Court Permits FDA to Carve Out Indications, Despite Brand Name’s Orphan Drug Status

A United States District Court has decided generic versions of aripiprazole (Abilify®) may proceed to market despite the brand name drug’s orphan drug status.  On April 28, 2015, the FDA approved four generic versions of aripiprazole (Abilify®), which is marketed and sold by Otsuka America Pharmaceutical, Inc.  Otsuka sought a temporary restraining order that would have blocked the marketing of these products based on its orphan drug exclusivity.  The District Court of Maryland denied Otsuka’s request. Otsuka Pharmaceutical Co., Ltd. v. Sylvia Mathews Burwell, et al.Case No. GJH-15-852 (D. Md. filed Apr. 29, 2015).

Background.  The FDA first approved aripiprazole in 2002 for the treatment of schizophrenia.  Since that time, the FDA has approved aripiprazole for the treatment of Bipolar I Disorder in both adult and pediatric patients, for certain aspects of autism, and as an add-on treatment for depression in adults.  In 2006, the FDA granted Otsuka “orphan drug” designation for the treatment of Tourette’s Syndrome in children and adolescents, which triggered an attendant seven-year period of market exclusivity.  See 21 U.S.C. § 360cc(a).

The Arguments.  Otsuka argued (1) FDA regulations require generic drug companies to include pediatric indications for Tourette’s syndrome, and (2) such labeling would violate Otsuka’s orphan drug exclusivity.  With respect to the first prong of its argument, Otsuka argued that the FDCA directly addresses the question of when generic drug companies can omit from their labels the pediatric information that is included in the brand’s label.[1] Otsuka argued that the FDCA permitted carve outs in only two circumstances—(1) when that information is protected by patent; and (2) when that information is protected by three-year new clinical study exclusivity.  When the FDA approved Otsuka’s sNDA for Abilify to treat Tourette’s in pediatric patients, the FDCA precluded the FDA from approving an ANDA for a generic version because the generic company cannot satisfy the labeling requirement.  Thus, Otsuka argued, generic drugs should be kept off the market altogether until expiration of its regulatory exclusivity when the generics can properly label their versions.

The FDA, on the other hand, argued that notwithstanding the FDCA’s silence on the issue, the FDA could waive, or carve out, the Tourette’s pediatric indications from the labeling requirement for the generic aripiprazole, thus avoiding the conflict with Otsuka’s exclusivity.

The Decision.  The court found that the FDA, consistent with the FDCA, is permitted to approve generic drugs that omit pediatric labeling.  Applying the Chevron two step analysis, the District of Maryland rejected Otsuka’s narrow reading of section 505A(o).  First, the Court determined that Congress did not make any clear statements to indicate that the exceptions set forth in 505(A)(o) were exclusive.  While the statute confirms that the FDA must approve labeling carve-outs under the identified circumstances, the statute is silent as to whether Congress may grant approval under other circumstances.  The Court went on to find that the FDA had operated within the statutory framework and had done so consistently, such that Otsuka was not likely to prevail on the merits of its arguments and could not be granted a temporary restraining order.

Commenting briefly on the public interest, the Court also recognized the public would suffer a disservice if generic drugs were kept off the market because of orphan drug designation and labeling conflicts.


[1] FDCA § 505A(o) reads “A drug for which an application has been submitted or approved under section 355(j) of this title shall not be considered ineligible for approval under that section or misbranded under section 352 of this title on the basis that the labeling of the drug omits a pediatric indication or any other aspect of labeling pertaining to pediatric use when the omitted indication or other aspect is protected by patent or by exclusivity under clause (iii) or (iv) of section 355(j)(5)(F) of this title.