Nonclinical strategy considerations for safety pharmacology: Evaluation of biopharmaceuticals

Expert Opinion on Drug Safety

Volumn 12, Issue 1, 2013, Pages 91-102

  Vargas, Hugo M ^a   Amouzadeh, Hamid R ^a   Engwall, Michael J ^a  

^a AMGEN INC   (United States)

Author keywords

Biopharmaceuticals; Cardiovascular safety; Central nervous system safety; HERG potassium channel; Monoclonal antibodies; QTc prolongation; Respiratory safety; Safety pharmacology

Indexed keywords

ANTIBODY; CALCIUM CHANNEL; CYTOKINE; ENZYME; GLYCINE; MONOCLONAL ANTIBODY; N METHYL DEXTRO ASPARTIC ACID; NEUROPEPTIDE Y1 RECEPTOR; NITRIC OXIDE; POTASSIUM CHANNEL; POTASSIUM CHANNEL HERG; POTASSIUM CHANNEL KV1.3;

ARTERIAL PRESSURE; BINDING AFFINITY; BODY PLETHYSMOGRAPHY; BREATHING MECHANICS; CARDIOVASCULAR SYSTEM; CENTRAL NERVOUS SYSTEM; CLINICAL EFFECTIVENESS; COGNITION; DRUG APPROVAL; DRUG EFFECT; DRUG EXPOSURE; DRUG SAFETY; DRUG SCREENING; ELECTRIC ACTIVITY; ELECTROCARDIOGRAM; FOOD AND DRUG ADMINISTRATION; FUNCTIONAL ASSESSMENT; HEART CONDUCTION; HEART MUSCLE CONTRACTILITY; HEART REPOLARIZATION; HEMODYNAMIC PARAMETERS; HUMAN; IC 50; LONG TERM EXPOSURE; LUNG RESISTANCE; NONHUMAN; PRACTICE GUIDELINE; QUALITY CONTROL; RESPIRATORY FUNCTION; REVIEW; RISK ASSESSMENT; TELEMETRY;

ANIMALS; BEHAVIOR, ANIMAL; BIOLOGICAL AGENTS; CARDIOVASCULAR DISEASES; CARDIOVASCULAR SYSTEM; DRUG DESIGN; HUMANS; LUNG; LUNG DISEASES; NERVOUS SYSTEM; NEUROTOXICITY SYNDROMES; RESPIRATION; RISK ASSESSMENT; SIGNAL TRANSDUCTION; TOXICITY TESTS;

EID: 84871506122     PISSN: 14740338     EISSN: 1744764X     Source Type: Journal    
DOI: 10.1517/14740338.2013.745851     Document Type: Review

References (82)

