560t and diagnostics, 509–512 Subcutaneous (SC) route of indications and use, 198 embryonic and induced pluripotent administration, 428 molecular characteristics and stem cells, 509–510 Subunit vaccines, 392, 396, 405 therapeutic use, 589t future prospects for, 512 “Sufficient time” allocation, toxicity recommended dosage and pluripotent stem cells and, 112 monitoring requirements, 198 in cardiotoxicity screening, 510 Suffixes (or stem) role in therapy, 199 concerns related to, 510 for antibodies, 619 route of administration, 198 hepatocytes from, 510–512 for interleukins, 620, 620t sponsors, indications, annual sales in Stem cell stimulating factors, naming naming conventions and, 617, 618, 618 millions, 6t conventions for, 619t for somatotropin growth hormones, target, product type, indications, Stem cell therapy, 496, 553 bovine and porcine, 619 FDA approval year, 148t for insulin production, 505 Sunbelt Melanoma Trial, 269, 270 Synarel (nafarelin acetate), 316 overview of, 500–501 Sunitinib, 262 dosage form, 344 for repairing heart attack damage, Superoxide dismutase dosage form, pharmacokinetics, and 503–505 molecular weight and volume of disposition data, 570t Stent restenosis, ACE inhibitors, distribution for, 84t indications and use, 344 genetic polymorphism and, therapeutic potential with, 365t molecular characteristics and 486–487 Supprelin (histrelin acetate), 316 therapeutic use, 603t Sterilizable-in-place vessel, 30-L bench dosage form, pharmacokinetics, and recommended dosage and fermentor, 67 disposition data, 568t monitoring requirements, 345 Stir tanks, precipitation and extraction molecular characteristics and role in therapy, 345 of proteins in, 74, 74 therapeutic use, 600t Synarel Nasal Solution for Central STK-1, cell source, functions, and Supprelin LA (histrelin acetate) Precocious Puberty, 344 molecular characteristics, 216t dosage form, 331 Synarel Nasal Solution for Stock market crashes, funding for indications and use, 331 Endometriosis, 344 biotechnology companies recommended dosage and SynCo BioPartners, development of and, 26 monitoring requirements, 331 meningococcal vaccine and, 21 Strategic acquisition, of biotechnology route of administration, 331 Synthetic hormones, therapeutic companies by integrated Surface modification strategies, 359, 448 application of, 309–318 pharmaceutical companies, 35t Susan G. Komen Breast Cancer Systemic juvenile idiopathic arthritis, Stratified medicine, 134 Foundation, 552 Actemra in treatment of, 206 Streptase (streptokinase) Sustained protein release, Systemic lupus erythematosus, Benlysta dosage form, pharmacokinetics, and biodegradable polymers tested in treatment of, 174, 175 disposition data, 564t for, 440t Systems approach, to drug delivery, 466 molecular characteristics and Sustained virologic response (SVR), therapeutic use, 593t chronic hepatitis C and, 274 TAAs. See Tumor-associated antigens Streptococcus pneumonia, developing Swammerdam, Jan, 218 Tachykinins, 54 vaccines against, 404 Sweden Tacrolimus, 482 Streptokinase (Streptase), 81, 97, 366 evidence and value data essential for Target-directed liposomes, 500 characteristics, pharmaceutical health care in, 542 Targeted therapy, reduction in source, mechanisms of action, health-care funding characteristics uncertainty and, 134t 366t and HTA programs in U.S. vs., Target indication, choosing, financial dosage form, pharmacokinetics, and 543t resources and, 26 disposition data, 564t Sylatron (peginterferon alfa-2b), 449 Targeting to sites of action, 449–458, molecular characteristics and dosage form, 304 466 therapeutic use, 593t dosage form, pharmacokinetics, and antibody toxin or effector conjugates, Stroke, stem cells and, 501 disposition data, 574t 454–456 Stromal cells, 213 indications and use, 304 ligand receptor-based targeting, 454 Structural genomics, functional, molecular characteristics and size-dependent targeting to description of, 522t therapeutic use, 609t lymphoid tissues, 450–452 Structure-based design, 52 route of administration, 304 targeting of liposomes based on STT. See Somatotropin Symlin (pramlintide acetate), 313 ligand-receptor interactions, Subcellular vaccines, 389, 392, 395, 405 dosage form, pharmacokinetics, and 456–458 Subcutaneous administration, 85 disposition data, 571t tissue targeting with peptide bioavailability, biologic response, and molecular characteristics and prodrugs, 452–453 ease of use with, 86t therapeutic use, 604t Target product profiles, 542

