Chemistry Amendment Saves Sun From Forfeiting 180-Day Exclusivity Eligibility for Generic GLEEVEC

By Kurt R. Karst –      

It’s been a while since we posted on a 180-day exclusivity forfeiture issue, though we suspect that we’ll be doing it more in the coming months with some interesting issues on the horizon. But for now, FDA Blog Readers will have to be content with an oldie but a goodie (at least insofar as 2015 is consider old in Hatch-Waxman time).

We recently got our hands on a Memorandum prepared by FDA’s Office of Generic Drugs concerning the Agency’s December 3, 2015 approval of Sun Pharma Global FZE’s (“Sun’s”) ANDA 078340 for generic versions of Novartis Pharmaceuticals Corporation’s GLEEVEC (imatinib mesylate) Tablets, 100 mg and 400 mg, that we though was worth sharing with folks. The ANDA, which contained a Paragraph IV certification qualifying Sun as a first applicant eligible for 180-day exclusivity, was considered received (i.e., filed) by FDA as of March 12, 2007, and was tentatively approved about 32 months later, on November 13, 2009. 

By way of background, 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 2003 Medicare Modernization Act (“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 came into play with Sun ANDA 078340, but we note them nevertheless.

FDA’s letter approving ANDA 078340 says, with respect to 180-day exclusivity, that:

Sun was the first ANDA applicant to submit a substantially complete ANDA for Imatinib Mesylate Tablets, 100 mg (base) and 400 mg (base) with a paragraph IV certification to the ‘051 patent. Therefore, with this approval, Sun is eligible for 180-days of generic drug exclusivity for Imatinib Mesylate Tablets, 100 mg (base) and 400 mg (base).  This exclusivity, which is provided for under section 505(j)(5)(B)(iv) of the FD&C Act, will begin to run from the date of the commercial marketing identified in section 505(j)(5)(B)(iv).  Please submit correspondence to this ANDA informing the agency of the date the exclusivity begins to run.

Although FDA sometimes drops a footnote in an approval letter to explain that an applicant who failed to obtain timely tentative approval neverless remains eligible for exclusivity because of some excuse excepting the applicant from the statutory 30-month period (e.g., ANDA 200156 for Armodafinil Tablets, 100 mg and 200 mg), FDA did not do so in the case of ANDA 078340.  But there’s a story there nevertheless. 

According to FDA’s July 1, 2015 Memorandum, despite Sun’s failure to obtain timely tentative approval by September 12, 2009, the company avoided forfeiting eligiblity for 180-day exclusivity because of a chemistry discipline review issue that remained pending on September 12, 2009.  The specifics of the chemistry review issue are redacted from FDA’s July 1, 2015 Memorandum; however, FDA explains that:

On September 8, 2009, FDA and Sun held [a] chemistry teleconference, during which FDA asked the firm, among other things, to provide a commitment to provide [the requested chemistry information] after tentative approval. Sun responded to this request on September 9, 2009, and provided a commitment to provide [the requested chemistry information] within 15 days of receiving tentative approval.  FDA’s review of Sun’s September 9, 2009 amendment, including the commitment to submit [the requested chemistry information], extended past the 30-month date. . . .  FDA reviewed Sun’s amendment and found chemistry to be acceptable on October 9, 2009, approximately one month after the 30-month forfeiture date.  Based on the above facts, we have determined that there was a change in requirements for approval related to [chemistry information] which FDA was actively addressing at the 30-month forfeiture date, and that this change was a cause of Sun’s failure to obtain tentative approval by the 30-month forfeiture date.

Although FDA could have ended the Agency’s analysis there, the Agency went on to address an argument from Sun that there was a change in ANDA bioequivalence requirements that caused the company to miss the 30-month tentative approval deadline. Specifically, Sun argued that after the submission of ANDA 078340, “FDA required for the first time that the [bioequivalence] studies for [imatinib mesylate tablets] be performed on a patient population” instead of a health volunteer population. FDA identified this as a bioequivalence deficiency in November 19, 2007 correspondence to Sun.  Sun performed new studies and amended ANDA 078340 on April 2, 2009, and again on July 29, 2009. FDA reviewed Sun’s submissions and found bioequivalence to be acceptable on August 27, 2009, about two weeks prior to the September 12, 2009 30-month forfeiture event date.  “Sun’s bioequivalence data was determined to be acceptable prior to the 30-month forfeiture date; therefore, any changes in bioequivalence requirements could not have caused Sun’s failure to obtain tentative approval within 30 months,” says FDA in the July 1, 2015 Memorandum.

Although FDA’s memorandum doesn’t relay the most scintillating 180-day exclusivity forfeiture story we’ve seen, the case provides greater visibility into FDA’s thinking on 180-day exclusivity forfeiture. In addition, it serves as a reminder that just because an ANDA approval letter is silent with respect to 180-day exclusivity forfeiture for failure to obtain timely tentative approval (or with respect to any of the other forfeiture provisions for that matter) doesn’t mean there’s not something else lurking out there providing an explanation.