Recommendations for Nanomedicine Human Subjects Research Oversight: An Evolutionary Approach for an Emerging Field

Journal of Law, Medicine and Ethics

Volumn 40, Issue 4, 2012, Pages 716-750

  Fatehi, Leili ^a   Wolf, Susan M ^a   Mccullough, Jeffrey ^a   Hall, Ralph ^a   Lawrenz, Frances ^a   Kahn, Jeffrey P ^b   Jones, Cortney ^a   Campbell, Stephen A ^a   Dresser, Rebecca S ^c   Erdman, Arthur G ^a   Haynes, Christy L ^a   Hoerr, Robert A ^d   Hogle, Linda F ^e   Keane, Moira A ^a   Khushf, George ^f   King, Nancy M P ^g   Kokkoli, Efrosini ^a   Marchant, Gary ^h   Maynard, Andrew D ⁱ   Philbert, Martin ⁱ   Ramachandran, Gurumurthy ^a   Siegel, Ronald A ^a   Wickline, Samuel ^c   more..

^a UNIVERSITY OF MINNESOTA   (United States)

^b JOHNS HOPKINS UNIVERSITY   (United States)

^c WASHINGTON UNIVERSITY   (United States)

^d Nanocopoeia Inc   (United States)

^e UNIVERSITY OF WISCONSIN MADISON   (United States)

^f UNIVERSITY OF SOUTH CAROLINA   (United States)

^g WAKE FOREST SCHOOL OF MEDICINE   (United States)

^h ARIZONA STATE UNIVERSITY   (United States)

ⁱ UNIVERSITY OF MICHIGAN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADVISORY COMMITTEE; ARTICLE; CONSENSUS DEVELOPMENT; ENVIRONMENTAL EXPOSURE; ETHICS; GOVERNMENT REGULATION; HUMAN; HUMAN EXPERIMENT; NANOMEDICINE; OCCUPATIONAL EXPOSURE; ORGANIZATION AND MANAGEMENT; RISK MANAGEMENT; UNITED STATES;

ADVISORY COMMITTEES; ENVIRONMENTAL EXPOSURE; GOVERNMENT REGULATION; HUMAN EXPERIMENTATION; HUMANS; NANOMEDICINE; OCCUPATIONAL EXPOSURE; RISK MANAGEMENT; UNITED STATES;

EID: 84872146492     PISSN: 10731105     EISSN: 1748720X     Source Type: Journal    
DOI: 10.1111/j.1748-720X.2012.00703.x     Document Type: Article

References (199)