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 691 0002007355.INDD 691 8/20/2013 1:45:01 AM 692 index

Target protein, encoding, identifying role in therapy, 387 TheraCys (Cannaught strain) (BCG best source for isolating gene, route of administration, 386 Live) 43–44 therapeutic response, 387 dosage form, pharmacokinetics, and Target recognition domains, fusion Terfenadine, 9, 9, 108 disposition data, 575t proteins and, 464 Teriparatide (Forteo), 314, 315 molecular characteristics and Target selection and validation, drug additional information, 354 therapeutic use, 611t discovery process and, 58 clinical pharmacology, 353 Therapeutic antibodies, worldwide Taxol (paclitaxel), BRCA1 tumor cell disposition, 354 clinical trials on, 139 lines resistant to, 484 dosage form, 353 Therapeutic candidates, integration of Taxotere (docetaxel), BRCA1 tumor dosage form, pharmacokinetics, and discovery and development of, cell lines resistant to, 484 disposition data, 572t 520–521 Tay Sachs disease, 529 drug interactions, 354 Therapeutic drug monitoring, 472 TBI. See Translational bioinformatics general description, 353 Therapeutic efficacy, demonstrating, T-cell growth factors, 252, 253 indications and use, 353 success in, 32 cell source, functions, and molecular molecular characteristics and Therapeutic index, 100, 427, 466 characteristics, 216t therapeutic use, 606t formula for, 96 T-cell growth factor II, cell source, pharmacokinetics, 353–354 increase in, targeting of drugs to functions, and molecular recommended dosage and tissues and cells, 450 characteristics, 216t monitoring requirements, 353 time course of plasma drug T-cell lymphoma, Ontak in treatment role in therapy, 354 concentration and, 436 of, 291, 292 route of administration, 353 Therapeutic proteins, 92 T-cell therapy, for metastatic skin sponsors, indications, annual sales in characterizing and evaluating, 80 cancer, 505–506 millions, 6t disposition of, after injection, 429 Technetium (99m Tc) fanolesomab therapeutic response, 354 evaluating immunogenicity of, 94 (NeutroSpec) Terminal amino acid sequences, formulation of, 430 clinical pharmacology, 205 identifying, PCR cloning and, 44 kidneys and filtration and dosage form, 205 Tesamorelin (Egrifta), 311 metabolism of, 91 dosage form, pharmacokinetics, and clinical pharmacology, 354 routes of administration, 430–436 disposition data, 561t dosage form, 354 buccal, 431–432 general description, 205 dosage form, pharmacokinetics, and nasal, 433–434 indications and use, 205 disposition data, 572t ocular, 432–433 molecular characteristics and drug interactions, 355 oral, 430–431 therapeutic use, 590t general description, 354 parenteral, 430 other applications, 205 indications and use, 354 pulmonary, 434 pharmacokinetics, 205 molecular characteristics and rectal and vaginal, 432 recommended dosage and therapeutic use, 606t transdermal and topical, 435–436 monitoring requirements, 205 pharmacokinetics, 354 volume of distribution for, 84t role in therapy, 205 recommended dosage and Therapeutic response, dose and, route of administration, 205 monitoring requirement, 354 95–97 therapeutic response, 205 role in therapy, 355 Therapeutic Target Database, 33, 518, TeGenero AG, 112 route of administration, 354 519 Telaprevir (Incivek), 274 therapeutic response, 355 Therapeutic targets Telbivudine (Tyzeka), 273 Tetanus immune globulin (human) developing novel biopharmaceuticals Temodar, off-label promotion of, (Bay Tet), dosage form, and, 33–34 settlement involving, 119t pharmacokinetics, and in drug development process, 27 Temozolimide (TMZ), 508 disposition data, 561t improving marketed Tenecteplase (TNKase), 33 Tev-Tropin (somatropin) biopharmaceuticals and, 32–33 clinical pharmacology, 386–387 dosage form, 351 treatment hypotheses and, 32 disposition, 387 dosage form, pharmacokinetics, and Therapeutic vaccines, 404 dosage form, 386 disposition data, 572t Thermal mass flow controller, 30-L dosage form, pharmacokinetics, and general description, 351 bench fermentor, 67 disposition data, 564t indications and use, 351 Thiopurine S-methyltransferase, drug interactions, 387 molecular characteristics and genetic variations found in, 478, general description, 386 therapeutic use, 605t 479t indications and use, 386 route of administration, 351 351(k) application, submission to FDA, molecular characteristics and TF2, 159t 116 therapeutic use, 594t TGN1412, unforseen toxicity with, 112 Threonine pharmacokinetics, 387 Thalidomide, 16, 111 residues, phosphorylation of, 90 recommended dosage and Theobromine, molecular structure of, 8 three- and one-letter code, linear monitoring requirements, 386 Theophylline, molecular structure of, 8 formula, structure for, 625t

