FDA's proposed regulations to expand access to Investigational drugs for treatment use: The status quo in the guise of reform

Food and Drug Law Journal

Volumn 64, Issue 1, 2009, Pages 183-223

  Rossen, Benjamin R ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

ACQUIRED IMMUNE DEFICIENCY SYNDROME; CANCER THERAPY; CLINICAL RESEARCH; CONSUMER; DRUG APPROVAL; DRUG CLASSIFICATION; DRUG COST; DRUG LEGISLATION; DRUG RESEARCH; DRUG USE; FOOD AND DRUG ADMINISTRATION; HEALTH CARE ACCESS; REVIEW;

ACQUIRED IMMUNODEFICIENCY SYNDROME; ANTINEOPLASTIC AGENTS; CLINICAL TRIALS AS TOPIC; DRUG APPROVAL; DRUG COSTS; DRUGS, INVESTIGATIONAL; HEALTH CARE REFORM; HEALTH SERVICES ACCESSIBILITY; HISTORY, 20TH CENTURY; HUMANS; INVESTIGATIONAL NEW DRUG APPLICATION; LEGISLATION, DRUG; NEOPLASMS; ORPHAN DRUG PRODUCTION; TERMINALLY ILL; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION;

EID: 61949320185     PISSN: 1064590X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (471)

1. Mr. Rossen was a Harvard Law School student when this article was written. He was the first place winner in the 2008 H. Thomas Austern Memorial Writing Awards Competition long paper.
2. Expanded Access to Investigational Drugs for Treatment Use, 71 Fed. Reg. 75,147 (proposed Dec. 14, 2006) (to be codified at 21 C.F.R. pt. 312) [hereinafter Proposed Rules to Expand Access].
3. Charging for Investigational Drugs, 71 Fed. Reg. 75,168 (proposed Dec. 14, 2006) (to be codified at 21 C.F.R., pt. 312) [hereinafter Proposed Rules for Charging].
4. See infra notes 211 to 270, Section IV, and accompanying text.
5. See Press Release, FDA Proposes Rules Overhaul to Expand Availability of Experimental Drugs (Dec. 11, 2006) available at http://www.fda.gov/bbs/topics/NEWS/2006/NEW01520.html.
6. Although Congress had enacted various drug regulation statutes during the 19th century, the 1906 Act can fairly be described as the birth of the modern era of food and drug regulation. For a discussion of the first drug regulation in the United States, see Heath, Wesley J., America's First Drug Regulation Regime: The Rise and Fall of the Import Drug Act of 1848, 59 FOOD & DRUG. L.J. 169 (2004).
7. For additional background, see Hutt, Peter Barton, Drug Regulations in the United States, 2 INTL. J. OF TECH. ASSESSMENT IN HEALTH CARE 619, 619 (1986).
8. Act of 1906, Pub. L. No. 59-384, 34 Stat. 768 (1906), repealed by Federal Food, Drug, and Cosmetic Act (FDCA), Pub L. No. 75-717, 52 Stat. 1040 (1938) (codified as amended at 21. U.S.C. §§ 301 et seq). The 1906 Act passed with overwhelming support despite heavy opposition from both food and drug manufacturers.
9. For a more detailed discussion of the origins of the 1906 Act see Janssen, Wallace F., The U.S. Food & Drug Law: How it Came; How it Works, 35 FOOD DRUG COSM. L.J. 132, 134(1980).
10. Among other things, the 1906 Act prohibited false and misleading labeling of drugs, the distribution of adulterated or misbranded drugs, and required labeling the quantity and ingredients of a small number of particularly dangerous drugs. See, e.g, Young , James Harvey, Pure Food: Securing the Federal Food and Drugs Act of 1906 (1989);
11. Zelenay, Jr., James L., The Prescription Drug User Fee Act: Is a Faster Food and Drug Administration Always a Better Food and Drug Administration?, 60 FOOD & DRUG L.J. 261, 263-264 (2005).
12. Wardell, William M. & Lasagna, Louis, REGULATION AND DRUG DEVELOPMENT 6 (1975).
13. For additional background about federal food and drug policy in the early 20th century, see Temin, Peter, Taking Your Medicine: Drug Regulation in the United States 35-37 (1980).
14. See, e.g., Dept. of Agric, 1917 Report of the USDA Bureau of Chemistry, in HUTT & MERRILL, FOOD AND DRUG LAW: CASES AND MATERIALS 11 (2d ed. 1991).
15. See Janssen, supra note 6, at 135-137 (discussing defeat of proposed food and drug reforms in 1933 in the wake of massive opposition by the drug and advertising industries).
16. See, e.g., Greenberg, Michael D., AIDS, Experimental Drug Approval, and the FDA New Drug Screening Process, 3 N.Y.U. J. LEGIS. & PUB. POLY 295, 302 (2000).
17. For a detailed description of the sulfanilamide tragedy and the federal response, see Ballentine, Carol, Taste of Raspberries, Taste of Death: The 1937 Elixir Sulfanilamide Incident, FDA CONSUMER MAGAZINE (Jun. 1981) available at http://www.fda.gov/oc/history/ elixir.html.
18. See Ballentine, supra note 12.
19. See also Temin, supra note 9 at 43.
20. Ballentine, supra note 12.
21. Id.
22. Id.
23. See also Report of the Sec'y of Agric. on Deaths Due to Elixir Sulfanilamide, S. Doc. No. 75-124, at 1-3 (2d Sess., (1937)).
24. Ballentine, supra note 12.
25. FDCA, Pub. L. No. 75-717, 52 Stat. 1040 (1938) (codified as amended at 21 U.S.C. §§ 301 et seq. [hereinafter FDCA].
26. FDCA § 505 (current version at 21 U.S.C. § 355 (2000).
27. The FDCA defined a "new drug" as " 1) Any drug the composition of which is such that such drug is not generally recognized, among experts qualified by scientific training and experience to evaluate the safety of drugs, as safe for use ⋯;or 2) Any drug the composition of which is such that such drug, as a result of investigations to determine its safety for use under such conditions, has become so recognized, but which has not, otherwise than in such investigations, been used to a material extent or for a material time under such conditions." FDCA, Ch. 675, § 201(p), 52 Stat. 1040, 1042 (1938).
28. Id. at § 505(a).
29. Id. at § 505(b).
30. Id. at § 505(c).
31. Id. at § 505(i).
32. Greenberg, supra note 12, at 302-303.
33. See, e.g., Teflf, Harvey & Munro, Colin R., Thalidomide: The Legal Aftermath 1-10 (1976).
34. For a detailed history of the Thalidomide crisis, see The Insight Team of the SUNDAY TIMES OF LONDON, Suffer the Children: The Story of Thalidomide (1979).
