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Activated Protein C, 5, 121, 265, 280, 307Adalimumab, 6, 344Adventitious agents , 21, 28, 30, 37, 41, 52, 84, 85,

93,95, 100, 102, 105, 109, 114, 116, 124, 126,127, 132, 133, 134, 135, 146, 147, 148, 150, 151,161, 164, 171, 173, 180, 183, 189, 196, 197, 212,244, 245, 292, 294, 299

Affinity, 6, 166, 167, 168, 172 , 173, 178, 182, 184,189, 193, 234, 306 , 310

Agg rega tion, 30, 225, 228, 234, 236, 277Alefacept , 5, 276, 280Alemtuzumab, 6, 280Antibiotics, 2, 14, 126, 141, 147, 174, 185, 186, 197,

234,263Antigenici ty, 28APHIS (Animal and Plant Health Inspection

Service), 155, 156, 157, 338AVAX Technolog ies, 77

Bacteria, 23, 90, 103, 105, 106, 109, 120Basilixirnab, 6, 204Bayer, 74, 283, 284, 334Becaplermin, 208, 272, 343Bioactivity, 22, 30, 49 , 224, 228, 231, 232 , 237,

238, 251, 252, 253, 264, 270 , 300Bioassay, 30, 31, 248 , 249, 250 , 252, 253, 255, 256,

257 ,273Bioburden, 74, 98, 104, 133, 153, 174, 179, 183, 184,

202, 206 , 208, 247 , 248, 249, 250 , 273, 280 ,281, 306

Bioreactor , 6, 89, 105, 108, 115, 11 8, 119, 120, 123,129, 132, 133, 134, 135, 136, 137, 138, 140, 141,144, 145, 157, 158, 164, 292, 306

BLA (Biologics Licen se Application), 10, 23, 30, 31,32, 33 , 38, 43, 48, 49, 51, 52, 53, 54, 81, 83,99, 100, 108, 114, 125, 126, 128, 130, 135, 136,146, 155, 159, 172, 173, 177, 184, 196, 199 , 210,212, 219, 231, 240, 243, 252 , 254, 256, 259,

Index

BLA (Biologics License Application) (cont.)

261, 262 , 263, 265, 270 , 276 , 277, 279, 280,282, 285 , 290, 291, 304, 310, 313, 321, 334,339, 343

Bovine, 22, 109, 110, III , 112, 113, 143, 168, 184,188, 189, 191, 194

BPDR (Biological product dev iation report ), 75, 76BSE (Bov ine spongiform encepha lopathy), 22, III ,

112, 113, 126, 142, 143, 144, 173, 323, 336

CBER (Center for Biologics Evaluat ion andResearch), 10, II , 15, 19, 22, 25, 75, 76, 11 2,11 3, 142, 221,281, 282, 287, 303 , 304 , 321,322, 323, 331, 332, 333, 335, 336, 337, 338 ,342, 343, 344, 345

CDER (Center for Drug Evaluation and Research),10, I I. 19,75,281, 321, 322,323,327,332,339

Cell Therapy Research Foundat ion , 77Cell bank characteriza tion, 28, 30, 41, 106, 107, 312Cell culture, 20, 22, 69, 81, 104, 119, 120 , 123, 127,

132, 133, 134, 141, 142, 144, 145, 146, 147, 157,158, 184, 186, 188, 197 , 231, 244, 306, 312

Cent ocor, 188, 218, 283, 340CHO (Chinese hamster ova ry) cells, 106, 107, 120,

135, 182, 192, 238, 308, 309CJD (Creutzfe ldt-Jakob Disease), 4, IIICleanin g validation, 60, 138, 139, 140, 180, 183, 197Cole y's toxin, 17Comparability , 25, 30, 31, 32, 288, 290 , 295 , 296,

297, 298, 299, 300, 301, 302, 303, 304, 305,306, 307 , 308, 309, 310, 315, 344 , 345

Comparabilit y protocol , 19, 304, 305Comparabil ity study, 300, 301, 302, 304, 308 , 309Consultant s, 2, 18, 27Cont ract manufacturer, 31, 65, 206, 312, 314, 315,

316, 317, 319, 345Cro ss-contamination, 14, 58, 64, 65, 66, 68, 71. 73,

81, 94, 100, 104, 114, 126, 127, 129, 130, 138,

347

348

Cross-contamination (cant .)

