A Pre-MMA 180-Day Exclusivity Punt? What Gives?

By Kurt R. Karst –

Although the number of cases involving 180-day exclusivity under the version of the FDC Act in effect before the December 8, 2003 enactment of the Medicare Modernization Act (“MMA”) is nearing an end, the pre-MMA statute, and the handling of it by FDA and the courts, never fails to surprise us.  Take, for example, the December 28, 2012 approval of ANDA No. 202608 for Mallinckrodt Inc.’s (“Mallinckrodt”) generic version of Janssen Pharmaceuticals, Inc.’s CONCERTA (methylphenidate HCl) Extended-Release Tablets, 27 mg, 36 mg, and 54 mg.  Mallinckrodt’s December 31, 2012 press release on the approval, and, in particular, the announcement that “Mallinckrodt believes it holds a separate 180-day exclusivity period for each of the 27, 36 and 54 mg dosage strengths” (emphasis added), left a lot of jaws on the floor and a lot of people scratching their heads.  First, nobody really expected Mallinckrodt to be a player for 180-day exclusivity.  How did they do it?  Second, why would a company only believe it has 180-day exclusivity?  Wouldn’t the ANDA approval letter remove any doubt?  Some answers were provided when FDA finally posted the approval letter for ANDA No. 202608.  But before we get into that, a quick refresher on some pre-MMA 180-day exclusivity issues . . . .

Under the pre-MMA version of the statute, 180-day exclusivity is patent-based, such that an ANDA applicant (or different applicants) may be eligible for 180-day exclusivity with respect to different Orange Book-listed patents covering the Reference Listed Drug (“RLD”) if the applicant submitted the first ANDA to FDA containing a Paragraph IV certification to a particular patent.  Pre-MMA 180-day exclusivity is triggered by either first commercial marketing (for all relevant patents), or by a court decision favorable to an ANDA applicant (with respect to a particular patent), whichever is earlier.  The marketing of an authorized generic by a first filer eligible for 180-day exclusivity is commercial marketing that triggers exclusivity.  

When the first ANDA containing a certification to any Orange Book-listed patent was submitted to FDA before December 8, 2003, but the first Paragraph IV certification is submitted post-MMA, then, as FDA explained in the Agency’s April 2009 “pre-MMA/post-MMA Straddle” Letter Decision (see our previous post here), exclusivity for that drug is governed by the pre-MMA statute.  Also, as a result of the pre-MMA’s patent-by-patent approach to 180-day exclusivity, there is the possibility of shared exclusivity, which FDA clarified in 2010 (see here) applies only where “two applicants have submitted paragraph IV certifications to two different patents, and one applicant was first to file a paragraph IV certification on one patent and the other was first to file on a different patent” (i.e., an “exclusivity stand-off”).  Finally, for our purposes here, it is important to note that the pre-MMA patent-by-patent approach to 180-day exclusivity means that a new Orange Book patent listing can significantly complicate and alter the 180-day exclusivity calculus.  On-the-ball companies that submit so-called “serial Paragraph IV certifications” to FDA for newly issued patents in anticipation of Orange Book listing may qualify for 180-day exclusivity based on their certification.  

CONCERTA, which is approved under NDA No. 021121, is currently listed in the Orange Book with three patents – U.S. Patent Nos. 6,919,373 (“the ‘373 patent”), 6,930,129 (“the ‘129 patent”), and 8,163,798 (“the ‘798 patent”).  All three patents are scheduled to expire on July 31, 2017, but are subject to a period of pediatric exclusivity that expires on January 31, 2018.  According to FDA’s Paragraph IV Patent Certifications List, the first ANDA containing a Paragraph IV certification for all four approved strengths of CONCERTA (18 mg, 27 mg, 36 mg, and 54 mg) was submitted to the Agency post-MMA on July 19, 2005.  Nevertheless, the first ANDA containing a certification to an Orange Book-listed patent for CONCERTA was made pre-MMA, thereby making generic CONCERTA a pre-MMA/post-MMA straddle drug governed by the pre-MMA rules on 180-day exclusivity.  Although the ‘373 patent, the ‘129 patent, and the ‘798 patent were all issued and listed in the Orange Book post-MMA (the ‘373 and ‘129 patents were issued in 2005, and the ‘798 patent was issued in 2012), CONCERTA was initially listed in the Orange Book with patents that expired in 2002 and 2003.  Presumably the first ANDA submitted to FDA contained Paragraph III certifications to those patents.