35. See Zelenay, supra note 7, at 265.
36. Bren, Linda, Frances Oldham Kelsey: FDA Medical Reviewer Leaves Her Mark on History, FDA CONSUMER MAGAZINE (Mar.-Apr. 2001) available at http://www.fda.gov/fdac/features/2001/201-kelsey. html.
37. See also Temin, supra note 9, at 123.
38. Temin, supra note 9, at 123.
39. Id. at 124.
40. See 108 CONG. REC. 21,070 (1962) (statement of Rep. Reuss) (arguing that the Thalidomide tragedy demonstrated need for increased FDA authority to prevent a similar incident).
41. See also Zelenay, supra note 7, at 266.
42. Pub. L. No. 87-781, 76 Stat. 780 (1962) (codified as amended in scattered sections of 21 U.S.C. §§ 301-381). For a detailed description of the origins and effects of the Drug Amendments of 1962, see Note, Drug Efficacy and the 1962 Drug Amendments, 60 GEO. L.J. 185 (1972).
43. Drug Amendments of 1962, § 102(c), amending FDCA of 1938, §505(d).
44. Id. at § 104(b), amending FDCA of 1938, § 505(c).
45. Id. at § 102(b), amending FDCA of 1938, § 505(i).
46. See Jordan, David W., International Regulatory Harmonization: A New Era in Prescription Drug Approval, 25 VAND J. TRASNAT'L L. 471, 478 (1992).
47. Drug Amendments of 1962 at § 102(b).
48. See 21 C.F.R. §§ 312.20-312.130 (2007).
49. See 21 C.F.R. §§ 312.20-312.38 (2007).
50. See 21 C.F.R. § 312.23(a)(8) (2007) (mandating disclosure of pharmacological and toxicological effects on laboratory animals).
51. See 21 C.F.R. § 312.22 (2007). The IND application must additionally include general information about the drug sponsor and any planned clinical investigations, protocols for the planned studies, detailed information about the drug's chemical nature and any human experience with the drug, and any other relevant information about the drug. See 21 C.F.R. § 312.23.
52. See Zelenay, supra note 7, at 267.
53. See 21 C.F.R. § 312.21 (2007). After submitting the IND application, a drug sponsor must wait 30 days to allow FDA to review the application. 21 C.F.R. § 312.40(b)(1) (2007). If FDA responds favorably, or does not respond within the 30-day time period, the sponsor may begin clinical investigations pursuant to the standards set forth in the IND application and in agency regulations.
54. See 21 C.F.R. §§ 312.40(b), 312.50 (2007).
55. 21 C.F.R. § 312.21.
56. See Greenberg, supra note 12, at 304.
57. See, e.g., McCabe, Alison R., Note, A Precarious Balancing Act: The Role of FDA as Protector of Public Health and Industry Wealth, 36 SUFFOLK U. L. REV. 787, 790 n.26 (2003) (citing average of 12 months for Phase I testing).
58. Cf. Walsh, Charles J. & Pyrich, Alyssa, Rationalizing the Regulation of Prescription Drugs and Medical Devices; Perspectives on Private Certification and Tort Reform, 48 RUTGERS L. REV. 883, 906 (1995) (stating typical Phase I tests of approximately six months).
59. 21 C.F.R. §312.21(b).
60. Id.
61. Id.
62. See Zelenay, supra note 7 at 267 (stating average Phase II testing lasts for two years).
63. See also Walsh & Pyrich, supra note 46, at 907 (reporting average length of 18 months for Phase II trials).
64. 21 CFR. § 312.21(c).
65. Id.
66. Id.
67. See Zelenay, supra note 7 at 267.
68. See also McCabe, supra note 46, at 790, n.26.
69. 21 U.S.C. § 355(b)( 1 )(A) (2000).
70. See also 21 C.F.R. § 314.50 (2007). Some drugs, such as generic copies of existing brand name drugs, are eligible to file an abbreviated new drug application (ANDA), which requires substantially less information, in order to expedite the approval process. 21 U.S.C. § 355(j) (2000); 21 C.F.R. § 314.92(a) (2007).
71. See 21 U.S.C. § 355(b);
72. C.F.R. § 314.50. The application must include 1) full reports from the preclinical and clinical trials which have been made to show whether the drug is safe and effective for use; 2) a full list of the drug's ingredients or components; 3) a full statement of the drug's composition; 4) a full description of manufacturing, processing, and packaging methods and controls; 5) any samples of the drug or of the articles used as components in the drug as may be required by FDA; and 6) samples of the proposed labeling. The NDA must additionally disclose all investigators who worked on the clinical trials and their reports, as well as the patent number and expiration dates of any patents related to or impacted by the drug under consideration. 21 U.S.C. § 355(b)(1); 21 C.F.R. § 314.53(b) (2007).
73. 21 U.S.C. § 355(c)(1).
74. 21 C.F.R. §314.125 (2007).
75. See Zelenay, supra note 7, at 268.
76. Id. at 268-269. Other limitations can arise even after approval of the NDA. FDA can withdraw or suspend approval at any time if new evidence suggests the drug is not safe or effective.
77. See 21 U.S.C. § 355(e). FDA therefore requires sponsors to provide periodic reports about any adverse effects associated with the drug.
78. See FDA, U.S. Dep't of Health & Human Servs., Managing the Risks from Medical Product Use: Creating a Risk Management Framework 52 (1999), available at: http://www.fda. gov/oc/tfrm/1999report.html. Additionally, FDA can require the drug manufacturer to conduct "Phase IV" postmarket surveillance studies to obtain additional safety and effectiveness data.
79. See 21 C.F.R. § 310.303-310.305 (2007).
80. See also Zelenay, supra note 7, at 270.
81. See Revitalizing New Product Development From Clinical Trials Through FDA Review: Hearing on S. 1477 Before the Senate Comm. on Labor and Human Resources, 104th CONG. 219-230 (1996) (statement of Fred W. Lyons, Jr., Chairman, Hoechst Marion Roussel, Inc.). For a summary of the various barriers to drug development,
82. see Greenberg, supra note 12.
83. See Drugs and Biologies: Hearings Before the Subcomm. oh Oversight and Investigations of the House Comm. on Commerce, 104th CONG. 1-2 (1995) (statement of Congressman Joe Barton).
84. See HUTT, MERRILL & GROSSMAN, FOOD AND DRUG LAW: CASES AND MATERIALS 776-778 (3d ed. 2007).
85. For further statistical information on the rising cost and delay of drug development, see generally Tufts Center for the Study of Drug Development, Longer Clinical Times are Extending Time to Market for New Drugs in U.S., 1 IMPACT REP., No. 6 (Nov./Dec. 2005);
86. DiMasi, Joseph A., New Drug Development in the United States 1963 to 1999, 69 CLINICAL PHARMACOLOGY & THERAPEUTICS 286 (2001).
