Inhaled biopharmaceutical drug development: Nonclinical considerations and case studies

Inhalation Toxicology

Volumn 25, Issue 4, 2013, Pages 219-232

  McElroy, Mary C ^a   Kirton, Chris ^b   Gliddon, Dan ^c   Wolff, Ron K ^d  

^a CHARLES RIVER LABORATORIES   (United Kingdom)

^b WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^c HUNTINGDON LIFE SCIENCES   (United Kingdom)

^d RK Wolff Safety Consulting   (United States)

Author keywords

Biopharmaceuticals; Clinical; Inhalation; Nonclinical; Safety assessment

Indexed keywords

DEOXYRIBONUCLEASE; DORNASE ALFA; DRUG ANTIBODY; ERYTHROPOIETIN; GAMMA INTERFERON; HUMAN GROWTH HORMONE; INSULIN; INTERLEUKIN 2; ISOPHANE INSULIN; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; PLACEBO; PLASMID DNA; PLASMID VECTOR; RECOMBINANT HUMAN INSULIN; VACCINE;

ABSENCE OF SIDE EFFECTS; AEROSOL; ALPHA 1 ANTITRYPSIN DEFICIENCY; ANTIGEN PRESENTING CELL; ASTHMA; CHRONIC OBSTRUCTIVE LUNG DISEASE; COGNITIVE DEFECT; CYSTIC FIBROSIS; DRUG BIOAVAILABILITY; DRUG MANUFACTURE; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; GENE THERAPY; GOOD LABORATORY PRACTICE; HUMAN; HYPERGLYCEMIA; HYPOGLYCEMIA; IMMUNOGENICITY; LOW DRUG DOSE; MEASLES; NEBULIZER; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PATIENT COMPLIANCE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; REVIEW; SINGLE DRUG DOSE;

ADMINISTRATION, INHALATION; ANIMALS; BIOLOGICAL AGENTS; BIOLOGICAL AVAILABILITY; BIOPHARMACEUTICS; DRUG DISCOVERY; HUMANS; IMMUNOMODULATION;

EID: 84875205085     PISSN: 08958378     EISSN: 10917691     Source Type: Journal    
DOI: 10.3109/08958378.2013.769037     Document Type: Review

References (69)

