FDA is Sued After Approving Generic Topical Corticosteroid Drug Products; Lawsuit Seeks Withdrawal or Suspension of ANDA Approvals

By Kurt R. Karst –      

In a lawsuit filed in the U.S. District Court for the District of Columbia, Florida-based Hill Dermaceuticals, Inc. (“Hill”) is seeking declaratory and injunctive relief after FDA approved, on October 17, 2011, three ANDAs submitted by Identi Pharmaceuticals Inc. (“Identi”) – ANDA Nos. 091306, 201759, and 201764 – for AT-rated generic versions of Hill’s peanut-oil containing fluocinolone acetonide drug products Derma-Smoothe/FS Topical Oil, 0.01% (Scalp Oil and Body Oil) and Derm-Otic Oil Ear Drops, 0.01%, which are approved under NDA No. 019452 to treat certain moderate to severe skin conditions, such as eczema and atopic dermatitis.  Copies of the Complaint and Motion for a Preliminary Injunction are available here and here. 

The lawsuit comes more than two years after FDA partially granted and denied a citizen petition submitted by Hill in September 2004 (Docket No. FDA-2004-P-0215) requesting that FDA, in light of the “novel and innovative application and delivery systems” of Derma-Smoothe, withhold approval of any ANDA unless certain requirements are met concerning active ingredients, conditions of use, labeling, bioequivalence, and chemistry, manufacturing and controls.  Among other things in the petition decision, FDA, in response to Hill’s requests that the Agency require ANDA sponsors to set an upper limit for the amount of peanut protein that can be present in the vehicle and to demonstrate that their peanut oil meets this specification by using a test that is “validated and capable of quantifying very low levels of peanut protein,” stated that “[g]iven the gap between the quantity of orally administered peanut proteins required to cause an allergic reaction and the level of peanut proteins left in fully refined peanut oil, it is reasonable to conclude that the USP NF refining process reduces peanut protein to acceptable levels for the indications in question.”  Hill also requested that FDA categorically reject any request from an ANDA sponsor for a waiver of in vivo bioequivalence testing (i.e., “biowaiver”) for a generic Derma-Smoothe drug product.  FDA denied this request, stating that the Agency could grant a biowaiver because Derma-Smoothe “is a solution for purposes of 21 C.F.R. § 320.22(b)(3).”

FDA decided Hill’s citizen petition more than a year after the D.C. District Court denied Hill’s motion for a stay to prevent the approval of any ANDAs for generic Derma-Smoothe until FDA issues a substantive response to Hill’s September 2004 citizen petition.  At that time, the court stated that Hill “would have an opportunity to seek emergency relief from this Court once the FDA denied its citizen petition and improperly approved an ANDA.” 

Hill’s five-count Complaint alleges that FDA’s approval of the Identi ANDAs violates various provisions of the FDC Act and the Administrative Procedure Act (“APA”).  For starters, Hill alleges that contrary to the statutory requirement at FDC Act § 505(j)(2)(A)(v) that the labeling for a generic drug be “the same” as the labeling approved for the brand-name, reference listed drug relied on for approval, “the generic forms of fluocinolone acetonide that FDA has approved will almost certainly include labeling that is substantially different from the labeling used on Hill’s products.  In particular, the generic labeling cannot be the same as the labeling on Hill’s products because Identi’s products have not been subjected to the same tests that FDA has required Hill to perform to protect against serious risks associated with peanut allergies.”  And even if the Hill and Identi drug products do have the same labeling, says Hill, “then the generic drug is misbranded” under the FDC Act.  According to Hill:

[I]f the labeling for Identi’s products includes the same representation as the FDA-approved labeling for Hill’s products – namely, “that the, product is routinely tested for peanut proteins through amino acid analysis; the quantity of amino acids is below 0.5 parts per million (PPM)” – that would not be a truthful statement.  In addition, because the labeling does not provide accurate information about the quantity of residual peanut protein and suggests that Identi’s products have been tested in the same manner as Hill’s products, the labeling omits material facts and lacks adequate information for use.  Accordingly, because the labeling for Identi’s products are false and misleading and otherwise do not comply with the statutory requirements, the purported generic drugs are misbranded and may not be sold or marketed.

Moving on to the APA, Hill alleges that FDA violated the law by not treating like cases alike and by imposing arbitrary and unequal burdens on similarly situated parties.  “FDA has violated these settled principles of reasoned decision-making by, on one hand, compelling Hill to invest millions in developing and performing a proprietary test to determine and control the quantity of residual peanut proteins in its products on an ongoing basis and, then, on the other hand, not requiring generic manufacturers to satisfy the same onerous and important testing requirements,” says Hill in its Motion for a Preliminary Injunction.

Finally, Hill alleges that FDA violated the FDC Act in approving Identi’s ANDAs without adequate testing data:

[T]he FDCA requires applicants seeking to obtain approval through the ANDA process to demonstrate that the purported generic product is bioequivalent to the approved.  Identi cannot satisfy that requirement because its products have not undergone adequate testing. . . .  Nor do Identi’s products satisfy the regulatory criteria for waiving the requirement that Identi establish in vivo bioequivalence.  The products manufactured by Hill are topical oils and do not qualify as “solutions” subject to the limited biowaiver exception under 21 C.F.R. § 320.22(b)(3)(i).  Similarly, the products do not fall within the catch-all provision for products in a “similar other [solubilized] form.”  [(Citations omitted)]

Hill is seeking from the DC District Court declaratory and injunctive relief, including the entry of a preliminary and permanent injunction directing FDA to withdraw or suspend the Identi ANDA approvals, require Identi to conduct in vivo bioequivalence testing and to use the “same labeling” before approving such ANDAs, and to take any action necessary “to prevent the marketing and distribution of purported generic products that are not bioequivalent to, and do not use the same labeling as,” the Derma-Smoothe product line.