87. For a comprehensive discussion of the ways in which the rise of AIDS challenged the traditional paradigm of FDA's drug approval scheme, see Greenberg, supra note 12.
88. See Arno, Peter S. & Feiden, Karyn L., Against the Odds: The Story of AIDS Drug Development. Politics, and Profits 15-17(1992).
89. Id. at 2-4.
90. Id. at 4.
91. Greenberg, supra note 12, at 309.
92. Id. at 310.
93. See also Arno & Feiden, supra note 65, at 4-5.
94. Greenberg, supra note 12, at 310.
95. Id. at 311.
96. Id. at 311 (describing treatment with remedies such s AL-721, derived from egg yolks, attempts by persons with AIDS to synthesize remedies using "kitchen chemistry," and the rise of black market buying clubs to facilitate purchase of drugs available overseas.
97. See also Arno & Feiden, supra note 65, at 60-70.
98. See Greenberg, supra note 12, at 310-312.
99. Id. at 311-312.
100. See also Arno & Feiden, supra note 65, at 65-68, 73-82.
101. See Greenberg, supra note 12, at 312.
102. Id. at 315.
103. See infra notes 134 to 158, Section III, and accompanying text.
104. See21 C.F.R. §312.80(2007).
105. See21 C.F.R. § 314.500 (2007) (providing for accelerated approval of drugs); 21 C.F.R. § 601.4 (2007) (providing for accelerated approval of biologicals, such as vaccines.)
106. Subpart E established a variety of measures to expedite review of new drugs for serious diseases such as AIDS, including early and repeated FDA consultation with pharmaceutical developers to speed the clinical trial process, consolidation of Phase II and III clinical testing, and use of increased "Phase IV" postmarketing trials to postpone the burden of additional safety research until after approval.
107. See 21 C.F.R. § 312.82 (2007) (early consultation between FDA and drug sponsors); 21 C.F.R. § 312.87 (2007) (FDA involvement in clinical trials); 21 C.F.R. § 312.85 (2007) (Phase IV postmarketing trials). Accelerated approvals regulations went even further, allowing for the use of "surrogate endpoints" in clinical trials, allowing FDA to approve a drug based on measurements other than increased patient survival, such as measuring CD4 cell counts in AIDS patients.
108. See21 C.F.R. § 314.510 (2007).
109. See Expanded Availability of Investigational New Drugs Through a Parallel Track Mechanism for People With AIDS and other HIV-Related Disease, 57 Fed. Reg. 13,250 (1992).
110. The parallel track policy, while similar to the Treatment IND regulations, derived from an earlier expanded access collaboration with the NCI, described infra notes 173 to 182, Section III, and accompanying text. For a more detailed description of the parallel track policy,
111. see infra notes 163 to 172, Section III, and accompanying text.
112. Greenberg, supra note 12, at 328.
113. See infra, Section III.
114. See HUTT, MERRILL & GROSSMAN, supra note 63 at 652.
115. See infra, Section III.
116. See Proposed Rules to Expand Access, supra note 1, at 75,149.
117. FDA MA of 1997, Pub. L. No. 105-115,111 Stat. 2296 (1997) (codified as amended in scattered sections of 21 U.S.C.) [hereinafter FDA MA].
118. FDA MA § 402, 21 U.S.C. § 360bbb (2000) (expanded access to unapproved therapies and diagnostics).
119. 21 C.F.R. §312.36 (2007).
120. 21 U.S.C. § 360bbb(a).
121. 21 C.F.R. §312.34(2007).
122. 21 U.S.C. §360bbb(c)(l)-(4).
123. Id. at § 360bbb(c)(5).
124. Id. at § 360bbb(c)(6).
125. Id. at § 360bbb(c)(7) (emphasis added).
126. Id. at § 21 U.S.C. § 360bbb(b).
127. See Proposed Rules to Expand Access, supra note 1, at 75,148.
128. See also HUTT, MERRILL & GROSSMAN, 'supra note 63, at 653.
129. 21 U.S.C. § 360bbb(b).
130. See infra, Section IV.
131. Proposed Rules to Expand Access, supra note 1, at 75,149.
132. Id.
133. Proposed Rules for Charging, supra note 2.
134. See supra, notes 24 & 35 and accompanying text.
135. 21 C.F.R. § 130.2(a)(2)(1962).
136. See also HUTT, MERRILL & GROSSMAN, supra note 63, at 651.
137. HUTT, MERRILL & GROSSMAN, supra note 63, at 651.
138. Id.
139. 27 Fed. Reg. 7990 (Aug. 10, 1962), 28 Fed. Reg. 179 (Jan. 8, 1963), codified at 21 C.F.R. 130.3(a)(l 1), 130.3(d)(8) (1962)
140. See also HUTT, MERRILL & GROSSMAN, supra note 63, at 651.
141. HUTT, MERRILL & GROSSMAN, supra note 63, at 651.
142. See, e.g. Proposed Rules for Expanded Access, supra note 1, at 75,148;
143. see also FDA, Speeding Access lo Important Therapeutic Agents, http://www.fda.gov/oashi/speedaccess.html (last accessed Mar. 30, 2008);
144. HUTT, MERRILL & GROSSMAN, supra note 84 at 651;
145. Marlin, Myron L., Treatment INDs: A Faster Route to Drug Approval?, 39 AM. U. L. REV. 171, 187(1989);
146. Young, Frank E., Norris, John A., Levitt, Joseph A. & Nightingale, Stuart L., The FDA's New Procedures for the Use of Investigational Drugs in Treatment, 259 JAMA 2267 (Apr. 15, 1988) (describing instances of access to investigational drugs dating back to 1976).
147. See infra notes 195 to 203 and accompanying text.
148. See Young, supra note 109, at 2267.
149. Id.
150. Id.
151. See also FDA, Report to Congress: Patient Access to New Therapeutic Agents for Pediatric Cancer (Dec. 2003), available at: http://www.fda.gov/oashi/speedaccess.html (follow "Expanded Access" hyperlink) (last visited Mar. 30, 2008);
152. Proposed New Drug, Antibiotic and Biologic Drug Product Regulations, 48 Fed. Reg. 26,720, 26,728 (Jun. 9, 1983) (describing informal access to investigational drugs under a physician or commercial-sponsored IND or protocol where literature reflects that a new drug "shows promise for a serious disease").
153. Young, supra note 109 at 2267.
154. Proposed New Drug, Antibiotic and Biologic Drug Product Regulations, 48 Fed. Reg. at 26,729.
155. Id.
156. Id. at 26,730.
157. Id.
158. See FDA, Report to Congress: Patient Access to New Therapeutic Agents for Pediatric Cancer, supra note 113 at 13.
159. See HUTT, MERRILL & GROSSMAN, supra note 63, at 652.
160. See, e.g., FDA, Briefing Document for the ODAC: Single Patient Use of Investigational Cancer Agents (2000); available at http://www.fda.gov/OHRMS/DOCKETS/AC/01/briefing/3757b 1 .html (last accessed Mar. 31, 2008) [hereinafter Briefing Document for the ODAC].
