Endo Sues FDA; Seeks Court Orders for FDA Determinations on the Discontinuation of “Old” Opana® ER and With Respect to Approved and Pending ANDAs

December 2, 2012

By Kurt R. Karst –    

Last Friday afternoon, Endo Pharmaceuticals Inc. (“Endo”) filed a Complaint and a Motion for Preliminary Injunction in the U.S. District Court for the District of Columbia seeking declaratory and injunctive relief concerning the company’s non-crush-resistant formulation of Opana® ER approved under NDA No. 021610 (identified in Endo’s Complaint as “Original Formulation Opana® ER”).  Endo alleges that FDA violated the FDC Act and the Administrative Procedure Act by failing to make a determination as to whether Original Formulation Opana® ER, which was discontinued from marketing earlier this year, was withdrawn for reasons of safety.  Endo currently markets a crush-resistant version of Opana® ER approved under NDA No. 201655 (identified in Endo’s Complaint as Opana® ER CRF).  Endo is also seeking a preliminary injunction ordering FDA to make a decision by December 31, 2012 on whether Original Formulation Opana® ER was discontinued for safety reasons.  FDA has approved two ANDAs for generic versions of Original Formulation Opana® ER – ANDA No. 079087 (Impax) and ANDA No. 079046 (Actavis) – and the companies are expected to begin marketing their drug products on January 1, 2013.  In the interim, Endo wants a court order directing FDA to withdraw or suspend those approvals.

The lawsuit follows a pair of citizen petitions Endo submitted to FDA in August. The first Citizen Petition (Docket No. FDA-2012-P-0895) requests that FDA determine that Original Formulation Opana® ER was discontinued for reasons of safety and can no longer serve as the basis of approval for an ANDA, that FDA refuse to approve any pending ANDA for a generic version of Original Formulation Opana® ER, and that FDA suspend and withdraw the approval of any ANDA referencing Original Formulation Opana® ER as its basis for approval.  The second Citizen Petition (Docket No. FDA-2012-P-0951), which was recently supplemented, primarily concerns the requirements to obtain approval of an ANDA for a generic version of Opana® ER CRF, but also brings Original Formulation Opana® ER into the mix.

“FDA has not carried out its responsibility under 21 C.F.R. § 314.161(a) to make a determination sua sponte as to whether Endo discontinued Original Formulation Opana® ER for reasons of safety,” alleges Endo.  That regulation requires FDA to determine, prior to approving a pending ANDA that refers to a drug product that is no longer marketed, and “[w]henever a listed drug is voluntarily withdrawn from sale and [ANDAs] that referred to the listed drug have been approved,” whether such discontinuation was for reasons of safety or effectiveness.  In addition, the statute (FDC Act § 505(j)(4)(I)) and FDA’s implementing regulations ( 21 C.F.R. § 314.127) provide that FDA may refuse to approve an ANDA if the Agency determines that the RLD was withdrawn from sale for reasons of safety or effectiveness, and that FDA can suspend and withdraw approval of an ANDA if the Agency determines that the RLD was withdrawn from sale for reasons of safety (FDC Act § 505(j)(6)). 

“FDA has not taken any action in response to either of Endo’s Citizen Petitions or its recent Supplement that sought to prod the agency into fulfilling its statutory and regulatory obligations, triggered by Endo’s May 31, 2012 Notice that it had withdrawn Original Formulation Opana® ER,” says Endo.  Moreover, Endo alleges that FDA has failed to make the legally required discontinuation determination despite

mounting evidence of the public health crisis caused by abuse and misuse of prescription opioid pain relievers; FDA’s awareness that opioid pain relievers that are manufactured without safety features are more susceptible to abuse; FDA’s exhortations to pharmaceutical companies to invest in innovative crush-resistant formulations of opioid pain relievers; Endo’s data demonstrating the safety benefits of Opana® ER CRF over non-crush-resistant versions of the drug; the documented “squeezing-the-balloon effect,” whereby opioid abusers can be expected to quickly learn of and migrate to generic non-crush-resistant formulations, i.e., those pills that may be readily crushed and snorted; and FDA’s knowledge that a non-crush-resistant generic version of Opana® ER is poised to launch on or about January 1, 2013.

The issue of simultaneous marketing of abuse-deterrent brand-name drugs and non-abuse-deterrent generic drugs has been heating up over the past year – not only here in the United States, but, for example, in Canada as well. 

In addition to Opana ER, FDA has received several citizen petitions (Docket Nos. FDA-2011-P-0473, FDA-2010-P-0540, and FDA-2010-P-0526) requesting that the Agency determine whether the abuse-deterrent version of OxyContin (oxycodone hydrochloride) Controlled-Release Tablets was discontiued for safety reasons.  Congress has also expressed interest in the topic with the introduction of the Stop Tampering of Prescription Pills Act of 2012 (“STOPP Act”) in July.  As we previously reported, the STOPP Act would amend the FDC Act to, among other things, establish new requirements for the approval of brand-name and generic drugs that are otherwise available in a tamper-resistant formulation, and deem the discontinuation of a non-abuse-deterrent drug after the approval of an abuse-deterrent to be a discontinuation for safety reasons.