OGD Management Review Results in Forfeiture of Generic ACTONEL 180-Day Exclusivity Eligibility

By Kurt R. Karst –      

The hope is that years from now (but hopefully not too many years), once the review and performance metrics FDA agreed to as part of the Generic Drug User Fee Amendments are in full effect and 10-month ANDA reviews (resulting in timely tentative and final approvals) are the norm, we’ll look back at posts like this one just to refresh our recollection as to how FDA, in the “dark ages,” went about determining that a sponsor forfeited eligibility for a period of 180-day exclusivity under FDC Act § 505(j)(5)(D)(i)(IV).  We’re already in a period of relative calm when it comes to forfeiture, with only a dozen or so FDA decisions so far this year.  But that calm is probably a bit misleading, as forfeiture decisions that would have come up at 30 months after ANDA submission have been delayed to 40 months as a result of the enactment of Section 1133 of the 2012 FDA Safety and Innovation Act (“FDASIA”) (see our previous post here).  

It’s been a while since we last posted on an FDA forfeiture decision.  But that’s the topic of today’s post . . . a recent and interesting case concerning generic ACTONEL (risedronate sodium) Tablets approved under NDA No. 020835.  And the case serves as a gentle reminder of FDA’s “our failure is your failure position” when it comes to the failure-to-obtain-timely-approval forfeiture provision at FDC Act § 505(j)(5)(D)(i)(IV).  First things first, however . . . a little statutory background.

Under FDC Act § 505(j)(5)(D)(i)(IV), 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 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).  Forfeiture decisions involving this provision have been invariably linked to a change in or review of decision under FDC Act § 505(j)(5)(D)(i)(IV).  FDA has yet to make a stand-alone decision under FDC Act § 505(q), adding a specific number of days to the 30-month forfeiture date. 

FDASIA made further changes with respect to the application of FDC Act § 505(j)(5)(D)(i)(IV) to certain ANDAs.  In particular (though not relevant to the case at hand), for an ANDA submitted to FDA between January 9, 2010 and July 9, 2012 initially containing a Paragraph IV certification (or that is amended during that time to first contain a Paragraph IV certification), the time to obtain timely tentative approval (or final approval if tentative approval is not warranted) is 40 months during the period of July 9, 2012 and September 30, 2015, and not 30 months.

FDA’s application of the exception (i.e., the “unless”) provision at FDC Act § 505(j)(5)(D)(i)(IV) was, at first, very narrow and draconian (and it still is to some extent).  For example, FDA explained in an October 2008 Letter Decision that “[t]his express description of the circumstances in which exclusivity will not be forfeited for failure to obtain tentative approval makes it clear that, under other circumstances in which an applicant has failed to obtain tentative approval, regardless of what party might be responsible for that failure, the first applicant will forfeit exclusivity” (emphasis added).  Although FDA still sticks to a “our failure is your failure position,” as we explained in a post back in June 2013, the Agency has shown some willingness to allow a little wiggle room under FDC Act § 505(j)(5)(D)(i)(IV).  In particular, FDA has rejected as too draconian “but for” causation in its application of the statutory forfeiture provision.  As we explained back then:

FDA has determined that even if one of the causes of failure to get tentative approval by the 30-month forfeiture date was a change in or a review of the requirements for approval imposed after the application was submitted, a first applicant will not forfeit eligibility notwithstanding that there may have been other causes for failure to obtain tentative approval by the 30-month forfeiture date that were not caused by a change in or review of the requirements for approval.  That is, to avoid forfeiture, an applicant need only show that acceptability of one aspect of its ANDA (e.g., chemistry, labeling, or bioequivalence) was delayed due, at least in part, to a change in or review of the requirements for approval, irrespective of what other elements may also have been outstanding at the 30-month date.  In other words, “but-for” causation is not required in order to qualify for the exception under FDC Act § 505(j)(5)(D)(i)(IV).  FDA has apparently determined that this interpretation best effectuates the policy embodied in the exception, insofar as it does not penalize first applicants for reviews of or changes in approval requirements imposed after their ANDAs are submitted that cause the failure to obtain approvals or tentative approvals within 30 months, and continues to incentivize applicants to challenge patents by preserving (in many instances) the opportunity to obtain 180-day exclusivity.

In the case of forfeiture of 180-day exclusivity eligibility for generic ACTONEL Tablets, 150 mg, FDA builds on to and hammers home the Agency’s “our failure is your failure position.” 

Teva Pharmaceuticals USA (“Teva”) submitted the first ANDA to FDA – ANDA No. 079215 – containing a Paragraph IV certification for two strengths of generic ACTONEL Tablets: 75 mg and 150 mg.  The first Paragraph IV for the 75 mg strength was submitted on September 10, 2007 as part of the company’s original ANDA submission, and a second Paragraph IV for the 150 mg strength was submitted on August 12, 2008 as part of an amendment to ANDA No. 079215.  Teva’s eligibility for 180-day exclusivity for the 75 mg strength was forfeited pursuant to FDC Act § 505(j)(5)(D)(i)(II) when the company withdrew the strength from ANDA No. 079215 on December 98, 2009, but Teva continued to pursue approval of the remaining 150 mg tablet strength. 

Years passed, and it was not until August 17, 2011 that FDA finally tentatively approved ANDA No. 079215.  This is, of course, more than six months past the date that is 30 months from the August 12, 2008 submission of the 150 mg strength amendment to the ANDA (i.e., February 12, 2011).  (Final ANDA approval was granted on June 13, 2014.) 

Although FDA has not yet posted on the Agency’s Drugs@FDA website a copy of the approval letter for ANDA No. 079215, we were able to get our hands on a copy of FDA’s internal 180-Day Exclusivity Forfeiture Memorandum.  In that memorandum, FDA’s Office of Generic Drugs (“OGD”) details the basis for the Office’s conclusion that Teva forfeited 180-day exclusivity eligibility pursuant to FDC Act § 505(j)(5)(D)(i)(IV), even though as of February 11, 2011, one day prior to the 30-month forfeiture date, all OGD review disciplines had completed review of the ANDA:

We note that although no individual disciplines were outstanding at the 30-month forfeiture date, FDA had not completed its final review of the ANDA by that date.  The decision to approve (or tentatively approve) an ANDA involves not only the disciplines’ evaluations of their respective portions of the ANDA, but final review by [OGD] management.  That final step did not take place by the 30-month forfeiture date, and was complete on August 17, 2011.  We also note that any claim that a company should not forfeit because of the possibility that FDA’s delays caused the company’s failure to obtain tentative approval by the 30-month forfeiture date is unavailing.  Under section 505(j)(D)(1)(IV) of the FD&C Act, exclusivity is forfeited “unless” there is a review of or change in the requirements that has delayed approval or tentative approval of the ANDA.  The statute does not permit, let alone require, either FDA or an ANDA applicant to comb through the ANDA review records and decide whether, had the review been conducted more quickly, the application could have received tentative approval before the 30-month forfeiture date.  Notably, section 1133 of FDASIA . . . , which, among other things, extended the 30-month forfeiture period to 40 months for certain ANDAs, reflects Congress’s understanding both that the length of time that it takes FDA to review an ANDA might contribute to a sponsor’s failure to obtain tentative approval by the 30-month forfeiture date, and that in such instances forfeiture nonetheless may occur.

We’ve always found FDA’s “our failure is your failure position” problematic from a fairness standpoint; however, no company has yet taken FDA to task in a lawsuit challenging the Agency’s interpretation and application of this position.  That’s probably because finding the perfect case is very difficult.  After all, what ANDA file is clean enough from a response timeframe to make such a challenge?