ISTA Sues FDA Over Generic XIBROM Approval, Says ANDA Approval Should Disappear in the Blink of An Eye

By Kurt R. Karst –      

Last Friday, ISTA Pharmaceuticals, Inc. (“ISTA”) filed a Complaint and a Motion for a Temporary Restraining Order and a Preliminary Injunction in the U.S. District Court for the District of Columbia seeking to vacate FDA’s May 11, 2011 approval of Coastal Pharmaceuticals’ (“Coastal’s”) ANDA No. 201211 for a generic version of ISTA’s ophthalmic nonsteroidal anti-inflammatory drug for use after cataract surgery, XIBROM Ophthalmic Solution, 0.09% (Twice Daily Administration).  The lawsuit comes on the heels of FDA’s May 11, 2011 decision in which the Agency denied ISTA’s March 2011 Citizen Petition and granted in part and denied in part a June 2008 ISTA Citizen Petition, and a Federal Register notice in which FDA determined that XIBROM was not withdrawn from sale for reasons of safety or effectiveness and that the Agency can approve ANDAs for Bromfenac Ophthalmic Solution, 0.09%, if all other legal and regulatory requirements are met.  (ISTA had submitted another Citizen Petition to FDA in between the 2008 and 2011 petitions, but withdrew that petition in March 2011 after ISTA allegedly ceased shipping XIBROM in late February 2011.)

FDA first approved XIBROM under NDA No. 21-664 on March 24, 2005 for twice daily administration.  On October 16, 2010, FDA approved a supplement under NDA No. 21-664 for a new once daily dosing regime of Bromfenac Ophthalmic Solution, 0.09%, marketed by ISTA as BROMDAY, and granted ISTA a period of three-year new clinical investigation exclusivity (identified as “NP,” for “new product,” in the Orange Book) that expires on October 16, 2013.  ISTA subsequently discontinued marketing XIBROM and its approved labeling for twice daily administration.  Meanwhile, Coastal was pursuing approval of its ANDA for a generic version of XIBROM with labeling for the now discontinued twice daily administration.

ISTA’s March 2011 Citizen Petition, the only petition relevant to the lawsuit, requested that FDA refrain from approving (either tentatively or fully) an ANDA for a generic version of Bromfenac Ophthalmic Solution, 0.09%, as a result of the period of 3-year exclusivity FDA granted the company.  According to ISTA, the company’s petition “stressed that a sponsor of an ANDA must include in the application a copy of the reference listed drug’s ‘currently approved labeling,’” pursuant to 21 C.F.R. § 314.94(a)(8)(i), and that “[b]ecause of the labeling change, ‘the currently approved labeling’ for ISTA’s bromfenac ophthalmic solution product is for once-per-day dosing.”  Furthermore, ISTA’s petition “argued that FDA cannot permit an ANDA to omit the once-per-day dosing instructions, because it would have the effect of rendering the drug less safe,” pursuant to 21 C.F.R. § 314.127(a)(11) and § 314.161(a).  FDA promptly denied ISTA’s petition, saying that “(1) we consider Xibrom and Bromday two separate drug products rather than one product with old and new labeling, (2) we do not think the Bromday dosing regimen is less safe than the Xibrom dosing regimen, and (3) we did not require Xibrom to be withdrawn as a condition of the Bromday approval,” and the lawsuit ensued. 

ISTA argues in its court filings that FDA’s approval of Coastal’s ANDA and FDA’s denial of ISTA’s Citizen Petition violated the FDC Act and the Administrative Procedure Act (“APA”), and requests that the court grant declaratory and injunctive relief – i.e., a declaratory judgment that FDA acted unlawfully in approving Coastal’s ANDA and “[a] temporary restraining order and a preliminary injunction directing FDA to vacate approval of Coastal’s ANDA and to block the approval of other ANDAs that fail to reference currently approved labeling.”  Specifically, ISTA argues that “[c]ontrary to the statute and its own regulations, FDA has approved a generic product without requiring the ANDA applicant to provide ‘a copy of the currently approved labeling’ and without requiring the ANDA applicant to utilize ‘the same labeling’ as Xibrom, the reference listed drug.”

FDA, in the Agency’s Opposition Brief, says that ISTA’s lawsuit “represents the latest in a long line of cases in which a manufacturer of a brandname drug product has attempted to block generic competition by challenging the bases for FDA’s approval,” and that just as “[e]ach of these challenges failed,” so should ISTA’s challenge.  According to FDA,

The essence of Ista’s argument is that Xibrom and Bromday are not two products but rather one product with revised labeling, and that FDA’s approval of Coastal’s ANDA, which relied on the “obsolete” Xibrom labeling, was therefore unlawful.  Ista is wrong. Xibrom did not simply replace Bromday, as evidenced by the fact that Bromday was approved on October 16, 2010, and Ista did not remove Xibrom from the market until February 28, 2011, four and a half months later.  In other words, Ista offered both Xibrom and Bromday for sale until 11 weeks ago, and stopped the day before it filed its second citizen petition, in an obvious bid to delay generic competition.  And because the regulations make clear that FDA can approve an ANDA based on a withdrawn innovator drug so long as that drug is not withdrawn for safety or effectiveness reasons, see 21 C.F.R. §§ 314.127(a)(11), 314.161(a), FDA appropriately approved Coastal’s ANDA with reliance on the Xibrom labeling. [(Citations omitted; italics in original)]

Yesterday, Judge Royce C. Lamberth denied ISTA's Temporary Restraining Order.  A status conference in the case has been scheduled for Wednesday, May 18, 2011 at 10:30 AM before Judge Emmet G. Sullivan.