139, 145, 152, 153, 173, 174, 175, 178,214,216,217,251

CSF (Colony Stimulating Factor), 4, 8, 206, 285CTD (Common Technical Document), 48, 49, 213,

321, 323, 334Cutter Incident , 13

Daclizumab, 6, 248Denileukin diftitox, 4, 52, 283, 334DMF Drug Master File), 30, 32, 43, 210, 212, 213Dornase alfa, 208, 284

Eli Lilly, 282, 283, 307, 308, 343, 345EMEA (European Agency for Evaluation of

Medicinal Products) , 10, 11, 12, 20, 33, 49, 76,109, 113, 128, 142, 143, 146, 153, 154, 187, 246,295, 296, 297, 306, 312, 322, 329, 332, 333,335, 336, 337, 338, 340, 344, 345

Endotox in, 28, 136, 166, 168, 174, 179, 180, 184,185, 186, 197, 198, 206, 242, 247, 248, 249,250, 251, 257, 262, 263, 273, 280, 306, 323,327,342

Environmental monitoring, 52, 67, 76, 145, 146, 154,175, 176, 177, 214, 215, 218

EOP2 (End of Phase 2), 25, 29, 30, 31, 32, 47, 238,290

EPC (End of Product ion Cells) , 106, 107, 108, 127,137

EPO (Erythropoietin), 5, 8, 266, 308, 309, 345Excipients, 28, 43, 202, 203, 204, 205, 209, 210,

212, 272, 292, 296, 309Expansion, 84, 86, 117, 120, 123, 137, 144, 146Expiration date, 62, 221, 222, 229, 267, 269, 271,

274, 275, 276, 279, 283, 292, 294Expression , 7, 25, 86, 94, 96, 97, 98, 100, 103, 104,

105, 116, 117, 118, 123, 129, 132, 133, 136, 137,141, 144, 150, 152, 155, 157,237,274, 308, 329

Expression construct, 86, 93, 94, 96, 97, 100, 103,105, 137, 148, 239, 323, 327, 336

Factor VIla ,S, 120, 194, 204, 338Factor V111, 3, 5, 53, 283, 284Filtration , 74, 119, 144, 145, 158, 165, 168, 182, 183,

190, 196, 206, 218, 221, 250, 273, 275, 276,284, 293, 296

Formulation, 32, 51, 52,112,164,203,204,205 ,208 ,211,219, 231, 270, 290, 292, 299, 300, 301, 309

Gemtuzumab ozogamicin , 6, 10Gene therapy, 3, 7, 8, 11 , 14, 15, 37, 39, 46, 47, 63,

88, 140, 146, 147, 148, 162, 197, 239, 250, 251,257, 323, 331, 333

Genentech , 74, 158, 198, 206, 218, 282, 284, 296,306, 310, 334, 338, 339, 343

Index

General Safety Test, 248, 251Generic , 23, 135, 167, 194Genetic construction , 85, 86, 90Genetic stability, 41, 105, 108, 125, 130, 136, 154, 341Genetic s Institute, 281Gentam icin, 2, 120, 141, 184, 306Glaxo, 284Glycosylation, 5, 22, 30, 41, 90, 225, 230, 231, 232,

233, 234, 236, 237, 238, 253, 280, 300, 306,308,309

Harvest, 49, 51, 67, 95, 108, 112, 117, 118, 119, 120,123, 127, 128, 130, 132, 136, 137, 145, 146, 152,153, 154, 155, 162, 177, 188, 189, 195, 244, 245,294, 306

