Country Report U.S.A.

Jost, Timothy Stoltzfus

doi:10.1007/978-3-642-13177-6_9

Timothy Stoltzfus Jost⁶

Part of the book series: Veröffentlichungen des Instituts für Deutsches, Europäisches und Internationales Medizinrecht, Gesundheitsrecht und Bioethik der Universitäten Heidelberg und Mannheim ((IMGB,volume 37))

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Abstract

This paper examines the influence of the European Good Clinical Practices Guidelines, Directive 2001/20/EC of 4 April 2001 on the law and legal discussion of the United States. It begins with a description of the U.S. approach to the regulation of clinical trials and new drug approval. It next discusses the U.S. participation in the process of pharmaceutical regulation harmonization and U.S. recognition of foreign drug trials for supporting U.S. new drug applications. It then compares contemporary U.S. drug regulation with the requirements of Directive 2001/20/EC. Finally, it briefly reviews recent controversies in drug regulation in the U.S.

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Notes

1.
See FDA, Human Subjects Protection: Foreign Clinical Studies Not Conducted Under an Investigational New Drug Application, 82 Fed. Reg. 22800, 22803 (April 28, 2008) (amending 21 C.F.R. § 312.120).
2.
Food and Drug Modernization Act of 1997, 21 U.S.C. § 383(c)(3).
3.
See FDA, Notice: International Conference on Harmonization; Good Clinical Practices: Consolidated Guideline; Availability, 62 Fed. Reg. 25692, 25692 (May 9, 1997).
4.
82 Fed. Reg. 22800, 22801 (April 28, 2008).
5.
The previous version of the rule required that clinical trials comply with the Declaration of Helsinki.
6.
See Harold Y. Vanderpool, ‘Introduction and Overview: Ethics, Historical Case Studies, and the Research Enterprise’, in Harold Y. Vanderpool (ed.), The Ethics of Research Involving Human Subjects: Facing the 21st Century (1996), 1-30; Advisory Committee on Human Radiation Experiments, Final Report of the Advisory Committee on Human Radiation Experiments (1995), at 41-131.
7.
Radiation Experiments, supra note 6, at 131-37.
8.
Id., at 173.
9.
Id., at 174-76.
10.
Harold Y. Vanderpool, supra note 6, at 10.
11.
The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research (1978).
12.
Harold Y. Vanderpool, supra note 6, at 10.
13.
Federal Policy for the Protection of Human Subjects, 56 Fed. Reg. 28002, 28002 (June 18, 1991). The Common Rule now covers seventeen federal departments and agencies.
14.
See Peter B. Hutt, ‘The Transformation of United States Food and Drug Law’, 60 J. Assn of Food & Drug Officials, 1-17 (1996); Richard A. Merrill, ‘The Architecture of Government Regulation of Medical Products’, 82 Va. L. Rev. 1753, 1758-1764 (1996). A law authorizing federal regulation of biologics such as vaccines was adopted even earlier in 1902 following outbreaks of tetanus from contaminated vaccines, and biologics are still regulated somewhat differently than drugs, though there has been a convergence of regulation, in particular since the Food and Drug Administration Modernization Act of 1997, which directed the FDA to minimize differences between the review and approval of drugs and biologics. See Food and Drug Modernization Act of 1997, Pub. L. No. 105-115, § 123(f), 111 Stat. 2295, 2324.
15.
By one recent count, nine states ban research involving embryos. See Lori Andrews, ‘State Regulation of Embryo Stem Cell Research’, in National Bioethics Advisory Commission (ed.), Ethical Issues in Stem Cell Research II, Commissioned Papers, A-1, A-4 (2000).
16.
See Mo. Ann. Stat. § 630.115(8) (2006) (mental patients); Cal. Health & Safety Code, § 24175(b) (West 2006). State courts also occasionally address research issues in the context of private litigation. See Grimes v. Kennedy-Krieger Institute, 782 A.2d. 807, 855-56 (2001) (Maryland case holding that parents cannot consent for their children to participate in non-therapeutic research posing serious health risks).
17.
Jeffrey N. Gibbs, ‘State Regulation of Pharmaceutical Clinical Trials’, 59 Food & Drug L. J. 265, 269 (2004).
18.
21 U.S.C. § 355. Actually the marketing of unsafe or ineffective drugs has been outlawed in the United States since 1938, but the present procedures for approving drugs were established by the 1962 amendments.
19.
