In a long sought-after and potentially groundbreaking decision, the US Food and Drug Administration (FDA) has determined that generic non-abuse-resistant formulation of Purdue Pharma's drug Oxycontin (oxycodone HCl) cannot be marketed, citing the drug's original non-abuse-resistant formulation was withdrawn for reasons of safety or effectiveness.
Purdue had been pushing for the decision, arguing its innovations in creating abuse-resistant formulations of the drug have been crucial in making sure it is used safely. It is one of the most abused products in the US, and drugmakers have been playing a cat-and-mouse game for years with addicts who have tried to subvert the abuse-resistant formulations. Some of those formulations delay the drug's release, making it more difficult for users to achieve the high they seek, while others make the drug more difficult to crush. Still others require metabolization to become effective.
In its Federal Register posting on 16 April 2013-the same day Oxycontin was set to lose its patent protection-FDA said that all extended-release tablets, of which there are eight forms, referencing the 20-553 New Drug Application (NDA) used to approve Oxycontin would not be accepted or approved, throwing a significant if not impenetrable roadblock in front of generic manufacturers that had wished to market generic versions of the drug.
Put simply, FDA keeps a list of all approved NDAs and their generic equivalents in a database, more commonly known as the "Orange Book." The agency may not approve abbreviated new drug applications, used to approve generic drugs, if it does not reference an approved NDA.
There is, however, one exception: FDA may approve a drug product if it was withdrawn for reasons not related to its safety or efficacy.
Generic manufacturers have argued that the 553 NDA had not been taken off the market for reasons of safety or efficacy, but that its market removal was done to extend the patent protection for Purdue Pharma's drug.
Public safety officials and Purdue, among others, meanwhile argued that approving generic, non-abuse-resistant painkillers risked fueling an epidemic of abuse that would roll back decades of hard work by law enforcement officials, likely triggering a public health crisis.
Generic Versions Taken Off the Market
In the end, those arguments seemed to resonate with FDA-a conclusion that was not unexpected. In January 2013, FDA Commissioner Margaret Hamburg said in a letter to legislators "if FDA determines that a formulation of a product significantly deters abuse, we have legal authority under the drug approval and drug safety provisions of the Federal Food, Drug and Cosmetic Act to require generic versions of that product to have abuse-deterrent formulations as well."
FDA cited that same reasoning in a press statement released on Tuesday, saying that it had approved new labeling for the drug indicating that "the product has physical and chemical properties that are expected to make abuse via injection difficult and to reduce abuse via the intranasal route (snorting)."
"Additionally, because original OxyContin provides the same therapeutic benefits as reformulated OxyContin, but poses an increased potential for certain types of abuse, the FDA has determined that the benefits of original OxyContin no longer outweigh its risks and that original OxyContin was withdrawn from sale for reasons of safety or effectiveness," the agency added.
"Accordingly, the agency will not accept or approve any abbreviated new drug applications (generics) that rely upon the approval of original OxyContin."
FDA elaborated on the new abuse-deterrent qualities of the drug, noting that they are "more difficult to crush, break, or dissolve," and form a viscous hydrogel" that prevents it from being injected. While abuse is still possible, FDA said the reformulated version was sufficiently abuse-deterrent and that agency officials felt compelled to require generics to have the same abuse-deterrent qualities.