By Kurt R. Karst –
Each month we pore over the latest Orange Book Cumulative Supplement in an effort to keep our popular 180-Day Exclusivity Tracker as current as possible, and to look for interesting precedents. Last month, one entry in particular caught our attention. It was for ANDA 200828 for Lamotrigine Orally Disintegrating Tablets, 25 mg, 50 mg, 100 mg, and 200 mg, a generic version of GlaxoSmithKline LLC’s LAMICTAL ODT (NDA 022251). The Orange Book Cumulative Supplement showed the addition of periods of “PC” exclusivity (i.e., 180-day patent challenge exclusivity) expiring on September 28, 2015 for all four strengths covered under the ANDA now owned by Impax Laboratories, Inc. (“Impax”) (formerly owned by Watson Laboratories, Inc. (“Watson”)). What made the entry of 180-day exclusivity interesting is that FDA’s July 15, 2013 letter approving the ANDA included the Agency’s all-too-familiar 180-day exclusivity “punt” language:
With respect to 180-day generic drug exclusivity, we note that Watson was the first ANDA applicant for Lamotrigine Orally Disintegrating Tablets, 25 mg, 50 mg, 100 mg, and 200 mg, to submit a substantially complete ANDA with a paragraph IV certification. Therefore, with this approval, Watson may be eligible for 180 days of generic drug exclusivity for Lamotrigine Orally Disintegrating Tablets, 25 mg, 50 mg, 100 mg, and 200 mg. This exclusivity, which is provided for under section 505(j)(5)(B)(iv) of the Act, would begin to run from the date of the commercial marketing identified in section 505(j)(5)(B)(iv). The agency notes that Watson failed to obtain tentative approval of this ANDA within 40 months after the date on which the ANDA was filed. See section 505(j)(5)(D)(i)(IV) (forfeiture of exclusivity for failed to obtain tentative approval). The agency is not, however, making a formal determination at this time of Watson’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 after Watson begins commercial marketing of Lamotrigine Orally Disintegrating Tablets, 25 mg, 50 mg, 100 mg, and 200 mg, or (b) at any time prior to the expiration of the listed patents if Watson has not begun commercial marketing. Please submit correspondence to this ANDA informing the agency of the date commercial marketing begins.
FDA’s Orange Book entry showing the addition of 180-day exclusivity could mean only one thing: that the Agency was forced into a position of determining whether or not eligibility for 180-day exclusivity was forfeited. So we obtained a copy of FDA’s exclusivity determination to make sure. And sure enough, FDA ruled on October 29, 2014 – just one day before tentatively approving Par’s ANDA 204158 for Lamotrigine Orally Disintegrating Tablets, 25 mg, 50 mg, 100 mg, and 200 – that Watson (now Impax) maintained eligibility for exclusivity because of a change in the requirements for approval with respect to labeling.
By way of background, under FDC Act § 505(j)(5)(D)(i)(IV), one of the six 180-day exclusivity provisions added to the FDC Act by Title XI of 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 the Secretary 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 (see our previous post here). Although the FDAAA provision did not come into play in the case of ANDA 200828, the FDASIA provision did, as noted below.
For years – ever since the July 31, 2006 approval of ANDA 076969 for Metoprolol Succinate Extended-Release Tablets USP, 25 mg (see our previous post here) – FDA has been deciding not to decide on eligibility for 180-day exclusivity when there is no immediate need to do so. It’s been rare that FDA has had to resolve 180-day exclusivity punts.
The first punt resolution was made in the context of ANDA No. 200899 for Dutasteride Capsules, 0.5 mg. As we previously posted, in that case, FDA ruled that eligibility for 180-day exclusivity was forfeited. The second punt resolution was made in the context of ANDA 202608 for Methylphenidate HCl Extended-release Tablets, 27 mg, 36 mg, and 54 mg, as we previously noted. Although FDA ruled that 180-day exclusivity was not forefeited (a punt return), it was a bit of an oddball case. First, the drug at issue – a generic version of CONCERTA Extended-release Tablets – is a pre-MMA drug not subject to the failure-to-obtain-timely-tentative-approval forfeiture provision at FDC Act § 505(j)(5)(D)(i)(IV). Second, FDA appears to have made the punt decision in the context of then-ongoing litigation that could have affected an exclusivity determination. So the latest decision out of FDA concerning Lamotrigine Orally Disintegrating Tablets might be the first post-MMA punt return decision.