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 692 0002007355.INDD 692 8/20/2013 1:45:02 AM index 693

Thrombate III (antithrombin III, TICE BCG (TICE strain) (BCG Live) recommended dosage and human) dosage form, pharmacokinetics, and monitoring requirements, 206 dosage form, pharmacokinetics, and disposition data, 575t role in therapy, 206 disposition data, 565t molecular characteristics and route of administration, 206 molecular characteristics and therapeutic use, 611t target, product type, indications, therapeutic use, 596t Tiered-copayment formulary system, FDA approval year, 149t Thrombin, 212, 225, 227 538 therapeutic response, 206 Thrombin, topical (recombinant) TIGR. See Institute for Genomic Tofacitinib, clinical leverage strategy (Recothrom) Research, The and, 32t dosage form, pharmacokinetics, and TILs. See Tumor-infiltrating Tolerance studies, of drugs, 81 disposition data, 567t lymphocytes Toll-like receptors, 398 molecular characteristics and Time-course drug concentration pathogen components recognized therapeutic use, 599t sampling, basis of, 429 by, 399 Thrombocytopenia, 92 Time-course therapeutic response, 430 Topical route of administration, IFNs and, 270 Timone, Emanuel, 391 therapeutic proteins and, Neumega in treatment of, 246, 255 TIMP-3, 502 435–436 Thromboembolic disease, Refludan in Tisseel kit (fibrinogen, human and Topoisomerase II, 456 treatment of, 244, 245 thrombin, human) Tositumomab I-131 (Bexxar) Thrombolytic agents, 86, 428 dosage form, pharmacokinetics, and additional information, 208 Thrombolytic enzymes, 365–366 disposition data, 575t clinical pharmacology, 207 cross section of blood vessel with molecular characteristics and disposition, 207 blood clot and, 359 therapeutic use, 610t dosage form, 207 Thrombophilia, 475, 477 Tissue plasminogen activator dosage form, pharmacokinetics, and Thrombopoietin, 92, 215, 223–224 (alteplase), 33, 365, 428 disposition data, 562t cell source, functions, and molecular characteristics, pharmaceutical general description, 207 characteristics, 216t source, mechanisms of action, indications and use, 207 cell types increased/activated and 366, 366t molecular characteristics and therapeutic uses for, 223t glycosylation linkage to peptide therapeutic use, 590t Thrombosis, 212, 227, 365–366 backbone, 82t pharmacokinetics, 207 Thrombotic thrombocytopenia purpura Tissue targeting, with peptide prodrugs, recommended dosage and aptamer-based therapies and, 497 452–453 monitoring requirements, 207 IFNs and, 270 Tissue transplantation products, CBER role in therapy, 208 Thymoglobulin (Sangstat) review of, 18 route of administration, 207 dosage form, pharmacokinetics, and TLRs. See Toll-like receptors target, product type, indications, disposition data, 561t T lymphocytes (T cells), 140, 141, 215, FDA approval year, 148t molecular characteristics and 218, 393 therapeutic response, 207 therapeutic use, 590t TNF-alpha, 464 Total body clearance of drug, Thyrel TRH (protirelin) TNF-alpha-receptor-Fc fusion protein, estimating, 85 dosage form, pharmacokinetics, and 153, 465 TOUCH Prescribing Program, 195, 196, disposition data, 571t TNKase (tenecteplase), 366, 366t 279 molecular characteristics and dosage form, 386 Toxicities therapeutic use, 604t dosage form, pharmacokinetics, and dose, therapeutic response and, 95 Thyrogen (thyrotropin alfa) disposition data, 564t late-stage drug development failure dosage form, pharmacokinetics, and indications and use, 386 and, 552 disposition data, 572t molecular characteristics and “sufficient time” allocation and, 112 molecular characteristics and therapeutic use, 594t Toxicological assessments, of therapeutic use, 606t role in therapy, 387 biopharmaceuticals, 99 Thyroid dysfunction, IFNs and, 270– route of administration, 386 Toxicological drug effects, 271 Tocilizumab (Actemra), 156 metabolomics and, 529 Thyroid-stimulation hormone, 33 additional information, 206 Toxicological responses, preclinical Thyrotropin alfa (Thyrogen) clinical pharmacology, 206 studies on, 14 dosage form, pharmacokinetics, and dosage form, 206 Toxicological studies, done at genomic disposition data, 572t dosage form, pharmacokinetics, and levels, 531 molecular characteristics and disposition data, 562t Toxicology therapeutic use, 606t drug interactions, 206 pharmacogenomics and, 521 Thyrotropin-releasing hormone, 33 general description, 205 pharmacology and, 81–82 Thyrotropin-releasing hormone indications and use, 206 tPA. See Tissue plasminogen activator analogs, 452 molecular characteristics and TPMT. See Thiopurine Thyrotropin-stimulating hormone, therapeutic use, 590t S-methyltransferase sources and clinical use of, 309t pharmacokinetics, 206 TPO. See Thrombopoietin