21 U.S.C. § 321(p)(1). In reality, the GRASE alternative to the general requirement of FDA approval turns out to be illusory, since a drug cannot be marketed under this exception unless the manufacturer can present “substantial evidence” that the drug is GRASE, and the term “substantial evidence” is defined by the FDA regulations to require “adequate and well-controlled investigations, including clinical investigations, by experts”, essentially the requirement for general FDA new drug approval. See Weinberger v. Hynson, Westcott & Dunning, Inc., 412 U.S. 609, 632 (1973); U.S. v. 50 Boxes More or Less, 909 F.2d. 24, 26 (1st Cir. 1990).
20.
21 U.S.C. §§ 331(d), 332, 333, 334.
21.
The distinction between non-prescription and over-the-counter drugs is in fact found in the sections of the FDCA dealing with labeling, as over-the-counter drugs must be labeled for consumer use. 21 U.S.C. § 353(b)(1).
22.
See 21 C.F.R. pts. 331-58. See also Alan H. Kaplan et al., ‘Over-The-Counter Drugs’, in David G. Adams et al. (eds.), Fundamentals of Law and Regulation: An In-depth Look at Therapeutic Products II (1997), at 233-38.
23.
See 21 C.F.R. § 330.1.
24.
21 U.S.C. § 321(ff)(1).
25.
21 U.S.C. §§ 343(r)(6).
26.
21 U.S.C. § 350(b)(a)(2).
27.
21 U.S.C. § 342(f)(1)(A).
28.
See When Diets Turn Deadly: Consumer Safety and Weight Loss Supplements: Before the Subcomm. on Oversight of Govn’t Mgmt. of the S. Comm. on Govn’t Affairs, 107th Cong. (2002) (statement of Joseph A. Levitt, Director Center for Food Safety and Applied Nutrition, FDA).
29.
21 U.S.C. § 355(j).
30.
21 U.S.C. § 355(a) & (i).
31.
21 U.S.C. § 355(i)(2); 21 C.F.R. pt. 312.
32.
21 C.F.R. § 312.23.
33.
Id.
34.
21 C.F.R. § 312.23(a)(1)(iv).
35.
21 U.S.C. § 355(i)(2).
36.
21 U.S.C. § 355(i)(3); 21 C.F.R. § 312.42.
37.
See Geoffrey M. Levitt et al., ‘Human Drug Regulation’, in David G. Adams et al. (eds.), Fundamentals of Law and Regulation: An In-depth Look at Therapeutic Products II (1997), at 159-63.
38.
See 21 C.F.R. § 312.23(a)(8).
39.
21 C.F.R. pt. 58.
40.
21 C.F.R. §§ 56.103; 312.23(a)(1)(iv).
41.
See Institute of Medicine, ‘Responsible Research: A Systems Approach to Protecting Research Participants’, (2002), at 85-86.
42.
21 C.F.R. §§ 56.109(b) & (c), 56.111(a)(4).
43.
21 C.F.R. § 56.111.
44.
21 C.F.R. § 56.109(f).
45.
21 C.F.R. § 312.21(a).
46.
21 C.F.R. § 312.21(b).
47.
21 C.F.R. § 321.21(c).
48.
21 C.F.R. § 312.21(c).
49.
21 C.F.R. § 312.42(b).
50.
21 C.F.R. § 312.44.
51.
21 U.S.C. § 355(b).
52.
21 C.F.R. § 314.101(a).
53.
21 C.F.R. § 314.101(a)(1).
54.
21 C.F.R. § 314.101(d).
55.
21 U.S.C. § 355(c)(1).
56.
See Geoffrey M. Levitt et al., supra note 37, at 174-76.
57.
21 U.S.C. § 355(d).
58.
Id.
59.
Id.
60.
See 21 C.F.R. pt. 201.
61.
See 21 C.F.R. § 314.125(b)(1).
62.
See Geoffrey M. Levitt et al., supra note 37, at 179.
63.
Office of Inspector General (HHS), The Food and Drug Administration’s Oversight of Clinical Trials (OEI-01-06-00160) (2007), at ii, available at http://www.oig.hhs.gov/oei/reports/oei-01-06-00160.pdf (last visited Feb. 9, 2009).
64.
See 21 C.F.R. §§ 56.120, 56.121, 312.70, 812.119.
65.
GAO, Human Subjects Research: Undercover Tests Show the Institutional Review Board System is Vulnerable to Unethical Manipulation (2009).
66.
Ibid., two other IRBs refused to approve it.
67.
See History and Future of the ICH, http://www.ich.org/cache/html/355-272-1.html.
68.
See Structure of the ICH, http://www.ich.org/cache/html/510-272-1.html.
69.
See Council Directive 2001/20/EC, 2001 O.J. (L 106) 34 (EC) hereinafter EC Directive; Kai Purnhagen, ‘The Challenge of Globalization in Pharmaceutical Law—Is an International Drug Approval System Modeled After the European System Worth Considering?’, 63 Food & Drug L. J. 623, 638 (2008); Markus Schott, ‘Medical Research on Humans: Regulation in Switzerland, the European Union, and the United States’, 60 Food & Drug L. J. 45, 64 (2005).
70.
EMEA, Note for Guidance on Good Clinical Practice, (CPMP/ICH/135/95) (Jul. 1997), available at http://www.emea.europa.eu/pdfs/human/ich/013595en.pdf (last visited Feb. 9, 2009).
71.
FDA, Notice: International Conference on Harmonization; Good Clinical Practice: Consolidated Guideline; Availability, 62 Fed. Reg. 25692, 25692 (May 9, 1997).
72.
