PLAN B Revisited: FDA Rules on One-Step Exclusivity and ANDA Labeling Carve-Outs

By Kurt R. Karst –      

Even before FDA gave up an appeal of Judge Edward R. Korman’s April 2013 Judgment and Order that Teva Branded Pharmaceutical Products R&D, Inc.’s (“Teva’s”) PLAN B One-Step (levonorgestrel) Tablets, 1.5 mg (“PBOS”), be made available Over-the-Counter (“OTC”) without age or point-of-sale restrictions (see our previous post here), we were wondering how FDA was going to address approval of generic versions of the drug product in light of 3-year marketing exclusivity the Agency had, at the time, indicated it would grant to Teva’s PBOS NDA No. 021998 (see our previous post here).  Of course, FDA ultimately did grant exclusivity based on two supplemental NDAs the Agency approved: one on April 30, 2013 (S-002) to make PBOS “available over the counter to women of childbearing potential aged 15 years and over who are in need of emergency contraception,” and another (S-003) on June 20, 2013 to make PBOS “available as a nonprescription product without point-of-sale or age restrictions” consistent with Judge Korman’s April 5, 2013 Order.  Under FDA’s so-called “balance exclusivity policy,” those exclusivity periods both expire on April 30, 2016, and are identified in an Orange Book addendum as “RTO*” (defined as “OTC USE FOR WOMEN AGES 15 AND 16”) and “RTO**” (defined as “OTC USE FOR WOMEN 14 AND BELOW”).  Subsequently, questions arose as to the scope of those exclusivity periods and whether an ANDA sponsor could “carve out” of its labeling the exclusivity-protected information.  FDA addresses both of those questions in a February 25, 2014 “Dear NDA/ANDA Applicant” letter.

Before we delve into FDA’s determination, we feel the need to address what is to us a new exclusivity term: “balance exclusivity.”  Certainlty we’re all familiar with “umbrella exclusivity” in the 5-year New Chemical Entity exclusivity space.  As we mentioned earlier this week, FDA explained “umbrella policy” in the July 10, 1989 preamble to the proposed rule implementing the Hatch-Waxman Amendments.  There, FDA said:

[W]hen exclusivity attaches to an active moiety or to an innovative change in an already approved drug, the submission or effective date of approval of ANDA’s and 505(b)(2) applications for a drug with that active moiety or innovative change will be delayed until the innovator’s exclusivity has expired, whether or not FDA has approved subsequent versions of the drugs entitled to exclusivity, and regardless of the specific listed drug product to which the ANDA or 505(b)(2) application refers.

“Balance exclusivity” is somewhat similar, but occurs in the 3-year exclusivity space.  As FDA explains it:

If an application or supplement earns 3-year exclusivity because it is approved based on new clinical studies that are essential to approval conducted by or for the applicant and the same applicant subsequently obtains approval of an additional application or supplement that references those same clinical studies, technically the studies are no longer “new” for purposes of the second supplement and the change approved in the subsequent application or supplement is not eligible for its own exclusivity period.  Under FDA’s longstanding practice, however, if the studies are essential to the approval of the subsequent application or supplement, the subsequent application or supplement would be eligible for the balance of the previously awarded exclusivity period such that its 3-year exclusivity will end on the same date as that of the application or supplement that obtained the original exclusivity period.  This practice (known informally as the “balance exclusivity” policy) encourages innovation by protecting the 3-year exclusivity previously awarded and expanding its scope when the studies are essential to additional labeling changes that were not approved when the supplement was approved initially, without providing additional exclusivity time for studies that are no longer “new.”

In any case, moving on to FDA’s rulings on the scope of the PBOS exclusivity periods and whether ANDA sponsors can omit the protected information from their labeling, FDA first addresses that to which the exclusivity attaches.  Teva apparently argued that the exclusivity should be tied to all point-of-sale restrictions, as well as to the nonprescription use of PBOS.  At a minimum, argued Teva, generic PBOS sold over the counter must be subject to point-of-sale restrictions that prevent those generic versions  from being dispensed to women 16 and under.  FDA disagreed:

In FDA’s view, however, this characterization of the exclusivity is too broad and Teva’s proposal for conditions on ANDA labeling and marketing is too restrictive.  In the absence of the actual use study in women ages 16 and below, and prior to the approval of S-002 and S-003, PBOS was already approved for use without a prescription in women ages 17 and older.  It has been approved for nonprescription use in this age group since 2009.  As of the April 30, 2013 approval of S-002, Teva’s actual use study was determined to be essential to approval of PBOS for nonprescription use in 15 and 16 year olds.  The change approved in S-003 on June 20, 2013, for which the actual use study was essential was the approval of PBOS for use without a prescription in women ages 14 and below. It is nonprescription use in these populations (women ages 15 and 16 and women ages 14 and below) which Teva’s PBOS exclusivity protects. . . .

Although PBOS may now be sold on the retail shelf because there is no longer a prescriptiononly requirement for any of the intended population, this does not mean that Teva is entitled to broad exclusivity covering PBOS’s status as a nonprescription product for women of all ages.  Rather, Teva has been and should be granted exclusivity incrementally and sequentially for what its studies showed (i.e., that PBOS can be labeled for safe and effective use in a nonprescription setting first by women 17 and older, then by 15 and 16 year old women, and finally by those ages 14 and below), not for the regulatory consequences in terms of packaging or retail availability that may follow from these conclusions.

From there, it seems that it was relatively easy for FDA to conclude that ANDA sponsors could omit the exclusivity-protected information.  According to FDA:

Given that the actual use studies were essential to approval of PBOS for nonprescription use for women ages 16 and below and given that exclusivity covers nonprescription use of PBOS in this population, it follows that the labeling for ANDAs referencing PBOS should carve out nonprescription use of PBOS in this age group.  With the carved out labeling, the ANDAs will not be approved for any of the age groups which Teva’s actual use study (and Teva’s exclusivity) covered.  FDA declines to require ANDAs to bear additional labeling on the principal display panel that reinforces the age limit and declines to impose point of sale restrictions on the approved ANDAs. FDA has concluded that additional labeling of the type Teva proposes and any point of sale restrictions to limit actual sales to the various populations are not appropriate, nor are they necessary for safe use of the generic versions of the PBOS product.  The labeling protected by Teva’s exclusivity does not contain information that is required for safe and effective use of a generic product for the unprotected uses.  Therefore, FDA may approve ANDAs referencing PBOS that omit reference in labeling to use by the age groups as to which Teva has exclusivity (i.e., 15 and 16 year old women, and those 14 and below).

Whether FDA’s exclusivity and labeling carve-out determinations will be challenged in court remains to be seen.  If so, another chapter in the storied history of PBOS will begin.