Vanda Pharm., Inc. v. Food & Drug Admin.

• Decision Date: 31 January 2020
• Docket Number: Civil No. 19-301 (JDB)
• Parties: VANDA PHARMACEUTICALS, INC., et al., Plaintiffs, v. FOOD AND DRUG ADMINISTRATION, et al., Defendants.
• Court: U.S. District Court — District of Columbia

436 F.Supp.3d 256

VANDA PHARMACEUTICALS, INC., et al., Plaintiffs,

v.FOOD AND DRUG ADMINISTRATION, et al., Defendants.

Civil No. 19-301 (JDB)

United States District Court, District of Columbia.

Signed January 31, 2020

Andrew A. Lyons-Berg, Michael Branch Kimberly, Paul Whitfield Hughes, III, McDermott Will & Emery LLP, Washington, DC, for Plaintiffs.

James William Harlow, David Michael Morrell, U.S. Department of Justice, Washington, DC, for Defendants.

MEMORANDUM OPINION

JOHN D. BATES, United States District Judge

In December 2018, the Food and Drug Administration placed a partial clinical hold on long-term human testing of the drug tradipitant. The hold was based on FDA's conclusion that it could not properly assess the risks of long-term tradipitant use in humans until the drug's sponsor, plaintiff Vanda Pharmaceuticals, Inc., conducted a long-term toxicity study on nonrodent animals. Vanda filed this lawsuit to challenge the clinical hold. Pending before the Court are Vanda's motion for summary judgment and FDA's cross-motion for summary judgment, as well as Vanda's motion to complete and supplement the administrative record and a motion by The Humane Society of the United States for leave to file an amicus brief.

For the reasons that follow, the Court will grant summary judgment to FDA and deny each of the other motions.

Background

A. Legal Framework

New drugs cannot be sold or distributed in interstate commerce without FDA approval. 21 U.S.C. § 355(a). To obtain FDA approval, drug sponsors must submit an application to FDA containing, among other things, data demonstrating that a new drug is safe and effective for human use. Id. § 355(b)(1). So that drug sponsors can obtain such data, the Federal Food, Drug, and Cosmetic Act ("FD&C Act") provides for a limited investigational exception to the ban on distribution of experimental drugs in interstate commerce. Id. § 355(i). Sponsors who wish to take advantage of this exception must submit an Investigational New Drug Application ("IND") to FDA containing "information on [the] design of the investigation and adequate reports of basic information ... necessary to assess the safety of the drug for use in clinical investigation." Id. § 355(i)(2).

By statute and regulation, FDA does not need to affirmatively approve INDs for sponsors to move ahead with investigational testing. Instead, testing may automatically begin 30 days after an IND is submitted, unless FDA places a clinical hold on testing. See id. § 355(i)(3)(A). FDA can choose to impose a full or partial clinical hold at "any time," id., for a variety of reasons, see 21 C.F.R. § 312.42(b)(iv), including if FDA concludes that an IND lacks "[a]dequate information about pharmacological and toxicological studies of the drug involving laboratory animals or in vitro," id. § 312.23(a)(8). Importantly, the "kind, duration, and scope of animal and other tests required varies with the duration and nature of the proposed clinical investigations." Id. § 312.23(a)(8). A primary purpose of this regulatory framework is to ensure that testing of a given drug does not "represent[ ] an unreasonable risk to the safety of the persons who are the subjects of the clinical investigation." 21 U.S.C. § 355(i)(3)(B).

B. Vanda's Tradipitant IND

Tradipitant is an experimental drug that has been studied as a possible treatment for a variety of disorders but has not yet been approved by FDA for any purpose. Remand Resp. at FDA-11109.¹ On September 2, 2016, plaintiff Vanda submitted IND 131545 to begin clinical trials of tradipitant as a treatment for gastroparesis

, a chronic but nonfatal digestive disorder that causes those suffering from it to experience nausea, vomiting, unusual feelings of fullness, and abdominal pain. Id. Vanda initially sought to conduct a 4-week clinical trial, supporting its proposal with animal toxicity studies that were "limited to durations of 6 months in rats and 3 months in dogs." Id. at FDA-11109–10. FDA allowed Vanda's proposed 4-week human trial to proceed. Id.

Then, on April 10, 2018, Vanda amended its study proposal, proposing a 12-month extension to the 4-week trial. Id. at FDA-11110. FDA informed Vanda that the 12-month extension was not permissible because, without a 9-month nonrodent toxicity study, FDA did not have sufficient data as to the safety or effects of long-term tradipitant use in humans. Id. On May 22, 2018, Vanda submitted another amendment, this time reducing the 12-month-extension proposal to 8 weeks. Id. FDA informed Vanda that that three-month trial (4 weeks plus the 8-week extension) was acceptable but reiterated that anything over three months could not move forward without long-term nonrodent studies. Id. at FDA-11110–11.