161. See also HUTT, MERRILL & GROSSMAN, supra note 63 at 653 (noting agency use of single patient exceptions since 1962).
162. Briefing Document for the ODAC, supra note 121.
163. See FDA, Report to Congress: Patient Access to New Therapeutic Agents for Pediatric Cancer, supra note 113 at 13.
164. Id.
165. Id.
166. Briefing Document for lite ODAC, supra note 121.
167. See FDA, Physician Request for a Single Patient IND for Compassionate or Emergency Use, available at http://www.fda.gov/cder/cancer/ singlind.htm (last accessed Mar. 31, 2008).
168. Id.
169. See also FDA. Report to Congress: Patient Access to New Therapeutic Agents for Pediatric Cancer, supra note 113, at 13.
170. See. e.g. Kuromiya v. United States, 37 F. Supp 2d 717, 78 F. Supp. 2d 367 (E.D. Pa. (1999)) (upholding decision of Dept. of Health & Human Services (HHS) to cease enrolling participants in a medical marijuana program established under single patient INDs in 1978, and to gradually phase out the program as participants died or voluntarily left).
171. See 21 C.F.R. §312.42(2007). In Smith v. Shalala, 954 F. Supp. 1 (D.D.C. (1996)), the plaintiff, suffering from Hodgkin's disease, sought a preliminary injunction against FDA preventing the agency from terminating his use of Antineoplasatons, an unapproved drug improperly administered by his physician outside the provisions of an IND. The court denied the injunction, holding that, where a terminally ill patient had failed to make use of available FDA-approved drugs for his condition, the agency could lawfully disallow a single patient exception for an investigational drug, pursuant to 21 C.F.R. § 312.42(b)(l)(i).
172. See supra, notes 96 to 98 and accompanying text.
173. 21 U.S.C. § 360bbb(b).
174. Id.
175. 52 Fed. Reg. at 8820-8821 (Mar. 19 1987) (codified at 21 C.F.R. § 312.36).
176. See HUTT, MERRILL & GROSSMAN, supra note 63, at 653.
177. 21 U.S.C. §312.36.
178. See 21 C.F.R. § 56.102(d).
179. See 21 C.F.R. § 56.104(c).
180. Id.
181. FDA, Guidance for Institutional Review Boards and Clinical Investigators, 1998 Update, available at http://www.fda.gOv/oc/ohrt/irbs/ drugsbiologics.html#emergency (last accessed Mar. 31, 2008).
182. See 21 C.F.R. § 50.23(a).
183. 21 C.F.R. § 50.23(b).
184. 21 U.S.C. § 360bbb(a).
185. Id.
186. Pub L. No. 108-276, § 4(a), 118 Stat. 835 (2004).
187. 21 U.S.C. § 360bbb(3).
188. See 70 Fed. Reg. 5450 (Feb. 2, 2005), 70 Fed. Reg. 44,657 (Aug. 3, 2005).
189. See supra notes 115 to 117 and accompanying text.
190. See IND, Antibiotic and Biological Drug Product Regulations; Treatment Use and Sale, 52 Fed. Reg. 19,466 (May 22, 1987).
191. 21 C.F.R. §312.34.
192. Id.
193. 21 C.F.R. § 312.34(b)(2).
194. 21 C.F.R.§ 312.34(3)(i).
195. 21 C.F.R. §312.34(b)(3)(ii).
196. 21 C.F.R. §50 (2007). I5" 21 C.F.R. §56 (2007).
197. See21 C.F.R. § 312.34(c).
198. See21 C.F.R. § 312.7(d)(2).
199. See 21 C.F.R. § 312.7(d)(1).
200. 21 C.F.R. § 312.7(d)(3).
201. 21 U.S.C. § 360bbb(c).
202. See supra, notes 91 to 95 and accompanying text.
203. See, e.g., FDA Responds to Act Up Demands, FDA Talk Paper No. T88-74 (Oct. 5, 1988);
204. see also Thompson, Dick, Drugs from the Underground, TIME MAG., (July 10, 1989), at 49.
205. See Expanded Availability of Investigational New Drugs Through a Parallel Track Mechanism for People With AIDS and Other HIV-Related Diseases, 55 Fed. Reg. 20,856 (May 21, 1990).
206. See Expanded Availability of Investigational New Drugs Through a Parallel Track Mechanism forPeople With AIDS and other HIV-Related Diseases, 57 Fed. Reg. 13,250, 13,256(Apr. 15, 1992).
207. See Shulman, Sheila R. & Brown, Jeffrey S., The Food and Drug Administration's Early Access and Fast-Track Approval Initiatives: How Have They Worked?, 50 FOOD & DRUG L.J. 503, 509 (1995).
208. Expanded Availability of Investigational New Drugs Through a Parallel Track Mechanism for People With AIDS and other HIV-Related Diseases, 57 Fed. Reg. at 13256.
209. Id. at 13,257.
210. Id. at 13,258.
211. Id. at 13,257.
212. Id. See also Shulman & Brown, supra note 166 at 509.
213. Shulman & Brown, supra note 166, at 517.
214. See Anticancer Drug Development: Memorandum of Understanding with the National Institutes of Health, 44 Fed. Reg. 25,510 (May 1, 1979).
215. See, e.g., Young, supra note 109, at 2268.
216. See FDA, Report to Congress on Patient Access to New Therapeutic Agents for Pediatric Cancer, supra note 113 at 16.
217. See NCI, Understanding the Approval Process for New Cancer Treatments (Jan 6. 2004), available at: http://www.cancer.gov/ clinicaltrials/learning/approval-process-for-cancer-drugs/page4 (last accessed Apr. 1, 2008).
218. See Anticancer Drug Development: Memorandum of Understanding with the National Institutes of Health, 44 Fed. Reg. at 25,510:
219. see also HUTT, MERRILL & GROSSMAN, supra note 63. at 655.
220. See FDA., Report to Congress on Patient Access to New Therapeutic Agents for Pediatric Cancer, supra note 105, at 16.
221. Id.
222. ,80 See NCI. Understanding the Approval Process of New Cancer Treatments, supra note 176.
223. See Anticancer Drug Development: Memorandum of Understanding with the National Institutes of Health, 44 Fed. Reg. at 25,510.