Hepatitis B, 4, 8, 120HGH (Human Growth Hormone) , 4, 8, 10, 11 ,208,

282, 341Hoffman-La Roche, 284Hydrophobicity , 164, 166, 178, 226

Ibritumomab tiuxetan , 6ICH (International Conference on Harmonization) ,

20, 21, 48, 49, 63, 66, 69, 70, 99, 100, 104, 110,114, 131 , 139, 145, 175, 198, 232, 253, 254, 260,262, 277, 297, 322, 323, 327, 331, 332, 334,335, 336, 340, 341, 342, 343

IDEC, 157, 158, 198,206, 336, 339Identity testing, 22, 76, 102, 103, 106, 107, 147, 184,

247, 248, 249, 250, 251, 272, 273IEF (lsoelectric focusing) , 184, 227, 228, 248, 249,

250, 256, 273Immunoa ssay, 234, 252, 253Immunogenicity , 6, 22, 205, 222, 224, 238, 287,

300, 308, 309IND (Investigation New Drug), 10, 25, 27, 28, 29,

38, 39,41,43,46,47,77,99, 100, 107, 108,122, 123, 124, 146, ISS, 169, 170, 171, 172, 177,197, 208, 209, 210, 211, 229, 230, 241, 242,267, 268, 269, 289, 303, 313, 323, 327, 332,333, 342

Infliximab,6, 168, 184, 187, 188,204, 244, 250, 273,283,336

In-process controls, 41, 43, 49, 62, 65, 79, 94, 123,124, 125, 126, 127, 128, 129, 130, 133, 147, 170,171 , 172, 173, 174, 178, 183, 184, 211, 213, 217,301

Insect, 91, 109, 237Insulin, 4, 8, 9, 10, 11 , 187, 253, 282, 283, 341Interferons, 8, 204, 206, 208, 248, 253, 261, 276,

283, 284, 296, 308, 323, 331, 337, 345Interleukins, 4, 6, 120, 169, 204, 208, 264, 280, 285,

307,310IQA (Intercompan y quality agreement), 313, 315,

316, 317, 318, 319

Index

Laronidase, 266, 280

Mammal ian, 91, 106, 120Mass spectrome try, 226, 227, 228, 233, 234, 235,

306Master cell bank, 86, 88, 94, 104, 105, 106, 107, 137,

294Medlmmune, 86, 197, 306, 339Minimum CMC continuum, 39, 40, 47, 48, 54, 55,

80, 122, 170, 219, 229, 240, 241, 257, 267, 278,285

Molecular variants, 129, 224, 225, 232, 234, 238,302

Muromonmab, 6MVM (Minute Virus of Mice), 110, 135, 182, 192,

198Mycophenolic acid , 188Mycoplasma, 21, 104, 107, 126, 133, 134, 148, 173,

182, 183, 244, 245, 251

Nanofiltration, 164, 167, 168, 182, 185, 191, 193NDA (New Drug Application), 10, 23, 30, 31, 32,

33,38,43,48,49, 51, 54, 75, 81,99, 100, 108,125, 126, 128, 130, 135, 136, 146, 155, 159, 172,173, 177, 184, 196, 199, 210, 212, 219, 231, 240,243, 252, 254, 256, 259, 261, 262, 263, 265,270, 276, 277, 279, 280, 282, 285, 290, 291,304, 313, 321

NIBSC (National Institue for Biologic al Standardsand Controls), 231, 257, 340, 342, 345

Novartis, 283Novo Nordisk, 283Nuclear magnetic resonance, 234

OOS (Out of specification), 79, 281, 282, 318, 327,343

ORA (Office of Regulatory Affairs), 57, 322, 328,338

PAl (Pre-approva l inspection), 10Palivizumab, 6, 86, 120, 168, 197, 204, 206, 235,

253, 306, 335PCR (Polymerase chain reaction), 86, 110, 134, 135,

154, 251PEG (po lyethylene glycol), 164, 205 , 206Penicillin, 2; 14, 331Peptide mapping, 30, 41, 106, 107, 226, 230, 233,