1. ICH S6(R1). Preclinical safety evaluation of biotechnology-derived biopharmaceuticals. 2011.Available from: http://www.ich.org [Retrieved February 2012]
2. Leader B, Baca QJ, Golan DE. Protein therapeutics: a summary and pharmacological classification. Nat Rev 2008;7:21-39
3. Dixit R, Iciek LA, McKeever K, et al. Challenges of general safety evaluations of biologics compared to small molecule pharmaceuticals in animal models. Expert Opin Drug Discov 2010;5:79-94
4. Crommelin DJA, Storm G, Verrijk R, et al. Shifting paradigms: biopharmaceuticals versus low molecular weight drugs. Int J Pharm 2003;266:3-16
5. Gosse ME, DiMasi JA, Nelson TF. Recombinant protein and therapeutic monoclonal antibody drug development in the United States from 1980-1994.Clin Pharmacol Ther 1996;60:608-18
6. Reichert JM. New biopharmaceutical in the USA: trends in development and approvals 1995-1999. Trends Biotech 2000;18:364-9
7. Tsuji K, Tsutani K. Approval of new biopharmaceuticals 1999-2006: comparison of US, EU and Japan situations. Eur J Pharm Biopharm 2008;68:496-502
8. Trusheim MR, Aitkin ML, Berndt ER. Characterizing markets for biopharmaceutical innovation: do biologics differ from small molecules? Forum Health Econ Policy 2010;13:1-45
9. DiMasi JA, Feldman L, Seckler A, et al. Trends associated with new drug development: success rates for investigational drugs. Clin Pharm Ther 2010;87:272-7
10. Reichert JM. Metrics for antibody therapeutics development. mAbs 2010;2:695-700
11. Reichert JM. Marketed therapeutic antibodies compendium. mAbs 2012;4:413-15
12. Tabrizi MA, Tseng CML, Roskos LK. Elimination mechanisms of therapeutic monoclonal antibodies. Drug Discov Today 2006;11:81-8
13. Vargas HM, Bass AS, Breidenbach A, et al. Scientific review and recommendations on preclinical cardiovascular safety evaluation of biologics. J Pharmacol Toxicol Methods 2008;58:72-6
14. Giezen TJ, Mantel-Teeuwisse AK, Straus SJJM, et al. Safety-related regulatory actions for biologicals approved in the United States and the European Union. J Am Med Assoc 2008;300:1887-96
15. Haller CE, Cosenza ME, Sullivan JT. Safety issues specific to the clinical development of protein therapeutics. Clin Pharmacol Ther 2008;84:624-7
16. Guengerich FP. Mechanisms of drug toxicity and relevance to pharmaceutical development. Drug Metab Pharmacokinet 2011;26:3-14
17. Pugsley MK, Authier S, Curtis MJ. Principles of safety pharmacology. Br J Pharmacol 2008;154:1382-99
18. Bernton EW. Safety pharmacology: similarities and differences between small molecules and novel biopharmaceuticals. In: Cavagnaro J, editor. Preclinical safety evaluation of biopharmaceuticals: a science-based approach to facilitating clinical trials. John Wiley & Sons; Hoboken, NJ: 2008. p. 311-35
19. De Haan L. Preclinical safety considerations for the development of antibody-based therapuetics. Chapter 10 In: Trabizi MA, et al. editors. Development of antibody-based therapuetics. Springer Science; New York: 2012
20. ICH S7A. Safety pharmacology studies for human biopharmaceuticals. 2000.Available from: http://www.ich.org [Retrieved February 2012]
21. ICH S7B. The nonclinical evaluation of the potential for delayed ventricular repolarization (QT interval prolongation) by human biopharmaceuticals. 2005.Available from: http://www.ich.org [Retrieved February 2012]
22. Leishman DJ, Beck TW, Dybdal N, et al. Best practice in the conduct of key nonclinical cardiovascular assessments in drug development: current recommendations from the Safety Pharmacology Society. J Pharmacol Toxicol Methods 2011;65:93-101
23. Sun Y, Gruber M, Matsumoto M. Overview of global regulatory toxicology requirements for vaccines and adjuvants. J Pharmacol Toxicol Methods 2012;65:49-57
24. Chapman K, Pullen N, Graham M, et al. Preclinical safety testing of biological: the significance of species relevance. Nat Drug Discov 2007;6:120-6
25. Bussiere JL. Species selection considerations for preclinical toxicology studies for biotherapeutics. Expert Opin Drug Metab Toxicol 2008;4:871-7
26. Baumann A. Foundation review: nonclinical development of biopharmaceuticals. Drug Discov Today 2009;14:1112-22
27. Olson H, Betton G, Robinson D, et al. Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul Toxicol Pharmacol 2000;32:56-67
28. Chui RW, Fosdick A, Conner R, et al. Assessment of two external telemetry systems (PhysioJacket-And JET-) in Beagle dogs with telemetry implants. J Pharmacol Toxicol Methods 2009;60:58-68
