FDA Denies Citizen Petition on Generic COMBIVIR 180-Day Exclusivity “First Applicant” Issue

By Kurt R. Karst –      

Last week, in a seven-page response, FDA denied an October 18, 2010 Citizen Petition submitted on behalf of Lupin Limited (“Lupin”) requesting that FDA determine that Teva Pharmaceuticals USA, Inc.’s (“Teva’s”) ANDA No. 79-081 for a generic version of COMBIVIR (lamivudine and zidovudine) Capsules, and that contains the first Paragraph IV certification to an Orange Book-listed patent on the Reference Listed Drug (“RLD”), is not eligible for 180-day exclusivity.  In its response, FDA affirms that the plain language of the definition of a “first applicant” at FDC Act § 505(j)(5)(B)(iv)(II)(bb) as added by the 2003 Medicare Modernization Act (“MMA”) simply requires a Paragraph IV certification, regardless of what Orange Book-listed patent that certification concerns. 

COMBIVIR is listed in the Orange Book with two unexpired patents – U.S. Patent No. 5,859,021 (“the ‘021 Patent”), which expires on May 15, 2012, and U.S. Patent No. 5,905,082 (“the ‘082 Patent”), which expires on May 18, 2016 and is subject to a period of pediatric exclusivity that expires on November 18, 2016.  Teva submitted ANDA No. 79-081 to FDA on June 26, 2007 containing a Paragraph IV certification to the earlier-expiring ‘021 Patent, and a Paragraph III certification to the later-expiring ‘082 Patent.  In October 2008, Teva reportedly amended its ANDA to contain a Paragraph IV certification to the ‘082 Patent.  In the meantime, Lupin submitted an ANDA in January 2008 containing Paragraph IV certifications to both the ‘021 and ‘082 patents. 

Under the FDC Act as amended by the MMA, a “first applicant” qualifies for 180-day exclusivity.  The term “first applicant” is defined as “an applicant that, on the first day on which a substantially complete application containing a [Paragraph IV certification] is submitted for approval of a drug, submits a substantially complete application that contains and lawfully maintains a [Paragraph IV certification] for the drug.”  Lupin argues in its Citizen Petition that Teva is “not a lawful ‘first applicant’” based on its Paragraph IV certification to the earlier-expiring ‘021 Patent.   Instead, Lupin says that it is the correct “first applicant” based on its Paragraph IV certification to the later-expiring ‘082 Patent.  FDA’s petition response boils Lupin’s Citizen Petition arguments down to the following: “According to Petitioner, Teva fails to qualify as a first applicant because its ANDA (1) cannot be considered to have contained a valid paragraph IV certification, (2) cannot be considered to have been substantially complete, and (3) cannot be considered to have lawfully maintained a paragraph IV certification.”

Hewing close to the statutory language, FDA reasons in its petition response that:

Regardless of Teva’s reason for initially challenging only the ‘021 patent, its paragraph IV certification to that patent qualified it for exclusivity.  The statute provides that an applicant submitting a paragraph IV certification will be a “first applicant” (i.e., eligible for exclusivity) if on the first day any applicant submits a substantially complete application containing a paragraph IV certification, the applicant “submits a substantially complete application that contains and lawfully maintains a [paragraph IV certification]” (section 505(j)(5)(B)(iv)(II)(bb) of the Act (emphasis added)).  The plain language of the MMA requires “a” certification; it does not require a first applicant to be the first to challenge with a paragraph IV certification more than a single patent or even the latest expiring patent.  If Teva was the first to file a paragraph IV patent certification for a listed patent for Combivir (and otherwise meets the statutory requirements), that is adequate in these circumstances; we need not second guess the particular strategy Teva has employed in its patent challenge.

Given this reasoning, FDA concludes that Teva, not Lupin, is a “first applicant” eligible for 180-day exclusivity based on Teva’s Paragraph IV certification to the ‘021 Patent contained in ANDA No. 79-081 (which the Agency approved on May 25, 2011).  A similarly strict reading of the statute also appears to be reflected in another recent FDA decision in which the Agency interpreted the 30-month date under FDC Act § 505(j)(5)(D)(i)(IV) for purposes of 180-day exclusivity forfeiture.