1. A. D. Maynard, "Don't Define Nanomaterials, " Nature 475, no. 7354 (2011): 31. See also J. P. Holdren, C. R. Sunstein, and I. A. Siddiqui, "Policy Principles for the U.S. Decision-Making Concerning Regulation and Oversight of Applications of Nanotechnology and Nanomaterials, " Memorandum for the Heads of Executive Departments and Agencies, Executive Office of the President (June 2011): at 3, available at (last visited October 17, 2012).
2. V. K. Varadan L. Chen and J. Xie, Nanomedicine: Design and Applications of Magnetic Nanomaterials, Nonsensors and Nanosystems ( Chichester, West Sussex, UK : John Wiley and Sons, 2008): at 1-2; V. S. Chan, "Nanomedicine: An Unresolved Regulatory Issue, "Regulatory Toxicology & Pharmacology 46, no. 3 (2006): 218-224, at 219.
3. N. Sadrieh and T. J. Miller, "Nanotechnology: Regulatory Perspective for Drug Development in Cancer Therapeutics, " in M. M. Amiji ed., Nanotechnology for Cancer Therapy ( Boca Raton, FL : Taylor & Francis Group, 2007): 139-156, at 141; C. H. Stickland, "Nano-Based Drugs and Medical Devices: FDA's Track Record, "Nanotechnology Law & Business 4, no. 2 (2007): 179-188, at 182.
4. M. L. Etheridge et al., "The Big Picture on Nanomedicine: The State of Investigational and Approved Nanomedicine Products, " Nanomedicine: Nanotechnology, Biology and Medicine (in press), available at (last visited November 28, 2012).
5. 21 C.F.R. parts 50, 56 (2012).
6. 45 C.F.R. part 46 (2011).
7. 21 C.F.R. § 56.111 (2012); 45 C.F.R. § 46.111 (2011).
8. 21 U.S.C. §§ 301 et seq. (2006).
9. M. S. Lesney, "A New Broom?" Modern Drug Discovery 3, no. 9 (2000): 31-33, available at (last visited October 17, 2012).
10. U.S. Department of Health and Human Services, Federal Policy for the Protection of Human Subjects ('Common Rule'), available at (last visited October 17, 2012).
11. 45 C.F.R. § 46.103 (2011).
12. U.S. Department of Health and Human Services, About OHRP, available at (last visited October 17, 2012).
13. Office for Human Research Protections, U.S. Department of Health and Human Services, IRB Guidebook, at Chapter IV, available at (last visited October 17, 2012); R. Barke, "Balancing Uncertain Risks and Benefits in Human Subjects Research, "Science, Technology & Human Values 34, no. 3 (2009): 337-364, at 345-346.
14. 21 C.F.R. part 314 (2012).
15. 21 C.F.R. part 814 (2012). See generally U.S. Department of Health and Human Services, Food and Drug Administration, Nanotechnology: A Report of the U.S. Food and Drug Administration Nanotechnology Task Force (2007), available at (last visited October 17, 2012) [hereinafter FDA Nanotechnology Task Force Report].
16. 21 C.F.R. part 312 (2012).
17. 21 C.F.R. part 812 (2012).
18. 21 C.F.R. part 812 (2012); U.S. Health and Human Services, Food and Drug Administration, U.S. Department of Health and Human Services, IDE Responsibilities, available at (last visited October 17, 2012).
19. FDA Nanotechnology Task Force Report, supra note 15, at 32.
20. 42 C.F.R. §§ 52a, 52h.4 (2011). The terms "Scientific Review Group" and "Peer Review Group" are used interchangeably. 42 C.F.R. § 52h.2 (u) (2011).
21. 42 C.F.R. § 52h.8 (2011).
22. See National Institute for Occupational Safety and Health, U.S. Department of Health and Human Services, Approaches to Safe Nanotechnology: Managing the Health and Safety Concerns Associated with Engineered Nanomaterials (2009), available at (last visited October 17, 2012) [hereinafter NIOSH Approaches to Safe Nanotechnology]; Department of Labor, Organizational Chart, available at (last visited October 17, 2012) [hereinafter DOL Chart]; Environmental Protection Agency, EPA Organizational Chart, available at (last visited October 17, 2012) [hereinafter EPA Chart]; U.S. Department of Health and Human Services, HHS Organizational Chart, available at (last visited October 17, 2012) [hereinafter HHS Chart].
23. See, e.g., Office of Biotechnology Activities, National Institutes of Health, Recombinant DNA Advisory Committee Meetings, "Minutes of Meeting September 15-17, 2010, "available at (last visited October 17, 2012).
24. FDA Nanotechnology Taskforce Report, supra note 15, at 19, 30, and 35.
25. Office of Pharmaceutical Science, Center for Drug Evaluation and Research, Manual of Policies and Procedures (MAPP), Reporting Format for Nanotechnology-Related Information in CMC Review (June 2010): 4-5, available at (last visited October 17, 2012) [hereinafter CDER Manual of Policies and Procedures].