224. See HUTT, MERRILL & GROSSMAN, supra note 63, at 656.
225. See Clinical Trial Subjects: Adequate FDA Protections?: Hearing Before the H. Comm. on Govt. Reform & Oversight, 105th CONG. 60-61 (1998) (Statement of Michael A. Friedman, MD, Lead Deputy Comm'r. of FDA).
226. Id.
227. Id.
228. Id.
229. See also HUTT, MERRILL & GROSSMAN, supra note 63 at 656.
230. HUTT, MERRILL & GROSSMAN, supra note 63, at 656.
231. See Clinical Trial Subjects: Adequate FDA Protections?, supra note 183, at 60-61 (Statement of Michael A. Friedman, MD) (describing large scale protocols for anti-retroviral drugs in which tens of thousands of patients were enrolled).
232. See HUTT, MERRILL & GROSSMAN, supra note 63 at 656.
233. See Clinical Trial Subjects: Adequate FDA Protections?, supra note 183, at 57 (Statement of Michael A. Friedman, MD).
234. See HUTT, MERRILL & GROSSMAN, supra note 63, at 656. A search on FDA's website for the exact phrase "compassionate use" uncovers more than 1,000 results.
235. H.R. REP. No. 97-840, at 11 (2d Sess. (1982)).
236. See Clinical Trial Subjects: Adequate FDA Protections?, supra note 183, at 58-59 (Statement of Michael A. Friedman, MD).
237. Id.
238. Orphan Drug Act of 1983, Pub. L. No. 97-414, 96 Stat. 2049 (1983) (codified as amended at 21. U.S.C. §§ 360aa-ee (2006)).
239. See generally, Rohde, David Duffield, The Orphan Drug Act: An Engine of Innovation? At What Cost?, 55 FOOD & DRUG L.J. 125, 126 (2000).
240. Id.
241. See also Kenny, Patricia J., The Orphan Drug Act Is it a Barrier to Innovation? Docs it Create Unintended Windfalls?, 43 FOOD DRUG COSM. L.J. 667 (1988).
242. Rohde, supra note 196 at 126.
243. See HUTT, MERRILL & GROSSMAN, supra note 63, at 656-657.
244. Id. at 657.
245. See also Perrin, Lois K., The Catch-22 For Persons With AIDS: To Have or Not To Have Easv Access to Experimental Therapies and Earlv Approval for New Drugs, 69 S.CAL. L.REV 105. 119(1995).
246. See 21 U.S.C. § 360dd.
247. Id.
248. See Orphan Drug Regulations, 57 Fed. Reg. 62,076 (Dec. 29, 1992) (codified at 21 U.S.C. § 316.40 (2007)).
249. See HUTT, MERRILL & GROSSMAN, supra note 63, at 657.
250. Id.
251. Id.
252. Id.
253. Id.
254. See FDA, Report to Congress. Patient Access to New Therapies for Pediatric Cancer, supra note 113, at 15.
255. Id.
256. SeeTerrizzi, Lisa, The Need for Improved Access to Experimental Drug Therapy: AIDS Activists and Their Call For a Parallel Track Policy, 4 ADMIN. L.J. 589, 608 (1991).
257. See Perrin, supra note 200, at 140.
258. See HUTT, MERRILL & GROSSMAN, supra note 63 at 654.
259. See Okie, MD, Susan, Access before Approve! A Right to Take Experimental Drugs?, 355 NEW ENG. J. MED. 437, 440 (Aug. 3, 2006);
260. Groopman, Jerome, The Right to a Trial?, THE NEW YORKER, (Dec. 18,2006).
261. 21 C.F.R. §312.34(b)(iv).
262. See Perrin, supra note 200, at 140 (noting that competition, financial status, and projected marketing demand can all affect a company's decision to pursue marketing approval.)
263. Id. at 141.
264. Proposed Rules to Expand Access, supra note 1, at 75,149,
265. see also Nat'l Coalition for Cancer Survivorship (NCCS) & Am. Soc'y of Clinical Oncology, Citizen Pet. to FDA, 1-2 (March 27, 2006) (Docket No. 2006P-0135) [hereinafter NCCS Citizen Pet.].
266. Proposed Rules to Expand Access, supra note 1, at 75149.
267. See Complaint, Abigail Alliance v. McClellan, 2003 WL 23781358, Civil Action No. 1:03CV 1601 ¶¶ 30, 32 (D.D.C., filed July 28, 2003).
268. Id. at ¶ 15.
269. See NCCS Citizen Pet, supra note 218, at 7.
270. See. e.g., Baldwin, Joyce, Demand Grows for Early Access to Promising Cancer Drugs, 94 J. NAT'L CANCER INST. 1668, 1670, (Nov. 20, 2002).
271. See also Gillis, Justin, Patients Press Pleas for Cancer Drugs; Experimental Medicine in Short Supply, WASH. POST, (Apr. 7, 2002) at Al.
272. See, e.g., Goetz, Thomas, Practicing Patients, NY TIMES MAG. (Mar. 23, 2008) (describing Patients Like Me.com, an online community in which patients share experiences with different treatments and compile hard data based on drugs, dosages, and effectiveness in relieving symptoms of illness.)
273. See also Cancer Action Now, http://www.canceractionnow.org (website for patient advocacy group detailing information for terminally ill patients about researching investigational therapies, finding clinical trials or expanded access programs, and navigating the regulatory landscape.).
274. Gillis, supra note 223 at Al.
275. Telephone Interview with Rick Hamm, Vice President and General Counsel, Dendreon Corp., in Seattle, WA, (Apr. 4, 2008) (on file with author).
276. Id.
277. Gillis, supra note 223 at Al.
278. Abigail Alliance & WLF, Citizen Pet. to FDA, In re Tier I Approval Program to Expedite the Availability of Lifesaving Drugs 1 (Jun. 11, 2003) (Docket No. 2003P-0274).
279. Id. at 9.
280. Id. Tiers 2 and 3 would consist of "Accelerated Approval" and "Full Approval," respectively, both already existing in current FDA regulations.
281. Id. at 5.
282. Id. at 5-6.
283. Id. at 4.
284. Letter from Peter J. Pitts, Associate Commissioner for External Relations, Department of Health and Human Services (HHS), to Frank Burroughs, President, Abigail Alliance for Better Access to Developmental Drugs 3 (Apr. 25, 2003).
285. Id. at 4.
286. Id.
287. Id. at 5.
288. Complaint, Abigail Alliance v. McClellan, supra note 220 at¶¶ 30, 32.
289. Abigail Alliance for Better Access to Developmental Drugs v. McClellan, No. 03-1601, 2004 WL 3777340, at * 1 (D.D.C. Aug. 30, 2004).
290. Abigail Alliance for Better Access to Developmental Drugs v. von Eschenbach, 445 F.3d 470, 486 (D.C. Cir. (2006)) [hereinafter Abigail I].
291. 5 21 U.S. 702, 710(1997).
