FDA Racks Up a Circuit Court Loss in Imported and Unapproved Thiopental Sodium Case; Will It Jeopardize FDA’s Drug Shortage Program?

By Kurt R. Karst –  

In a unanimous decision handed down on July 23rd by a 3-judge panel of the U.S. Court of Appeals for the District of Columbia Circuit in Cook v. FDA (Case No. 12-5176), the Court largely affirmed a March 2012 decision from the U.S. D.C. District Court (Judge Richard J. Leon) permanently enjoining FDA from permitting the entry of (or releasing any future shipments of) foreign manufactured thiopental into interstate commerce.  The decision is a blow to FDA on several fronts.

As we previously reported (here, here, and here), the case stems from a February 2011 lawsuit (amended in July 2011) brought against FDA by death row inmates in three states, over the importation of unapproved thiopental sodium, one of the drugs used by some states to administer a lethal injection.  The Plaintiffs alleged that FDA committed violations of the Administrative Procedure Act (“APA”) and the FDC Act.  Specifically, Plaintiffs alleged that FDA violated the law by improperly allowing shipments of a misbranded and unapproved new drug to enter the U.S., contrary to the statute (FDC Act § 801(a), 21 U.S.C. § 381(a)), and that FDA departed from longstanding policies and undermined the purpose of the FDC Act by permitting entry of the drug into the country.  Judge Leon agreed and concluded his opinion with a rather colorful statement:

In the final analysis, the FDA appears to be simply wrapping itself in the flag of law enforcement discretion to justify its authority and masquerade an otherwise seemingly callous indifference to the health consequences of those imminently facing the executioner’s needle.  How utterly disappointing!

The D.C. Circuit, in affirming Judge Leon’s decision, had similar (albeit less colorful) words for FDA, saying:

The FDCA imposes mandatory duties upon the agency charged with its enforcement.  The FDA acted in derogation of those duties by permitting the importation of thiopental, a concededly misbranded and unapproved new drug, and by declaring that it would not in the future sample and examine foreign shipments of the drug despite knowing they may have been prepared in an unregistered establishment.

The mandatory duties, said the Court, are found in the text of FDC Act § 801(a) concerning imports.  The statute states, in relevant part, that “[i]f it appears from the examination of such [imported] samples or otherwise” that the product violates the FDC Act’s misbranding or new drug approval requirements, “then such article shall be refused admission” (emphasis added).  

During the appeal, FDA pressed the so-called “Heckler defense” – that is, that under the U.S. Supreme Court’s decision in Heckler v. Chaney, 470 U.S. 821 (1985) (another death row inmate case), FDA’s decision not to take enforcement action with respect to thiopental sodium is not subject to judicial review because “agency refusals to institute investigative or enforcement proceedings are committed to agency discretion.”  But the D.C. Circuit, like Judge Leon, did not agree with FDA:

In sum, we hold 21 U.S.C. § 381(a) requires the FDA to (1) sample “any drugs” that have been “manufactured, prepared, propagated, compounded, or processed” in an unregistered establishment and (2) examine the samples and determine whether any “appears” to violate the prohibitions listed in § 381(a)(1)–(4).  If, “from the examination of such samples or otherwise,” the FDA finds an apparent violation of the Act, then it must (3) “refuse[] admission” to the prohibited drug.  Because these are clear statutory “guidelines for the agency to follow in exercising its enforcement powers,” Chaney, 470 U.S. at 833, the FDA’s compliance with § 381(a) is subject to judicial review under the standards of the APA. . . .

From the foregoing analysis it follows apodictically that the FDA’s policy of admitting foreign manufactured thiopental destined for state correctional facilities, as well as the several individual admissions of such shipments challenged by the plaintiffs, were “not in accordance with law.” 5 U.S.C. § 706(2)(A). . . .   The FDA’s individual admissions of thiopental shipments were not in accordance with law because § 381(a) requires the FDA to refuse admission to any drug that appears to violate the substantive prohibitions of the FDCA, and the FDA conceded before the district court that the thiopental in these shipments “clearly ‘appears’ to be an unapproved new drug.”

The D.C. Circuit’s decision may foreshadow the Court’s decision in another case concerning FDA’s exercise of enforcement discretion.  In K-V Pharmaceutical Co. v. FDA (Docket No. 12-5349), K-V is appealing a September 2012 decision from the D.C. District Court that stymied the company’s efforts to “restore” orphan drug exclusivity for the pre-term birth drug MAKENA (hydroxyprogesterone caproate) Injection, 250 mg/mL (see our previous post here).  K-V alleged that FDA violated the law by failing to take sufficient enforcement action to stop the unlawful competition with MAKENA by pharmacies that compound hydroxyprogesterone caproate injection.  The D.C. District Court found K-V’s claims unreviewable, because the APA “precludes judicial review of final agency action, including refusals to act, when review is precluded by statute or ‘committed to agency discretion by law,’” and because Heckler is controlling.  On appeal, K-V has vigorously argued that FDA’s refusal to take action is the equivalent of an order or license reviewable in court and that Heckler is inapplicable (see our previous post here).

Another area where the D.C. Circuit’s Cook decision may have a huge effect is in the context of drug shortages.  FDA has exercised enforcement discretion to allow the importation of unapproved drugs into the country (see here).  Does Cook put an end to that practice?

The Cook decision squarely addresses FDA’s concerns that enforcement discretion is needed in this area.  The Court rejected FDA’s arguments by ruling that FDA had other alternatives, such as allowing domestically manufactured unapproved drugs to be sold to alleviate drug shortages.  According to the Court:

By its own account, however, the FDA has ways short of allowing importation of inadmissible drugs to counteract a drug shortage, including: “Asking other firms to increase production (31%),” “Working with manufacturers” to mitigate quality problems (28%), and “Expediting review of regulatory submissions (26%).” Id.  The FDA may exercise enforcement discretion to allow the domestic distribution of a misbranded or unapproved new drug, as the Supreme Court recognized in Chaney, 470 U.S. at 837, and in some cases may invoke its express statutory authority to permit the importation of an unapproved new drug.  For example, the FDA may designate an unapproved foreign manufactured drug as an investigational new drug (IND), thereby allowing its lawful importation.  21 U.S.C. § 355(i); 21 C.F.R. § 314.410(a)(1)(ii); see also 21 C.F.R. 312.315(a)(3)(ii) (FDA may expand access to an IND “contain[ing] the same active moiety as an approved drug product that is unavailable through … a drug shortage”).  In any event, even if reading § 381(a) by its terms, as we do, deprives the FDA of one possible response to five percent of all drug shortages, that is hardly an absurd result.