Watson submitted ANDA 200828 to FDA on December 21, 2009. But at the time of submission, the ANDA did not contain a Paragraph IV certification, and therefore, Watson was not a “first applicant” eligible for 180-day exclusivity. First applicant status was conferred on April 14, 2011,when the ANDA was amended to include a Paragraph IV certification to U.S. Patent No. 7,919,115 listed in the Orange Book for LAMICTAL ODT. That made ANDA 200828 an application subject to the later-enacted provisions in the 2012 FDASIA extending the 30-month deadline under FDC Act § 505(j)(5)(D)(i)(IV) to 40 months. But as FDA noted in the Agency’s July 15, 2013 approval letter:
For applications submitted between January 9, 2010, and July 9, 2012, section 1133 of the Food and Drug Administration Safety and Innovation Act (FDASIA) (P.L. 112-144) extends this period to 40 months. This includes applications such as ANDA 200828 “amended during such period to first contain [a PIV certification]…” Watson therefore qualifies for 40 (not 30) months in the application of section 505(j)(5)(D)(i)(IV) (forfeiture of exclusivity for failed to obtain tentative approval). However, this 40-month period dates from the date of receipt of the ANDA (December 21, 2009), not the date the paragraph IV amendment was received. [sic] (April 14, 2011), because this ANDA does not meet the terms of section 1133(b) of FDASIA.
But that’s all irrelevant now given FDA’s October 29, 2014 exclusivity determination. After going through the relevant law, including FDA’s position rejecting “but-for” causation in analyzing FDC Act § 505(j)(5)(D)(i)(IV) (see our previous post here), FDA turned to the facts at hand. And, specifically, to changes to the RLD (LAMICTAL ODT) labeling. According to FDA:
A fifth labeling change was approved on August 1, 2012, approximately 8 months before the forfeiture date. This labeling change provided for Agency-requested updates to the Use in Specific Populations/Nursing Mothers (section 8.3) and Patient Counseling information/Pregnancy and Nursing (section 17.6) section of the labeling, as well as corresponding changes to the Medication Guide.
FDA initially reviewed Impax’s labeling on May 11, 2010, and identified a number of deficiencies. Impax submitted an amendment responding to FDA’s deficiencies on July 13, 2010. FDA reviewed Impax’s amendment on October 23, 2011, and identified additional deficiencies. One of the deficiencies asked Impax to update its package insert and medication guide labeling to be in accord with the August 4, 2011 approved labeling changes for the RLD. Impax submitted an amendment responding to FDA’s deficiencies on April 2, 2012. Before FDA reviewed lmpax’s April 2, 2012 amendment, Impax submitted another labeling amendment on September 10, 2012, to update their labeling to be consistent with the RLD labeling changes approved on August 1, 2012. FDA reviewed Impax’s April 2, 2012 and September 10, 2012 labeling amendments and on April 24, 2013, three days after the 40-month forfeiture date of April 21, 2013, FDA notified Impax of additional labeling deficiencies. Impax submitted an amendment on May 7, 2013. FDA reviewed Impax’s amendment, and ultimately determined Impax’s labeling to be acceptable on May 30, 2013. . . .
We conclude that there were changes to the requirements for approval with respect to labeling, as outlined above. We also find evidence that these labeling changes caused Impax's failure to obtain tentative approval by the forfeiture date. Specifically, changes to the RLD labeling were approved on August 1, 2012, and Impax submitted a labeling amendment on September 10, 2012 to update their labeling. At the 40-month date of April 21, 2013, Impax’s labeling amendment had not been reviewed by FDA, and the labeling deficiencies issued by FDA after the 40-month forfeiture date related to the changes to the RLD labeling that occurred after Impax submitted its ANDA.
So, there you have it – what seems to be the first true post-MMA 180-day exclusivity punt return.