By Kurt R. Karst –
Fumble!! For years now we have discussed and tracked various FDA decisions (or non-decisions as the case may be) on what have been referred to as “180-day exclusivity punts.” These are instances in which a first applicant eligible for 180-day exclusivity gets ANDA approval, but FDA decides not to decide on whether or not to grant exclusivity. The first instance of a “180-day exclusivity punt” occurred with the July 31, 2006 approval of ANDA No. 076969 for Sandoz Inc.’s Metoprolol Succinate Extended-Release Tablets USP, 25 mg (see our previous post here). In the years since then, FDA has used the punt mechanism with impunity, and in various contexts (see our previous post here), including in one instance under the law in effect prior to the December 2003 enactment of the Medicare Modernization Act (“MMA”) (see our previous post here). But FDA had never resolved a punt – whether in the form of a “punt return” where FDA affirms a first applicant’s eligibility for 180-day exclusivity, or in the form of a “fumble return” where FDA affirms a first applicant’s forfeiture of 180-day exclusivity eligibility. That all changed with the May 30, 2013 approval of Banner Pharmacaps’s (“Banner’s”) ANDA No. ANDA No. 200899 for a generic version of GlaxoSmithKline’s AVODART (dutasteride) Capsules, 0.5 mg.
FDA’s decision on Dutasteride Capsules, 0.5 mg, 180-day exclusivity came about in the context of the most familiar type of punt: failure to obtain timely tentative ANDA approval. 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 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). Neither the FDAAA, nor the FDASIA provisions are at issue in the Dutasteride case.
FDA’s application of FDC Act § 505(j)(5)(D)(i)(IV) has led to scores of forfeitures of 180-day exclusivity eligibility. Several more forfeitures have been avoided as a result of FDA’s application of the exception provisions above (see our previous post here), including one decision that led to an unsuccessful lawsuit last year over a generic version of DIOVAN (valsartan) Tablets (see our previous post here). Sometimes the 30-month date is missed by just a few days (see our previous post here), or even by a day because of a natural disaster (see our previous post here). Sometimes 180-day exclusivity eligibility is forfeited upon patent certification because of an FDA interpretation that FDASIA remedies on a limited basis (see our previous post here). In other instances, however, FDA is able to tease out a basis for determining that failure to obtain timely tentative approval was due to a change that led to, for example, an “irrecoverable delay” (akin to ripples in a pond when a stone is cast in) (see, e.g., ANDA No. 200156 for Armodafinil Tablets, 100 mg and 200 mg).
FDA has discussed its application of FDC Act § 505(j)(5)(D)(i)(IV) on several occasions, including in Citizen Petition responses – see, e.g., Docket No. FDA-2011-P-0486 and Docket No. FDA-2010-P-0632 – and in court briefs. For example, FDA has explained:
This provision [(i.e., FDC Act § 505(j)(5)(D)(i)(IV))] establishes a bright-line rule: If within 30 months of submission, an ANDA has been determined by the agency to meet the statutory standards for approval and it is only patent and/or exclusivity protection that prevents full approval, then an applicant will be given a tentative approval and will maintain its eligibility for 180-day exclusivity. If tentative approval is not obtained within 30 months, eligibility for 180-day exclusivity is generally forfeited unless “the failure (to obtain an approval) 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” (emphasis added). Under this provision it is not sufficient to show that FDA changed or reviewed the requirements for approval while the application was under review. The applicant must also show that its failure to obtain a tentative approval at the 30 month date is caused by this change in or review of approval requirements – that is, the issues holding up approval at the 30 month date must be causally connected to the approval requirements that FDA reviewed or changed.
A less known fact is that FDA has considered and rejected as too draconian “but for” causation in its application of FDC Act § 505(j)(5)(D)(i)(IV). Thus, 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 Dutasteride Capsules, 0.5 mg, Barr Laboratories, Inc. (“Barr”) was the first company to submit an ANDA with a Paragraph IV certification challenging an Orange Book-listed patent for the reference listed drug, AVODART. Specifically, ANDA No. 090095 was considered received by FDA as of October 29, 2007 with Paragraph IV certifications to the three listed patents on AVODART. Patent infringement litigation was initiated, but was ultimately dismissed by agreement of the parties on May 10, 2010. FDA approved ANDA No. 090095 on December 21, 2010 with the now all too familiar 180-day exclusivity punt language:
The agency notes that Barr failed to obtain tentative approval of this ANDA within 30 months after the date on which the ANDA was filed. See section 505(j)(5)(D)(i)(IV) (forfeiture of exclusivity for failure to obtain tentative approval). The agency is not, however, making a formal determination at this time of Barr’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 Barr begins commercial marketing of Dutasteride Capsules, 0.5 mg, or (b) at any time prior to the expiration of the last listed patent if Barr has not begun commercial marketing.
Barr never commercially marketed its drug product, presumably as a result of the settlement of patent infringement litigation, nor did Barr, to our knowledge, market an authorized generic version of the drug. Thus, Barr’s 180-day exclusivity was never triggered. Meanwhile, FDA’s review of Banner’s ANDA progressed, and a tentative approval was granted on March 25, 2013. This likely placed FDA in the position of having to decide on 180-day exclusivity for Dutasteride Capsules, 0.5 mg. A further review of Barr’s ANDA file presumably did not show that forfeiture of exclusivity eligibility could be avoided, and FDA approved ANDA No. 200899 on May 30, 2013. Thus, we now have the first instance in which FDA has resolved a 180-day exclusivity punt.