Last week, FDA denied a Citizen Petition filed by Jazz Pharmaceuticals, Inc (“Jazz”). The May 18, 2012 Petition concerned bioequivalence studies relating to Xyrem® (sodium oxybate), Jazz’s oral solution indicated for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy. Before issuing its decision, FDA received and considered public comment from Roxane Laboratories (“Roxane”), who had an Abbreviated New Drug Application (“ANDA”) referencing Xyrem accepted for review in late 2010.
Jazz asked FDA to take three actions. First, Jazz asked FDA to immediately publish in The Orange Book bioequivalence requirements specifying whether in vitro or in vivo bioequivalence studies, or both such studies, are required for ANDAs referencing Xyrem®. Jazz claimed that FDA’s failure to have done so within the first 30 days of Xyrem®’s approval was a violation of the Federal Food, Drug, and Cosmetic Act (“FD&C Act”) (See 21 U.S.C. § 355(j)(7)(A)(i)-(ii).) and the Administrative Procedure Act (“APA”) (See 5 U.S.C. § 706.). FDA disagreed; the Agency found several flaws with Jazz’s arguments. First, requiring the publication of bioequivalence data type for ANDAs within 30 days of new drug approval would be inconsistent with other sections of the FD&C Act, as well as certain FDA regulations. Second, adopting Jazz’s arguments would require the Agency to generate and evaluate the scientific data needed to understand bioequivalence characteristics at the time the reference listed drug (“RLD”) was approved. FDA disfavored this position, because it would prevent FDA from gaining insight into the characteristics of the RLD during its marketing. Many products never face generic competition, or only do so after the development of acceptable bioequivalence methodologies. As such, FDA reasoned it would be a waste of Agency resources to determine what types of bioequivalence studies are needed within the first 30 days of the RLD’s approval. Third, there is no indication Congress meant the statute to require what Jazz sought, and no court has construed the statute as requiring as much. Finally, FDA noted that Jazz’s interpretation would actually prejudice those who the statute was meant to protect, i.e., the ANDA sponsors. Requiring FDA to publish bioequivalence requirements within 30 days of the RLD approval would diminish FDA’s ability to provide ANDA sponsors with information about the best ways to demonstrate bioequivalence.
Next, Jazz asked FDA not accept for review, review, or approve any ANDA referencing Xyrem® unless and until FDA has published bioequivalence requirements in the Orange Book specifying whether in vitro bioequivalence studies, in vivo bioequivalence studies, or both such studies, are required for ANDAs referencing Xyrem®. Jazz argued that to do so would violate the APA. The drug company reasoned that an ANDA must reference an RLD, and an RLD does not become an RLD until FDA issues the bioequivalence requirements. As such, Jazz concluded that an ANDA can only be accepted for review after FDA issues bioequivalence requirements. Accordingly, Jazz asked FDA to set aside its acceptance of Roxane’s ANDA because this was “agency action . . . without observance of procedure required by law,” “not in accordance with law,” “in excess of statutory jurisdiction, authority, of limitations,” and “short of statutory right.” Again, FDA declined. The Agency claimed that refusing to accept an ANDA on those grounds would conflict with various FD&C Act sections, including Section 505(j)(2)(A), which delineates what information is required in an ANDA and does not list the bioequivalence requirements, as well as certain FDA regulations. It also refused to accept an interpretation of the statute that would punish ANDA applicants, even if in compliance with the statutory requirements, for FDA’s failure to publish the bioequivalence requirements.