Simultaneously Qualifying for and Forfeiting 180-Day Exclusivity Eligibility for Failure to Obtain Timely Tentative Approval

By Kurt R. Karst –      

On occasion we dream about Hatch-Waxman and wake up in the morning with a burning question.  One of the recent questions we wondered about is whether FDA would take the position that an ANDA sponsor who amends a long-pending ANDA to include a Paragraph IV certification to a newly (and timely) listed patent in the Orange Book and qualifies as a “first applicant” would simultaneously forfeit 180-day exclusivity eligibility for failure to obtain timely tentative approval.  FDA’s answer to that question appears to be “yes” absent application of one of the statutory savings provisions. 

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 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 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)). 

Under FDC Act § 505(j)(5)(D)(i)(IV), the date the 30-month period begins is the date of ANDA submission.  The statute does not specifically reference the date of the submission of a Paragraph IV certification.  Thus, the statute leaves open the possibility that an ANDA is initially submitted to FDA without a Paragraph IV certification, thereby beginning the 30-month period, and is only later amended to include the first Paragraph IV certification to an Orange Book-listed patent covering the Reference Listed Drug (“RLD”).  (Perhaps in the context of a later-listed patent, or where all ANDA sponsors initially – and post-MMA –  submitted Paragraph III certifications to all Orange Book-listed patents and one ANDA sponsor then changed a certification to a Paragraph IV.)  If, however, that first applicant-qualifying Paragraph IV certification is made more than 30 months after ANDA submission, then it seems that FDA could take the position that FDC Act § 505(j)(5)(D)(i)(IV) comes into play and 180-day exclusivity eligibility is automatically forfeited absent “a change in or a review of the requirements for approval of the application imposed after the date on which the application is filed” or a decision by FDA that “approval of the [ANDA] was delayed because of a [citizen] petition.” 

Indeed, FDA appears to have been faced with a similar circumstance in the context of ANDA approvals for generic versions of DORYX (doxycycline hyclate) Delayed-Release Tablets.  Two ANDAs – ANDA No. 90-431 and ANDA No. 90-505 – were reportedly submitted to FDA in March 2008 at a time when patents could not be submitted to FDA for Orange Book listing for so-called “old” antibiotics.  Section 4 of the “QI Program Supplemental Funding Act of 2008” (the “QI Act”), which was enacted on October 8, 2008 and amended the FDC Act to add new § 505(v) – “Antibiotic Drugs Submitted Before November 21, 1997” – created Hatch-Waxman benefits for “old” antibiotics, including the ability to list patents in the Orange Book.  A QI Act transition provision also provides for 180-day exclusivity eligibility for each ANDA sponsor that not later than 120 dates after enactment of the QI Act (i.e., February 5, 2009) amended a pending application to contain a Paragraph IV certification to a newly-listed antibiotic drug patent on the RLD.  ANDA Nos. 90-431 and 90-505 were both amended to contain a Paragraph IV certification, qualifying the applications for 180-day exclusivity. 

According to one Doxycycline Hyclate Delayed-Release Tablets ANDA approval letter, FDA calculated the 30-month period under FDC Act § 505(j)(5)(D)(i)(IV) from the date of original ANDA submission (March 18, 2008) and not from the date of the amendment adding the exclusivity-qualifying Paragraph IV certification (most likely December 9, 2008), thereby resulting in a 30-month period ending in September 2010 instead of June 2011.  FDA approved both ANDA Nos. 90-431 and 90-505 on December 28, 2010 without having previously granted tentative approval.  Although FDA determined that the 30-month period under FDC Act § 505(j)(5)(D)(i)(IV) was missed, the Agency says that there was a change in or a review of the requirements for approval of the applications and a related citizen petition (Docket No. FDA-2008-P-0586) that saved them from forfeiting 180-day exclusivity eligibility. 

The Doxycycline Hyclate Delayed-Release Tablets ANDA approvals thus appear to stand for FDA’s interpretation that 180-day exclusivity eligibility can be forfeited where the first exclusivity-qualifying Paragraph IV certification is submitted to FDA more than 30 months after a first applicant’s ANDA is submitted to FDA.  A cursory review of FDA’s Paragraph IV Certification List shows that there may be a few cases in which FDA’s interpretation of FDC Act § 505(j)(5)(D)(i)(IV) could come into play and result in a forfeiture (absent application of one of the statutory savings provisions). 

Of course, there may be instances in which, despite a forfeiture of 180-day exclusivity eligibility under FDA’s interpretation of the start of the 30-month period, there is still some benefit to being a “forfeited first applicant,” as FDA discussed in the Agency’s September 2009 Letter Decision concerning 180-day exclusivity for Nateglinide Tablets – see our previous post here.  Any benefit, however, would only materialize if there are multiple first applicants and where at least one first applicant has not forfeited 180-day exclusivity eligibility.  In the case of a single first applicant, FDA’s interpretation of FDC Act § 505(j)(5)(D)(i)(IV) would result in a total forfeiture unless one of the statutory savings provisions applies.

Presumably FDA will explain its various interpretations of FDC Act § 505(j)(5)(D)(i)(IV) and the other forfeiture provisions in regulations the Agency is drafting to implement the 2003 MMA, although it might be a while until these regulations see the light of day.  We understand that FDA plans to issue two sets of proposed regulations.  The first set will reportedly deal with all of the MMA’s non-180-day exclusivity provisions and might be out by the end of 2011.  (We’ve heard that those proposed regulations currently total about 350 double-spaced pages.)  The second set of regulations will reportedly deal with 180-day exclusivity and is still under development.