FDA Fixes Position on NCE Exclusivity for Certain FDCs; Prospective Effect Only Determination May Mean Some Companies Could be Fixin for a Fight

By Kurt R. Karst –      

Last Friday morning (October 10th) something interesting popped up out of the blue on FDA’s “What’s New Related to Drugs” webpage: the final version of FDA’s “Guidance for Industry – New Chemical Entity Exclusivity Determinations for Certain Fixed-Combination Drug Products.”  But both the timing and content of the final guidance might mean FDA is in store for some controversy in the not too distant future. 

FDA published a draft version of the guidance in February 2014 (see our previous post here) saying that the Agency would reinterpret the NCE exclusivity provisions of the FDC Act to award NCE exclusivity for a newly approved Fixed-Dose Combination Drug (“FDC”) containing an NCE and a previously approved drug.  The draft guidance states, however, that if the Agency’s new interpretation is adopted, it will apply only prospectively: “If the new interpretation is adopted, FDA intends to apply the new interpretation prospectively.  Therefore, this guidance does not apply to fixed-combination drug products that were approved prior to adopting the new interpretation.”  About a dozen comments were submitted to FDA.  Most of the comments applauded FDA’s proposal and urged the Agency to finalize the guidance promptly. 

FDA proposed the reinterpretation after having received three Citizen Petitions in 2013 requesting that FDA interpret the law to award NCE exclusivity for approved FDCs containing an NCE and a previously-approved drug – specifically STRIBILD (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate) Tablets (Docket No. FDA-2013-P-0058); PREPOPIK (sodium picosulfate, magnesium oxide and citric acid) for Oral Solution (Docket No. FDA-2013-P-0119); and NATAZIA (estradiol valerate and estradiol valerate/dienogest) Tablets (Docket No. FDA-2013-P-0471).  However, on the same day FDA posted the draft guidance on the Agency’s website, FDA issued a Consolidated Response denying the three petitions and saying that although FDA would reinterpret the law, that reinterpretation would not apply to previously-approved FDCs.  That move prompted two of the petitioners to each submit a Petition for Reconsideration (with respect to STRIBILD and PREPOPIK) (see our previous posts here and here). Along the way, another company entered the fray (or what we dubbed the “NCE for FDC Club”).  Specifically, Pfizer Inc. submitted a Citizen Petition petition (Docket No. FDA-2014-P-0737) to FDA saying that FDA erred in not granting NCE exclusivity with respect to Wyeth Pharmaceuticals, Inc.’s DUAVEE (conjugated estrogens/bazedoxifene) Tablets (see our previous post here).

Months passed without any word from FDA as to finalization of the guidance.  Some folks were beginning to wonder (and worry) whether or not the Agency would issue a final version of the guidance before the end of 2014.  After all, some NDAs for FDCs that would qualify for NCE exclusivity under FDA’s reinterpretation were scheduled to be acted on before the end of the year, including Eisai Inc.’s AKYNZEO (netupitant/palonosetron) Capsules and Gilead’s HARVONI (ledipasvir and sofosbuvir).  FDA approved both FDCs on October 10, 2014: AKYNZEO under NDA No. 205718 (see here), and HARVONI under NDA No. 205834 (see here).  (Yes, that’s the same day that the final guidance appeared on FDA’s website).

The final version of the guidance that appeared on FDA’s website on the morning of October 10th made only a few changes from the draft guidance.  With respect to applicability, FDA stated:

FDA intends to apply the new interpretation from the date of this guidance’s publication.  Therefore, the new interpretation will not apply to fixed-combination drug products that were approved prior to the publication of this guidance document.

Based on that statement, we knew that denials of the STRIBILD and PREPOPIK Petitions for Reconsideration, as well as a denial of the DUAVEE Citizen Petition, would be coming soon.  Indeed, just a few hours later, those petition denials (here and here) appeared on Regulations.gov.  FDA’s denial of the STRIBILD and PREPOPIK Petitions for Reconsideration notes that “[s]imultaneously with this response, the Agency will issue the Exclusivity Guidance in final form and apply its new interpretation of the relevant statutory and regulatory provisions to fixed-combinations approved from this day forward.” 

FDA’s statements “from this day forward” in the petition denial and “from the date of this guidance’s publication” in the final guidance document caught our attention.  Presumably FDA intends to grant NCE exclusivity for FDCs approved beginning on October 10th (like AKYNZEO and HARVONI).  But does the appearance of the final guidance on FDA’s website constitute publication?  Or is such a guidance document “published” only once a Federal Register notice announcing the guidance is issued?  The answer to that question could generate some controversy.  And even if that’s a non-issue, we may still see some controversy over FDA’s decision not to apply the Agency’s reinterpretation to previously approved FDCs.  We’ll be keeping an eye on the court dockets.