249,272Phase I, 10, 19, 27, 29, 30, 38, 40, 41, 43, 46, 47 ,

54,70, 81, 83, 99, 107, 108, 113, 114, 116, 122,123, 124, 129, 131, 132, 133, 139, 140, 144, 145,146, 162, 169, 170, 171, 175, 177, 186, 196, 197,208, 209, 210, 2 11 , 212, 216, 218, 219, 229, 241,252, 256, 257, 258, 262, 263, 264, 267, 285,289, 290, 301, 307, 313, 323, 332

349

Phase 2, 10, 25, 29, 30, 40, 41, 43, 47, 124, 129, 131,171, 177, 196, 199, 210, 211, 230, 238, 242, 252,262, 263, 267, 272, 290, 301, 313, 323, 327,333

Phase 3, 10, 29, 35, 40, 41, 47, 108, 114, 124, 129,136, 140, 172, 177, 178, 199, 211, 230, 231, 242,243, 252, 263, 268, 269, 276, 290, 307, 308,309, 310, 313, 327

Phase 4, 265, 280Polio, 13, 14, 331Potency, 19, 31, 73, 74, 76, 92, 129, 147, 178, 216,

217, 228, 230, 231, 236, 238, 239, 243, 247,248, 249, 250, 251, 252, 253, 257, 260, 263,272, 273, 275, 280, 282, 283, 284, 287, 291,292, 293, 294, 295, 297, 298, 299, 314, 317,340,341

Precip itation, 164, 165Process chan ges, 11, 23, 31, 32, 72, 124, 129, 171,

177, 187, 229, 260, 271, 275,287, 288, 289,290, 291, 292, 293, 294, 295, 296, 301, 303,304, 305, 306, 307, 308, 309, 345

Process validation , 20, 30, 49, 50, 51, 54, 71, 72, 73,79, 128, 129, 130, 140, 174, 177, 178, 181, 182,213, 214, 216, 245, 246, 302, 304, 306, 323,327, 332, 338, 339, 340, 344

Process-related impur ities, 30, 66, 187, 234, 237,246, 249, 260, 261

Product characteriza tion, 31, 222, 223, 228, 240,272, 279, 301, 302, 305

Product-related impurities, 30, 66, 234, 238, 247,260, 261

Product-related substances, 30, 234, 238, 247, 260Protein A, 166, 167, 168, 182, 184, 187, 188, 189,

193,306Purification, 5, 18,28,41 ,49, 51, 63, 67, 69, 112,

120, 128, 136, 141, 144, 150, 158, 161, 162, 163,164, 165, 167, 168, 169, 170, 171 , 172, 173, 174,175, 176, 177, 178, 179, 180, 181, 182, 183, 184,185, 186, 187, 188, 189, 190, 191, 192, 193, 194,195, 196, 197, 198, 199, 201, 203, 230, 238,244, 245, 270, 292, 293, 306, 307, 310

Purity, 19, 28, 38,41, 61, 62, 73, 74, 76, 77, 92, 93,95,98, 102, 104, 106, 107, 122, 125, 127, 138,147, 148, 162, 169, 172, 184, 185, 198, 209, 228,231,234, 236, 239, 24 1, 243, 247, 248, 249,250, 251, 261, 262, 272, 273, 274, 275, 280,291, 292, 293, 294, 295, 297, 299, 306, 308,310,31 4,317,328,342

QA (Quality assu rance), 3, 18, 36, 46, 47, 63, 74,81, 106, 128, 134, 198, 218, 276, 318, 345

QC (Quality control), 3, 36, 46, 47, 63, 76, 81, 123,222, 223, 241, 244, 245, 256, 279, 280, 281,318, 328, 329, 341, 345

QCU (Quality contro l unit), 61, 62, 74, 218, 312

350

QU (Quality unit), 58, 63, 65, 71, 81, 109, 114, 134,135, 141, 181 , 183, 197, 282, 319

