“Opioid Spring” Blossoms: FDA Finds “Original” OXYCONTIN Discontinued for Safety or Effectiveness Reasons; Will Not Accept or Approve ANDAs

April 16, 2013

By Kurt R. Karst –      

The cherry blossoms are finally in full bloom in Washington, D.C., and so too is FDA’s thinking on one non-abuse-deterrent drug.  In a prepublication version of a notice that will be published in the Federal Register on April 18, 2013, FDA has determined that OXYCONTIN (oxycodone hydrochloride controlled-release) Tablets, 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, 80 mg, and 160 mg, approved under NDA No. 020553, have been discontinued for reasons of safety or effectiveness.  The highly anticipated decision was made on the same day that U.S. Patent No. 5,508,042 was set to expire, potentially paving the way for ANDA approvals, and on the same day FDA announced the approval of abuse-deterrent labeling for a reformulated version of OXYCONTIN approved under NDA No. 022272 (presumably in accordance with FDA’s draft guidance on the topic – see here).  The move also comes just a day after resolutions were introduced in the U.S. Senate (S. Res. 97) and House of Representatives (H. Res. 161) expressing the sense that FDA should encourage the use of abuse-deterrent formulations of drugs.  (Congress is currently considering legislation – the Stop Tampering of Prescription Pills Act of 2013 (H.R. 486) (see our previous post here) that would establish new requirements for tamper-resistant drugs.  In addition, several Members of Congress and the National Association of Attorneys General recently urged FDA to adopt standards requiring manufacturers and marketers of generic prescription opioids to develop tamper-resistant versions of such products (see here and here).)

FDA’s decision was made in response to several Citizen Petitions submitted to the Agency over the past 12 years (Docket Nos. FDA-2001-P-0238, FDA-2010-P-0526, FDA-2010-P-0540, and FDA-2011-P-0473), but primarily after FDA approved NDA No. 022272 on April 5, 2010 for a reformulated version of OXYCONTIN with physicochemical properties that are intended to make the drug product more difficult to manipulate for purposes of abuse or misuse.  Just days later, Purdue Pharma, L.P. (“Purdue”), the sponsor of both OXYCONTIN drug products, notified FDA that the company ceased shipment all of the strengths of the original version of OXYCONTIN, and FDA then moved the drug products to the “Discontinued Drug Product List” section of the Orange Book.  Under FDA’s regulations at 21 C.F.R. § 314.161, the Agency must determine whether a listed drug that has been voluntarily withdrawn from sale was withdrawn for safety or effectiveness reasons before approving an ANDA for a generic version of the drug.

According to FDA’s notice concerning original OXYCONTIN:

FDA has conducted an extensive review of data available to the Agency regarding reformulated OxyContin, including in vitro, pharmacokinetic, clinical abuse potential, and postmarketing study data.  The data show that, when compared to original OxyContin, reformulated OxyContin has an increased ability to resist crushing, breaking, and dissolution using a variety of tools and solvents. . . .

FDA has long considered the abuse potential of a drug in numerous regulatory contexts.  Where appropriate, FDA may take into account abuse potential as part of the safety profile of a drug when weighing its benefits and risks.  In this case, FDA has considered the abuse potential as part of the Agency’s determination of whether the original formulation of OxyContin was withdrawn from sale for reasons of safety or effectiveness.  This approach is particularly appropriate here in light of the extensive and well-documented history of OxyContin abuse.

Original OxyContin has the same therapeutic benefits as reformulated OxyContin.  Original OxyContin, however, poses an increased potential for abuse by certain routes of administration, when compared to reformulated OxyContin.  Based on the totality of the data and information available to the Agency at this time, FDA concludes that the benefits of original OxyContin no longer outweigh its risks.

As a result, original OXYCONTIN will be removed from the Orange Book entirely and FDA will not approve any ANDA for a generic version of the drug product. 

FDA’s decision might have been foreshadowed by an April 15th approval of a supplement to NDA No. 022272 for reformulated OXYCONTIN concerning modifications to the approved Risk Evaluation and Mitigation Strategy (“REMS”) for the drug (among other drugs identified in Appendix 1 to the approval letter).  According to the approval letter, FDA approved REMS modifications, including “[r]evision to the REMS document to remove ANDA holders from the Timetable for Submission of Assessments.”  (Additional information on FDA’s REMS for extended-release and long-acting opioids is available here.)

Still pending at FDA is a Citizen Petition (Docket No. FDA-2012-P-0895) Endo Pharmaceuticals Inc. (“Endo”) submitted to FDA last August requesting that the Agency determine that the company’s non-crush-resistant formulation of OPANA ER (oxymorphone HCI) Extended-release Tablets approved under NDA No. 021610 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.  An FDA decision on that petition is expected in May.  Last November, Endo sued FDA seeking a preliminary injunction ordering FDA to make a decision on the Citizen Petition by December 31, 2012 (see our previous post here).  On December 19, 2012, the D.C. District Court denied the motion and dismissed the case.

A natural question raised by FDA's decision on original OXYCONTIN is whether it has any read-through to the upcoming FDA decision on Endo's OPANA ER Citizen Petition.  Whether it does (and the extent to which it does) or not will likely be debated at length over the next few weeks.  Within hours of FDA releasing its OXYCONTIN decision, RBC Capital Markets was already commenting that “FDA is likely taking a 'case by case' approach and the risk/benefit for generics of OxyContin may not be the same as for Opana.”

It is unclear whether any ANDA sponsor will challenge FDA’s determination on original OXYCONTIN in court.  If someone does, however, rest assured that we will be on the case.

Categories: Hatch-Waxman