292. Id. at 721 (quoting Moore v. City of East Cleveland, 431 U.S. 494, 503 (1977); Snyder v. Massachusetts, 291 U.S. 97 (1934)).
293. Id., (quoting Palko v. Connecticut, 302 U.S. 319, 325-26 (1937)).
294. Abigail I, 445 F.3d at 483. A detailed recounting of the substantive due process analysis applied in the Abigail cases goes beyond the scope of this article and can be found in numerous other sources.
295. See, e.g. Lee, Won Bok, Abigail Alliance v. von Eschenbach: Constitutional Rights of Terminally III Patients Reconsidered, 36 L.J. MED. & ETHICS 391 (Spring 2008);
296. Majority Upholds Restrictions on Access to Experimental Drugs, 26 BIOTECHNOLOGY L. REP. 469 (2007);
297. Kovatis, Stephen R., The Right to Live: Do the Terminally III Have a Constitutional Right to Use Experimental Drugs? Abigail Alliance v. von Eschenberg, 445 F.3d 470 (D.C. Cir. (2006)), 26 J. SCI. TECH. & ENVTL. L. 149 (Spring 2007).
298. Abigail I, 445 F.3d at 486.
299. See, e.g., Okie, supra note 214, (quoting William Schultz, former deputy commissioner for policy at FDA, describing the ruling as "a huge, huge, devastating decision")
300. See also Annas, George J., Cancer and the Constitution: Choice at Life's End, 357 NEW ENG. J. MED. 408, (Jul. 26, 2007) ("In direct response to Abigail Alliance, FDA proposed amending its rules to encourage more drug companies to offer their investigational drugs through compassionate use programs.");
301. Groopman, supra note 214, ("The opinion ⋯ shocked legal scholars and officials at the F.D.A., ⋯ .The agency, determined not to cede control of drug regulation to Congress or the courts, intends to release some of the proposals for public comment ⋯ .").
302. See Abigail Alliance for Better Access to Developmental Drugs v. von Eschenbach, 495 F.3d 695 (DC Cir. (2007)) (en banc), cert, den'd 128 S.Ct. 1069 (2008) [hereinafter Abigail 11].
303. Id. at 703.
304. Id. at 703-706.
305. Id. at 712 (citing Glucksberg, 521 US. at 722).
306. Id.
307. Id. at 713.
308. ACCESS Act, S. 1956 & H.R. 6303, 109th Cong. (2005).
309. Id. at §2(1).
310. Id. at § 2(4).
311. Id. at § 3(b)(1)(A). (i)-(ii).
312. Id. at§3(b)(l)(A)(ii).
313. Id. at§3(b)(l)(A)(iii).
314. Id. at § 3(b)(2).
315. Id. at § 3(b)(5)(B).
316. Id. at § 4.
317. NCCS Citizen Pet., supra note 218.
318. Id. at 1.
319. Id. at 4.
320. Id. at 3.
321. Id. at 5.
322. Id.
323. Id.
324. Id. at 7.
325. Proposed Rules to Expand Access, supra note 1;
326. Proposed Rules for Charging, supra note 2.
327. Proposed Rules to Expand Access, supra note 1, at 75,150.
328. Proposed Rules for Charging, supra note 2, at 75,171.
329. Proposed Rules to Expand Access, supra note 1, at 75,149.
330. Id.
331. Id. at 75,149-175,150.
332. Id. at 75,150-175,151. Because of "the difficulty of specifically describing the criteria that characterizes a 'serious disease or condition,'" the proposal does not provide a definition but rather points to other agency documents in which the term is described.
333. See FDA Guidance for Industry, Fast Track Drug Development Programs Designation. Development and Application Review, 63 Fed. Reg. 64.093 (Nov. 18, 1998). FDA suggests that the term applies to conditions that have "an important effect on functioning," such as stroke, schizophrenia or rheumatoid arthritis, or have important effects on "other aspects of quality of life," such as chronic depression or seizures.
334. See Proposed Rules to Expand Access, supra note 1 at 75,151. The proposed rules define "immediately life-threatening" as "a stage of disease in which there is reasonable likelihood that death will occur within a matter of months or in which premature death is likely without early treatment."Id. at 75,166;
335. proposed 21 C.F.R. § 312.300(b). FDA states that a "lack of comparable or satisfactory therapeutic alternatives" ordinarily means either no available therapy to treat the patient's condition exists, or that the patient has tried available therapies and either failed to respond adequately or proved intolerant to them. Generally, "available" refers only to FDA approved products labeled for treatment for the patient's disease or condition, but in some cases could refer either to treatment not regulated by FDA, such as surgery, or off-label use supported by "compelling literature evidence." Id. at 75,151.
336. See also FDA Guidance for Industry. Available Therapy, 69 Fed. Reg. 44,039 (July 23, 2004).
337. Proposed Rules to Expand Access, supra note 1, at 75,151; proposed 21 C.F.R. § 312.305(a)(2).
338. Id. at proposed 21 C.F.R. § 312.305(a)(3).
339. Id.
340. Id. The new proposal continues the use of the terms "treatment IND" or "treatment protocol" for expanded access programs making investigational drugs available to large patient populations for treatment use.
341. Id.
342. Id.
343. Id.
344. Id. at 75,151 -175,152; proposed 21 C.F.R. § 312.305(b)(1).
345. Id. at 75,152; proposed 21 C.F.R. § 312.305(b)(2)-(3).
346. Id. at proposed 21 C.F.R. § 312.305(c).
347. Id. at proposed 21 C.F.R. §312.305(d). The proposed rule contains two exceptions about when access may begin. First, proposed § 312.305(d)(2)(i) provides that treatment of an individual patient in an emergency situation may begin upon authorization by a FDA reviewing official. Second, proposed § 312.305(d)(2)(ii) requires a 30-day wait to begin any Treatment IND or treatment protocol use even if an existing IND is on file with FDA, in order to build in sufficient time for the agency to review proposed expanded access uses that can potentially affect large numbers of patients.
348. Id. at 75,153; proposed 21 CF.R. § 312.310(a)(1).
349. Id. at proposed 21 C.F.R.§ 312.310(a)(2).
350. Id. at proposed 21 C.F.R. § 312.310(b).
351. Id.
352. Id. at proposed 21 C.F.R. § 312.310(c). The rules further allow FDA to require a sponsor to monitor extended individual patient expanded access use. and would require the sponsor or physician to provide FDA with a written summary of the results of the treatment use, including any unexpected adverse events.
353. Id. at proposed 21 C.F.R. § 312.310(c)(2)-(3). A "significant number of similar requests" for individual access-such as, perhaps, ten requests for the same treatment within six months-may cause FDA to request the sponsor to submit a protocol under § 312.315 or § 312.320 of the proposed rules.