29. Guth BD, Bass AS, Briscoe R, et al. Comparison of electrocardiographic analysis for risk of QT interval prolongation using safety pharmacology and toxicology studies. J Pharmacol Toxicol Methods 2009;60:107-16
30. Derakhchan K, Chui RW, Vargas HM. Evaluation of cardiac conduction disturbances using jacketed external telemetry (JET) in conscious non-human primates. J Pharmacol Toxicol Methods 2011;64:e46
31. Vargas HM, Derakhchan K, Chui RW, et al. Evaluation of D,L-sotalol using jacketed external telemetry (JET) in conscious non-human primates over 4 weeks of evaluation. J Pharmacol Toxicol Methods 2010;64:e24-5
32. Chui RW, Derakhchan K, Vargas HM. Long-term assessment of non-human primate ECG using jacketed external telemetry (JET): evaluation of heart rate and QTc interval variation over 6 months of observation. J Pharmacol Toxicol Methods 2011;64:e45
33. Santostefano MJ, Kirchner J, Vissinga C, et al. Off-target platelet activation in macaques unique to a therapeutic monoclonal antibody. Toxicol Sci 2012;40:899-917
34. Sarazan RD, Mittelstadt S, Guth B, et al. Cardiovascular function in nonclinical drug safety assessment: current issues and opportunities. Int J Toxicol 2011;30:272-86
35. McMahon C, Mitchell AZ, Klein JL, et al. Evaluation of blood pressure measurement using a miniature blood pressure transmitter with jacketed external telemetry in Cynomolgus monkeys. J Pharmacol Toxicol Methods 2010;62:127-35
36. Kaiser RA, Erwin R, Tichenor SD, et al. Integration of cardiovascular safety pharmacology endpoints into general toxicology studies. J Pharmacol Toxicol Methods 2010;62:e30
37. Schmelting B, Neihoff M, Egner B, et al. High-definition oscillometry: a novel technique for non-invasive blood pressure monitoring in the Cynomolgus monkey. J Med Primatol 2009;38:293-301
38. Kurtz TW, Griffin KA, Bidani AK, et al. Recommendations for blood pressure measurement in humans and animals. Hypertension 2005;45:299-310
39. Wernick MB, Hopfner RM, Francey T, et al. Comparison of arterial blood pressure measurements and hypertension scores obtained by use of three indirect measurement devices in hospitalized dogs. J Am Vet Med Assoc 2012;240:962-8
40. Ward G, Milliken P, Patel B, McMahon N. Comparison of non-invasive and implanted telemetric measurement of blood pressure and electrocardiogram in conscious beagle dogs. J Pharmacol Toxicol Methods 2012;66(2):106-13
41. Klein PM, Dybdal N. Trastuzumab and cardiac dysfunction: update on preclinical studies. Semin Oncol 2003;30:49-53
42. Qu Y, Fang M, Gao B, et al. BeKm-1, a peptide inhibitor of hERG potassium currents, prolongs QTc interval in isolated rabbit hearts. J Pharmacol Exp Ther 2011;337:2-8
43. Nakazawa T, Kurokawa Kimura K, et al. Safety assessment of biopharmaceuticals: japanese perspective on ICH S6 guideline maintenance. J Toxicol Sci 2008;33:277-82
44. Hondeghem L, De Clerck F. Preclinical cardiovascular safety evaluations of biologics. BioDrugs 2012;26:2275-82
45. Porsolt RD, Durmuller N, Castagne V, Moser P. CNS safety pharmacology. Chapter 8 In: Sietsma WK, Schwen R, editors. Nonclinical drug safety assessment: practical considerations for successful registration. FDAnews, Falls Church, VA: 2007
46. Korte S, Fuchs A, Weinbauer GF, et al. Modified Irwin test as diagnostic tool to monitor neurobehavioral changes in monkeys. J Pharmacol Toxicol Methods 2007;56:e47
47. Gauvin DV, Baird TJ. A functional observational battery in non-human primates for regulatory-required neurobehavioral assessments. J Pharmacol Toxicol Methods 2008;58:88-93
48. Moscardo E, McPhie G, Fasdelli N, et al. An integrated cardiovascular and neurobehavioral functional assessment in the conscious telemetered Cynomolgus monkey. J Pharmacol Toxicol Methods 2010;62:95-106
49. Pardridge WM. Blood-brain barrier drug targetting: the future of brain drug development. Mol Interv 2003;3:90-105
50. Freeman GB, Lin JC, Pons J, et al. 39-Week toxicity and toxicokinetic study of ponezumab (PF-04360365) in cynomolgus monkeys with 12-week recovery period. J Alzheimers Dis 2012;28:531-41
51. Misra A, Ganesh S, Shah SP. Drug delivery to the central nervous system: a review. J Pharm Pharm Sci 2003;6:252-73
52. Pardridge WM. The blood brain barrier: bottleneck in brain drug development. NeuroRx 2005;2:3-14
53. Gabathuler R. Approaches to transport therapeutic drugs across the blood brain barrier to treat brain diseases. Neurobiol Dis 2010;37:48-57
54. Pan W, Kastin AJ. Why study transport of peptides and proteins at the neurovascular surface. Brain Res Rev 2004;46:32-43
55. Braen AP, Perron J, Tellier P, et al. A 4-week intrathecal toxicity and pharmacokinetic study with trastuzumab in Cynomolgus monkeys. Int J Toxicol 2010;29:259-67
