by Brian Malkin
On March 12, AstraZeneca Pharmaceuticals LP ("AstraZeneca") sued FDA in the District Court for the District of Columbia requesting declaratory and injunctive relief to prevent FDA from granting final approval to generic versions of Seroquel® (quetiapine fumarate) or Seroquel XR® (extended-release quetiapine fumarate). In its complaint (including AstraZeneca's original citizen petitions, FDA response, and other documents related to the Seroquel® products' new drug applications ("NDAs")), AstraZeneca asserts that FDA could, based on FDA's denial of AstraZeneca's citizen petitions, approve generic versions of both products as early as March 27, 2012, after the pediatric exclusivity associated with a product patent expires.
Aside from whether AstraZeneca's arguments have merit, the heart of the issue appears to be whether AstraZeneca has standing to sue FDA when FDA denied its citizen petitions on March 7, 2012. FDA denied AstraZeneca's petitions "without comment on whether [FDA] will take the actions that [AstraZeneca] request[s]." While FDA's actions on citizen petitions are typically considered final agency action, in this case, FDA only has tentatively approved several generic applicants referencing both Seroquel® and Seroquel XR®. Specifically, FDA stated in its response:
FDA has not yet made a final determination with respect to whether to approve or not approve any ANDA relying on Seroquel or Seroquel XR as the RLD. FDA's decision to approve or not approve a specific application will be based on the particular facts that are applicable to that application at the time of the decision. The periods of exclusivity described above for Seroquel or Seroquel XR may or may not apply or be relevant to the Agency's final decisions with respect to any individual application and its labeling depending on the particulars of an ANDA and the timing of its approval. Such decisions are made by the Agency on a case-by-case basis in the normal course of the review process.
AstraZeneca asserts in its Memorandum in Support of Plaintiff's Motion for Summary Judgment or, in the Alternative, Application for Preliminary Injunction ("Memorandum") that "[i]t now appears virtually certain that FDA intends to grant final approvals to those generic products [generic Seroquel® and Seroquel XR® within the next two weeks, in disregard of AstraZeneca's position that such approvals would be unlawful." (emphasis in original) In support of this position, AstraZeneca stated that it "has information from its customers that at least Teva and Dr. Reddy's expect to receive final approval on or about March 27, 2012, when the pediatric exclusivity period associated with the Seroquel substance patent expires." At stake is AstraZeneca's Seroquel® franchise, which AstraZeneca represented to the Court represented $3.344 billion in sales in 2011 and could lose $2 billion in sales from March 27, 2012 to December 3, 2012.
AstraZeneca's citizen petitions, Docket Nos. FDA-2011-P-0662 (Seroquel®) and FDA-2011-P-0663 (Seroquel XR®), both dated September 2, 2011, assert that FDA cannot approve ANDAs referencing Seroquel® or Seroquel XR® that omit certain labeling: 1) safety data regarding hyperglycemia and diabetes, 2) boxed warning regarding increased suicidality in children, adolescents, and young adults, and 3) a warning regarding clinical worsening of depression and the risk of suicide. AstraZeneca believes that if this labeling cannot be omitted, then FDA could not approve generic versions until after a certain data exclusivity expired on December 2, 2012, I-618 "ADJUNCTIVE THERAPY IN THE TREATMENT OF MAJOR DEPRESSIVE DISORDER (MDD)." While Seroquel® and Seroquel XR® are both approved for indications other than MDD, including schizophrenia, AstraZeneca contends that the data for the three labeling sections referenced above were obtained from studies conducted by AstraZeneca for the treatment of bipolar disorder and MDD with Seroquel XR®.
FDA's response, however, appears consistent with its guidance, "Citizen Petitions and Petitions for Stay of Action Subject to Section 505(q) of the Federal Food, Drug, and Cosmetic Act" (June 2011), which stated that FDA did not interpret Section 505(q) of the Federal Food, Drug, and Cosmetic Act as requiring a substantive final Agency decision within 180 days from submission on an specific aspect of a pending application (such as labeling carve outs) when a final decision of the approvability of the application as a whole has not been made. FDA's guidance explains FDA then "would expect to deny a petition without comment on the substantive approval issue," because this type of decision would deprive the applicant of procedural rights, such as FDA's internal hearing process, before the petitioner could seek a review of FDA's decision by the courts.
AstraZeneca, therefore, is attempting to override FDA's attempt to deliberately not render final agency action by seeking immediate declaratory and injunctive relief by the courts. AstraZeneca argues that FDA's refusal to answer is not entitled to any deference, because FDA allegedly ruled on similar citizen petitions prior to final approval of particular generic applications and that FDA has already granted tentative approval to one or more generics for each product. According to AstraZeneca, for FDA to issue those tentative approvals, FDA must have already reviewed the generic products' labeling for sameness when compared to their referenced products.
According to a Minute Order issued by the District of Columbia Court today, an expedited schedule was established in view of the Motion for Summary Judgment or Preliminary Injunction in advance of March 27, 2012: 1) FDA must file its opposition by March 15, 2) AstraZeneca must file its reply by March 16, 3) FDA must file its administrative record by March 16, and 4) the parties must state the exhibits that they intend to rely on by March 17.
Given the precedential nature of this challenge to FDA's citizen petition process, we will continue to keep you updated on additional substantive developments.