FDA Sued Over Generic DIOVAN 180-Day Exclusivity; Lawsuit Takes Issue With FDA Forfeiture Decision and “Trust Me” Approach to Exclusivity Decisions

By Kurt R. Karst –      

The question was not whether, but when, FDA would be sued over a decision involving 180-day generic drug exclusivity and the so-called “failure to obtain timely tentative approval” forfeiture provision at FDC Act § 505(j)(5)(D)(i)(IV).  That day has finally come.  Earlier this week, Mylan Laboratories Limited and Mylan Pharmaceuticals Inc. (collectively, “Mylan”) filed a Complaint and Motion for a Preliminary Injunction (for which Mylan is seeking an Order to file under seal) against FDA in the U.S. District Court for the District of Columbia challenging the Agency’s decision that Ranbaxy Inc. (“Ranbaxy”) is eligible for 180-day exclusivity for its generic versions of Novartis Pharmaceuticals Corp.’s blockbuster antihypertensive drug DIOVAN (valsartan) Tablets, 40 mg, 80 mg, 160 mg, and 320 mg approved under NDA No. 021283.  

Under FDC Act § 505(j)(5)(D)(i)(IV), which is one of the six 180-day exclusivity forfeiture provisions added to the FDC Act by the 2003 Medicare Modernization Act (“MMA”), 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.

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 [FDA] 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.  Neither the FDAAA, nor the FDASIA provisions are at issue in the Mylan case, although a future lawsuit may very well involve them.  Over the years, FDA’s application of FDC Act § 505(j)(5)(D)(i)(IV) has led to scores of forfeitures of 180-day exclusivity (see our 180-Day Exclusivity Tracker) – and, probably, more than all of the other forfeiture provisions combined.  Curiously, however, until the Mylan lawsuit, FDA had never been dragged into court on this MMA provision. 

Over the years, FDA has issued numerous explanations of the Agency’s application of FDC Act § 505(j)(5)(D)(i)(IV).  For example, in a recent Citizen Petition decision (Docket No. FDA-2011-P-0486), FDA explained that under FDC Act § 505(j)(5)(D)(i)(IV),

it is not sufficient to show that FDA changed or reviewed the requirements for approval while the application was under review.  The applicant must also show that its failure to obtain tentative approval at the 30 month date is caused by this change in or review of approval requirements – that is, the issues holding up approval at the 30 month date must be causally connected to the approval requirements that FDA reviewed or changed. [(Emphasis added)]

DIOVAN Tablets is listed in FDA’s Orange Book with three patents, each subject to a period of pediatric exclusivity: U.S. Patent Nos. 5,399,578 (“the ‘578 patent”), 5,972,990 (“the ‘990 patent”), and 6,294,197 (“the ‘197 patent”).  Pediatric exclusivity for the ‘578 patent expired on September 21, 2012, and pediatric exclusiviy for the ‘990 and ‘197 patents expires on April 26, 2017 and December 18, 2017, respectively.  According to FDA’s List of Paragraph IV Patent Certifications, the first ANDA submitted to FDA containing a Paragraph IV certification to any of the Orange Book-listed patents for all four DIOVAN strengths approved under NDA No. 021283 was December 28, 2004.  That application – ANDA No. 077492 – was submitted by Ranbaxy and contains a Paragraph IV certification to the ‘197 patent (as well as a Paragraph III certification – now Paragraph II certification – to the ‘578 patent, and a “section viii” statement to the ‘990 method-of-use patent).  Ranbaxy was not sued with repect to its Paragraph IV certification to the ‘197 patent, so the earliest FDA could approve  ANDA No. 077492 was September 21, 2012, when pediatric exclusivity applicable to the ‘578 patent expired.  September 21, 2012 came and went, however, without an FDA approval decision on the Ranbaxy ANDA.  Meanwhile, Mylan, a subsequent ANDA Paragraph IV applicant, was awaiting an FDA approval decision on its Valsartan Tablets ANDA No. 090866, which was submitted to FDA on September 15, 2008.