1. Alavi F. (2004). Pharmacology/toxicology review and evaluation: Exubera-(inhaled insulin). Food and Drug Administration Center for Drug Evaluation and Research. Available from: http://www.fda.-gov/ohrms/dockets/ac/ 05/briefing/2005-4169B1-02-04-FDAClinPharm-Toxicology.pdf. [Last accessed: 11 Feb 2013].
2. Alton EW, Stern M, Farley R, et al. (1999). Cationic lipid-mediated CFTR gene transfer to the lungs and nose of patients with cystic fibrosis: a double-blind placebo-controlled trial. Lancet 20: 947-54.
3. Alton EWFW, Ashby D, Boyd AC, et al. (2012). Update on the UK CF gene therapy consortium multidose, non-viral, gene therapy trial. Pediat Pulmonol 47: abstract 245. Available from: http://www.cfgenetherapy. org.uk/publications/ AltonNACFC2012.html. [Last accessed: 11 Feb 2013].
4. Baker MP, Carr FJ. (2010). Pre-clinical considerations in the assessment of immunogenicity for protein therapeutics. Curr Drug Saf, 5, 308-13.
5. Baker MP, Reynolds HM, Lumicisi B, Bryson CJ. (2010). Immunogenicity of protein therapeutics: the key causes, consequences and challenges. Self Nonself 4: 314-22.
6. Becker RH, Sha S, Frick AD, Fountaine RJ. (2006). The effect of smoking cessation and subsequent resumption on absorption of inhaled insulin. Diabetes Care 29: 277-82.
7. Birchall JC, Kellaway IW, Gumbleton M. (2000). Physical stability and in-vitro gene expression efficiency of nebulised lipid-peptide-DNA complexes. Int J Pharm 197: 221-31.
8. Bitonti AJ, Dumont JA. (2006). Pulmonary administration of therapeutic proteins using an immunoglobulin transport pathway. Adv Drug Deliv Rev 58: 1106-18.
9. Brain JD. (2007). Inhalation, deposition, and fate of insulin and other therapeutic proteins. Diabetes Technol Ther 9: S4-S15.
10. Burger JL. (2008). Stabilising formulations for inhalable powders of live attenuated measles virus vaccine. J Aerosol Med Pulm Drug Deliv 21: 25-34.
11. Cavagnaro J. (2008). The principles of the ICH S6 and the case-by-case approach. In: Cavagnaro J, ed. Preclinical safety evaluation of biopharmaceuticals: a science-based approach to facilitating clinical trials. NJ: John Wiley & Sons, 45-65.
12. Cheng YS, Bowen L, Rando RJ, et al. (2010). Exposing animals to oxidant gases nose only vs. whole body. Proc Am Thorac Soc 7: 264-8.
13. Clarke J, Hurst C, Martin P, et al. (2008). Duration of chronic toxicity studies for biotechnology-derived pharmaceuticals: is 6 months still appropriate? Regul Toxicol Pharmacol 50: 2-22.
14. Commission Directive 2003/63/EC of 25 June 2003 amending Directive 2001/83/EC of the European Parliament and the Council on the Community code relating to medicinal products for human use. Official Journal L159, 27.06.2003, p 46.
15. Cosenza ME. (2008). Implementation of the ICH S6: US perspective. In: Cavagnaro J, ed. Preclinical safety evaluation of biopharmaceuticals: a science-based approach to facilitating clinical trials. NJ: John Wiley & Sons, 111-21.
16. Cooper AE, Ferguson D, Grime K. (2012). Optimisation of DMPK by the inhaled route: challenges and approaches. Curr Drug Metab 13: 457-73.
17. Craft S, Baker LD, Montine TJ, et al. (2012). Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol 69: 29-38.
18. De Swart RL, Kuiken T, Fernandez-de CJ, et al. (2006). Aerosol measles vaccination in macaques: preclinical studies of immune responses and safety. Vaccine 24: 6424-36.
19. Driscoll KE, Costa DL, Hatch G, et al. (2000). Intratracheal instillation as an exposure technique for the evaluation of respiratory tract toxicity: uses and limitations. Toxicol Sci 55: 24-35.
20. Eastman SJ, Tousignant JD, Lukason MJ, et al. (1997). Optimization of formulations and conditions for the aerosol delivery of functional cationic lipid: DNA complexes. Hum Gene Ther 10: 313-22.
21. Exubera (2006). US product insert, NDA 21-868 Version date: 2006-01-27. Available from http://www.accessdata.fda.gov/drugsat fda-docs/label/2006/ 021868lbl.pdf. [Last accessed: 7 Nov 2012]
22. FDA. (1993). Summary basis of approval for dornase alfa, recombinant pulmozyme inhalation solution. Washington, DC: FDA.