26. Food and Drug Administration, U.S. Department of Health and Human Services, "Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology, "Federal Register 76, no. 114 (June 14, 2011): 34715-34716.
27. See NIOSH Approaches to Safe Nanotechnology, supra note 22; Environmental Protection Agency, "Pesticides; Policies Concerning Products Containing Nanoscale Materials; Opportunity for Public Comment, "Federal Register 76, no. 117 (June 17, 2011): 35383-35395 [hereinafter EPA Nanoscale Materials].
28. Holdren et al., supra note 1, at 5.
29. National Research Council, Committee to Develop a Research Strategy for Environmental, Health, and Safety Aspects of Engineered Nanomaterial, A Research Strategy for Environmental, Health, and Safety Aspects of Engineered Nanomaterials (Washington, DC: National Academies Press, 2012) [hereinafter NRC Research Strategy].
30. National Nanotechnology Initiative, National Science and Technology Council Committee on Technology Subcommittee on Nanoscale Science, and Technology, National Nanotechnology Initiative Strategic Plan (2011), at 30, available at (last visited October 17, 2012) [hereinafter NNI Strategic Plan].
31. Executive Office of the President, PCAST Report to the President and Congress on the Fourth Assessment of the National Nanotechnology Initiative (2012), April 27, 2012, at 22-23, available at (last visited October 17, 2012) [hereinafter EOP Assessment of NNI].
32. See, e.g., E. J. Emanuel et al., The Oxford Textbook of Clinical Research Ethics (New York: Oxford University Press, 2008); R. J. Levine, Ethics and Regulation of Clinical Research, 2nd ed. (New Haven: Yale University Press, 1988).
33. See S. M. Wolf and C. M. Jones, "Designing Oversight for Nanomedicine Research in Human Subjects: Systematic Analysis of Exceptional Oversight for Emerging Technologies, "Journal of Nanoparticle Research 13, no. 4 (2011): 1449-1465.
34. W. H. De Jong and P. J. Borm, "Drug Delivery and Nanoparticles: Applications and Hazards, " International Journal of Nanomedicine 3, no. 2 (2008): 133-149, at 139-140; W. H. De Jong et al., "Particle Size-Dependent Organ Distribution of Gold Nanoparticles after Intravenous Administration, "Biomaterials 29, no. 12 (2008): 1912-1919, at 1913.
35. M. A. Dobrovolskaia and S. E. McNeil, "Immunological Properties of Engineered Nanomaterials, " Nature Nanotechnology 2, no. 8 (2007): 469-478, at 469.
36. N. Sanvicens and M. P. Marco, "Multifunctional Nanoparticles: Properties and Prospects for Their Use in Human Medicine, " Trends in Biotechnology 26, no. 8 (2008): 425-433, at 430; D. F. Emerich and C. G. Thanos, "Targeted Nanoparticle-Based Drug Delivery and Diagnosis, "Journal of Drug Targeting 15, no. 3 (2007): 163-183, at 164.
37. V. Wiwanitkit A. Sereemaspun and R. Rojanathanes, "Effect of Gold Nanoparticles on Spermatozoa: The First World Report, " Fertility and Sterility 91, no. 1 (2009): e7-e8.
38. L. Tran and J. M. Navas Anton, "Nanotoxicology and Engineered Nanoparticle Risk Assessment, " Seguridad y Medio Ambiente 29, no. 114 (2009): 1-45, at 3, available at (last visited October 17, 2012).
39. V. Murashov, "Occupational Exposure to Nanomedical Applications, " Nanomedicine and Nanobiotechnology 1, no. 2 (2009): 203-213.
40. G. Oberdörster, "Safety Assessment for Nanotechnology and Nanomedicine: Concepts of Nanotoxicology, " Journal of Internal Medicine 267, no. 1 (2010): 89-105, at 100; D. B. Warheit, "Debunking Some Misconceptions About Nanotoxicology, "Nano Letters 10, no. 12 (2010): 4777-4782, at 4781; D. B. Resnik and S. S. Tinkle, "Ethical Issues in Clinical Trials Involving Nanomedicine, "Contemporary Clinical Trials 28, no. 4 (2007): 433-441, at 436.
41. A. A. Shvedova and V. E. Kagan, "The Role of Nanotoxicology in Realizing the 'Helping without Harm' Paradigm of Nanomedicine: Lessons from Studies of Pulmonary Effects of Single-Walled Carbon Nanotubes, " Journal of Internal Medicine 267, no. 1 (2010): 106-118; H. Fischer and W. Chan, "Nanotoxicity: The Growing Need for In Vivo Study, "Current Opinion in Biotechnology 18, no. 6 (2007): 565-571.
42. A. D. Maynard D. B. Warheit and M. A. Philbert, "The New Toxicology of Sophisticated Materials: Nanotoxicology and Beyond, " Toxicological Sciences 120, no. S1 (2011): S109-S129.
43. Wolf and Jones, supra note 34, at 1450.
44. See, e.g., Institute of Medicine, D. D. Federman, K. E. Hanna, and L. L. Rodriguez, eds., Responsible Research: A Systems Approach to Protecting Research Participants (Washington, DC: National Academies Press, 2002): at 236.