354. Id. at proposed 21 C.F.R. § 312.310(d).
355. Id. at 75,154; proposed 21 C.F.R. § 312.310(d)(1).
356. Id. at proposed 21 C.F.R. § 312.310(d)(2). FDA insists that such emergency use will be limited only to "true emergencies" in which there is no time to file a prior written submission, and notes that FDA's experience with emergency use indicates that a follow-up written submission is rarely provided after emergency use is obtained.
357. Id.
358. Id. at proposed 21 C.F.R. § 312.315.
359. Id.
360. Id. at proposed 21 C.F.R. § 312.315(a)(1).
361. Id. at proposed 21 C.F.R. § 312.315(a)(2). Patients may not be eligible for clinical trials because they have a different disease or stage of disease from the one under investigation, or do not otherwise meet particular enrollment criteria; because enrollment in the trial is closed; or because the trial site is too geographically inaccessible for the patient.
362. Id.
363. Id. at proposed 21 C.F.R. § 312.315(a)(3). An approved drug might cease to be marketed for safety reasons or for failure to meet conditions of the drug approval, 21 C.F.R § 312.315(a)(3)(f), or because the drug contains the same active moiety as an approved drug product that is unavailable for marketing, 21 C.F.R. § 312.315(a)(3)(ii). Where the drug is not available due to safety concerns, the rules provide that a subset of patients may exist for whom the benefits of treatment use outweigh the potential safety risks.
364. See Proposed Rules for Expanded Access, supra note 1, at 75,154, proposed 21 C.F.R. § 312.315(a)(3)(i).
365. Proposed Rules to Expand Access, supra note 1, at 75,154; proposed 21 C.F.R. § 312.315(b).
366. Id. at proposed 21 C.F.R. § 312.315(b)(1). As in the traditional model of drug development, FDA requires more data about an investigational treatment as the number of patients exposed to potential risks increases. Therefore, more clinical experience is required for an intermediate-size patient population than would be for individual patient expanded access.
367. Id. at 75,154.
368. Id. at proposed 21 C.F.R. § 312.315(b)(2).
369. Id. at proposed 21 C.F.R. § 312.315(c)(1).
370. Id. at proposed 21 C.F.R. § 312.315(c)(2).
371. Id. at proposed 21 C.F.R. § 312.315(c)(3).
372. Id. at 75,155; proposed 21 C.F.R. §312.315(d)(1). For instance, if thedrug is not being developed, the agency will consider whether clinical studies are possible to develop the drug for marketing. Proposed 21 C.F.R. § 312.315(d)(l)(i). If the drug is being actively developed, FDA will consider whether the expanded access use is interfering with ongoing investigations. Proposed 21 C.F.R. § 312.315(d)(l)(ii). If the patient population increases in size, FDA will consider whether the sponsor should provide treatment under a treatment IND or treatment protocol under proposed § 312.320. Proposed 21 C.F.R. § 312.315(d)(l)(iii).
373. Proposed Rules for Expanded Access, supra note 1 at 75,155; proposed 21 C.F.R. § 312.315(d)(2).
374. See id. at 75,154.
375. See supra notes 150 to 154 and accompanying text.
376. Proposed Rules to Expand Access, supra note 1, at 75,155; proposed 21 C.F.R. § 3I2.20(a)(l)(i).
377. Id. at proposed 21 C.F.R. § 312.20(a)(l)(ii).
378. Id. at proposed 21 C.F.R. § 312.20(a)(2).
379. Id. at proposed 21 C.F.R. § 312.20(a)(3)(i).
380. Id. at proposed 21 C.F.R. § 312.20(a)(3)(H).
381. Id. at proposed 21 C.F.R. § 312.320(b) (requiring information adequate to satisfy FDA that the general criteria for expanded access use and those specific to the treatment IND or treatment protocol have been met.)
382. Id. at proposed 21 C.F.R. § 312.320(c).
383. Id. at 75,155.
384. Id.
385. Id.
386. Id. at 75,155-75,156.
387. See Proposed Rules for Charging, supra note 2.
388. Id. at 75,169. Drug sponsors might to charge for a third party's approved drug for use as an active control, or in combination with the sponsor's drug. Third parties conducting off-label use studies, or comparing the effectiveness of various drugs, might also seek to charge for drugs during clinical investigations.
389. Id.
390. Id. at 75,169-75,170.
391. Id. at 75,180, proposed 21 C.F.R. §312.8(a)(1). The new proposal requiring written authorization from FDA in order to charge changes the current treatment IND authorization, under which a sponsor could charge automatically 30 days after submission. FDA intends to review applications carefully to ensure compliance with all applicable criteria and that only permissible costs are recovered.
392. Id.
393. Id. at 75,170.
394. Id. at 75,180; proposed 21 C.F.R. § 312.8(b)(i)-(iii).
395. Id. at 75,171.
396. Id. at 75,181; proposed 21 C.F.R. § 312.8(b)(2).
397. Id. at proposed 21 C.F.R. § 312.8(b)(3). In the preamble, FDA notes that the sponsors of post-approval investigations are sponsor-investigators that do not conduct the research for purposes of commercialization and are therefore unlikely to recoup costs by marketing the drug upon approval.
398. Id. at 75,172.
399. Id. at 75,172, 75,181; proposed 21 C.F.R. § 312.2(c)(1).
400. Id. at 75,181; proposed 21 C.F.R. § 312.2(c)(2).
401. Id. at 75,172.
402. Id. at 75,181; proposed 21 C.F.R. § 312.8(c)(2)(i).
403. Id. at proposed 21 C.F.R. § 312.8(c)(2)(ii). Evidence could include "successful meetings with FDA before submission of an [NDA], submission of an NDA, or completion of other significant drug development milestones."
404. Id. at 75,172.
405. See 21 C.F.R. § 312.23(a)(3)(iv) (2007).
406. Proposed Rules for Charging, supra note 2, 71 Fed. Reg. at 75181; proposed 21 C.F.R. § 312.8(c)(2)(iii).
407. Id. at proposed 21 C.F.R. § 312.8(c)(3).
408. Id. at proposed 21 C.F.R. § 312.8(c)(4).
409. Id. at proposed 21 C.F.R. § 312.8(d).
410. Id. at proposed 21 C.F.R. § 312.8(d)(1).
411. Id. at 75,172, 75181; proposed 21 C.F.R. § 312.8(d)(l)(i).
412. Id. at proposed 21 C.F.R § 312.8(d)(l)(i).
413. Id. at proposed 21 C.F.R. § 312.8(d)(l)(i).
414. Id. at proposed21 C.F.R. § 312.8(d)(2). These costs would include "the costs of monitoring the expanded access IND or protocol, complying with IND reporting requirements, and other administrative costs directly associated with the expanded access."
