FDA Solicits Comments on 180-Day Exclusivity Forfeiture & Orange Book Patent “Delisting” Issues

September 26, 2007

Earlier today, FDA’s Office of Generic Drugs posted a letter on its website requesting comment on certain 180-day exclusivity forfeiture and Orange Book patent “delisting” issues concerning at least one ANDA submitted to the Agency containing a paragraph IV patent certification requesting FDA approval for a generic version of Bayer Pharmaceuticals’ PRECOSE (acarbose) Tablets.

Under changes made to the FDC Act by the 2003 Medicare Modernization Act (“MMA”), generic applicants that are “first applicants” are eligible for 180-day exclusivity, unless such eligibility is forfeited.  180-day exclusivity eligibility may be forfeited if, among other reasons, a “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” (FDC Act § 505(j)(5)(D)(i)(IV)), or if such applicant fails to market the drug “30 months after the date of submission of the application” (FDC Act § 505(j)(5)(D)(i)(I)(aa)(BB)).  Although FDA was previously confronted by a potential forfeiture case involving a company’s failure to obtain tentative approval within 30 months of ANDA submission, the Agency ultimately did not have to resolve the situation. 

With respect to Orange Book patent “delisting,” the U.S. Court of Appeals for the District of Columbia Circuit ruled in November 2006 on the question of “whether the FDA may delist a patent upon the request of the NDA holder after a generic manufaturer has filed an ANDA containing a paragraph IV certification so that the effect of delisting is to deprive the applicant of a period of marketing exclusivity.”  In striking down FDA’s policy decision on the matter, the court reasoned:

Not only does the statute not require litigation to preserve a generic applicant’s eligibility for exclusivity . . . such a requirement is inconsistent with the structure of the statute because, if the patent is delisted before a pending ANDA is approved, then the generic manufacturer may not initiate a period of marketing exclusivity.

By thus reducing the certainty of receiving a period of marketing exclusivity, the FDA’s delisting policy diminishes the incentive for a manufacturer of generic drugs to challenge a patent listed in the Orange Book in the hope of bringing to market a generic competitor for an approved drug without waiting for the patent to expire.  The FDA may not, however, change the incentive structure adopted by the Congress.

In the matter currently before FDA concerning Acarbose Tablets, there is one patent listed in the Orange Book for PRECOSE (NDA #20-482), U.S. Patent No. 4,904,769 (“the ‘769 patent”), which expires on September 6, 2009.  At least one generic applicant submitted an ANDA to FDA on March 22, 2005 containing a paragraph IV certification to the ‘769 patent.  According to FDA’s September 26, 2007 letter:

As of the date of this letter, which is more than 30 months from March 22, 2005, no first applicant’s ANDA has been approved. Also, on April 16, 2007, Bayer requested that the ‘769 patent be “delisted” as to Precose, i.e., they withdrew the patent information.  On September 26, 2007, FDA indicated in [the Orange Book] that the request to delist this patent had been submitted on April 16, 2007.

To determine whether any ANDA referencing Precose is eligible for final approval, the agency must consider how the 180-day generic drug exclusivity forfeiture provisions at section 505(j)(5)(D) of the [FDC Act] apply to this set of facts.  As part of the process for making such a determination, we are seeking your views regarding the applicability of sections 505(j)(5)(D)(i)(IV) — failure to obtain tentative approval within 30 months — and 505(j)(5)(D)(i)(I)(aa)(BB) — failure to market by 30 months. We also are interested in your views regarding the applicability of section 505(j)(5)(D)(i)(I)(bb)(CC) — relating to the delisting of a patent.

FDA’s letter requests that comments be submitted to the Agency by October 10, 2007.  FDA’s decision to request comment on Acarbose Tablets exclusivity issues is part of an increasing trend at FDA to ask for input to help resolve complicated exclusivity issues.  In March 2007, FDA requested comment on amlodipine besylate 180-day and pediatric exclusivity issues, and in August 2007, FDA requested comment on midodrine HCl three-year exclusivity issues.  Presumably FDA will continue this trend as new issues crop up, particularly post-MMA 180-day exclusivity issues.  

Categories: Hatch-Waxman