45. Holdren et al., supra note 1, at 2.
46. Wolf and Jones, supra note 34, at 1450.
47. S. Crowe, "Understanding the Ethical Implications of Nanotechnology: Highlights of a Limited Inquiry by the President's Council on Bioethics, " Staff Paper, President's Council on Bioethics (January 2008), available at (last visited October 17, 2012).
48. M. Roco O. Renn and A. Jäger, "Nanotechnology Risk Governance, " in O. Renn and K. Walker eds., Global Risk Governance: Concept and Practice Using IRGC Framework ( Dordrecht, The Netherlands : Springer, 2008): 301-327, at 307.
49. See generally, F. G. Miller and S. Joffe, "Limits to Research Risks, "Journal of Medical Ethics 35, no. 7 (2009): 445-449, at 448-449; S. Joffe and F. G. Miller, "Bench to Bedside: Mapping the Moral Terrain of Clinical Research, "Hastings Center Report 38, no. 2 (2008): 30-42, at 39-40.
50. Maynard, supra note 1, at 31.
51. NRC Research Strategy, supra note 29, at 36-37.
52. Maynard, supra note 1, at 31.
53. National Nanotechnology Initiative, About the NNI, available at (last visited October 18, 2012); National Nanotechnology Initiative, NSET's Participating Federal Partners, available at (last visited October 18, 2012).
54. National Nanotechnology Initiative, The NSET Subcommittee, available at (last visited October 18, 2012) [hereinafter NNI NSET].
55. National Nanotechnology Initiative, What It Is and How It Works, available at (last visited October 18, 2012) [hereinafter NNI What It Is]; National Nanotechnology Initiative, Frequently Asked Questions, available at (last visited October 18, 2012).
56. Center for Biological and Environmental Nanotechnology, CBEN Annual Report: Program Year 2009 (2009), available at (last visited October 18, 2012) [hereinafter CBEN Annual Report]; L. Goldenberg, "The 'Integration/Penetration Model:' Social Impacts of Nanobiotechnology Issues, " in M. C. Roco and W. S. Bainbridge, eds., Nanotechnology: Societal Implications II: Individual Perspectives (Dordrecht, The Netherlands: Springer, 2007): at 141-152.
57. J. M. Balbus et al., "Getting It Right the First Time: Developing Nanotechnology While Protecting Workers, Public Health, and the Environment, " Annals of the New York Academy of Sciences 1076, no. 1 (2006): 331-342, at 333-334; M. Garnett and P. Kallinteri, "Nanomedicines and Nanotoxicology: Some Physiological Principles, "Occupational Medicine 56, no. 5 (2006): 307-311, at 310; V. Wagner et al., "The Emerging Nanomedicine Landscape, "Nature Biotechnology 24, no. 10 (2006): 1211-1217, at 1212.
58. A. G. Spagnolo and V. Daloiso, "Outlining Ethical Issues in Nanotechnologies, " Bioethics 23, no. 7 (2009): 394-402, at 399-400.
59. J. W. Moore C. L. Stanitski and P. C. Jurs, Principles of Chemistry: The Molecular Science ( Belmont, CA : Brooks/Cole, Cengage Learning, 1st ed. 2010): at 16.
60. R. Brasseur J. Ruysschaert and P. Chatelain, "Semi-Empirical Conformational Analysis of Propranolol Interacting with Dipalmitoylphosphatidylcholine, " Biochimica et Biophysica Acta (BBA) - Biomembranes 815, no. 3 (1985): 341-350, at 341, available at (last visited August 21, 2012; restricted access).
61. W. J. Koolage and R. Hall, "Chemical Action: What Is It, and Why Does It Really Matter?" Journal of Nanoparticle Research 13, no. 4 (2011): 1401-1417, at 1416; Spagnolo and Daloiso, supra note 59, at 399.
62. CDER Manual of Policies and Procedures, supra note 25, at 3.
63. Food and Drug Administration, Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology, available at (last visited October 18, 2012) (emphasis added) [hereinafter FDA Application of Nanotechnology].
64. NRC Research Strategy, supra note 29, at 49.
65. Maynard, supra note 1, at 31.
66. Etheridge et al., supra note 4.
67. D. C. Litzinger et al., "Effect of Liposome Size on the Circulation Time and Intraorgan Distribution of Amphipathic Poly(ethylene glycol)-containing Liposomes, " Biochimica et Biophysica Acta 1190, no. 1 (1994): 99-107, at 105.
68. Etheridge et al., supra note 4.
69. Holdren et al., supra note 1, at 5.
70. Barke, supra note 13, at 341; J. Kimmelman, "Valuing Risk: The Ethical Review of Clinical Trial Safety, "Kennedy Institute of Ethics Journal 14, no. 4 (2004): 369-393, at 371.
71. D. M. Hausman, "Third-Party Risks in Research: Should IRBs Address Them?" IRB 29, no. 3 (2007): 1-5, at 5; D. B. Resnik and R. R. Sharp, "Protecting Third Parties in Human Subjects Research, "IRB 28, no. 4 (2006): 1-7, at 3.
