Improving decision-making in drug development using in vitro toxicology screening

International Journal of Pharmaceutical Medicine

Volumn 21, Issue 5, 2007, Pages 347-355

  Suter, Willi ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; CARCINOGEN; CISPLATIN; GENTAMICIN; METHOTREXATE; NEUTRAL RED; NONSTEROID ANTIINFLAMMATORY AGENT; POTASSIUM CHANNEL HERG; QUINOLONE DERIVATIVE;

CARCINOGENICITY; CELL ASSAY; CELL LINE; DATA ANALYSIS; DECISION MAKING; DRUG EFFICACY; DRUG INDUSTRY; DRUG SAFETY; DRUG SCREENING; FALSE POSITIVE RESULT; GENETIC TOXICOLOGY; GENOTOXICITY; HIGH THROUGHPUT SCREENING; HUMAN; IN VITRO STUDY; LIVER TOXICITY; MAMMAL CELL; NEPHROTOXICITY; NONHUMAN; PATIENT SAFETY; PHOTOALLERGY; PHOTOSENSITIZATION; PHOTOTOXICITY; PRIORITY JOURNAL; QT PROLONGATION; REVIEW; RISK ASSESSMENT; SENSITIVITY AND SPECIFICITY; STEM CELL; ULTRAVIOLET RADIATION;

EID: 34548729124     PISSN: 13649027     EISSN: 14735679     Source Type: Journal    
DOI: 10.2165/00124363-200721050-00005     Document Type: Review

References (100)

1. Rawlins MD. Cutting the cost of drug development? Nature Rev Drug Discov 2004; 3: 360-4
2. Jacobson-Kram D, Contreras JF. Genetic toxicology assessment: employing the best science for human safety evaluation part I: early screening for potential human mutagens. Toxicol Sci 2007; 96: 16-20
3. Cianchetta G, Li Y, Kang J, et al. Predictive models for hERG potassium channel blockers. Bioorgan Med Chem Let 2005; 15: 3637-42
4. McGee P. Modeling success with in silico tools. Drug Discov Dev 2005; 8: 24-8
5. Snodin DJ. An EU perspective on the use of in vitro methods in regulatory pharmaceutical toxicology. Toxicol Let 2002; 127: 161-8
6. ICH Harmonised Tripartite Guideline. The non-clinical evaluation of the potential for delayed ventricular repolarization (QT interval prolongation) by human pharmaceuticals S7B [online]. Available from URL: http://www.ich.org/LOB/ media/MEDIA2192.pdf [Accessed 2007 Jul 25]
7. Committee for Proprietary Medicinal Products. Note for the guidance on photosafety testing. Adopted 2002 [online]. Available from URL: http://www.emea.europa.eu/pdfs/human/swp/039801en.pdf [Accessed 2007 Jul 25]
8. Botham PA. The validation of in vitro methods for skin irritation. Toxicol Let 2004; 149: 387-90
9. Zuang V, Alonso EA, Botham PA, et al. Skin irritation and corrosion. Altern Lab Anim 2005; 33 Suppl. 1: 35-46
10. Merril J, Hamernik K, Schechtman LM. ICCVAM progress in evaluating in vitro test methods for identifying severe ocular irritants/corrosives. ALTEX 2006; 23 Suppl.: 246-9
11. Spielmann H. Predicting the risk of developmental toxicity from in vitro assays. Toxicol Appl Pharmacol 2005; 207: S375-80
12. Genschow E, Spielmann H, Scholz G. The ECVAM international validation study on in vitro embryotoxicity tests: results of the definitive phase and evaluation of prediction models. Altern Lab Anim 2002; 30: 151-76
13. Chapin R, Stedman D, Paquette J. Struggles for equivalence: in vitro developmental toxicity model evolution in pharmaceuticals in 2006. Toxicol In Vitro 2006 Oct 17. Epub ahead of print
14. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100: 57-70
15. McCann J, Ames BN. Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals: discussion. Proc Nat Acad Sci U S A 1976; 73: 950-4
16. Ashby J, Tennant RW. Chemical structure, Salmonella mutagenicity and extent of carcinogenicity as indicators of genotoxic carcinogenesis among 222 chemicals tested in rodents by the US/NCI/NTP. Mutat Res 1988; 204: 17-5
17. ICH Harmonised Tripartite Guideline. Guidance on specific aspects of regulatory genotoxicity tests for pharmaceuticals: S2A. 1995 Jul 19 [online]. Available from URL: http://www.ich.org/LOB/media/MEDIA493.pdf [Accessed 2007 Aug 1]