FDA had already tentatively approved ANDA No. 077492.  That tentative approval came on October 25, 2007, however, which is well after the 30-month anniversary date of the submission of ANDA No. 077492 (i.e., June 28, 2007 by FDA’s calculation), and before FDA took regulatory action against the company by invoking the Agency’s Application Integrity Policy (see our previous post here).  FDA’s October 25, 2007 tentative approval letter for ANDA No. 077492, which was only recently posted on FDA’s Drugs@FDA website, states the following with respect to 180-day exclusivity:

This letter does not address issues related to the 180-day exclusivity provisions under section 505(j)(5)(B)(iv) of the Act, except to note that for purposes of sections 505(j)(5)(B)(iv) and 505(j)(5)(D)(i)(IV), the agency regards the change in the USP monograph for Valsartan, published on May 1, 2007, . . . to be a change in the requirements for approval imposed after the date on which your ANDA was filed.

Thus, it would seem that FDA has determined that Ranbaxy did not forfeit 180-day exclusivity eligibility for failure to obtain timely tentative approval, because such failure was “caused by a change in or a review of the requirements for approval of the application imposed after the date on which the application [was] filed” – that is, by a change in the USP monograph for valsartan.  Indeed, FDA’s September 28, 2012 decision to only tentatively approve Mylan’s ANDA No. 090866 cements this view.

Mylan’s Complaint alleges that FDA violated the FDC Act and the Administrative Procedure Act (“APA”) by granting Ranbaxy 180-day exclusivity.  Mylan seeks declaratory and injunctive relief, including entry of a judgment setting aside and vacating FDA’s award of 180-day exclusivity to Ranbaxy and an injunction directing FDA to immediately grant final approval of Mylan’s Valsartan Tablets ANDA.  In the alternative, Mylan seeks entry of an iterim injunction staying the approval of all Valsartan Tablets ANDAs pending resolution of the lawsuit.

According to Mylan, FDA has “impermissibly found that Ranbaxy did not forfeit its l80-day exclusivity for Valsartan Tablets, despite Ranbaxy’s failure to obtain tentative approval within the 30-month statutory timeframe,” and that “FDA has taken this final agency action without providing any reasoned basis for its decision . . . .”  Mylan apparently sought an explanation from FDA, but the Agency refused to provide one.  Mylan states in its Complaint that:

the USP monograph update/in-process revision referenced by FDA in the October 25, 2007, Tentative Approval Letter was first proposed and published by USP in January-February 2006 – well over a year before Ranbaxy’s 30-month tentative approval deadline.  The October 25, 2007, Tentative Approval Letter does not provide any explanation or reasoned basis for why this proposed update constituted a “change” in the approval requirements, or how these proposed changes, that Ranbaxy and FDA were aware of as early as February 2006, directly “caused” or otherwise was “causally connected” to Ranbaxy’s failure to meet the 30-month deadline.

Because the October 25, 2007, Tentative Approval Letter does not provide any explanation or reasoned basis for why a USP update can constitute a “change” in the approval requirements, or how these proposed changes directly “caused” or were otherwise “causally connected” to Ranbaxy’s failure to meet the 30-month deadline, Mylan sought such an explanation from the Agency. [(Italics in original)]

FDA refused to provide an explanation, stating in a response to Mylan that:

[W]e cannot provide you the basis on which the Agency detennined that the first applicant for valsartan tablets has not forfeited its eligibility for exclusivity because that analysis rested on confidential infonnation contained in that application.  FDA appreciates the challenge this presents to you and other parties affected by a forfeiture analysis, but the Agency is nonetheless prohibited at this time from disclosing any additional infonnation regarding the forfeiture decision.

FDA’s “express refusal to timely and publicly disclose the basis for its determination that Ranbaxy has not forfeited its exclusivity,” and “express refusal to timely and publicly disclose the basis for its determnination that Mylan is not entitled to final approval” violates the APA, alleges Mylan.  Mylan goes on to note how the courts have “expressly admonished FDA’s practice of frustrating judicial review by refusing to timely address generic exclusivity,” quoting Hi-Tech Pharmacal Co., Inc. v. FDA and Teva Pharm. USA, Inc. v. Sebelius.  (Judge John D. Bates, who handled the Hi-Tech case, has been assigned to the Mylan case.  In Hi-Tech, Judge Bates was particularly critical of FDA's handling of exclusivity decisions – see here.)  “Neither Mylan nor the judicial system need to accept FDA’s ‘trust me’ approach to administering a statute that it is charged with lawfully administering.  Indeed, such a response directly runs afoul of FDA’s obligations under Hatch-Waxman and the APA,” says Mylan.