23. Fernandez-de CJ, Kumate-Rodriguez J, Sepulveda J, et al. (1997). Measles vaccination by the aerosol method in Mexico. Salud Publica Mex 39: 53-60.
24. Fineberg SE, Kawabata T, Finco-Kent D, et al. (2005). Antibody response to inhaled insulin in patients with type 1 or type 2 diabetes. J Clin Endocrinol Metab 90: 3287-94.
25. Forbes B, Asgharian B, Dailey LA, et al. (2011). Challenges in inhaled product development and opportunities for open innovation. Adv Drug Deliv Rev 63: 69-87.
26. Forster R, Appleqvist T, Brown D, et al. (2008). Pulmonary delivery of measles vaccine: non-human primate safety study 2008: annual meeting of SOT, Seattle. Toxicologist 2297: 473 (abstract).
27. Freemantle N, Blonde L, Duhot D, et al. (2005). Availability of inhaled insulin promotes greater perceived acceptance of insulin therapy in patients with type 2 diabetes. Diabetes Care 28: 427-8.
28. Gopalakrishnan V, Uster P, Cow G, McDonald P. (2001). Four week repeat dose inhalation safety of insulin in dogs. J Aerosol Med 14: 379-421 (abstract).
29. Green, JD. (1994). Pharmaco-toxicological expert report: Pulmozyme-, rhDNase, Genentech, Inc. Hum Exp Toxicol 13: SI-S42.
30. Griesenbach U, Alton EWFW. (2009). Gene transfer to the lung: lessons learned from more than 2 decades of CF gene therapy. Adv Drug Deliv Rev 61: 128-39.
31. Gumbleton M, Al-Jayyoussi G, Crandon-Lewis A, et al. (2011). Spatial expression and functionality of drug transporters in the intact lung: objectives for further research. Adv Drug Deliv Rev 63: 110-8.
32. Henao-Restrepo AM, Greco M, Laurie X, et al. (2010). Measles aerosol vaccine project. Proc Vaccinol 2: 147-50.
33. Himmelmann A, Jendle J, Mellén A, et al. (2003). The impact of smoking on inhaled insulin. Diabetes Care 26: 677-82.
34. Hyde SC, Pringle IA, Abdullah S, et al. (2008). CpG-free plasmids confer reduced inflammation and sustained pulmonary gene expression. Nat Biotechnol 26: 549-51.
35. Kim KJ, Malik AB. (2003). Protein transport across the lung epithelial barrier. Am J Physiol Lung Cell Mol Physiol 284: L247-59.
36. Kohlmeier JE, Woodland DL. (2009). Immunity to respiratory viruses. Annu Rev Immunol 27: 61-82.
37. Lam AP, Dean DA. (2008). Cyclic stretch-induced nuclear localization of transcription factors results in increased nuclear targeting of plasmids in alveolar epithelial cells. J Gene Med 10: 668-78.
38. Leong LK. (2012). Refinements in inhaled drug delivery enhances growth prospects as global markets emerge. Available from: http://www.pharmaasia.com/ article/refinements-in-inhaled-drug-deliveryenhances-growth-prospects-as-global- markets-emerge/9367. [Last accessed: 28 Apr 2012].
39. Legakis G, Causton B, Zhu J, et al. (2011). Strain-specific differences in pulmonary gene transfer efficiency: releVance for toxicology studies in mice (abstract). Available from: http://www.cfgenetherapy.org.uk/publications/ LegakisASGT2011.html. [Last accessed: 11 Feb 2013].
40. Mack P, Horvath K, Garcia A, et al. (2012). Particle engineering for inhalation formulation and delivery of biotherapeutics. Inhalation Available from: http://www.inhalationmag.com/(Content/getArticle. aspx? ItemID¼0992431a-53ae-4828-b89f-210da3aa4c32&AuthorID¼ cc2fbfff-7bd0-45e1-a871-87fabe3d2912&Author¼Mack%2c\+Peter). [Last accessed: 11 Feb 2013].
41. Mastrandea LD. (2010). Inhaled insulin: overview of a novel route of insulin administration. Vasc Health Risk Manag 3: 47-58.
42. Martin PL. (2008). Reproductive toxicity testing for biopharmaceuticals. In: Cavagnaro J, ed. Preclinical safety evaluation of biopharmaceuticals: a science-based approach to facilitating clinical trials. NJ: John Wiley & Sons, 357-77.
43. McConnell WR, Finch GL, Elwell MR, et al. (2006). Toxicological investigations on inhaled insulin (abstract). Society of Toxicology Annual Meeting; 2006 Mar 5-9; San Diego, CA.
44. McLachlan G, Davidson H, Holder E, et al. (2011). Pre-clinical evaluation of three non-viral gene transfer agents for cystic fibrosis after aerosol delivery to the ovine lung. Gene Ther 18: 996-1005.
45. Moore S, Goodway R, Cracknell S, Paul G. (2012). Capsule based aerosol generation-test article conservation during the conduct of in vivo lead optimisation respiratory safety assessment studies (abstract). Presented at the AIT; 2012 Oct 16-18; Edinburgh, UK.