18. ICH Harmonised Tripartite Guideline. Genotoxicity: a standard battery for genotoxicity testing for pharmaceuticals S2B (1997) [online]. Available from URL: http://www.ich.org/LOB/media/MEDIA494.pdf [Accessed 2007 Aug 1]
19. Walmsley RW. Genotoxicity screening: the slow march to the future. Expert Opin Drug Metab Toxicol 2005; 1: 261-8
20. Kiskinis E, Suter W, Hartmann A. High throughput comet assay using 96-well plates. Mutagenesis 2002; 17: 37-43
21. Frieauff W, Poetter-Locher F, Cordier A, et al. Automatic analysis of the in vitro micronucleus test on V79 cells. Mutat Res 1998; 423: 57-68
22. Frieauff W, Hartmann A, Suter W. Automatic analysis of slides processed in the comet assay. Mutagenesis 2001; 16: 133-7
23. Witte I, Plappert U, de Wall H, et al. Genetic toxicity assessment: employing the best science for human safety evaluation: part III. The comet assay as an alternative to in vitro clastogenicity tests for early drug candidate selection. Toxicol Sci 2007; 97: 21-6
24. Flückiger-Isler S, Baumeister M, Braun K, et al. Assessment of the performance of the Ames II™ assay: a collaborative study with 19 coded compounds. Mutat Res 2004; 558: 181-97
25. Hastwell PW, Chai L-L, Roberts KJ, et al. High-specificity and high sensitivity genotoxicity assessment in a human cell line: validation of the GreenScreen HC GADD45a-GFP genotoxicity assay. Mutat Res 2006; 607: 160-75
26. Kirkland D, Aardema M, Henderson L, et al. Evaluation of the ability of a battery of three in vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens I: sensitivity, specificity and relative predictivity. Mutat Res 2005; 584: 1-256
27. Matthews EJ, Kruhlak NL, Cimino MC, et al. An analysis of genetic toxicity, reproductive and development toxicity, and carcinogenicity data. Regul Toxicol Pharmacol 2006; 44: 83-96
28. Redfern WS, Carlsson L, Davis AS, et al. Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development. Cardiovasc Res 2003; 58: 32-45
29. Spielmann H, Balls M, Dupuis J, et al. The International EU/COLUPA in vitro phototoxicity validation study: results of phase II (blind trial). Part 1: the 3T3 NRU phototoxicity test. Toxicol In Vitro 1998; 12: 305-27
30. Müller L, Kikuchi W, Probst G, et al. ICH-harmonized guidances on genotoxicity testing of pharmaceuticals: evolution, reasoning and impact. Mutat Res 1999; 436: 185-225
31. Snyder RD, Green JW. A review of the genotoxicity of marketed pharmaceuticals. Mutat Res 2001; 488: 151-69
32. Kirkland D, Pfuhler S, Tweats D, et al. How to reduce false positive results when undertaking in vitro genotoxicity testing and thus avoid unnecessary follow-up animal tests: report of the ECVAM workshop. Mutat Res 2007; 628: 31-55
33. Thybaud V, Aardema M, Clements J, et al. Strategy for genotoxicity testing: hazard identification and risk assessment in relation to in vitro testing. Mutat Res 2007; 627: 41-58
34. Ku WW, Bigger A, Brambilla G, et al. Strategy for genotoxicity testing: metabolic considerations. Mutat Res 2007; 627: 59-77
35. Lazarova M, Labaj J, Eckel P, et al. Comparative evaluation of DNA damage by genotoxicants in primary rat cells applying the comet assay. Toxicol Lett 2006; 165: 54-62
36. Vian L, Yusuf A, Guyomard C, et al. The liverbeads® as a tool for the comet assay. Mutat Res 2002; 519: 163-70
37. Bernauer U, Glatt H, Heinrich-Hirsch B, et al. Heterologous expression of mouse cytochrome P450 2e1 in V79 cells: construction and characterization of the cell line and comparison with V79 cell lines stably expressing rat P450 2E1 and human P450 2E1. Altern Lab Anim 2003; 31: 21-30
