FDA OxyContin Decision Has Generic Drug-Makers Scrambling

On April 18, 2013, the Food and Drug Administration (FDA) posted a notice in the federal register stating that it was withdrawing approval of OxyContin, as approved in 1995, because the drug’s manufacturer had created a reformulated version of the drug with abuse-deterrent properties.  Like other opioid analgesics used for the management of moderate to severe pain, OxyContin has increasingly been abused, particularly via injection and snorting.  Deaths from prescription opioids increased from 4,000 to 14,800 from 1999 to 2008.  In 2008, they resulted in more deaths than heroin and cocaine combined, and in 2010, they accounted for more than 75 percent of all prescription drug overdose deaths. The FDA announced that it had approved Purdue Pharma LP’s (Purdue’s) new labeling for the reformulated version of the drug and would no longer approve abbreviated new drug applications (ANDAs) for generic drugs that referred to the original formulation.  This leaves generic manufacturers without products to market and at the mercy of Purdue’s patent on the new drug, set to last until 2025.

Drug Approval Process

Brand-name drug-makers creating a new drug must submit a New Drug Application (NDA) to the FDA and receive approval, based in part on safety and effectiveness, before marketing the drug.  The FDA sometimes grants manufacturers marketing exclusivity of the drug for a period of three years.  Manufacturers who receive FDA approval do not face competition from generic drug-makers until their patent and/or exclusivity periods expire.  Once those time periods have expired, generic drug makers are permitted to file ANDAs that demonstrate bioequivalence to the drug in the NDA, sometimes referred to as the “innovator” or “reference” drug.  The ANDA process is abbreviated because there is no need for ANDA applicants to submit pre-clinical or clinical trials regarding safety and effectiveness.  The patent for the version of OxyContin that received FDA approval in 1995 was set to expire this month, and generic drug-makers were poised to take advantage of the newly open market; in fact, both Teva Pharmaceuticals Industries, Ltd. and Impax Laboratories, Inc. had already filed ANDAs referencing original OxyContin.

Mixed Motives?

Generic pharmaceutical manufacturers and others worry that Purdue pursued patent and NDA approval for reformulated OxyContin as a way of maintaining its stronghold on the market, rather than a legitimate attempt to curb prescription drug abuse. The Generic Pharmaceuticals Association submitted comments to the FDA in 2011, suggesting that companies were developing abuse-deterrent versions of existing drugs as a form of “product protection.” Sheldon Bradshaw, co-chair of Hunton & Williams’ FDA practice group and former chief counsel of the FDA was more blunt. “Companies will develop a new formulation that’s tamper resistant, get a patent on that technology and then withdraw the old formulation once the new one is approved.”  In light of the FDA’s decision, generic drug-makers must develop their own abuse-deterrent formulation of opioid analgesics, being careful not to infringe on Purdue’s patent; their other option is to wait until the patent’s expiration in 2025 to file an ANDA.

Future of Abuse-Deterrence

While the generic pharmaceuticals industry worries about its future, others are largely praising the FDA for its decision. Senators Tom Coburn (R-OK) and Fred Upton (R-MI) issued a joint statement, noting, “It is clear that Commissioner Hamburg and her staff carefully reviewed the available scientific data to make a regulatory decision in the best interest of patients. We believe this decision will help protect patients and consumers while thwarting abuse.  Our hope is that FDA builds upon this decision to promote patient safety and prevent further abuse of opioids.” Endo Health Solutions, Inc. has also reformulated its opioid painkiller, Opana, and is hoping that FDA will grant its NDA, although the FDA reviews such applications on a case-by-case basis, weighing the risks and benefits of the new formulations.  Given that the government is encouraging reformulation, expect more brand-name drug manufacturers to embark on the process–but don’t expect the generic manufacturers to remain silent.