In 2005, pending ANDAs for generic CONCERTA were amended to include Paragraph IV certifications to the ‘373 and ‘129 patents – although questions about who was first (Andrx or Impax) remained.  Patent infringement litigation was brought against ANDA sponsors with respect to these patents in the U.S. District Court for the District of Delaware, resulting in a decision of non-infringement and invalidity of the ‘373 patent, which the U.S. Court of Appeals for the Federal Circuit affirmed in an April 26, 2010 decision and mandated on June 2, 2010, thereby triggering 180-day exclusivity with respect to that patent.  Infringement claims and defendant counterclaims concerning the ‘129 patent were dismissed with and without prejudice, respectively.  The door was apparently left open on litigation over the ‘129 patent depending on 180-day exclusivity associated with that patent.  Meanwhile, in May 2011, Watson, which had acquired Andrx in 2006, announced that the company had launched an authorized generic version of all strengths of CONCERTA.  And in July 2012, FDA affirmed in a response to a citizen petition (Docket No. FDA-2004-P-0151) what many had already suspected – that the Agency would depart from conventional bioequivalence metrics and set partial AUC parameters for generic CONCERTA.  FDA’s decision may have led to some reformulation efforts on the part of ANDA sponsors.

The ‘798 patent, which issued on April 24, 2012, was listed in the Orange Book on May 18, 2012.  And in what might be a case of serial certifications, FDA states in a footnote to the approval letter for ANDA No. 202608 that “Mallinckrodt’s paragraph IV certification to the ‘798 patent was submitted in an amendment to its ANDA on May 18, 2012, the same day on which this patent was submitted for listing in the Orange Book.”  This certification made Mallinckrodt eligible for 180-day exclusivity with respect to the ‘798 patent.  ANDA No. 202608 also contains Paragraph IV certifications to the ‘373 and ‘129 patents, thereby raising the prospect of shared exclusivity with respect to the ‘129 patent, if there is any exclusivity remaining on that patent.  FDA’s ANDA approval letter does not delve into the issue.  But what the ANDA approval letter does say with respect to 180-day exclusivity associated with the ‘798 patent is quite interesting:

With respect to 180-day generic drug exclusivity, we note that Mallinckrodt was the first ANDA applicant for Methylphenidate Hydrochloride Extended-Release Tablets USP, 27 mg, 36 mg, and 54 mg, to submit a substantially complete ANDA with a paragraph IV certification to the ‘798 patent.  Therefore, with this approval, Mallinckrodt may be eligible for 180 days of generic drug exclusivity for Methylphenidate Hydrochloride Extended-Release Tablets USP, 27 mg, 36 mg, and 54 mg.  This exclusivity would begin to run from the earlier of the commercial marketing or court decision dates identified in section 505(j)(5)(B)(iv).  The agency is not, however, making a formal determination at this time of Mallinckrodt’s eligibility for 180-day generic drug exclusivity.  It will do so only if another paragraph IV applicant becomes eligible for full approval (a) within 180 days of the earlier of the commercial marketing or court decision dates identified in section 505(j)(5)(B)(iv), or (b) at any time prior to the expiration of the ‘798 patent if neither the commercial marketing nor court decision events identified in section 505(j)(5)(B)(iv) has occurred. [(Emphasis added)]

Similar language punting on 180-day exclusivity has appeared in ANDA approval letters for years, dating back to FDA’s July 31, 2006 approval of ANDA No. 076969 for Metoprolol Succinate Extended-Release Tablets (see our previous posts here, here, and here).  All of FDA’s 180-day exclusivity punts, however, have involved post-MMA 180-day exclusivity.  The approval of ANDA No. 202608 marks the first instance in which FDA has punted on pre-MMA 180-day exclusivity.

Naturally, the question is why FDA would have punted on exclusivity in this case.  Certainly, 180-day exclusivity for generic CONCERTA is complicated.  Lingering dispute concerning exclusivity associated with the ‘129 patent may be to blame, perhaps in part.  But we think the primary reason FDA punted in this case is because of the recent decision by Judge Amy Berman Jackson of the U.S. District Court for the District of Columbia in a pre-MMA 180-day exclusivity case concerning generic ACTOS (pioglitazone HCl) Tablets.  In that case, which is on appeal to the U.S. Court of Appeals for the District of Columbia Circuit (see the opening briefs of FDA and Mylan here and here), Judge Jackson ruled against FDA and ordered the approval of Watson’s ANDA No. 076798.  (Motions to expedite the appeal – here and here – were denied.)  As we previously discussed, Judge Jackson’s decision could potentially be interpreted to say that what is in an amendment to an ANDA does not count for 180-day exclusivity purposes.  Rather, it is the original ANDA submission that counts.  In the case of generic CONCERTA, the prospect for Mallinckrodt to become eligible for 180-day exclusivity was the result of an ANDA amendment (as was the case for all of the ANDA first filers here).  So, from FDA’s perspective, it would seem a punt in any pre-MMA case in which exclusivity depends on a Paragraph IV certification contained in an ANDA amendment is warranted until the generic ACTOS case is resolved on appeal.  Reasonable minds may differ, however.