38. Knasmuller S, Mersch-Sundermann V, Kevekordes S, et al. Use of human-derived liver cell lines for the detection of environmental and dietary genotoxicants: current state of knowledge. Toxicology 2004; 198: 315-28
39. Ohno K, Tanaka-Azumo Y, Yoneda Y, et al. Genotoxicity test system based on p53R2 gene expression in human cells: examination with 80 chemicals. Mutat Res 2005; 588: 47-57
40. Speit G, Hartmann A. The comet assay. A sensitive genotoxicity test for the detection of DNA damage. In: Keohavong P, Grant SG, editors. Molecular toxicology protocols. Totowa (NJ): Humana Press, 2005: 85-95
41. Zhang H, Borman HD, Myhr BC. Enhancement of the morphological transformation of Syrian hamster embryo (SHE) cells by reducing incubation time of the target cells. Mutat Res 2004; 548: 1-7
42. Engelhardt G, Schwind KR, Mussler B. The testing of chemicals in the Syrian hamster embryo (SHE) cell transformation assay for assessment of carcinogenic potential. Toxicol In Vitro 2004; 18: 213-8
43. Aubrecht J, Caba E. Gene expression profile analysis: an emerging approach to investigate mechanisms of genotoxicity. Pharmacogenomics 2005; 6: 419-28
44. Hu T, Gibson DP, Carr GJ, et al. Identification of a gene expression profile that discriminates indirect-acting genotoxins from direct-acting genotoxins. Mutat Res 2004; 549: 5-27
45. Amundson SA, Do KT, Vinikor L, et al. Stress-specific signatures: expression profiling of p53 wild-type and -null human cells. Oncogene 2005; 24: 4572-9
46. Shah RR. Drugs, QT interval prolongation and ICH E14: the need to get it right. Drug Saf 2005; 28: 115-25
47. Stansfeld PJ, Sutcliffe MJ, Mitcheson JS. Molecular Mechanisms for drug interactions with hERG that cause long QT syndrome. Expert Opin Drug Metab Toxicol 2005; 2: 81-94
48. Yao JA, Du X, Lu D, et al. Estimation of potency of HERG channel blockers: impact of voltage protocol and temperature. J Pharmacol Toxicol Meth 2005; 52: 146-53
49. Deacon M, Singleton D, Szalkai N, et al. Early evaluation of compound QT prolongation effects: a predictive 384-well fluorescence polarization binding assay for measuring hERG blockade. J Pharmacol Toxicol Meth 2007; 55: 238-47
50. Ly JQ, Shyy G, Misner DL. Assessing hERG channel inhibition using PatchX-press. Clin Lab Med 2007; 27: 201-8
51. Wible BA, Hawryluk P, Ficker E, et al. HERG-Lite®: a novel comprehensive high-throughput screen for drug-induced hERG risk. J Pharmacol Toxicol Meth 2005; 52: 135-45
52. Lawrence CL, Pollard CE, Hammond TG, et al. Nonclinical proarrhythmia models: predicting torsade de pointes. J Pharmacol Toxicol Meth 2005; 52: 46-59
53. Hondeghem LM. Computer aided development of antiarrhythmic agents with class IIIa properties. J Cardiovasc Electrophysiol 1994; 5: 711-21
54. Valentin J-P, Hoffmann P, De Clerck F, et al. Review of the predictive value of the Langendorff heart model (Screenit system) in assessing the proarrhythmic potential of drugs. J Pharmacol Toxicol Meth 2004; 49: 171-81
55. Shah RR, Hondeghem LM. Refining detection of drug induced proarrhythmia: QT interval and TRIad. Heart Rhythm 2005; 2: 758-72
56. Hondeghem LM, Lu HR, Van Rossem K, et al. Detection of proarrhythmia in the female rabbit heart: blinded validation. J Cardiovasc Electrophysiol 2003; 14: 287-94
57. Di Diego JM, Belardinelli L, Antzelevitch C. Cisapride-induced transmural dispersion of repolarization and torsade de pointe in the canine left ventricular wedge preparation during epicardial stimulation. Circulation 2003; 108: 1027-33
