FDA Sued Over 180-Day Exclusivity Determination for Generic NAMENDA XR; It’s All About the “Causal Connection”

In a Complaint filed on January 27, 2017 in the U.S. District Court for the District of Columbia, ANDA applicant Amneal Pharmaceuticals LLC (“Amneal”) alleges that FDA incorrectly ruled that Amneal forfeited eligibility for 180-day exclusivity for generic versions of NAMENDA XR (memantine HCl) Extended-release Capsules, 7 mg, 14 mg, 21 mg, and 28 mg. As such, Amneal seeks declaratory and injunctive relief, asking the  court to vacate FDA’s forfeiture determination, declare that Amneal has not forfeited 180-day exclusivity, and to enter an order vacating or setting aside FDA’s final approval of several ANDAs already approved for generic versions of NAMENDA XR.

The lawsuit involves forfeiture of 180-day exclusivity under FDC Act § 505(j)(5)(D)(i)(IV). That provision, added by the 2003 Medicare Modernization Act, states that 180-day exclusivity eligibility is forfeited if:

The first applicant fails to obtain tentative approval of the application within 30 months after the date on which the application is filed, unless the failure is caused by a change in or a review of the requirements for approval of the application imposed after the date on which the application is filed.  [(Emphasis added)]

The 2007 FDA Amendments Act (“FDAAA”) clarified FDC Act § 505(j)(5)(D)(i)(IV), such that if “approval of the [ANDA] was delayed because of a [citizen] petition, the 30-month period under such subsection is deemed to be extended by a period of time equal to the period beginning on the date on which the Secretary received the petition and ending on the date of final agency action on the petition (inclusive of such beginning and ending dates) . . . .” (FDC Act § 505(q)(1)(G)). The 2012 FDA Safety and Innovation Act (“FDASIA”) made further changes with respect to the application of FDC Act § 505(j)(5)(D)(i)(IV) to certain ANDAs (see our previous post here). Neither the FDAAA, nor the FDASIA provisions came into play with Amneal ANDA 205825, but we note them nevertheless.

What does come into play, however, is the causation clause under FDC Act § 505(j)(5)(D)(i)(IV). FDA’s position has been that even if one of the causes of failure to obtain tentative approval by the 30-month forfeiture date was a change in or a review of the requirements for approval imposed after the application was submitted, a first applicant will not forfeit eligibility notwithstanding that there may have been other causes for failure to obtain tentative approval by the 30-month forfeiture date that were not caused by a change in or review of the requirements for approval.  That is, to avoid forfeiture, an applicant need only show that acceptability of one aspect of its ANDA (e.g., chemistry, labeling, or bioequivalence) was delayed due, at least in part, to a change in or review of the requirements for approval, irrespective of what other elements may also have been outstanding at the 30-month date.  In other words, “but-for” causation is not required in order to qualify for the exception under FDC Act § 505(j)(5)(D)(i)(IV).  FDA’s position is that this interpretation best effectuates the policy embodied in the exception, insofar as it does not penalize first applicants for reviews of or changes in approval requirements imposed after their ANDAs are submitted that cause the failure to obtain approvals or tentative approvals within 30 months, and continues to incentivize applicants to challenge patents by preserving (in many instances) the opportunity to obtain 180-day exclusivity.  FDA recently reiterated this position in draft guidance on 180-day exclusivity (see our previous post here).

Amneal submitted ANDA 205825 to FDA on June 10, 2013 containing Paragraph IV certifications challenging certain patents listed in the Orange Book for NAMENDA XR. FDA initially Refused to Receive (“RTR”) the ANDA, but rescinded that RTR decision on February 18, 2014 and acknowledged receipt of ANDA 205825 as of the initial June 10, 2013 receipt date.  As a result, Amneal is a “first applicant” – and apparently the sole first applicant – eligible for 180-day exclusivity for generic NAMENDA XR.

Seven months after rescinding the RTR determination for ANDA 205825, FDA issued a Complete Response Letter refusing to approve the ANDA and raising several questions, including a request for data from the manufacture of a commercial size lot (batch). Amneal supplied that information to FDA approximately eight months later, and provided additional information in September 2015, just a few months before the December 10, 2015 30-month forfeiture date under FDC Act § 505(j)(5)(D)(i)(IV).  In October 2015, FDA issued an Import Alert against Amneal’s API manufacturer, necessitating a change in API supplier by Amneal, which Amneal proposed in November 2015.  After other back-and-forth with FDA, including a second Complete Response Letter dated December 7, 2015, the Agency finally approved Amneal ANDA 205825 on October 12, 2016. . . . as well as ANDAs from other, subsequent Paragraph IV ANDA applicants.

As to Amneal’s eligibility for 180-day exclusivity, the last sentence above says it all. FDA determined in a September 21, 2016 Memorandum to ANDA 205825, and later in a September 28, 2016 Letter Decision sent to counsel for Amneal, that Amneal forfeited eligibility for 180-day exclusivity.  According to FDA, Amneal failed to obtain timely tentative approval or ANDA approval by the forfeiture date (i.e., December 10, 2015), and such failure was not caused by a change in or review of the requirements for approval.

It’s the causality element that Amneal takes particular issue with in the company’s Complaint: “FDA should not impose forfeiture if, as a factual matter, there is any causal connection between the failure to obtain tentative approval and a change in or review of approval requirements for the application,” according to Amneal (emphasis in original). To that end, Amneal argues that FDA’s forfeiture decision violates the FDC Act and the Administrative Procedure Act and must be vacated and set aside for at least four reasons:

1. FDA’s application of an irrebuttable adverse presumption of no causation if the change in or review of the approval requirements is resolved as of the forfeiture date is contrary to the causation analysis required by the FDCA and is arbitrary and capricious;

2. FDA’s decision is not the product of reasoned decision making because it failed to provide an explanation for rejecting any causal connection between the 14-month delay resulting from FDA’s demand for commercial-scale batch information and Amneal’s ability to obtain timely tentative approval;

3. FDA’s conclusion that its demand for commercial-scale batch information was not a change in or review of approval requirements because FDA had not changed a secret, undisclosed policy is contrary to the FDCA and is arbitrary and capricious;

4. FDA failed to consider the impact, either alone or in the aggregate, of the months-long delay in deciding whether to receive Amneal’s ANDA. The delay in receipt was itself the product of a change in or review of approval requirements and should have been considered by FDA as a potential cause for the failure to timely obtain tentative approval. FDA should also have considered the delay in receipt in an analysis of the causal effect of FDA’s demand for commercial-scale information.

In addition to requesting that the court set aside current ANDA approvals and declare that Amneal has not forfeited 180-day exclusivity eligibility, Amneal also requests that the court preliminarily and permanently enjoin FDA from granting final approval to any ANDA, other than Amneal ANDA 205825, until the expiration of Amneal’s 180-day exclusivity.