46. Moss RB, Milla C, Colombo J, et al. (2007). Repeated aerosolized AAVCFTR for treatment of cystic fibrosis: a randomized placebocontrolled phase 2B trial. Hum Gene Ther 18: 726-32.
47. Patton JS, Brain JD, Davies LA, et al. (2010). The particle has landed-characterizing the fate of inhaled pharmaceuticals. J Aerosol Med Pulm Drug Deliv 23: S71-87.
48. Patton JS, Byron PR. (2007). Inhaling medicines: delivering drugs to the body through the lungs. Nat Rev Drug Discov 6: 67-74.
49. Patton JS, Platz RM. (1992). Routes of delivery: case studies. "Pulmonary delivery of peptides and proteins for systemic action". Adv Drug Deliv Rev 8: 179-96.
50. Perricone MA, Morris JE, Pavelka K, et al. (2001). Aerosol and lobar administration of a recombinant adenovirus to individuals with cystic fibrosis. II. Transfection efficiency in airway epithelium. Hum Gene Ther 12: 1383-94.
51. Ponce R, Abad L, Amaravadi L, et al. (2009). Immunogenicity of biologically-derived therapeutics: assessment and interpretation of nonclinical safety studies. Regul Toxicol Pharmacol 54: 164-82.
52. Praetor A, Ellinger I, Hunziker W. (1999). Intracellular traffic of the MHC class I-like IgG Fc receptor, FcRn, expressed in epithelial MDCK cells. J Cell Sci 112: 2291-9.
53. Rader RA. (2005). What is a biopharmaceutical: part 1: (bio)technologybased definitions. BioExecutive Int March: 60-5.
54. Randall TD. (2010). Bronchus-associated lymphoid tissue (BALT) structure and function. Adv Immunol 107: 187-241.
55. Rave K, de la Peña A, Tibaldi FS, et al. (2007). AIR inhaled insulin in subjects with chronic obstructive pulmonary disease. Diabetes Care 30: 1777-82.
56. Rudolph C, Müller RH, Rosenecker J. (2002). Jet nebulization of PEI/DNA polyplexes: physical stability and in vitro gene delivery efficiency. J Gene Med 4: 66-74.
57. Sabin AB. (1983). Immunization against measles by aerosol. Rev Infect Dis 5: 514-23.
58. Sabin AB, Flores Arechiga A, Fernández de Castro J, et al. (1984). Successful immunization of infants with and without maternal antibody by aerosolized measles vaccine. II. Vaccine comparisons and evidence for multiple antibody response. JAMA 251: 2363-71.
59. Serabian MA, Huang Y. (2008). Preclinical safety evaluation of biopharmaceuticals. In: Cavagnaro J. ed. Preclinical safety evaluation of biopharmaceuticals: a science-based approach to facilitating clinical trials. NJ: John Wiley & Sons, 45-65.
60. Shoyele SA, Cawthorne S. (2006). Particle engineering techniques for inhaled biopharmaceuticals. Adv Drug Delivery Rev 58: 1009-29.
61. Siekmeier R, Scheuch G. (2008a). Systemic treatment by inhalation of macromolecules-principles, problems and examples. J Physiol Pharmacol 59: 53-79.
62. Siekmeier R, Scheuch G. (2008b). Inhaled insulin-does it become reality? J Physiol Pharmacol 59: 81-113.
63. Valdespino-Gomez JL, de Lourdes Garcia-Garcia M, Fernandezde-Castro J, et al. (2006). Measles aerosol vaccination. Curr Top Microbiol Immunol 304: 165-93.
64. Vick A, Wolff R, Koester A, et al. (2007). A 6-month inhalation study to characterize the toxicity, pharmacokinetics, and pharmacodynamics of human insulin inhalation powder (HIIP) in Beagle dogs. J Aerosol Med 20: 112-26.
65. Wan F, Møller EH, Yang M, Jørgensen L. (2012). Formulation technologies to overcome unfavourable properties of peptides and proteins for pulmonary delivery. Drug Discover Today 9: e141-6.
66. Wise S, Chien J, Yeo K, Richardson C. (2006). Smoking enhances absorption of insulin but reduces glucodynamic effects in individuals using the Lilly-Dura inhaled insulin system. Diabet Med 23: 510-15.
67. Wolff RK. (1998). Safety of inhaled proteins for therapeutic use. J Aerosol Med 11: 197-219.
68. Wolzt M, de la Pena A, Berclaz PY, et al. (2008). AIR inhaled insulin versus subcutaneous insulin: pharmacokinetics, gluco-dynamics and pulmonary function in asthma. Diabetes Care 31: 735-40.
69. Yew NS, Wang KX, Przybylska M, et al. (1999). Contribution of plasmid DNA to inflammation in the lung after administration of cationic lipid: pDNA complexes. Hum Gene Ther 10: 223-34.