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 693 0002007355.INDD 693 8/20/2013 1:45:02 AM 694 index

TPPs. See Target product profiles therapeutic response, 209 Tumor-cell biology, advances in, 40 Transcription, of genetic information, TRC 105, 150t Tumor-infiltrating lymphocytes, 505, 7, 41 Treatment hypotheses, therapeutic 506 Transcytosis, 86 targets and, 32 Tumor mass, antibody distribution Transdermal patches, 435 Treatment Investigational New Drugs, into extravascular space across Transdermal route of administration, 108 endothelial cells lining blood therapeutic proteins and, Trelstar (triptorelin pamoate) capillaries and into, 155, 155 435–436 dosage form, 355 Tumor necrosis factor, kidney Transferrin, expressing on liposomes, dosage form, pharmacokinetics, and metabolism and elimination of, enhancing delivery of disposition data, 572t 92 anthracyclines and, 457 indications and use, 355 Tumorogenesis, iPSC-derived products Transgenes, 498 molecular characteristics and and, 510 Translation, of genetic information, 41 therapeutic use, 607t Tumor-specific antigens, 454 Translational bioinformatics, 550 route of administration, 355 Turner syndrome, 310 Translational research Tripedia (diphtheria and tetanus somatropin in treatment of, 351, 352, goal of, 24 toxoids and acellular pertussis 353 partnerships in, 550–551 vaccine adsorbed) Twinrix (hepatitis A, inactivated and pharmaceutical drug discovery and dosage form, pharmacokinetics, and hepatitis B (recombinant) development and, 25 disposition data, 576t vaccine) Translational technologies, expanding, molecular characteristics and dosage form, pharmacokinetics, and for commercialization, 24 therapeutic use, 612t disposition data, 578t Transplantations, gene and cell therapy Triptorelin pamoate (Trelstar) molecular characteristics and and, 496, 497 clinical pharmacology, 355 therapeutic use, 613t, 614t Transposon tagging, 526 disposition, 356 Two-dimensional gel electrophoresis, TransVax, 509 dosage form, 355 protein characterization and Trastuzumab (Herceptin), 134, 490, 492 dosage form, pharmacokinetics, and stability assessment and, 51t clinical pharmacology, 208–209 disposition data, 572t Type 2 diabetes mellitus, Byetta in disposition, 209 general description, 355 treatment of, 323, 324 dosage form, 208 indications and use, 355 Typhoid vaccine, 395 dosage form, pharmacokinetics, and molecular characteristics and Tyrosinase, canine, 508 disposition data, 562t therapeutic use, 607t Tyrosine, 90 dose-dependent nonlinearity in other applications, 356 three- and one-letter code, linear clearance and plasma half-life pharmacokinetics, 355–356 formula, structure for, 625t of, 152t recommended dosage and Tysabri (natalizumab), 156 dose-dependent pharmacokinetics monitoring requirements, 35 dosage form, pharmacokinetics, and of, 152 role in therapy, 356 disposition data, 560t drug interactions, 209 route of administration, 355 molecular characteristics and FDA approval of as therapy, HER2 therapeutic response, 356 therapeutic use, 588t expression test on tumor tissues Trisenox, off-label promotion of, for multiple sclerosis, 279 and, 491 settlement involving, 119t target, product type, indications, general description, 208 Trypsin, 431 FDA approval year, 148t indications and use, 208 Tryptophan, 90 Tyzeka (telbivudine), 273 levels of HER2 antigen expression TSH. See Thyrotropin-stimulating and overall response rate to, hormone UA. See Unstable angina 491t TTD. See Therapeutic Target Database UGT (1A1), 479t molecular characteristics and TTP. See Thrombotic UGT2, 476t therapeutic use, 591t thrombocytopenia purpura Ulcerative colitis, Remicade in nonproprietary USANC assigned T2-18C3, 151t treatment of, 190, 191 name, 618 Tuberculosis vaccines, 395, 404, 404t Ultrafiltration technologies, for protein other applications and additional Tubular bowl configuration, separation concentration, 74 information, 209 of cell lysates containing UltraLente injections, 462 pharmacokinetics, 209 pharmaceutical products and, Ultraviolet: visible spectroscopy, recommended dosage and 71, 72 protein characterization, monitoring requirements, 208 Tufts Center for the Study of Drug stability assessment and, 51t role in therapy, 209 Development, 518 Uncertainty, targeted therapy and route of administration, 208 Tufts University, CEA Registry, 128 reduction in, 134t sponsors, indications, annual sales in Tularemia, vaccines against, 404, 404t Unit cost, increased product yield millions, 6t Tumor-associated antigens, 454 or titer as function of time target, product type, indications, IFNs and, 262 and, 66 FDA approval year, 148t tumor-specific antigens vs., 151 United Kingdom

