495 F.3d 695 (D.C. Cir. 2007), 04-5350, Abigail Alliance for Better Access to Developmental Drugs v. von Eschenbach

Docket Nº:04-5350.
Citation:495 F.3d 695
Party Name:ABIGAIL ALLIANCE FOR BETTER ACCESS TO DEVELOPMENTAL DRUGS and Washington Legal Foundation, Appellants v. Andrew von ESCHENBACH, In His Official Capacity as Commissioner, Food and Drug Administration and Michael O. Leavitt, In His Official Capacity as Secretary, U.S. Dept. of Health and Human Services, Appellees.
Case Date:August 07, 2007
Court:United States Courts of Appeals, Court of Appeals for the District of Columbia Circuit

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495 F.3d 695 (D.C. Cir. 2007)



Andrew von ESCHENBACH, In His Official Capacity as Commissioner, Food and Drug Administration and Michael O. Leavitt, In His Official Capacity as Secretary, U.S. Dept. of Health and Human Services, Appellees.

No. 04-5350.

United States Court of Appeals, District of Columbia Circuit.

August 7, 2007

Argued March 1, 2007

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Appeal from the United States District Court for the District of Columbia (No. 03cv01601).

J. Scott Ballenger argued the cause for appellants. With him on the briefs were Daniel J. Popeo, David A. Price, and Richard A. Samp.

Brian P. Brooks and Arthur W.S. Duff were on the brief for amici curiae John E. Calfee, et al. in support of appellants.

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John J. Edmonds was on the brief for amici curiae Emil Freireich and Stephen Strum in support of appellants.

Jonathan F. Cohn, Deputy Assistant Attorney General, U.S. Department of Justice, argued the cause for appellees. With him on the brief were Peter D. Keisler, Assistant Attorney General, Jeffrey A. Taylor, U.S. Attorney, Jeffrey S. Bucholtz, Principal Deputy Assistant Attorney General, Michael J. Ryan and Rhonda C. Fields, Assistant U.S. Attorneys, Mark B. Stern and Scott R. McIntosh, Attorneys, Daniel Meron, General Counsel, U.S. Department of Health and Human Services, Eric M. Blumberg, Deputy Chief Counsel for Litigation, and Karen E. Schifter, Associate Chief Counsel. R. Craig Lawrence, Assistant U.S. Attorney, entered an appearance.

Samuel D. Turner was on the brief for amici curiae American Society of Clinical Oncology, et al. in support of appellees.

William B. Schultz was on the brief for amici curiae National Organization for Rare Disorders, et al. in support of appellees.



GRIFFITH, Circuit Judge

This case presents the question whether the Constitution provides terminally ill patients a right of access to experimental drugs that have passed limited safety trials but have not been proven safe and effective. The district court held there is no such right. A divided panel of this Court held there is. Because we conclude that there is no fundamental right "deeply rooted in this Nation's history and tradition" of access to experimental drugs for the terminally ill, see Washington v. Glucksberg, 521 U.S. 702, 720-21, 117 S.Ct. 2258, 138 L.Ed.2d 772 (1997) (quoting Moore v. East Cleveland, 431 U.S. 494, 503, 97 S.Ct. 1932, 52 L.Ed.2d 531 (1977) (plurality opinion)), we affirm the judgment of the district court.



The Abigail Alliance for Better Access to Developmental Drugs (the "Alliance") is an organization of terminally ill patients and their supporters that seeks expanded access to experimental drugs for the terminally ill. The Food, Drug, and Cosmetic Act ("FDCA" or "Act"), however, generally prohibits access to new drugs unless and until they have been approved by the Food and Drug Administration ("FDA"). See 21 U.S.C. § 355(a). Gaining FDA approval can be a long process. First, an experimental drug's sponsor (e.g., a drug company) must submit an application for approval. See id. § 355(a). Because no drug may be approved without a finding of "substantial evidence that the drug will have the effect it purports or is represented to have," id. § 355(d)(5), an application must contain "full reports of investigations which have been made to show whether or not such drug is safe for use and whether such drug is effective in use," id. § 355(b)(1)(A). Such reports rely in large measure on clinical trials with human subjects.

But before a sponsor can even begin human testing, it must submit for the FDA's approval an investigational new drug application ("IND"), see id. § 355(i)(1); see also 21 C.F.R. pt. 312,

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containing detailed information establishing that human testing is appropriate, see 21 C.F.R. § 312.23. Once the application for human testing has been approved, see id. § 312.20, several phases of clinical testing begin. The Alliance's amended complaint alleges that this testing process is an extremely lengthy one, requiring nearly seven years for the average experimental drug.1 Am. Compl. ¶ 15.