Carolyne R. Hathaway et al., ‘Looking Abroad: Clinical Drug Trials’, 63 Food & Drug L. J. 673, 674 (2008); see also Office of Inspector General (HHS), The Globalization of Clinical Trials: A Growing Challenge of Protecting Human Subjects (OEI-01-00-00190) (2001), available at http://oig.hhs.gov/oei/reports/oei-01-00-00190.pdf (last visited Feb. 9, 2009).
73.
21 C.F.R. § 312.120(a)(1)(i).
74.
EC Directive, art. 22. The EC Directive also recognizes that further detailed Guidelines will be published by the Commission.
75.
EC Directive, arts. 1.1, 2(a) & (c).
76.
21 C.F.R. §§ 312.1, 312.2(a).
77.
21 C.F.R. § 312.2.
78.
EC Directive, art. 9.1.
79.
21 U.S.C. § 355(i)(2); EC Directive, art. 9.
80.
EC Directive, arts. 9.5, 9.6, 9.7.
81.
EC Directive, art. 9.3.
82.
21 C.F.R. §§ 312.34, 312.35.
83.
21 C.F.R. § 312.36.
84.
21 C.F.R. § 56.107.
85.
21 C.F.R. § 56.107(e).
86.
EC Directive, art. 2(k).
87.
Institute of Medicine, supra note 41, at 70-72.
88.
EC Directive, art. 3.2(a).
89.
21 C.F.R. § 56.111(a)(2); EC Directive, art 3.2.
90.
21 C.F.R. pt. 50.
91.
Cf. EC Directive, arts. 3.2(e), 3.4, 6.3(h); 21 C.F.R. § 50.25(a)(6), (7) & (8).
92.
21 C.F.R. § 56.111(a)(1).
93.
Compare 21 U.S.C. § 355(i)(1)(B), with EC Directive, art. 3.3.
94.
EC Directive, art. 9.6. See also arts. 6.7 and 9.4, providing longer time periods for review of clinical trials concerning genetic intervention.
95.
See Nancy M.P. King, ‘RAC Oversight of Gene Transfer Research: A Model Worth Extending?’, 30 J. L. Med. & Ethics 381, 381 (2002).
96.
21 U.S.C. § 56.111(a)(3) & (b).
97.
EC Directive, arts. 4, 5.
98.
EC Directive, art. 4.
99.
21 C.F.R. §§ 50.51, 50.55(d), (e)(1).
100.
21 C.F.R. §§ 50.52, 50.55(c), (e)(1).
101.
21 C.F.R. §§ 50.53, 50.55(e)(2).
102.
21 C.F.R. § 50.54.
103.
EC Directive, art. 5(e).
104.
21 C.F.R. § 50.20.
105.
21 C.F.R. § 50.23.
106.
21 C.F.R. § 50.24.
107.
21 C.F.R. § 50.25(a)(7); EC Directive, art. 3.2(c).
108.
21 C.F.R. § 56.114; EC Directive, art. 7.
109.
21 C.F.R. §§ 50.23, 50.24, 56.104, 56.110.
110.
Compare 21 C.F.R. § 50.25(a)(6), with EC Directive, art. 6.3(h).
111.
EC Directive, arts. 3.2(f), 6.3(i).
112.
Institute of Medicine, supra note 41, at 188-95. If research is conducted negligently, the researcher or sponsor may be liable for injury caused by the negligence under regular state tort law.
113.
21 C.F.R. §§ 56.109(f), 312.66; EC Directive, art. 10(a).
114.
EC Directive, arts. 16, 17.
115.
EC Directive, art. 17.
116.
EC Directive, art. 18.
117.
21 C.F.R. §§ 312.33, 312.64(b).
118.
See Institute of Medicine, supra note 41, at 154-156; U.S. Food and Drug Administration, Draft Guidance of Clinical Trial Sponsors: On the Establishment of Clinical Trial Data Monitoring Committees (2001).
119.
EC Directive, art. 12.
120.
EC Directive, art. 15.
121.
21 C.F.R. §§ 312.42-312.48; EC Directive, art. 12.
122.
Government Accountability Office, High Risk Series: An Update, GAO-09-271 (2009), at 18.
123.
Peter B. Hutt, ‘The State of Science at the Food and Drug Administration’, 60 Admin. L. Rev. 431, 452-55 (2008).
124.
Id., at 450-59.
125.
21 U.S.C. § 356; 21 C.F.R. §§ 312.80-312.88.
126.
21 C.F.R. § 314.510.
127.
21 C.F.R. § 312.34.
128.
Peter S. Reichertz & Melinda S. Friend, ‘Hiding Behind Agency Discretion: The Food and Drug Administration’s Personal Use Drug Importation Policy’, 9 Cornell J. L. & Pub. Pol’y 493, 493-94 (2000).
129.
Government Accountability Office, Drug Safety: Improvement Needed in FDA’s Postmarket Decision-making and Oversight Process, GAO-06-402 (2006), at 36-38; Institute of Medicine, The Future of Drug Safety: Promoting and Protecting the Health of the Public (2006), §§ 5-1–5-17.
130.
Abigail Alliance for Better Access to Developmental Drugs v. von Eschenbach, 495 F.3d 695, 701 (D.C.Cir. 2007).
131.
Id., at 703, 713.
132.
See Lars Noah, Law, Medicine, and Medical Technology: Cases and Materials (2nd ed. 2007), at 826-41, 861-90.
133.
21 U.S.C. § 355(j).
134.
Lars Noah, supra note 132, at 890-908.
135.
Public Law 111-148, Title VII.
136.
See Alastair J.J. Wood, Jeffrey M. Drazen & Michael F. Greene, ‘A Sad Day for Science at the FDA’, 353(12) New Eng. J. Med. 1197, 1197-99 (2005).
137.
Government Accountability Office, Decision Process to Deny Initial Application for Over-the-Counter Marketing of the Emergency Contraceptive Plan B Was Unusual, GAO-06-109 (2006), at 13-28.
138.
Tummino v. Torti, 2009 WL 750004 (S.D.N.Y. 2009).

