FDA Petitioned on 180-Day Exclusivity Forfeiture for Tentative Approvals that Occur on the 30-Month ANDA Submission Anniversary Date

June 27, 2012

By Kurt R. Karst –    

We’ve been wondering for a while now when FDA might be asked in a public forum to decide on the issue of whether a “first applicant” eligible for a period of 180-day generic drug marketing exclusivity has forfeited such eligibility if FDA tentatively approves the ANDA on the date that is 30 months from the date of application submission.  That day has come with Sandoz Inc.’s (“Sandoz’s”) June 19, 2012 citizen petition (Docket No. FDA-2012-P-0661) seeking FDA’s determination as to whether purported first applicant Ranbaxy, the sponsor of ANDA No. 077830 for a generic version of NEXIUM (esomeprazole magnesium) Delayed-release Capsules, 20 mg and 40 mg, forfeited 180-day exclusivity eligibility in connection with its ANDA as a result of FDA’s February 5, 2008 tentative approval of the application.  According to FDA’s Paragraph IV Certifications List, August 5, 2005 is the first date on which an ANDA was submitted to FDA containing a Paragraph IV certification to a patent listed in the Orange Book for NEXIUM (NDA No. 021153).

Under FDC Act § 505(j)(5)(D)(i)(IV), which is one of the six 180-day exclusivity forfeiture provisions added to the FDC Act by the 2003 Medicare Modernization Act, 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. [(Emphasis added)]

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 [FDA] 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 FDA Safety and Innovation Act (“FDASIA”) (§ 1133), which is awaiting the President’s signature, would further clarify FDC Act § 505(j)(5)(D)(i)(IV) with respect to certain ANDAs by extending the period during which a first applicant must obtain tentative approval (or final approval if tentative approval is not warranted).  FDASIA § 1133 would not come into play in this case given the 2005 submission date of ANDA No. 077830.

According to Sandoz:

Based on the apparent date on which Ranbaxy’s ANDA was submitted to FDA and the date on which it received tentative approval, Ranbaxy has forfeited its 180-day exclusivity under forfeiture condition (IV), failure to receive tentative approval “within” 30 months after ANDA submission, because Ranbaxy did not obtain tentative approval until the first day of the 31st month and thus not “within” 30 months. (Emphasis in original)

An FDA forfeiture decision is warranted in this case, argues Sandoz, for several reasons.  First, applying common dictionary definitions of the word “within” means that, “‘[w]ithin 30 months’ must be inside that 30-month time period, not outside it” (emphasis in original).  Moreover, counting months – i.e., “the first month after submission of Ranbaxy‘s ANDA on August 5, 2005 ended on September 4, 2005, the second month ended on October 4, 2005, and so on” – means that “February 4, 2008 is the last day that is ‘within’ 30 months of August 5, 2005, ” and as such, “Ranbaxy‘s tentative approval date of February 5, 2008 is one day after expiration of the statutory 30-month period.”  Second, long-standing FDA interpretations and applications of 5-year New Chemical Entity (“NCE”) exclusivity and 7-year orphan drug exclusivity support a forfeiture determination in the case of ANDA No. 077830.  In particular, Sandoz argues with respect to NCE exclusivity that:

[T]the NCE statutory language provides that a Paragraph IV ANDA “may be submitted . . . after the expiration of four years from the date of the approval” of the reference product. . . .  Since FDA has long allowed Paragraph IV ANDAs in this situation to be submitted on the NCE-1 date (the fourth anniversary of the approval of the reference product), FDA must regard the NCE-1 date as the first day of the fifth year after the approval of the reference product.  The logical conclusion is that the last day of “four years from the date of the approval” of the reference product is the day before a Paragraph IV] ANDA may be filed on the NCE-1 date.  (Emphasis in original)

Similarly, Sandoz argues with respect to orphan drug exclusivity that:

Seven-year orphan drug exclusivity prohibits FDA from, in relevant part, approving a generic version of the drug “until the expiration of seven years from the date of the approval of the approved application.” . . .  Just as FDA cannot accept a Paragraph IV ANDA where the RLD is protected by five-year NCE exclusivity until after the expiration of four years from the date of approval of the RLD, FDA cannot approve a generic drug where the innovator product is protected by seven-year orphan drug exclusivity until after the expiration of seven years from the date of approval of the innovator product.  (Emphasis in original)

Finally, Sandoz says that its interpretation of FDC Act § 505(j)(5)(D)(i)(IV) “best serves the public health and the intent of the Hatch-Waxman Amendments,” becuase it “would potentially open the generic market much sooner.”

Interestingly, this is not the first time Sandoz has raised the “within 30 months” issue with FDA.  As we previously reported, back in 2010, Caraco Pharmaceutical Laboratories, Ltd. (“Caraco”), a subsidiary of Sun Pharmaceutical Industries Limited, issued a quarterly report stating with respect to 180-day exclusivity for generic PRANDIN (repaglinide) Tablets that:

The Company believes that it is the first to file an ANDA with a Paragraph IV certification for this drug product and it intends to defend this action vigorously to capitalize on the potential for obtaining 180 days exclusivity available for this product.  On May 26th, 2010, the Company received correspondence from the FDA forwarding a letter sent by Sandoz Inc. to the FDA challenging the Company’s 180 day exclusivity based on when the Company received tentative approval for its product.  The Company responded to the FDA on June 17, 2010.  On June 28th, 2010, Sandoz Inc. replied to the Company’s correspondence.  The Company issued a further letter to the FDA stating its position regarding the 180 day exclusivity on July 9, 2010.  The Company believes it received tentative approval timely, and that it has the potential to obtain 180 day exclusivity for this product.  It intends to defend that position vigorously.

Sandoz notes in the company’s June 2012 petition (footnote 17) that the arguments the company raises with respect to generic NEXIUM Delayed-release Capsules apply “with equal force to the same factual scenario as found for generic versions of PRANDIN® (repaglinide) Tablets.”

Making things even more interesting is speculation that Ranbaxy’s ANDA No. 077830 for generic NEXIUM Delayed-release Capsules is one of the unidentified ANDAs in the Consent Decree (see here and here) the United States filed against Ranbaxy earlier this year and for which Ranbaxy agreed to forfeit 180-day exclusivity.  Although the list of ANDAs subject to forfeiture has not been made public, we note that FDA’s most recent update to the Paragraph IV Certifications List shows that long-pending ANDAs for generic DEPAKOTE ER (divalproex sodium) Extended-release Tablets, 250 mg, and DETROL (tolterodine tartrate) Tablets, 1 mg and 2 mg, were withdrawn (and presumably resulted in a forfeiture of any associated 180-day exclusivity under FDC Act § 505(j)(5)(D)(i)(II)).  FDA tentatively approved Ranbaxy’s ANDA No. 076953 for generic DETROL Tablets, 1 mg and 2 mg, on September 15, 2005.  FDA tentatively approved Ranbaxy’s ANDA No. 077143 for generic DEPAKOTE ER Extended-release Tablets, 250 mg, on September 12, 2005.