Later in 2018, Vanda twice more proposed 12-month extensions to its tradipitant trial; FDA continued to reject the extensions because of its concerns about proceeding without long-term nonrodent studies. Id. at FDA-11111. In December 2018, FDA staff consulted with members of FDA's Medical Policy and Program Review Council ("MPPRC"), who agreed with the staff view that a 9-month nonrodent study was necessary prior to allowing 12-month human trials to ensure humans were not put at undue risk. Id. at FDA-11111–12.

At that point, on December 19, 2018, FDA issued a formal decision placing a partial clinical hold on Vanda's proposed 12-month trial. Partial Clinical Hold Decision at FDA-10184. The decision noted that 9-month nonrodent toxicity studies "are required ... per the ICH Guidance for Industry: M3(R2) Nonclinical Safety Studies for the Conduction of Human Clinical Trials and Marketing Authorization for Pharmaceuticals." Id. at FDA-10185. The decision then cited a scientific study as summarizing the "rationale to support the ICH requirement." Id. It also cited a specific regulation, 21 C.F.R. § 312.42(b)(2)(i), and listed the particular deficiency that Vanda needed to correct: "Insufficient information to assess risks to human subjects; because you do not have adequate nonclinical safety data to support clinical trials beyond 3 months." Partial Clinical Hold Decision at FDA-10185.

C. The Present Lawsuit

Vanda filed this action on February 5, 2019, challenging FDA's partial clinical hold decision on two grounds: first, that FDA had failed to "articulate an adequate scientific basis" for its decision; and second, that FDA had allegedly applied the "non-binding ICH guidance as a binding regulation." Compl. [ECF No. 1] at 48. Just over a week later, FDA moved for a voluntary remand so it could have an "opportunity to address certain procedural issues" noted in Vanda's complaint. Mem. in Supp. of Defs.' Mot. for a Voluntary Remand ("Mot. to Remand") [ECF No. 6-1] at 2. In particular, FDA stated that it would "re-evaluate [Vanda's] scientific arguments and provide a full written explanation of the agency's analysis and ultimate position" and "review and clarify the regulatory basis for its decision, addressing the legal import of the guidance document." Id. at 6. This Court granted the remand motion to "allow FDA to cure its mistakes." Vanda Pharm. v. Food & Drug Admin., 2019 WL 1198703, at *2 (D.D.C. Mar. 14, 2019).

After completing its reevaluation of Vanda's extension proposals, FDA issued a lengthy "Remand Response," which consists of two basic parts. First, the Response analyzes Vanda's original submissions and concludes that existing tradipitant studies in nonrodents contain sufficient troubling indications of toxicity such that—while shorter-term human studies may be safe enough to proceed—FDA needs to see if those toxicity markers increase during long-term nonrodent studies before allowing long-term human studies. Remand Resp. at FDA-11115–20. Second, the Response sets out the scientific basis for a nine-month nonrodent study requirement as the scientific minimum for clinical investigations. Id. at FDA-11120–24.

As noted, both parties have now moved for summary judgment, Vanda has moved to supplement or complete the administrative record, and the Humane Society has requested leave to file an amicus brief. The Court heard oral argument on the motions for summary judgment on December 13, 2019.

Analysis: Motions for Summary Judgment

Vanda's motion for summary judgment argues that FDA's decision to impose a partial clinical hold lacked an articulated scientific basis and that the decision treated the ICH Guidance as binding. FDA's cross-motion argues that the Remand Response leaves no question as to the scientific basis for the hold and does not treat the ICH Guidance as binding. Before reaching the merits of these arguments, however, the Court first addresses Vanda's procedural arguments that it should not consider most, or even all, of the Remand Response.

A. Procedural Arguments Against the Remand Response

1. Post Hoc Rationalization

Vanda's first procedural argument is that virtually everything contained in the Remand Response is "impermissible post hoc rationalization." Pls.' Combined Resp./Reply Mem. Regarding Summ. J. ("Pls.' Resp.") [ECF No. 35] at 10. In Vanda's view, FDA relied exclusively on the ICH Guidance as the basis for the pre-remand partial clinical hold, and any new arguments contained in the Remand Response should be disregarded. See id.

In general, when a court "remand[s] for further explanation, it is incumbent upon the court to consider that explanation when it arrives." Menkes v. U.S. Dep't of Homeland Sec., 637 F.3d 319, 337 (D.C. Cir. 2011) (quoting Alpharma, Inc. v. Leavitt, 460 F.3d 1, 6 (D.C. Cir. 2006) ). While there is a rule against post hoc rationalizations, this rule "is not a time barrier which freezes an agency's exercise of its judgment after an initial decision has been made and bars it from further articulation of its reasoning." Alpharma, 460 F.3d at 6–7 (quoting Local 814, Int'l Bhd. of Teamsters v. NLRB, 546 F.2d 989, 992 (D.C. Cir. 1976) ). Instead, as this Court outlined in NAACP v. Trump, 315 F. Supp. 3d 457 (D.D.C. 2018), cert....