The Last Shall Be First . . . . The Case of Generic FLOMAX

By Kurt R. Karst –      

FDA’s recent announcement that the Agency approved IMPAX Laboratories, Inc.’s (“IMPAX”) ANDA No. 90-377 for the first generic version of Boehringer Ingelheim Pharmaceuticals, Inc.’s (“BI”) popular ($2.1 billion/year) treatment for benign prostatic hyperplasia, FLOMAX (tamsulosin hydrochloride) Capsules, has an interesting Hatch-Waxman backstory to it.  In the words of the A-Team's Hannibal Smith, the folks at IMPAX must have been saying “I love it when a plan comes together” when word came of the ANDA approval. 

FLOMAX is listed in the Orange Book with a single patent – U.S. Patent No. 4,703,063 (“the ‘063 patent”).  The ‘063 patent expired on October 27, 2009, but is subject to a period of pediatric exclusivity scheduled to expire on April 27, 2010.  Several companies, including IMPAX and Ranbaxy, submitted ANDAs for generic FLOMAX prior to expiration of the ‘063 patent.  The IMPAX and Ranbaxy ANDAs contained a Paragraph IV certification to the ‘063 patent.  (Other applicants presumably submitted a Paragraph III certification to the patent.)  Ranbaxy is reported to be a first applicant eligible for 180-day exclusivity.  BI filed patent infringement lawsuits in response to the Paragraph IV certifications: (1) Astellas Pharma Inc. et al. v. Ranbaxy, Inc., Civil Action No. 3:05-cv-02563 (filed May 13, 2005 in the District Court of New Jersey); and (2) Astellas Pharma Inc. et al. v. Impax Laboratories, Inc., Civil Action No. 5:08-cv-03466 (filed July 18, 2008 in the Northern District of California). 

In the patent infringement case against Ranbaxy, the district court ruled in February 2007 in favor of the plaintiffs (ruling that the ‘063 patent is not invalid on grounds of double-patenting).  Ranbaxy appealed the decision to the Federal Circuit.  During the appeal, however, the parties settled the case and entered into a joint stipulation of dismissal without prejudice.  Under the terms of the settlement agreement, Ranbaxy had the opportunity to launch its generic tamsulosin drug product on March 2, 2010, which is 8 weeks prior to the expiration of pediatric exclusivity applicable to the ‘063 patent.  FDA tentatively approved Ranbaxy’s ANDA in June 2007.

In the patent infringement case against IMPAX, IMPAX filed a motion for summary judgment of patent invalidity for double-patenting.  The plaintiffs and IMPAX settled the case in October 2009 before a district court decision, and after FDA tentatively approved ANDA No. 90-377.  The court entered a Consent Judgment acknowledging a negotiated settlement between the plaintiffs and IMPAX.  According to FDA’s ANDA approval letter and an IMPAX press release, the agreement is similar to the agreement reached with Ranbaxy insofar as an early launch date is concerned.  FDA’s approval letter provides additional details on the terms of the agreement: 

This settlement applies to [BI’s] selective and limited waiver of its pediatric exclusivity to IMPAX Laboratories, Inc. for the ‘063 patent as of March 2, 2010, with respect to this ANDA. Concurrent with the agency’s approval of this ANDA, the waiver effectively permits IMPAX Laboratories, Inc. to market Tamsulosin Hydrochloride Capsules, USP beginning on March 2, 2010, prior to the expiration of [BI’s] pediatric exclusivity for the ’063 patent on April 27, 2010.  The selective waiver also applies to [BI’s] exclusivity with respect to product labeling associated with the M-54 exclusivity code due to expire on June 22, 2013.

Interestingly, of the 7 ANDA applicants identified by FDA with tentative approval, IMPAX was the last applicant to obtain tentative approval (in October 2009), but the first company to obtain final ANDA approval.  Although Ranbaxy was eligible for 180-day exclusivity, that exclusivity was forfeited when the ‘063 patent expired, thereby opening the door to subsequent ANDA approvals. 

As we previously reported, Ranbaxy has had good manufacturing practice problems with FDA.  In early 2009, FDA announced that the Agency was taking the unusual step of invoking its Application Integrity Policy (“AIP”) against Ranbaxy’s Paonta Sahib manufacturing facility in India.  FDA takes such regulatory action under the Agency’s AIP procedures when FDA believes that a company’s actions raise significant questions about the integrity of data in marketing applications.  Importantly, FDA notes in the AIP letter with respect to pending ANDAs that:

In accordance with FDA policy, the Agency will assess the validity of the data and information in all of Ranbaxy’s affected applications which contain data developed at the Paonta Sahib site. . . .  This means that the Agency does not intend ordinarily to conduct or to continue its normal substantive scientific review (including review of data and labeling) of any such pending application or supplement, or of any new application or supplemental applications filed after the date of this letter, that contain data developed at the Paonta Sahib site, during a validity assessment of that application.

It is unclear whether Ranbaxy’s inability to obtain final ANDA approval for the company’s ANDA for its generic FLOMAX is due to FDA’s AIP and whether information supporting the ANDA file was generated from the company’s Paonta Sahib facility.  This is reportedly the case, but the basis for this report is not known.  Because 180-day exclusivity for generic FLOMAX was forfeited when the ‘063 patent expired, the issue of how FDA will handle Ranbaxy’s 180-day exclusivity eligibility for pending ANDAs implicated in the Agency’s AIP will apparently have to be saved for another day.

Although the Federal Trade Commission is generally opposed to generic drug settlement agreements, and has expressed support for legislation that would ban such agreements, FDA’s approval of ANDA No. 90-377 is a good example of the benefits of such agreements.  And it is also a good example of how a settlement agreement and a little bit of luck can take an ANDA applicant from last to first.