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 694 0002007355.INDD 694 8/20/2013 1:45:02 AM index 695

evidence and value data essential for target, product type, indications, molecular characteristics and health care in, 542 FDA approval year, 149t therapeutic uses for, 611t–616t health-care expenditure growth rate therapeutic response, 210 monographs list, 409 in, 536 Uterine leiomyoma, Lupron novel carrier and delivery modes, 401t infant mortality and life expectancy (leuprolide acetate) in papilloma viral, 18 rankings in, 537t treatment of, 340, 342 polio, 20, 390, 395 United Kingdom Hemophilia Center prostate cancer, 404 Doctors’ Organization, 227 Vaccination, humoral and cell- recombinant, 392, 396–397, 405 United States mediated immune responses review with PLA by CBER, 104 growing aging population in, 536 induced by, 393 safety of, FDA and, 397 health-care expenditure growth rate Vaccine Adverse Event Reporting smallpox, 390, 391, 395, 404 in, 536 System, 397 social entrepreneurs and HTA programs in five nations vs., Vaccine development, collaborations development of, 20–21 comparison of health-care involved in, 13 subcellular, 392, 395–396, 405 funding characteristics, 543t Vaccine-preventable childhood subunit, 392, 396, 405 infant mortality and life expectancy diseases, death rate of, therapeutic, 404 rankings in, 537t progression in U.S., 390 timeline of select human vaccine United States Adopted Names Vaccines, 3, 389–405 development, 396 (USAN) Council, 617 adjuvants, 398, 400, 405 traditional approaches with, 394–395 registered name for trastuzumab annual worldwide sales of, 403 tuberculosis, 395 (Herceptin), 618 BCG, 395 typhoid, 395 role of, 618 biological properties of pathogen varicella zoster, 395 website for, 620 and successful development of, whole-killed, 394, 395, 396, 405 United States Pharmacopoeia, 76 394t Vaccines and Related Biological Universities, pharmaceutical drug cancer, 404, 405 Products Advisory Committee, discovery and development CBER and regulation of, 18 397 and, 25 contraceptive, 404 Vaginal route of administration, Unstable angina, Integrilin in treatment delivery mode and route for, therapeutic proteins and, 432 of, 243 400–402 Validated drug tragets, completion of Upregulation mechanism, drug DNA-based, 553 human genome project and, 518 interactions and, 92 dosage form, pharmacokinetics, and Valine, 90 Urate oxidase (uricase), derivatives disposition data, 575t–580t three- and one-letter code, linear and, 367–368 FDA and approval of, for human formula, structure for, 625t Uric acid in chemotherapy, Elitek in use, 397 Valtropin (somatropin) treatment of, 384, 385 future directions with, 403–405 dosage form, 351 Uridine diphosphate (UDP)- future generations of, new and dosage form, pharmacokinetics, and glycuronosyltransferase (UGT), reemerging disease targets for, disposition data, 572t genetic variations found 404t general description, 351 in, 478 hepatitis B, 9, 11 indications and use, 351 Urine samples, profiling engodenous HIV/AIDS, challenges in molecular characteristics and metabolites with, 528 development of, 402 therapeutic use, 606t Urokinase, characteristics, human health and impact of, 390, route of administration, 351 pharmaceutical source, 392–393 Valveperistaltic pumps, 30-L bench mechanisms of action, 366t increase in life expectancy and, 389, fermentor, 67 USP. See United States Pharmacopoeia 390 van Leeuwenhoek, Antoni, 218 Ustekinumab (Stelara) influenza, 395 Vantas (histrelin acetate) clinical pharmacology, 210 interplay among immune system, dosage form, 330 dosage form, 210 diseases and, 393–394 dosage form, pharmacokinetics, and dosage form, pharmacokinetics, and intramuscular injection of, 401 disposition data, 568t disposition data, 562t licensed, designed for pathogens that indications and use, 330 drug interactions, 210 infect humans through mucosa, molecular characteristics and general description, 210 402t therapeutic use, 600t indications and use, 210 licensed, for immunization and recommended dosage and molecular characteristics and distribution, in U.S., 392t monitoring, 330 therapeutic use, 591t live attenuated, 394–395, 405 route of administration, 330 pharmacokinetics, 210 meningococcal, 21 Vaqta (hepatitis A vaccine, inactivated) recommended dosage and milestones of enabling concepts/ dosage form, pharmacokinetics, and monitoring requirements, 210 technologies in development of, disposition data, 578t role in therapy, 210 391t molecular characteristics and route of administration, 210 MMR, 395 therapeutic use, 614t