72. Wolf and Jones, supra note 34, at 1450.
73. National Institutes of Health, Frequently Asked Questions About the NIH Review Process for Human Gene Transfer Trials, available at (last visited October 18, 2012).
74. National Institutes of Health, NIH Guidelines for Research Involving Recombinant DNA (2011), available at (last visited October 18, 2012) [hereinafter NIH Guidelines]. Note that changes in the NIH Guidelines to expand coverage to synthetic biology will go into effect in 2013. See National Institutes of Health, Final Action Under the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines), Federal Register 77, no. 172 (2012): 54584-54597, available at (last visited November 13, 2012).
75. See HHS Chart, supra note 22; EPA Chart, supra note 22; DOL Chart, supra note 22.
76. Etheridge et al., supra note 4.
77. E. M. Merisko-Liversidge and G. G. Liversidge, "Drug Nanoparticles: Formulating Poorly Water-Soluble Compounds, " Toxicologic Pathology 36, no. 1 (2008): 43-48, at 43-44.
78. Roco et al., supra note 49.
79. De Jong and Borm, supra note 35, at 136-137; De Jong et al., supra note 35, at 1913.
80. Dobrovolskaia and McNeil, supra note 36; Resnik and Tinkle, supra note 41; M. Geiser et al., "Ultrafine Particles Cross Cellular Membranes by Nonphagocytic Mechanisms in Lungs and in Cultured Cells, "Environmental Health Perspectives 113 (2005): 1555-1560; G. Oberdörster, E. Oberdörster, and J. Oberdörster, "Nanotoxicity: An Emerging Discipline Evolving for Studies of Ultrafine Particles, "Environmental Health Perspectives 113, no. 7 (2005): 823-839; P. H. M. Hoet, I. Bruske-Hohlfield, and O. V. Salata, "Nanoparticles: Known and Unknown Health Risks, "Journal of Nanobiotechnology 2, no. 12 (2004): 1-15, available at (last visited October 18, 2012).
81. Shvedova and Kagan, supra note 42; Wiwanitkit et al., supra note 38, at e7-e8; Fischer and Chan, supra note 42, at 565-566.
82. Tran and Navas Anton, supra note 39, at 1, 3.
83. Oberdörster, supra note 41, at 102; D. B. Warheit, "Debunking Some Misconceptions about Nanotoxicology, "Nano Letters 10, no. 12 (2010): 4777-4782, at 4782.
84. NRC Research Strategy, supra note 29, at 3; NNI Strategic Plan, supra note 31, at 18.
85. NNI Strategic Plan, supra note 31, at 18.
86. Resnik and Tinkle, supra note 41, at 436.
87. NNI Strategic Plan, supra note 31, at 30-31, 48.
88. Maynard et al., supra note 43, at S111; Resnik and Tinkle, supra note 41, at 435-436; Oberdörster et al., supra note 85, at 836.
89. F. Graur et al., "Ethical Issues in Nanomedicine, " IFMBE Proceedings 36, no. 1 (2011): 9-12, at 10.
90. F. Jotterand and A. A. Alexander, "Managing the 'Known Unknowns': Theranostic Cancer Nanomedicine and Informed Consent, " in S. J. Hurst ed., Biomedical Nanotechnology (Methods in Molecular Biology, vol. 726) ( New York : Humana Press, 2011): 413-429, at 426.
91. J. Kimmelman and A. J. London, "Predicting Harms and Benefits in Translational Trials: Ethics, Evidence, and Uncertainty, " PLoS Medicine 8, no. 3 (2011): e1001010 (5 pages), available at (last visited October 18, 2012).
92. R. Chin and B. Y. Lee, Principles and Practice of Clinical Trial Medicine ( Burlington, MA : Elsevier, 1996): at 33-36.
93. Center for Drug Evaluation and Research, Guidance for Industry, Investigators, and Reviewers: Exploratory IND Studies (2006), available at (last visited October 18, 2012) [hereinafter Exploratory IND Studies].
94. See R. Kinders et al., "Phase 0 Clinical Trials in Cancer Drug Development: From FDA Guidance to Clinical Practice, "Molecular Interventions 7, no. 6 (2007): 325-334.
95. NNI Strategic Plan, supra note 31, at 30.
96. Resnik and Tinkle, supra note 41, at 436.
97. Kimmelman et al., supra note 50, at 1894; Resnik and Tinkle, supra note 41, at 436.
98. L. K. Aguilar and E. Aguilar-Cordova, "Evolution of a Gene Therapy Clinical Trial, " Journal of Neuro-Oncology 65, no. 3 (2003): 307-315, at 312.
99. Resnik and Tinkle, supra note 41, at 436-437.
100. Kimmelman et al., supra note 50, at 1894.
101. NRC Research Strategy, supra note 29, at 85.
102. Shvedova and Kagan, supra note 42, at 108-109; Fischer and Chan, supra note 42, at 566.
103. J. Kimmelman, Gene Transfer and the Ethics of First-in Human Research: Lost in Translation ( New York : Cambridge University Press, 2010): at 21-22.
104. See NIH Guidelines, supra note 78.