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Washington and Lee University School of Law, 24450, Lexington, VA, USA
Timothy Stoltzfus Jost

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Juristisches Seminar, Abt. Arzt- / Arzneimittelrecht, Univ. Göttingen, Platz der Göttinger Sieben 6, Göttingen, 37073, Germany
Erwin Deutsch
, Zentrum für Medizinrecht des Juristische, Universität Göttingen, Goßlerstraße 19, Göttingen, 37073, Germany
Gunnar Duttge
Juristische Fakultät, LS Strafrecht und Allg. Rechtstheorie, Universität Göttingen, Göttingen, Germany
Hans-Ludwig Schreiber
, Zentrum für Medizinrecht des Juristische, Universität Göttingen, Goßlerstraße 19, Göttingen, 37073, Germany
Andreas Spickhoff
Inst. Medizinrecht, Universität Mannheim, Mannheim, 68131, Germany
Jochen Taupitz

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Jost, T.S. (2010). Country Report U.S.A.. In: Deutsch, E., Duttge, G., Schreiber, HL., Spickhoff, A., Taupitz, J. (eds) Die Implementierung der GCP-Richtlinie und ihre Ausstrahlungswirkungen. Veröffentlichungen des Instituts für Deutsches, Europäisches und Internationales Medizinrecht, Gesundheitsrecht und Bioethik der Universitäten Heidelberg und Mannheim, vol 37. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-13177-6_9

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DOI: https://doi.org/10.1007/978-3-642-13177-6_9
Published: 12 January 2011
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