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 695 0002007355.INDD 695 8/20/2013 1:45:02 AM 696 index

Varicella virus vaccine, live (Varivax) Vectors molecular characteristics and clinical pharmacology, 415 bacterial expression systems and, 48 therapeutic use, 610t dosage form, pharmacokinetics, and defined, 43t Vitreous humor, 433 disposition data, 580t VEGF. See Vascular endothelial growth Vivaglobin, 144t drug interactions, 415 factor VKOR. See Vitamin K 2,3-epoxide general description, 415 VEGF121, 497 reductase indications and use, 415 VEGF165, 497 VKORC1 genotype, dosing molecular characteristics and VEGF-A. See Vascular endothelial recommendation range therapeutic use, 616t growth factor-A according to, of individuals recommended dosage and VEGFR-1, 169 on warfarin anticoagulation monitoring requirements, 415 VEGFR-2, 169 therapy, 483t role in therapy, 415 Velaglucerace alpha (Vpriv) VKORC1 polymorphism, warfarin route of administration, 415 clinical pharmacology, 388 response and, 483 therapeutic response, 415 dosage form, 387 VKOR gene polymorphism, 483 Varicella-zoster virus, 416 dosage form, pharmacokinetics, and Volume of distribution Varicella zoster (VZV) vaccine, 395 disposition data, 564t defined, 84 Variolae, 140 for Gaucher’s disease, 362 dose-dependent effects on, 84t Variolation, 391 general description, 387 for selected therapeutic proteins, Variola virus, smallpox and, 391 indications and use, 387 84t Varivax (varicella virus vaccine, live) molecular characteristics and symbol, mathematical relationship, dosage form, 415 therapeutic use, 594t and physiological variables, 83 dosage form, pharmacokinetics, and pharmacokinetics, 388 von Hippel-Lindau (VHL) syndrome, disposition data, 580t recommended dosage and aptamer-based therapies and, indications and use, 415 monitoring requirements, 497 molecular characteristics and 387–388 von Willebrand disease, IV formulation therapeutic use, 616t role in therapy, 388 of desmopressin, surgery and, route of administration, 415 route of administration, 387 318 Vascular endothelial growth factor, 507 therapeutic response, 388 von Willebrand factor, 225, 227 wet age-related macular Velosulin BR (insulin) von Willebrand factor-related disorders, degeneration and, 423 dosage form, pharmacokinetics, and aptamer-based therapies and, Vascular endothelial growth factor-A, disposition data, 569t 497 aflibercept and, 168, 169 molecular characteristics and Vpriv (velaglucerace alpha) Vasoactive intestinal peptide (VIP) therapeutic use, 601t dosage form, 387 tumors, 312 Veltuzumab, 150t dosage form, pharmacokinetics, and Vasopressin, 308, 318t, 431, 432 Venture capital, for start-up disposition data, 564t amino acid sequence and cyclic biotechnology companies, 26 for Gaucher’s disease, 362 structure, 317t Verluma, technetium Tc 99m indications and use, 387 derivatives, therapeutic application (nofetumomab), 158 molecular characteristics and of, 317–318 dosage form, pharmacokinetics, and therapeutic use, 594t sequences, analogs of, 318t disposition data, 560t recommended dosage and Vasopressin receptors, V1 and V2, 317 molecular characteristics and monitoring requirements, 387 Vectibix (panitumumab) therapeutic use, 588t role in therapy, 388 dosage form, 199 Viault, Francois, 218 route of administration, 387 dosage form, pharmacokinetics, and Vical Inc., 508, 509 VQGEESNDK, 57 disposition data, 561t Victrelis (boceprevir), 274 VZV. See Varicella-zoster virus dose-dependent nonlinearity in Viewing window, 30-L bench clearance and plasma half-life fermentor, 67 Warfarin anticoagulation effects, of, 152t Viral hepatitis genetic variation in CYP2C19, dose-dependent pharmacokinetics future prospects in treatment of, 274 vitamin K 2,3-epoxide reductase of, 152 interferons in, 271–272 and, 482–483 indications and use, 199 “Virtual drug development” model, 36 Warfarin anticoagulation therapy molecular characteristics and Vitamin K 2,3-epoxide reductase, bleeding-related hospitalization therapeutic use, 589t warfarin anticoagulation effects, and, 482 recommended dosage and genetic variation in CYP2C19 dosing recommendation range monitoring requirements, and, 482–483 according to CYP2C9 and 199–200 Vitaxin, 150t VKORC1 genotype of role in therapy, 200 Vitravene, 34 individuals on, 483t route of administration, 199 Vitravene (fomivirsen sodium), 496 Waterfall hypothesis, 212 target, product type, indications, dosage form, pharmacokinetics, and Water solubility, 521 FDA approval year, 148t disposition data, 564t, 575t Weber, Wendell W., 473