105. N. M. P. King, "RAC Oversight of Gene Transfer Research: A Model Worth Extending?" Journal of Law, Medicine & Ethics 30, no. 3 (2002): 381-389, at 386.
106. 21 C.F.R. § 50.25 (2012); 45 C.F.R. § 46.116 (2011).
107. 21 C.F.R. §§ 50.25(b)(1), 50.25(b)(5) (2012); 45 C.F.R. §§ 46.116(b)(1), 46.116(b)(5) (2011).
108. Wiwanitkit et al., supra note 38, at e8.
109. G. E. Henderson et al., "Clinical Trials and Medical Care: Defining the Therapeutic Misconception, " PLoS Medicine 4, no. 11 (2007): e324, 1735-1738, available at (last visited October 18, 2012); F. G. Miller and H. Brody, "A Critique of Clinical Equipoise: Therapeutic Misconception in the Ethics of Clinical Trials, "Hastings Center Report 33, no. 3 (2003): 19-28; S. Hornig and C. Grady, "Misunderstanding in Clinical Research: Distinguishing Therapeutic Misconception, Therapeutic Misestimation, and Therapeutic Optimism, "IRB 25, no. 1 (2003): 11-16; P. S. Appelbaum, L. H. Roth, and C. Lidz, "The Therapeutic Misconception: Informed Consent in Psychiatric Research, "International Journal of Law and Psychiatry 5, no. 3-4 (1982): 319-329.
110. P. S. Appelbaum C. W. Lidz and T. Grisso, "Therapeutic Misconception in Clinical Research: Frequency and Risk Factors, " IRB 26, no. 2 (2004): 1-8, at 4-5; C. W. Lidz et al., "Therapeutic Misconception and the Appreciation of Risks in Clinical Trials, "Social Science & Medicine 58, no. 9 (2004): 1689-1697, at 1695.
111. Miller and Brody, supra note 116, at 25-26.
112. J. Kimmelman, "Ethics at Phase 0: Clarifying the Issues, " Journal of Law, Medicine & Ethics 35, no. 4 (2007): 727-733, at 729.
113. Appelbaum et al., supra note 117, at 7.
114. Resnik and Tinkle, supra note 41, at 439.
115. R. Bawa, "Regulating Nanomedicine: Can the FDA Handle It?" Current Drug Delivery 8, no. 3 (2011): 227-234, at 229; R. Bawa and S. Johnson, "The Ethical Dimensions of Nanomedicine, "Medical Clinics of North America 91, no. 5 (2007): 881-887, at 882; T. T. Faunce and K. K. Shats, "Researching Safety and Cost-Effectiveness in the Life Cycle of Nanomedicine, "Journal of Law & Medicine 15, no. 1 (2007): 128-135, at 131.
116. E.g., EuroNanoForum 2007: Nanotechnology in Industrial Applications, Nano Techwire website, August 21, 2006, available at (last visited October 18, 2012); M. D. Cobb and J. Macoubrie, "Public Perceptions about Nanotechnology: Risks, Benefits and Trust, "Journal of Nanoparticle Research 6, no. 4 (2004): 395-405.
117. T. Satterfield et al. "Anticipating the Perceived Risk of Nanotechnologies, " Nature Nanotechnology 4, no. 11 (2009): 752-758.
118. See D. M. Berube, "The Public Acceptance of Nanomedicine: A Personal Perspective, "Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology 1, no. 1 (2009): 2-5. See also B. Nerlich, D. D. Clarke, and F. Ulph, "Risks and Benefits of Nanotechnology: How Young Adults Perceive Possible Advances in Nanomedicine Compared with Conventional Treatments, "Health, Risk & Society 9, no. 2 (2007): 159-171.
119. Bawa, supra note 122, at 230.
120. Maynard, supra note 1, at 31.
121. 21 C.F.R. § 56.111(a)(g) (2012); 45 C.F.R. § 46.111(a)(6) (2011).
122. 21 C.F.R. §§ 312.50, 312.56, 812.40, 812.46 (2012).
123. Food and Drug Administration, Guidance for Clinical Trial Sponsors: Establishment and Operation of Clinical Trial Data Monitoring Committees (2006), available at (last visited October 18, 2012) [hereinafter Guidance for Clinical Trial Sponsors].
124. 21 C.F.R. §§ 312.56, 812.46 (2012).
125. Guidance for Clinical Trial Sponsors, supra note 130, at 3-4.
126. National Institutes of Health, Further Guidance on a Data and Safety Monitoring for Phase I and Phase II Trials (NOT-OD-00-038) (2000), available at (last visited October 18, 2012).
127. National Institutes of Health, NIH Policy for Data and Safety Monitoring (NOT-98-084) (1998), available at (last visited August 24, 2012).
128. A. S. Slutsky and J. V. Lavery, "Data Safety and Monitoring Boards, " New England Journal of Medicine 350, no. 11 (2004): 1143-1147, at 1143.
129. NNI Strategic Plan, supra note 31 at 29-32.
130. NRC Research Strategy, supra note 29, at 78.
131. V. Murashov and J. Howard, "Essential Features for Proactive Risk Management, " Nature Nanotechnology 4, no. 8 (2009): 467-470, at 467.
132. NRC Research Strategy, supra note 29, at 5; NNI Strategic Plan, supra note 31, at 27-32.
133. 45 C.F.R. § 46.102 (2011).
134. Hausman, supra note 75, at 3-5; Resnik and Sharp, supra note 75, at 3.
135. Resnik and Sharp, supra note 75, at 3.
136. Hausman, supra note 75, at 5.