58. Extramiana F, Antzelevitch C. Amplified transmural dispersion of repolarization as the basis for arrhythmiogenesis in a canine ventricular-wedge model of short QT syndrome. Circulation 2004; 110: 3661-6
59. Antzelevitch C. Modulation of transmural repolarization. Ann N Y Acad Sci 2005; 1047: 314-23
60. Snejina G, Mateev G, Parish LC. Antimicrobial photosensitive reactions. Arch Intern Med 1998; 158: 1993-2000
61. OECD guideline for testing of chemicals. In vitro 3T3 NRU phototoxicity test 432. Adopted 2004 Apr 13 [online]. Available from URL: http://www.oecd.org/ document/55/0,3343,en_2649_34377_2349687_1_1_1_1,00.html [Accessed 2007 Aug 20]
62. Guidance for industry: photosafety testing. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). 2003 May [online]. Available from URL: http://www.fda.gov/cder/ guidance/3640fnl.pdf [Accessed 2007 Aug 2]
63. Liebsch M, Spielmann H, Pape W, et al. UV-induced effects. Altern Lab Anim 2005 Jul; 33 Suppl. 1: 131-46
64. Guillot JP, Martini MC. A new method for the assessment of phototoxic and photoallergic potentials by topical applications in the albino guinea pig. J Toxicol Cutaneous Ocul Toxicol 1985; 4: 117-33
65. Scholes EW, Basketter DA, Lovell WW, et al. The identification of photoallergic potential in the local lymph node assay. Photodermatol Photoimmunol Photomed 1991; 8: 249-54
66. Ulrich P, Streich J, Suter W. Intralaboratory validation of alternative endpoints in the murine local lymphnode assay for the identification of contact allergic potential: primary ear skin irritation and ear-draining lymph node hyperplasia induced by topical chemicals. Arch Toxicol 2001; 74: 733-44
67. Struwe M, Greulich K-O, Suter W. The photo comet assay: a fast screening assay for the determination of phototoxicity in vitro. Mutat Res 2007 Aug 15; 632 (1-2): 44-57
68. Olson H, Betton G, Stritar J, et al. The predictivity of the toxicity of pharmaceuticals in humans from animal data: an interim assessment. Toxicol Lett 1998; 102/103: 535-8
69. Morelli JK, Buehrle M, Pognan F, et al. Validation of an in vitro screen for phospholipidosis using a high content biology platform. Cell Biol Toxicol 2006; 22: 15-27
70. Vickers AEM, Fisher RL. Organ slices for the evaluation of human drug toxicity. Chem Biol Interact 2004; 150: 87-96
71. Xu JJ, Diaz D, O'Brien PJ. Applications of cytotoxicity assays and prelethal mechanistic assays for assessment of human hepatotoxicity potential. Chem Biol Interact 2004; 150: 115-28
72. Lasser KE, Allen PD, Woodhandler DU, et al. Timing of new blackbox warnings and withdrawals for prescription medications. JAMA 2002; 287: 2215-20
73. Farkas D, Tannenbaum SR. In vitro methods to study chemically-induced hepatotoxicity: a literature review. Curr Drug Metabol 2005; 6: 111-25
74. O'Brien PJO, Chan K, Silber PM. Human and animal hepatocytes in vitro with extrapolation in vivo. Chem Biol Interact 2004; 150: 97-114
75. Hengstler JG, Utesch D, Steinberg P, et al. Cryopreserved primary hepatocytes as constantly available in vitro model for the evaluation of human and animal drug metabolism and enzyme induction. Drug Metabol Rev 2000; 32: 81-118
76. Li AP, Lu C, Brent JA, et al. Cryopreserved human hepatocytes: characterization of drug metabolizing enzymes activities and application in higher throughput screening assays for hepatotoxicity, metabolic stability, and drug-drug interaction potential. Chem Biol Interact 1999; 121: 17-35
77. Bilello JA. The agony and ecstasy of "OMIC" technologies in drug development. Curr Mol Med 2005; 5: 39-52
78. Shackel NA, Seth D, Haber PS, et al. The hepatic transcriptome in human liver disease. Comp Hepatol 2006; 5: 1-19