Clinical testing for safety and effectiveness requires three or sometimes four phases. See 21 C.F.R. § 312.21. Phase I involves the initial introduction of a new drug into human subjects. A Phase I study usually consists of twenty to eighty subjects and is "designed to determine the metabolism and pharmacologic actions of the [new] drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness." Id. § 312.21(a)(1). Although gathering data on effectiveness may be part of Phase I, its primary focus is to determine whether the drug is safe enough for continued human testing. See id. Phase II studies are "well controlled" and "closely monitored" clinical trials of no more than several hundred subjects, used to evaluate both the "effectiveness of the drug for a particular indication" and its "common short-term side effects and risks." Id. § 312.21(b).

Phase III studies are expanded clinical trials of several hundred to several thousand subjects designed to "gather ... additional information about effectiveness and safety that is needed to evaluate the overall benefit-risk relationship of the drug and to provide an adequate basis for physician labeling." Id. § 312.21(c).2 At any time during the clinical trials, a drug sponsor is required to notify the FDA of "[a]ny adverse experience associated with the use of the drug that is both serious and unexpected," id. § 312.32(c)(1)(A), and the FDA may order a "clinical hold" halting the trials if it determines that safety concerns so warrant, id. § 312.42. To guide the clinical testing process, Congress has directed the FDA to establish "[s]cientific advisory panels" to "provid[e] expert scientific advice and recommendations to the Secretary regarding a clinical investigation of a drug or the approval for marketing of a drug." 21 U.S.C. § 355(n)(1). These panels must include scientists from a variety of disciplines. See id. § 355(n)(3).3

Terminally ill patients need not, however, always await the results of the clinical testing process. The FDA and Congress have created several programs designed to

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provide early access to promising experimental drugs when warranted. For example, under the "treatment IND" program, the FDA may approve use of an investigational drug by patients not part of the clinical trials for the treatment of "serious or immediately life-threatening disease[s]" if there exists "no comparable or satisfactory alternative drug or other therapy," 21 C.F.R. § 312.34(a), (b)(1)(i)-(ii); if "[t]he drug is under investigation in a controlled clinical trial," id. § 312.34(b)(1)(iii); and if the drug's sponsor "is actively pursuing marketing approval of the investigational drug with due diligence," id. § 312.34(b)(1)(iv). The FDA reserves the right, however, to deny any treatment IND request if (1) the agency believes there is no "reasonable basis" to conclude that the drug is effective; or (2) granting the request "[w]ould ... expose the patient[ ] ... to an unreasonable and significant additional risk of illness or injury." Id. § 312.34(b)(3). Sponsors may not profit from any approved treatment IND program and may only "recover costs of manufacture, research, development, and handling of the investigational drug." Id. § 312.7(d)(3).4


Concluding that the FDA's current process for early access to new drugs was inadequate to meet the needs of its terminally ill members, the Alliance submitted its own proposals to the FDA. Those proposals culminated in a "citizen petition" to the FDA, see 21 C.F.R. § 10.25, arguing that there is a "different risk-benefit tradeoff facing patients who are terminally ill and who have no other treatment options." Abigail Alliance Citizen Petition, In re Tier 1 Initial Approval Program to Expedite the Availability of Lifesaving Drugs 9 (June 11, 2003). Although the Alliance agreed that "[e]xtensive marshalling of evidence regarding drug interactions, dose optimization, and the like" is "appropriate for new drugs to treat patients with other alternatives ...[,] these steps may well entail a delay that is fatal" for terminally ill patients. Id. The Alliance contended that these patients "should have the ability to opt for a new treatment that has met a lower evidentiary hurdle with respect to safety and efficacy." Id. The Alliance's proposal suggested that the FDA allow early access based upon "the risk of illness, injury, or death from the disease in the absence of the drug." Id. at 4. Accordingly, the Alliance requested that the FDA promulgate new regulations that would allow sponsors to market experimental drugs, under some circumstances, after the completion of Phase I trials.

The FDA never responded to the Alliance's citizen petition, but did respond to the Alliance's earlier submissions. After noting that a number of senior FDA officials

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had reviewed those submissions, the agency concluded that the Alliance "raised several important questions about expanded access that we believe deserve further consideration, " but questioned whether the specific proposal put forward by the Alliance "would have the intended desirable effects for patients." Letter from Peter J. Pitts, Associate Commissioner for External Relations, Department of Health and Human Services, to Frank Burroughs, President, Abigail Alliance for Better Access to Developmental Drugs 3 (Apr. 25, 2003). The officials concluded that the early access proposed by the Alliance "points to an area of significant range of opinion...

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