137. J. Kimmelman, "Missing the Forest: Further Thoughts on the Ethics of Bystander Risk in Medical Research, "Cambridge Quarterly of Healthcare Ethics 16, no. 4 (2007): 483-490, at 486-487; Resnik and Sharp, supra note 75, at 3.
138. Resnik and Sharp, supra note 75, at 3.
139. Centers for Disease Control and Prevention & National Institutes of Health (CDC/NIH), Biosafety in Microbiological and Biomedical Laboratories: Centers for Disease Control and Prevention, National Institutes of Health (5th ed. 2009), available at (last visited October 18, 2012) [hereinafter CDC Biosafety].
140. 29 C.F.R. part 1910 (2012).
141. NIOSH Approaches to Safe Nanotechnology, supra note 22.
142. Occupational Safety and Health Administration, "Nanotechnology OSHA Standards, "available at (last visited August 20, 2012).
143. Centers for Disease Control and Prevention, Nanotechology: 10 Critical Topic Areas, available at (last visited October 18, 2012).
144. Centers for Disease Control and Prevention, Nanotechnology: Guidance and Publications, available at (last visited October 18, 2012).
145. Nanoparticle Information Library, available at (last visited October 18, 2012).
146. EOP Assessment of NNI, supra note 32, at xiv.
147. 42 U.S.C. §§ 4321 et seq. (1969).
148. S. Z. Rahman et al., "Pharmacoenvironmentology: A Component of Pharmacovigilance, " Environmental Health 6 (2007): article 20, available at (last visited October 18, 2012).
149. Environmental Protection Agency, "Pesticides; Policies Concerning Products Containing Nanoscale Materials; Opportunity for Public Comment, " Federal Register 76, no. 117 (2011): 35383-35395, at 35387.
150. Environmental Protection Agency, Expanded Protections for Subjects in Human Research Involving Pesticides, available at (last visited October 18, 2012); Environmental Protection Agency, Office of the Science Advisor, "About the HSRB, "available at (last visited October 18, 2012).
151. NIH Guidelines, supra note 78.
152. Office of Biotechnology Activities, Frequently Asked Questions (FAQs) of Interest to IBCs, available at (last visited October 18, 2012).
153. EOP Assessment of NNI, supra note 32, at 40.
154. See HHS Announces Text4Health Task Force Recommendations and Global Partnership, HHS Press Office (2011), available at (last visited October 18, 2012); The White House, Office of the Press Secretary, "President Barack Obama Announces Key FDA Appointments and Tougher Food Safety Measures, " March 14, 2009, available at (last visited October 18, 2012) [hereinafter White House FDA Appointments]; Interagency Working Group on Import Safety, Import Safety: Action Plan Update, (2008), available at (last visited October 18, 2012) [hereinafter Interagency Working Group on Import Safety]; Department of Health and Human Services, "HHS Dot Gov Task Force, "available at (last visited October 18, 2012).
155. See Administration for Children & Families (ACF), Federal Interagency Work Group on Child Abuse & Neglect, available at (last visited October 18, 2012); White House FDA Appointments, supra note 165; Interagency Working Group on Import Safety, supra note 165; Executive Order 13439, "Establishing an Interagency Working Group on Import Safety, "Federal Register 72, no. 139 (2007): 40053-40055.
156. See HHS Chart, supra note 22; EPA Chart, supra note 22; DOL Chart, supra note 22.
157. Office for Human Research Protections, U.S. Department of Health and Human Services, Charter, Secretary's Advisory Committee on Human Research Protections, available at (last visited October 18, 2012) [hereinafter SACHRP Charter].
158. Office for Human Research Protections, U.S. Department of Health and Human Services, Secretary's Advisory Committee on Human Research Protections (SACHRP), available at (last visited October 18, 2012).
159. SACHRP Charter, supra note 168.
160. 5 U.S.C. Appendix 2 (1972).
161. 5 U.S.C. Appendix 1 (1972); S. P. Croley and W. F. Funk, "The Federal Advisory Committee Act and Good Government, "Yale Journal on Regulation 14, no. 2 (1997): 451-557, at 461-465.
162. R. Steinbrook, "Science, Politics, and Federal Advisory Committees, " New England Journal of Medicine 350, no. 14 (2004): 1454-1460, at 1454.
163. M. H. Cardozo, "The Federal Advisory Committee Act in Operation, " Administrative Law Review 33 (1981): 1-62, at 3-4.
164. See Steinbrook, supra note 173, at 1459; D. Michaels et al., "Advice without Dissent, "Science 298, no. 5594 (2002): 703, at 703.