415. Id.
416. Id. at proposed 21 C.F.R. § 312.8(d)(3).
417. See, e.g., FDA to let dying have experimental drugs, PHARMA MARKETLETTER, (Jan. 23, 2007).
418. Proposed Rules to Expand Access, supra note 1, at 75,149-75,150.
419. See Ames, George J., Cancer and the Constitution, 357 NEW ENG. J. MED. 408-413 (Jul. 26, 2007).
420. Id. But see "Pazdur's Message: Don't Fear Expanded Access Programs," DRUG INDUSTRY DAILY, (Mar. 13, 2008) (quoting Richard Pazdur, director of FDA's Office of Oncology Drug Products, urging industry "not to fear retaliation from [FDA] when side effects from drugs are discovered under expanded access programs.")
421. Telephone Interview with Steve Walker, Co-Founder, Abigail Alliance for Better Access to Developmental Drugs (Apr. 4, 2008) (on file with author).
422. See Arnst, Catherine, Dying Patients Fight the FDA, BUSINESS WEEK ONLINE (July 26, 2007), http://www.businessweek.com/technology/content/jul2007/tc20070724-550192.htm.
423. For background information on biotechnology, see generally Golden, John M., Biotechnology, Technology Policy and Patentability: Natural Products and Invention in the American System, 50 EMORY L.J. 101 (Winter, 2001).
424. Id. at 118.
425. See Mireles, Michael S., An Examination of Patents, Licensing, Research Tools, and the Tragedy of the Anticommons in Biotechnology Innovation, 38 U. MICH. J.L. REFORM 141, 163 (2004).
426. See also Smith, Mary Breen, Comment, An End to Gene Patents? The Human Genome Project Versus the United States Patent and Trademark Office's 1999 Utility Guidelines, 73 U. COLO. L. REV.747, 758;
427. Blowers, Stephen C, et. al, Guide to the IPO Value Journey, 284 (1999).
428. See, Mireles, supra note 357 at 164.
429. See Todd, Susan, Drugmakers Race for Cancer Vaccines, STAR-LEDGER (Newark, NJ), (Mar. 23, 2008).
430. See also Arnst, supra note 354.
431. Telephone Interview with Rick Hamm, supra note 226.
432. See Arnst, supra note 354;
433. Telephone Interview with Rick Hamm, supra note 226.
434. The advisory commi ttee voted 17-0 that Provenge was safe for use and 13-4 that the drug was effective.
435. See Provenge to See Early Results. FDA NEW DRUG DAILY BULLETIN, (Mar. 20, 2008).
436. See Arnst, supra note 354 (describing the Provenge "firestorm" resulting from FDA's decision to withhold approval. Prostate cancer activists and Dendreon investors have lobbied Congress, held demonstrations, and met with FDA Commissioner, Dr. Andrew von Eschenbach).
437. Telephone Interview with Rick Hamm, supra note 226.
438. Id.
439. See 2006 DENDREON CORP. ANNUAL REPORT 32, available at: http://www.dendreon.com (from home page, follow link to "View the 2006 Annual Report.) (noting accumulated deficit as of Dec. 31, 2006 was $392.4 million)
440. Telephone Interview with Rick Hamm, supra note 226.
441. See also Gonzalez, Angel, Dendreon Gathers $47 Million in Stock Sale, SEATTLE TIMES, (Apr. 4, 2008).
442. Gonzalez, supra note 368.
443. See Proposed Rules for Charging, supra note 2, at 75,181; proposed 21 C.F.R. § 312.8(d)(1).
444. 21 U.S.C. § 312.7(d)(3).
445. Telephone Interview with Rick Hamm, supra note 226.
446. Proposed Rules for Charging, supra note 2, at 75,169.
447. Telephone Interview with Rick Hamm, supra note 226.
448. See Comments on Docket Nos. 2006N-061 and -0062, RIN 0910-AF13 and AF-14, Terry Winters, PhD & Kameron Maxwell PhD, Vital Therapies Hybrid Liver Therapy, (Jan. 30, 2007).
449. Proposed Rules on Charging, supra note 2, at 75,177.
450. Proposed Rules to Expand Access, supra note 1 at 75,157.
451. See NCCS Citizen Pet., supra note 218.
452. See Press Release, Abigail Alliance for Better Access to Developmental Drugs, FDA Release of Draft Regulations for Treatment Use and Charging for Investigational Drugs, (Dec. 13, 2006) (on file with author).
453. See Comment of Mary K. Pendergast, President, Pendergast Consulting, Docket No. 2006N- 0062 and RIN 09I0-AF14, (Mar. 20, 2007) (on file with author).
454. Id. at 5-6. (Noting that although § 506(b)(2) of the FDCA allows FDA to determine whether there is "sufficient" evidence of safety and effectiveness to support use of an investigational drug, that section is embedded in another part of the law and "does not empower a risk determination").
455. Id. at 9.
456. Id.
457. See Mashaw, Rebecca, FDA's System for Access to Unapproved Drugs Broken, But Experts Question if Congress or "Abigail" Will Help, BIORESEARCH COMPLIANCE REPORT, (Mar. 1, 2007) at 1.
458. Id.
459. See, e.g., FDA, Innovation Stagnation, Challenge and Opportunity on the Critical Path to New Medical Products (2004) available at http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.pdf;
460. see also United States Government Accountability Office, New Drug Development, Report GAO-07-49. (2006).
461. See, Miller, MD, Richard A., Impact of FDA Regulation on Oncology Drug Research and Development (Mar. 14, 2008) available at http://www.aei.org/docLib/20080314-MillerPapcrl.pdf .
462. See FDA, Innovation Stagnation. Challenge and Opportunity on the Critical Path to New Medical Products, supra note 386 at ii.
463. Telephone Interview with Steve Walker, supra note 353.
464. Id.
465. See also Miller, supra note 387 at 8-9.
466. See FDA, FDA's Critical Path Initiative - Science Enhancing the Health and Weil-Being of All Americans, http://www.fda.gov/oc/initiatives/ criticalpath/initiative.html.
467. See FDA, Critical Path Opportunities List, http://www.fda.gov/oc/initiatives/criticalpath/reports/opp-list.pdf.
468. Id. at 8. The list also describes increased use of multiple endpoints and various methods of measuring patient response.
469. See Memorandum of Understanding Between the Food and Drug Administration and Duke University, 72 Fed. Reg. 65,745 (Nov. 23, 2007);
470. see also Clinical Trials Transformation Initiative, http://www.fda.gov/oc/initiatives/criticalpath/clinicaltrials.html.
471. Press Release, FDA, FDA and Duke Launch Public-Private Partnership to Modernize Clinical Trials (Nov. 26, 2007), available at http://www.fda.gov/oc/initiatives/criticalpath/partnership.html.