79. Diamond DL, Proll SC, Jacobs JM, et al. HepatoProteomics: applying proteomic technologies to the study of liver function and disease. Hepatology 2006; 44: 299-308
80. Lindon JC, Holmes E, Nicholson JK. Metabonomics in pharmaceutical R & D. FEBS J 2007; 274: 1140-51
81. Kikkawa R, Yamamoto T, Fukushima T. Investigation of a hepatotoxicity screening system in primary cell cultures: "What biomarkers would need to be addressed to estimate toxicity in conventional and new approaches?". J Toxicol Sci 2005; 30: 61-72
82. Boess F, Kamber M, Romer S, et al. Gene expression in two hepatic cell lines, cultured primary hepatocytes, and liver slices compared to the in vivo liver gene expression in rats: possible implications for toxicogenomics use of in vitro systems. Toxicol Sci 2003; 73: 386-402
83. Miret S, De Groene EM, Klaffke W. Comparison of in vitro assays of cellular toxicity in the human hepatic cell line HepG2. J Biomol Screen 2006; 11: 184-93
84. Dambach DM, Andrews BA, Moulin F. New technologies and screening strategies for hepatotoxicity: use of in vitro models. Toxicol Pathol 2005; 33: 17-26
85. O'Brien PJO, Siraki AG. Accelerated cytotoxicity mechanism screening using drug metabolising enzyme modulators. Curr Drug Metabol 2005; 6: 101-9
86. Kovacic P, Sacman A, Wu-Weis M, et al. Nephrotoxins: widespread role of oxidative stress and electron transfer. Curr Med Chem 2002; 9: 823-47
87. Zhang J, Mu X, Fu J, et al. In vitro cytotoxicity assay with selected chemicals using human cells to predict target-organ toxicity of liver and kidney. Toxicol In Vitro 2007; 21: 734-40
88. Li WW, Lam M, Choy D, et al. Human primary renal cells as a model for toxicity assessment of chemo-therapeutic drugs. Toxicol In Vitro 2006; 20: 669-76
89. Van der Harst MR, Bull S, Laffont CM, et al. Gentamycin nephrotoxicity: a comparison of in vitro findings with in vivo experiments in equines. Vet Res Commun 2005; 29: 247-61
90. Vickers AEM, Rose K, Fisher R, et al. Kidney slices of human and rat to characterize cisplatin-induced injury of cellular pathways and morphology. Toxicol Pathol 2004; 32: 577-90
91. Nozaki Y, Kusuhara H, Kondo T, et al. Species difference in the inhibitory effect of NSAIDs on the uptake of methotrexate by human kidney slices. J Pharmacol Exp Ther 2007 Jun 19. Epub ahead of print
92. Combes RD. Assessing risk to humans from chemical exposure by using non-animal test data. Toxicol In Vitro 2005; 19: 921-4
93. Wobus AM, Boheler KR. Embryonic stem cells: prospects for developmental biology and cell therapy. Physiol Rev 2005; 85: 635-78
94. Davila JC, Cezar GG, Thiede M, et al. Use and application of stem cells in toxicology. Toxicol Sci 2004; 79: 214-23
95. Chaudhari KW, Barrezueta NX, Bauchmann MB, et al. Embryonic stem cells in predictive cardiotoxicity: laser capture microscopy enables assay development. Toxicol Sci 2006; 90: 149-58
96. Ahuja YR, Vijayalakshmi V, Polasa K. Stem cell test: a practical tool in toxicogenomics. Toxicology 2007; 231: 1-10
97. Glatt H, Schneider H, Liu Y. V79-hCYP2E1-hSULT1A1, a cell line for the sensitive detection of genotoxic effects induced by carbohydrate pyrolysis products and other food-borne chemicals. Mutat Res 2005; 580: 41-52
98. Corvi R. Genomics: an in vitro toxicology point of view. Altern Lab Anim 2002; 30 Suppl. 2: 129-31
99. Luehe A, Suter L, Ruepp S. Toxicogenomics in the pharmaceutical industry: hollow promises or real benefit? Mutat Res 2005; 575: 102-15
100. Dumotier BM, Georgieva AV. Preclinical cardio-safety assessment of torsadogenic risk and alternative methods to animal experimentation: the inseparable twins. Cell Biol Toxicol 2007; 23: 293-302