Boning Up: FDA Revisits Pre-MMA 180-Day Exclusivity and Addresses a New Scenario

May 4, 2014

By Kurt R. Karst –      

We’ve said it before, and we’ll say it again: 180-day generic drug marketing exclusivity governed by the version of the FDC Act in effect prior to the December 2003 enactment of the Medicare Modernization Act (“MMA”) is alive and kicking. . . . and will likely be around for years to come.  Sometimes FDA’s decisions under that pre-MMA regime are contentious, as recent lawsuits against FDA (here, here, and here) concerning generic CELEBREX (celecoxib) Capsules and stemming from an FDA Letter Decision show.  Other times, FDA’s decisions are made quietly and go unnoticed (by most).  It’s this latter case that we want to bring to light today.  And it concerns a generic version of the bone resorption inhibitor EVISTA (raloxifene HCl) Tablets, 60 mg, approved under NDA No. 020815.

Under the pre-MMA version of FDC Act § 505(j), 180-day exclusivity is patent-based, such that an ANDA applicant is (or different applicants are) eligible for 180-day exclusivity with respect to different Orange Book-listed patents covering the brand-name Reference Listed Drug if such applicant submitted the first ANDA to FDA containing a Paragraph IV certification to a particular patent.  Pre-MMA 180-day exclusivity is triggered by the earlier of either the first commercial marketing (for all patents certified to as Paragraph IV by a first-filer), or by a court decision favorable to an ANDA applicant (with respect to a particular patent). 

As a result of an effective date provision in the MMA (Section 1102(b)(1)), a drug product subject to the pre-MMA rules on 180-day exclusivity is forever evaluated under the old version of the statute.  This means that if an application – an ANDA with a number less than or equal to 076933 – containing a patent certification was submitted to FDA before December 8, 2003, then any subsequent ANDA, whether or not it contains the first Paragraph IV certification to a patent, is subject to the pre-MMA 180-day exclusivity rules (see our previous post here).

Raloxifene HCl Tablets, 60 mg, is a pre-MMA drug.  As far as we can tell, Barr Laboratories, Inc. (“Barr”) submitted the first ANDA to FDA in the latter part of 2002 – ANDA No. 076441.  The ANDA contained Paragraph IV certifications to several patents listed in the Orange Book for EVISTA, including U.S. Patent Nos. 6,458,811 (“the ‘811 patent”), 6,797,719 (“the ‘719 patent”), and 6,894,064 (“the ‘064 patent”) (all expiring on March 10, 2017).   A fourth patent – U.S. Patent No. 8,030,330 (“the ‘330 patent”), also expiring on March 10, 2017 – was listed in the Orange Book in 2011 (as reflected in the October 2001 Cumulative Supplement).  Barr promptly certified Paragraph IV, making it a first-filer with respect to the ‘330 patent.

Meanwhile, in March 2006, Teva Pharmaceuticals USA (“Teva”) submitted ANDA No. 078193 to FDA for a generic version of EVISTA.  Teva’s original ANDA apparently contained certifications to the ‘811, ‘719, and ‘064 patents.  Like Barr, Teva also promptly amended its ANDA to contain a Paragraph IV certification to the ’330 patent.  In fact, Barr and Teva certified to the ‘330 patent on the same day. 

If we stop at this point in the story, then applying FDA’s seemingly ever-evolving pre-MMA patent-by-patent approach to 180-day exclusivity – see, e.g., here and here – would mean that Barr’s status as a first-filer on all four patents, and, therefore, Barr’s eligibility for 180-day exclusivity based on all four patents, would serve as a barrier to FDA’s approval of Teva’s ANDA No. 078193.  That is, this is not a scenario in which FDA has been willing to recognize shared 180-day exclusivity.  FDA has limited shared 180-day exclusivity to situations where there is an exclusivity stand-off – i.e., where there are cross-Paragraph IV certifications to different patents, such that one ANDA applicant is first-to-file on Patent 1 (but subsequent on Patent 2) and another applicant is first-to-file on Patent 2 (but subsequent on Patent 1), and each applicant’s eligibility for 180-day exclusivity blocks the other from getting approval.

The twist with Raloxifene HCl Tablets, 60 mg, came when Barr notified FDA that it relinquished any claim to 180-day exclusivity with respect to the ‘811, ‘719, and ‘064 patents, but not with respect to the ‘330 patent.  As such, FDA had to address for the first time the question of whether or not relinquishment of blocking 180-day exclusivity altered the ANDA approval equation such that the Agency could approve a subsequent filer’s application.  According to FDA’s approval letter, the relinquishment freed things up for Teva:

With respect to 180-day generic drug exclusivity, Teva and another applicant were the first ANDA applicants to submit a substantially complete ANDA with a paragraph IV certification to the ‘330 patent.  The other applicant was the first ANDA applicant to submit a substantially complete ANDA with a paragraph IV certification to the ‘811, ‘719 and ‘064 patents.  The other applicant has relinquished its entitlement to exclusivity with respect to these three patents.  Therefore, with this approval Teva is eligible for 180 days of generic drug exclusivity for Raloxifene Hydrochloride Tablets, 60 mg.  This exclusivity, which is provided for under section 505(j)(5)(B)(iv) of the Act, will begin to run from the earlier of the commercial marketing or court decision dates identified in section 505(j)(5)(B)(iv).

Although we don’t always agree with FDA’s decisions in the 180-day exclusivity realm, this one seems to make good sense and to have been decided correctly.