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 696 0002007355.INDD 696 8/20/2013 1:45:02 AM index 697

Wegener’s granulomatosis, Enbrel in Xarelto (rivaroxaban), 483 pharmacokinetics, 233 treatment of, 186 Xenobiotics, 479 recommended dosage and Welfare loss, 131 Xeomin (incobotulinumtoxin-A) monitoring requirements, Welferon (interferon alfa-n1) dosage form, 421 232–233 dosage form, pharmacokinetics, and dosage form, pharmacokinetics, and route of administration, 232 disposition data, 573t disposition data, 575t therapeutic response, 233 molecular characteristics and indications and use, 421 therapeutic use, 608t molecular characteristics and Yamanaka, Shinya, 510 source, indication, comments, 272t therapeutic use, 611t Yarrowia lipolytica strain, transgenic Well-characterized biotechnology role in therapy, 422 glycol-engineered, 548 products route of administration, 421 Yeast, genomic analysis of, 522 successful development of, rationale Xgeva (denosumab), target, product Yeast mRNA processing, proteins for, 32–34 type, indications, FDA approval involved in, 524 types of, 17 year, 149t Yeast two-hybrid systems “Well-characterized recombinant Xiaflex (collagenase Clostridium efficient study of protein-protein proteins,” 76 histolyticum) interactions in situ and, Western immunoblot, screening/ dosage form, pharmacokinetics, and 525, 525 verifying molecular clones from disposition data, 563t variations and improvements gene expression system and, 49t molecular characteristics and in, 526 West Nile virus, developing vaccines therapeutic use, 592t Yervoy (ipilimumab), 505 against, 404, 404t Xigris (drotrecogin alfa, activated) dosage form, 192 White blood cells, 140, 212, 218 dosage form, 376 dosage form, pharmacokinetics, and WHO. See World Health Organization dosage form, pharmacokinetics, and disposition data, 560t Whole-killed vaccines, 389, 394, 395, disposition data, 563t indications and use, 192 396, 405 indications and use, 376 molecular characteristics and WiCell lines, hESCs and, 511 molecular characteristics and therapeutic use, 588t William J. Clinton Foundation, 552 therapeutic use, 592t recommended dosage and Wilmut, Ian, 498 recommended dosage and monitoring requirements, 192 Wilson, James, 503 monitoring requirements, 376 role in therapy, 192 Winler, Keith, 489 role in therapy, 376 route of administration, 192 WinRho SDF route of administration, 376 target, product type, indications, therapeutic use for, 145t Xolair (omalizumab) FDA approval year, 149t WinRho SDF (immune globulin, dosage form, 197 Yield optimization, in host cells and human, against Rho D) dosage form, pharmacokinetics, and genetic constructs, 65, 66 dosage form, pharmacokinetics, and disposition data, 560t Y-90, 455, 456 disposition data, 559t indications and use, 197 Y-90 ibritumomab tiuxetan, 189 molecular characteristics and molecular characteristics and Y sex chromosomes, human gene therapeutic use, 587t therapeutic use, 589t number identified to date Wolchok, Jedd, 508 recommended dosage and according to their distribution Women, FDA requirements, clinical monitoring requirements, 197 in, 519t testing and, 113 role in therapy, 197–198 Woodcock, Janet, 116 