56. Yu YJ, Zhang Y, Kenrick M, et al. Boosting brain uptake of a therapeutic antibody by reducing its affinity for a transcytosis target. Sci Transl Med 2011;3:1-8
57. Pardridge WM. Biopharmaceutical drug targeting to the brain. J Drug Target 2010;18:157-67
58. Amouzadeh H, Williamson T, Vargas HM. A review of convulsion and seizure incidence: small versus large molecule experience. J Pharmacol Toxicol Methods 2012; 66:e193
59. Anon. Guidance for industry: assessment of abuse potential of drugs. 2010. Available from: www.fda.gov
60. Hoffman W, Kallman MJ, Sgro M. Respiratory safety pharmacology. Chapter 7 In: Sietsma WK, Schwen R, editors. Nonclinical drug safety assessment: practical considerations for successful registration. FDAnews, Falls Church, VA: 2007
61. Hoymann HG. Lung function measurements in rodents in safety pharmacology studies. Front Pharmacol 2012;3:156
62. Murphy DJ. Assessment of respiratory function in safety pharmacology. Fundam Clin Pharmacol 2002;16:183-96
63. Foster CD, Hunter TC, Gibbs PH, et al. Whole-body plethysmography in African green monkeys (Chlorocebus aethiops) with and without jackets. J Am Assoc Lab Anim Sci 2008;47:52-5
64. Authier S, Legaspi M, Gauvin D, et al. Respiratory safety pharmacology: positive control drug responses in Sprague-Dawley rat, Beagle dogs and cynmolgus monkeys. Regul Toxicol Pharmacol 2009;55:229-35
65. Iizuka H, Sasaki K, Odagiri N, et al. Measurement of respiratory function using whole-body plethysmography in unanesthetized and unrestrained non-human primates. J Toxicol Sci 2010;35:863-70
66. Lawler JV, Endy TP, Hensley LE, et al. Cynomolgus macaque as an animal model for severe acute respiratory syndrome. PloS Med 2006;3:e149
67. Nalca A, Livingston VA, Garza NL, et al. Experimental infection of cynomolgus macaques (Macaca fascicularis) with aerosolized monkeypox virus. PLoS One 2010;5:e12880
68. Chapman RW, Skeans S, Lamca J, et al. Effect of histamine, albuterol and deep inspiration on airway and lung tissue mechanics in cynomolgus monkeys. Pulm Pharmacol Ther 2005;18:243-9
69. Skeans S, Lamca J, House A, et al. Airway closure after antigen challenge in cynomolgus monkeys: effect of the histamine H1 receptor antagonist, chlorpeniramine maleate. Int Arch Allergy Immunol 2005;137:37-44
70. Curran AK, Skeans S, Landers D, et al. Differential effects of dexamethasone on the proximal and distal lung response to antigen challenge in allergic cynomolgus monkeys. J Asthma 2008;45:377-81
71. Ingram-Ross JL, Curran AK, Miyamoto M, et al. Cardiorespiratory safety evaluation in non-human primates. J Pharmacol Toxicol Methods 2012;66:114-24
72. Peerzada MM, Spiro TP, Daw HA. Pulmonary toxicities of biologicals: a review. Anticancer Drugs 2011;21:131-9
73. Whitebread S, Hamon J, Bojanic D, et al. In vitro safety pharmacology profiling: an essential tool for successful drug development. Drug Discov Today 2005;10:1421-30
74. Kooijman M, van Meer JK, Moors EHM, et al. Thirty years of preclinical safety evaluation of biopharmaceuticals: did scientific progress lead to appropriate regulatory guidance? Expert Opin Drug Saf 2012;11:797-801
75. Luft J, Bode G. Integration of safety pharmacology endpoints into toxicology studies. Fundam Clin Pharmacol 2002;16:91-103
76. Buttel IC, Chamberlain P, Chowers Y, et al. Taking immunogenicity assessment of therapuetic proteins to teh next level. Biologicals 2011;39:100-9
77. Polson AG, Fuji RN. The success and limitations of preclinical studies in predicting the pharmacodynamics and safety of cell-surface-targeted biological agents in patients. Br J Pharmacol 2012;166:1600-2
78. Martin PL, Bugelski PJ. Concordance of preclinical and clinical pharmacology and toxicology of monoclonal antibodies and fusion proteins: soluble targets. Br J Pharmacol 2012;166:806-22
79. Bugelski PJ, Martin PL. Concordance of preclinical and clinical pharmacology and toxicology of monoclonal antibodies and fusion proteins: cell surface targets. Br J Pharmacol 2012;166:823-46
80. Ponce R, Abad L, Amaravadi L, et al. Immunogenenicity of biologically-derived therapuetics: assessment and interpretation of nonclinical safety studies. Regul Toxicol Pharmacol 2009;54:164-82
81. Lynch CM, Hart BW, Grewal IS. Practical considerations for nonclinical safety evaluation of therapeutic monoclonal antibodies. mAbs 2009;1:2-11
82. Chapman K, Pullen N, Conney L, et al. Preclinical development of monoclonal antibodies: considerations for the use of non-human primates. mAbs 2009;1:505-16