A Second Company Asks FDA to Reconsider Denial of NCE Exclusivity for Approved FDC . . . and to Stay Application of the Agency’s New Interpretation

By Kurt R. Karst –

The battle over New Chemical Entity (“NCE”) exclusivity for Fixed-Dose Combination (“FDC”) drugs continues to heat up.  In a recent Petition for Reconsideration and Petition for Stay (Docket No. FDA-2013-P-0119), Ferring Pharmaceuticals, Inc. (“Ferring”) requestes that FDA reconsider its denial of NCE exclusivity for PREPOPIK (sodium picosulfate, magnesium oxide and citric acid) for Oral Solution.  Ferring also requests that FDA stay application of a new interpretation of the FDC Act to award NCE exclusivity to certain newly approved FDCs until the issues Ferring raises are resolved.

As we previously reported, on February 21, 2014, FDA denied three Citizen Petitions requesting that the Agency award NCE exclusivity to three previously approved FDCs containing an NCE and a previously approved drug.  Those petitions concern STRIBILD (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate) Tablets (Docket No. FDA-2013-P-0058), PREPOPIK (Docket No. FDA-2013-P-0119), and NATAZIA (estradiol valerate and estradiol valerate/dienogest) Tablets (Docket No. FDA-2013-P-0471).  On the same day FDA issued its petition response, the Agency announced that upon finalization of a draft guidance document, the Agency would reinterpret the NCE exclusivity provisions of the FDC Act to award NCE exclusivity for a newly approved FDC containing an NCE and a previously approved drug.  FDA refused to apply its new interpretation to previously approved drugs, such as PREPOPIK.  The 60-day comment period on FDA’s draft guidance document expires on April 25th, but it is unclear how quickly FDA will act to finalize the draft guidance. . . . and whether or not there will be a legal challenge to FDA’s reinterpretation of the statute.

Ferring is the second company to request that FDA reconsider its denial of NCE exclusivity.  As we recently reported, Gilead Sciences, Inc. (“Gilead”) submitted a Petition for Reconsideration asking FDA to rethink its position with respect to STRIBILD, and to refuse to accept any ANDA or 505(b)(2) application for a drug product containing either of the two NCEs in STRIBILD – elvitegravir and cobicistat – under the rules governing NCE exclusivity.  According to Gilead, none of the reasons FDA cites in its petition response, such as recognizing NCE exclusivity would burden sponsors with pending applications, fit the circumstances surrounding STRIBILD.

Ferring raises some of the same points in response to FDA’s petition denial as Gilead does in its reconsideration request.  According to Ferring:

• The Commissioner’s statutory interpretation of the five-year exclusivity provisions for fixed-combinations with at least one novel drug substance is the only correct interpretation, and must be applied to all relevant applications.  No change in the Agency's regulations is required legally or technically.
• The Commissioner failed to adequately consider all points raised in the original Citizen Petitions, including wildly inconsistent exclusivity results under its umbrella policy and the support in the legislative history for five-year exclusivity for fixed-combinations with novel ingredients.
• Due Process and fairness require that five-year exclusivity be recognized for all applicable drug applications with remaining exclusivity, particularly Ferring’s Prepopik.
• The Commissioner should adopt Petitioners’ statutory interpretation immediately.  The Commissioner’s decision to implement the interpretation prospectively at some indefinite future date (i.e., through final guidance) is arbitrary and capricious action that cannot be considered reasonable when all relevant factors are considered.

Among other things, Ferring highlights an alleged “irrational and arbitrary nature” of FDA’s application of the Agency’s “old rules” concerning NCE exclusivity for FDCs containing a new and a previously approved drug, and cites FDA’s recent approval of NDAs for alogliptin as a prime example.  As we previously reported, in the case of alogliptin, FDA approved three NDAs on the same day – one NDA for single-entity alogliptin (NDA No. 022271), and two NDAs for FDCs containing alogliptin and a previously approved drug (NDA Nos. 022426 and 203414).  FDA was careful to note that single-entity alogliptin (NDA No. 022271) was approved first in the day, thereby preserving NCE exclusivity for NDA No. 022271, and allowing that NCE exclusivity to apply under the Agency’s “umbrella exclusivity policy” to the other two approved NDAs.  According to Ferring:

This concocted process [] clearly shows the arbitrary nature of FDA’s current interpretation of the [statute’s] exclusivity provisions.  Based on FDA’s current (i.e., pre-Citizen Petition) policy on exclusivity, if either of the combination products had been deemed to have been approved first, none of the products would have been able to obtain five years of exclusivity, regardless of the fact that the same amount of effort would have been involved in the drug development process.  These conclusions produce precisely the type of result that courts have feared, whereby exclusivity periods are based on the order of NDA approval rather than any scientific, technical, economic, or other rationale.  Interpretation of the statute in a manner that permits such outcomes, when there is an alternate valid interpretation (one which FDA acknowledges in its decision), is arbitrary and capricious in violation of the Administrative Procedures Act (“APA”).  FDA’s approach here highlights the fears raised by the courts about the Agency juggling or manipulating the timing of approvals to accomplish a preconceived goal that affects intellectual property (here, market exclusivity) rights.  In fact, it raises those fears by orders of magnitude.

Ferring also objects to FDA’s decision to announce a new interpretation of the FDC Act’s NCE exclusivity provisions in guidance.  According to Ferring, that decision was legally incorrect and creates significant regulatory uncertainty:

This decision to issue draft guidance for public comment was legally incorrect because draft guidance is not binding, does not create or confer rights, is intended to help industry carry out its obligations, and may be deviated from in appropriate circumstances.  FDA’s change in statutory interpretation here is in fact binding, does create rights, is meant to help FDA (not industry) carry out an obligation, and cannot be departed from lest individual FDA reviewers decide to award exclusivity however they see fit.  Guidance is therefore not the appropriate legal means to implement FDA’s change in statutory interpretation with respect to NCE exclusivity for fixed-combination drug products. [(Emphasis in original)]

Instead, says Ferring, FDA should have regulated directly from the statute and immediately implemented its new interpretation of the NCE exclusivity provisions. 

Clearly, the battle over NCE exclusivity for FDCs is far from over.  To date, there has been verly little comment on FDA’s proposed reinterpretation of the FDC Act’s NCE exclusivity provisions.  Docket watchers will be looking closely at the docket this week as the 60-day comment period draws to a close.  And speculation on the timing of a final guidance will likely begin to grow.