route of administration, 197 Zantac, 34 World Health Organization, 21 target, product type, indications, Zenapax (daclizumab) on health-care expenditures, in U.S., FDA approval year, 148t dosage form, pharmacokinetics, and 536 XOMA 052, 151t disposition data, 557t on impact of vaccines, 390 X sex chromosomes, human gene molecular characteristics and International Nonproprietary Names number identified to date therapeutic use, 584t Committee, 617, 618 according to their distribution role in therapy, 172 website for, 620 in, 519t target, product type, indications, myeloproliferative neoplasms Xyntha (antihemophilic factor FDA approval year, 148t classified by, 263 (recombinant), plasma/albumin ZEST trial, 416 National Institute of Biological free) Zevalin (ibritumomab tiuxetan), 456 Standards and Control, 76 dosage form, pharmacokinetics, and dosage form, 188 World War I, fermentation technology disposition data, 565t dosage form, pharmacokinetics, and used in, 8 molecular characteristics and disposition data, 559t World War II, fermentation technology therapeutic use, 594t indications and use, 188 used after, 8 Xyntha (antihemophilic factor VIII) molecular characteristics and dosage form, 232 therapeutic use, 586t Xalkori (crizotinib), 471, 489, 492, 524 general description, 231–232 non-Hodgkin’s lymphoma and Xanthine, molecular structure of, 8 indications and use, 232 Rituxan vs., 158, 158t

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 697 0002007355.INDD 697 8/20/2013 1:45:02 AM 698 index

Zevalin (ibritumomab tiuxetan) role in therapy, 330 Zoster vaccine live (Zostavax) (cont’d) route of administration, 329 clinical pharmacology, 416 recommended dosage and Zorbitive (somatropin) dosage form, 416 monitoring requirements, dosage form, 351 dosage form, pharmacokinetics, and 188–189 dosage form, pharmacokinetics, and disposition data, 580t role in therapy, 189 disposition data, 572t drug interactions, 416 route of administration, 188 general description, 351 general description, 416 target, product type, indications, indications and use, 351 indications and use, 416 FDA approval year, 148t route of administration, 351 molecular characteristics and Zoladex (goserelin acetate), 316 Zostavax (zoster vaccine live) therapeutic use, 616t dosage form, 329 dosage form, 416 recommended dosage and dosage form, pharmacokinetics, and dosage form, pharmacokinetics, and monitoring requirements, disposition data, 568t disposition data, 580t 416 indications and use, 329 indications and use, 416 role in therapy, 416 molecular characteristics and molecular characteristics and route of administration, 416 therapeutic use, 600t therapeutic use, 616t therapeutic response, 416 recommended dosage and role in therapy, 416 Zyprexa, off-label promotion of, monitoring requirements, 329 route of administration, 416 settlements and, 118, 119t

Chapter No.: 3 Title Name: RodneyJHo Comp. by: TSanthosh Date: 20 Aug 2013 Time: 01:44:57 AM Stage: Printer Page Number: 698 0002007355.INDD 698 8/20/2013 1:45:02 AM 0002007355.INDD 699 8/20/2013 1:45:02 AM 0002007355.INDD 700 8/20/2013 1:45:02 AM 0002007355.INDD 701 8/20/2013 1:45:02 AM 0002007355.INDD 702 8/20/2013 1:45:02 AM