RAC (Recombinant DNA Advisory Committee) ,148,337

Raw materials , 37, 41, 49, 52, 53, 71, 76, 78, 105,109, 111 , 114, 123, 126, 140, 141, 142, 144, 147,170, 173, 189, 242, 307, 318, 337, 345

RCV (Replication-competent virus), 37, 147, 239,251

Reference standard , 41, 43, 49, 50, 231, 232, 257,280, 292, 294

Release testing, 3, 36, 43, 211 , 222, 237, 241, 243,244, 245, 246, 248, 249, 250, 294, 295, 296,306, 307, 313

Retrovirus , 7, 135, 196,245, 323Rituximab, 6, 182, 198, 206, 207, 237, 238, 249,

282, 296, 339RTF (Refusal to file), 33,51, 83, 125, 128, 172, 177,

196, 212, 291

SARS (Severe Acute Respiratory Syndrome) , 22,196, 332, 333

Schering , 283, 296, 344SDS-PAGE, 171 ,227, 228, 231, 234, 236, 248, 249,

250, 256, 273, 280Seragen, 53, 283Serum, 6, 23, 86, 101 , 109, 120, 132, 134, 141 , 142,

143, 147, 148, 168, 184, 185, 234, 262, 299, 310Shelf-life , 18, 222, 261, 271, 275, 276, 278, 294, 296Smallpox , 9, 196Specifications, 20, 21, 41, 43, 49, 50, 68, 76, 150,

152, 153, 188, 212, 217, 222, 237, 241, 242,243, 244, 245, 258, 259, 260, 261, 262, 263,264, 265, 269, 280, 281, 282, 283, 284, 292,294, 296, 308, 318, 323, 327, 332, 340

Stability protocols , 41, 43, 49, 50, 52, 221, 267, 268,269, 270, 292, 294, 323

Stability stress studies, 41, 47, 268, 269Sterility, 28, 37, 43, 76, 77, 104, 107, 132, 133, 145,

213, 216, 241, 242, 244, 247, 248, 249, 250,

Index

Sterility (cont .)251, 257, 264, 272, 273, 274, 293, 323

SV40, 14, 182, 194, 331

Test method validation , 71, 216, 244, 253, 254, 255,257, 258

Tissue Plasminogen Activator, 5, 120, 198, 281, 282TNF Receptor, 5, 204Tositumornab, 6, 275Transforrnant, 86, 94, 97, 98, 112Transgenics, 3, 8, 15, 28, 37, 63, 69, 81, 88, 91, 95,

97,98, 101, 111, 115, 117, 118, 119, 121, 122, 149,150, 151 , 152, 153, 154, 155, 156, 157, 164,274,323, 336

Trastuzumab , 6, 204, 306TSE (Transmissible spongiform encephalopathy), 37,

95, 108, 111, 112, 113, 132, 141 ,142, 143, 150,189

USP (United States Pharmacopoeia), 41, 43, 104,123, 141, 175, 183, 206, 210, 212, 231, 242, 243,254, 255, 264, 269, 337, 341

Vector, 7, 46, 49, 86, 94, 96, 98, 99, 102, 106, 107,140, 144, 147, 148, 162, 185,234, 239, 244, 251,323

Viability, 66, 77, 98, 101, 102, 104, 105, 106, 107,108, 127, 132, 135, 141 , 153

Viral clearance studies, 189, 191 , 193, 195, 196, 197,198,199

Warning letter, 74, 77, 198, 218, 281, 284, 285, 334,335, 339, 340, 343

West Nile Virus, 22, 196, 332WFI (Water for Injection), 141 , 152, 175, 183Working cell bank, 86, 88, 94, 104, 105, 106, 107,

120, 123, 137, 294, 307

Yeast, 4, 21, 88, 89, 90, 93, 101, 103, 109, 119, 120,122, 123, 133, 148, 273, 274