FDA Solicits Public Comment on Yet Another 180-Day Generic Drug Exclusivity Issue

For the third time in as many weeks, FDA has requested public comment to help resolve 180-day exclusivity issues.  This time FDA’s request concerns the antinauseant and antiemetic drug granisetron HCl, which is marketed by Roche under the tradename KYTRIL.  In late September, FDA solicited comment on acarbose (PRECOSE) (9/26/2007 FDA Law Blog post) generic exclusivity issues, and earlier this week the Orange Book Blog reported that FDA requested comment on ramipril (ALTACE) 180-day exclusivity issues.  These requests follow others from earlier this year on a variety of exclusivity issues concerning amlodipine besylate and midodrine HCl.

FDA’s latest solicitation is the result of a letter submitted by Teva Parenteral Medicines (“Teva”) and involves the “failure to market” 180-day exclusivity forfeiture provisions at FDC Act § 505(j)(5)(D)(i)(I).  Under these provisions, a generic applicant whose ANDA contains a paragraph IV patent certification and who is a “first applicant” eligible for 180-day exclusivity forfeits eligibility for such exclusivity if the firm fails to market the drug by the later of:

(aa) the earlier of the date that is --

(AA) 75 days after the date on which the approval of the application of the first applicant is made effective under subparagraph (B)(iii); or

(BB) 30 months after the date of submission of the application of the first applicant; or

(bb) . . . the date that is 75 days after the date as of which, as to each of the patents with respect to which the first applicant submitted and lawfully maintained a certification qualifying the first applicant for the 180-day exclusivity period under subparagraph (B)(iv), at least 1 of the following has occurred:

(AA) In an infringement action brought against that applicant with respect to the patent or in a declaratory judgment action brought by that applicant with respect to the patent, a court enters a final decision from which no appeal (other than a petition to the Supreme Court for a writ of certiorari) has been or can be taken that the patent is invalid or not infringed.

(BB) In an infringement action or a declaratory judgment action described in subitem (AA), a court signs a settlement order or consent decree that enters a final judgment that includes a finding that the patent is invalid or not infringed.

(CC) The patent information submitted under [FDC Act § 505(b) or (c)] is withdrawn by the holder of the application approved under [FDC Act § 505(b)].

These forfeiture provisions, which were added to the FDC Act by the Medicare Modernization Act (“MMA”) in December 2003, have been controversial.  Indeed, Senator Orrin Hatch (R-UT) expressed concern about how to interpret them within 24 hours of the MMA’s enactment.  Teva’s letter to FDA illustrates a current example of the complexity of the statutory forfeiture provisions. 

In May 2004, Teva submitted the first ANDA to FDA containing a paragraph IV certification for a generic version of KYTRIL.  The application also contained a paragraph III certification (date of patent expiration) and a section viii statement to a method-of-use patent.  Roche did not sue Teva (or any subsequent ANDA applicant) for patent infringement, and FDA tentatively approved Teva’s ANDA in August 2005.  To date, FDA has not approved Teva’s ANDA, and cannot do so until the patent subject to the paragraph III certification expires in December 2007.  Nevertheless, the 30-month period described in FDC Act § 505(j)(5)(D)(i)(I)(aa)(BB) above expired in November 2006. 

Teva argues that despite the expiration of the 30-month period, the firm remains eligible for 180-day exclusivity, which would be triggered by Teva’s commercial marketing of the drug.  Specifically, Teva’s letter states:

[T]he plain language and structure of the [FDC Act] compel the conclusion that Teva is entitled to 180-day exclusivity because Teva is the first applicant that submitted a substantially complete paragraph IV ANDA . . . .  Teva’s exclusivity has not been forfeited . . . because there is a continuing possibility of ANDA-based patent litigation that could result in a “later” forfeiture event under [FDC Act § 505(j)(5)(D)(i)(I)]. . . .

[The FDC Act] requires FDA to determine which is “the later of” (1) a determinate forfeiture trigger . . . “or” (2) a contingent forfeiture trigger . . . .  But there is no conceivable way for FDA to determine which of those 2 potential triggers occurs “later” until (a) one of the contingencies that could give rise to a forfeiture trigger [under FDC Act § FDC Act § 505(j)(5)(D)(i)(I)(bb)] has occurred, or (b) none of the contingencies can occur.  After all, it is impossible to know whether a contingent event has occurred before it does occur -- and twice as hard to determine that such an event will not occur until it no longer can occur.

FDA’s increasing trend to attempt to resolve post-MMA 180-day exclusivity issues on a case-by-case basis, instead of the Agency proactively addressing such issues more broadly in proposed and final regulations, may very well mean that the courts will end up setting the ground rules for interpreting the FDC Act’s exclusivity provisions, even more so than under the pre-MMA exclusivity provisions.