165. 5 U.S.C. Appendix 2 (1972).
166. NNI Strategic Plan, supra note 31, at 2.
167. EOP Assessment of NNI, supra note 32, at 40.
168. Michaels et al., supra note 175.
169. EOP Assessment of NNI, supra note 32, at 40-41.
170. Holdren et al., supra note 1, at 5.
171. Office of Biotechnology Activities, Appendix M, available at (last visited October 18, 2012) [hereinafter Appendix M].
172. King, supra note 112, at 386.
173. See Wolf and Jones, supra note 34, at 1451-1452.
174. J. Timmermans Y. Zhao and J. van den Hoven, "Ethics and Nanopharmacy: Value Sensitive Design of New Drugs, " Nanoethics 5, no. 3 (2011): 269-283, at 279.
175. Wolf and Jones, supra note 34, at 1461.
176. Bawa, supra, note 122, at 232.
177. B. Fadeel and A. E. Garcia-Bennett, "Better Safe Than Sorry: Understanding the Toxicological Properties of Inorganic Nanoparticles Manufactured for Biomedical Applications, " Advanced Drug Delivery Reviews 62, no. 3 (2009): 362-374, at 370-371.
178. S. Harris, "The Regulation of Nanomedicine: Will the Existing Regulatory Scheme of the FDA Suffice?" Richmond Journal of Law & Technology 16, no. 2 (2009): article 4, 25 pages, at 18-19, 23.
179. P. Hoet et al., "Do Nanomedicines Require Novel Safety Assessments to Ensure Their Safety for Long-Term Human Use?" Drug Safety 32, no. 8 (2009): 625-636, at 632.
180. R. Bawa and S. Johnson, "Emerging Issues in Nanomedicine and Ethics, " in F. Allhoff and P. Lin eds., Nanotechnology & Society ( Dordrecht, The Netherlands : Springer, 2008): 207-223, at 212-213.
181. K. A. Deville, "Law, Regulation and the Medical Use of Nanotechnology, " in F. Jotterand ed., Emerging Conceptual, Ethical and Policy Issues in Biotechnology ( Dordrecht, The Netherlands : Springer, 2008): 181-200, at 192-193.
182. N. Staggers et al., "Nanotechnology: The Coming Revolution and Its Implications for Consumers, Clinicians, and Informatics, " Nursing Outlook 56, no. 5 (2008): 268-274, at 273.
183. J. Virdi, "Bridging the Knowledge Gap: Examining Potential Limits in Nanomedicine, " Spontaneous Generations 2, no. 1 (2008): 25-44, at 32.
184. C. Lenk and N. Biller-Andorno, "Nanomedicine: Emerging or Re-emerging Ethical Issues? A Discussion of Four Ethical Themes, " Medicine, Health Care and Philosophy 10, no. 2 (2007): 173-184, at 181.
185. D. B. Resnik and S. S. Tinkle, "Ethics in Nanomedicine, " Nanomedicine 2, no. 3 (2007): 345-350.
186. FDA Application of Nanotechnology, supra note 63.
187. Food and Drug Administration, U.S. Department of Health and Human Services, Science and Research Special Topics, available at (last visited October 18, 2012).
188. CDER Manual of Policies and Procedures, supra note 25, at 3.
189. National Institutes of Health, U.S. Department of Health and Human Services, Nanotechnology at the National Institutes of Health: Innovative Medical Research at the Molecular Scale, NIH Publication no. 08-6443 (2008): 1-8, at 1, available at (last visited October 18, 2012).
190. National Cancer Institute, Learn About Nanotechnology in Cancer, available at (last visited October 18, 2012).
191. U.S. Department of Health and Human Services, Centers of Cancer Nanotechnology Excellence (CCNEs)(U54), available at (last visited October 18, 2012). See, e.g., National Institutes of Health, Cancer Nanotechnology Platform Partnerships, available at (last visited October 18, 2012).
192. National Institute of Environmental Health Sciences, National Institutes of Health, Since You Asked - Nanotechnology and NIEHS, available at (last visited November 5, 2012).
193. Environmental Protection Agency, Extramural Research: Nanotechnology, available at (last visited October 18, 2012); see EPA Nanoscale Materials, supra note 27.
194. W. Jordan, Office of Pesticide Programs, Nanotechnology and Pesticides, Pesticide Program Dialogue Committee Meeting, April 29, 2010, at 5, available at (last visited October 18, 2012).
195. Occupational Safety and Health Administration, "Safety and Health Topics: Nanotechnology, "available at (last visited October 18, 2012).
196. NIOSH Approaches to Safe Nanotechnology, supra note 22.
197. NRC Research Strategy, supra note 29, at 50, 63.
198. Wolf and Jones, supra note 34, at 1450.
199. Food and Drug Administration, U.S. Department of Health and Human Services, Guidance for Industry and Researchers: The Radioactive Drug Research Committee: Human Research Without an Investigational New Drug Application (August 2010): at 2, available at (last visited October 18, 2012).